What do I need to know for the exam?

A non-relevant crab. Nice photo though

Nothing. I'm not sitting the exam. You are. And what do you need to know? Well, everything. At this level, Biology involves a lot of memory work. The exam gets you to recall information and in a few cases apply this information.
A few hints:


Read the question.
I mean really read the question. What is it asking you? Sometimes there might be a slab of information and a nice little diagram of say, a cellular response to insulin. But the question may be something like "Define homeostasis". You're not required to talk about insulin, biochem pathways, signal transduction. Its asking for a definition.


Rule out answers.
Sometimes you might get a multiple choice question you don't know. Instead of not answering, rule out answers that are definitely incorrect. If you know that A and D are NOT the answer, but you are unsure about B and C, just by ruling out two of the answers you've increase the chance of getting that question right from a 1 in 4 chance to a 1 in 2.


Limit your answers:
You've studied hard and when you come to the short answer question you want to demonstrate this. Try and hold back a little. If the question is worth 1 mark, they are after a term or word or definition. If the question is worth 2 marks the question requires you to answer two things. Writing a mini essay may make you feel better but the examiner does not want to know everything you know about hormones for example, but may just need to know that steroid hormones are lipid-based and the receptors for these are within the target cell. Writing slabs of information runs the risk of contradicting yourself (no marks), writing something that is incorrect (no marks) or running out of time for a later question (no marks). Be clear and concise.


Practice:
Do previous exams. As many as you can. And complete them under exam conditions. Limit yourself to 1.5hrs. Then go back and read the examiners report/check your answers. Make a list of questions you got wrong. Know why you got these wrong. Is the list similar over several different exams? Are there areas you need to revise? Don't do prac exams while listening to music. It makes it harder to recall the information without the music. Also, I don't believe in study groups. I don't think they benefit everybody equally and tend to waste a huge amount of time but that is a personal view.


Seek help:
See your teacher, ask for their help. And when seeking help ask specific questions. Rather than "explain immunity to me", perhaps a better approach might be "I'm a little confused over the difference between humoral and cell mediated immunity". If help is offered, take it. If it isn't offered, ask. And a couple of days before your exam is too late. See your teacher. Email them. Pester your tutor / older sibling at university / cousin Jimmy who is smart.  Believe it or not, teachers love students who ask them questions or seek their help. It validates an otherwise meaningless existence. And for those of you who know me, email me anytime.


Don't study the night before:
If you don't know it by now, you are up the proverbial creek. You will get out of this exam a result proportional to the effort you have put in this year and over the last 13. Relax, watch TV, go out for dinner with a friend and get an early night. I suggest drinking several large mugs of chamomile tea before you go to bed. Might make you want to pee, but will help you sleep.


Believe in yourself:
You are awesome. Yep, you. Remember this always.


Good luck!

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Here is a practice exam. Here is another. Answers for the first and second. And a third with answers.

Here is a link to the VCE study guide. Look at the dot points on pages 21 -23. This is what you need to know. Make a list of dot points for each of the points in the study guide.

Here is something I found online. It's a 37 page Unit 3 summary

And here is a link to podcast for the entire Unit 3. Return to this link as they'll be posted over Unit 4 as well.

Allergies and Autoimmune disorders

Our immune system is incredible in its complexity and efficiency . However, occasionally, stuff goes wrong. Your body many initiate an immune response to an injury such as a sprain or over-respond to a foreign body, such as pollen and the hay fever that comes with it, or at the more severe end of the scale, fail to recognise self cells as self and begin to attack them, such as some forms of arthritis.

Autoimmune Disorders

It is not clear why the immune system initiates a response against its own tissues in the case of autoimmune disorders. In some cases foreign pathogens and antigens the body has been previously exposed to are similar in structure to some of our body’s own protein markers which can cause immune cells to ‘see’ these cells and tissues as foreign and commence an immune response by attacking them. Rheumatoid arthritis is an autoimmune disorder that primarily affects synovial joints such as the joints in your fingers and hand. Contracting rheumatic fever earlier in life may lead to the formation of antibodies that later mistakenly attack the connective tissue in your joints causing this type of arthritis. (Note: Not all arthritis is an autoimmune disease. If mentioning this in an exam you must say rheumatoid arthritis)

Autoimmune disorders may cause destruction of tissues, changes in organ function or abnormal organ growth. Examples of autoimmune disorders include Multiple Sclerosis (MS), Type 1 Diabetes and Celiac Disease.

This is not that detailed but the information you are required to retain and regurgitate come exam time is not in that much depth. If you don’t believe me, look at your textbook.

Allergies

Allergies are a term that covers the hypersensitivity response of the body. This is a response that is more severe or exaggerated than a response that is considered normal and differs from person to person. The reactions to an allergen is a response to immunological memory – your body remembers these antigens and renewed exposure triggers a fast and massive response. Come spring when the warm northerly winds bring high levels of pollen south to Melbourne, there is a dramatic increase in the cases of hay fever. It works like this: your body develops specific IgE on lymphocytes in response to first exposure to the pollen (or any other antigen). The next year when the winds blow the pollen south again the lymphocytes rapidly produce a large number of antibodies that are secreted and attach to mast cells. When the antibody-attached mast cells come in contact with the pollen the mast cells rupture releasing histamine, triggering an inflammatory response. Swelling of the tissues around the eyes, nose and throat, excessive mucus production, itchiness and all the other symptoms of hay fever. In an allergic or hypersensitive person this reaction is much more severe.

To counter these reactions we take antihistamines which reduce the impact of the inflammatory response and the symptoms of hay fever but blocking the body'd histamine receptors.

This animation shows histamine being released from a mast cell in response to pollen

This is a better animation in response to venom such as a bee sting

(I've just quickly rewritten this while supervising a test - original article was way too detailed. While this is short and brief, it is what you need to know. Hope it helps)


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And, on a completely different topic, here is a herd of 30 pygmy elephants and a group of 25 excited students. This trip to Malaysia left 6 months ago today...

Coordinating your defences

So you’re trekking through the rainforest in the Danum Valley trying to find the elusive orang utans and you slip twisting your ankle. As you fall you reach out and grab a vine which leaves you with several deep splinters from the thorns. Your friend, who has been feeling unwell ever since the flight to Malaysia, rushes over to help you up and in the process coughs in your face spreading the influenza virus that she has to you.

Your body is now dealing with three different injuries/diseases and I shall discuss the role of the specific and non-specific immune system as it fights to get you healthy again.

I’ll start with the injury to the ankle. Your ankle is injured and is not responding to a pathogen therefore all responses to this injury come from your non-specific defences. What you have done is stretch and stress the ligaments that connect the bones in your foot. In response to tissue damage and damage to blood vessels mast cells and platelets release histamine. The platelets work to repair any damaged blood vessels however the histamine has caused these vessels to dilate and become permeable. More blood is transported to the area and fluid moves into the interstitial fluid around the injury bringing many of the body’s white blood cells with it. These leukocytes run around looking for pathogens, often releasing more histamine as a result. At the same time the damaged capillaries are leaking blood into the interstitial fluid that will result in a bruise. The damage to the blood vessels causes a class of hormones, endothelins, to be released that act as vascular constrictors narrowing the damaged vessels to limit blood flow. These hormones work in antagonism to histamine, histamine causing the dilation in non-damaged vessels. The blood that has leaked into the interstitial fluid is gradually broken down by phagocytosis and this causes the changes in bruise colour over days.

So you are left with a sore, swollen, hot, bruised ankle as your body begins to repair the damaged tissues.

The splinters in your hand have allowed foreign particles to enter your body. Some of the splinters unfortunately had some dodgy bacteria on them. As the thorns pierced your skin they breach the skin barrier. In response, platelets begin the blood clotting around the site of the wound and release histamine. Mast cells, also present, release histamine and now the inflammatory response is triggered, the capillaries dilate, become permeable and neutrophils arrive on the scene. These neutrophils begin the phagocytosis and chemical attack of both the splinter (relatively unsuccessfully) and the bacterial pathogens that were also introduced to the wound. Responding a little slower than the neutrophils, macrophages arrive and continue the digestion of the bad guys while releasing cytokines that attract more leukocytes to the area of infection.

After destroying around 100 bacterium each the macrophages die and become the wonderful stuff we refer to as pus.  But before they die the macrophages have done something else. They have taken MHC markers from the surface of the pathogens and placed them on their own cell membrane. This allows T helper cells, that have now arrived on the scene, to recognise the antigen and kick start a clonal response and release of specific antibodies in B cells. It takes a bit of time but the specific and non-specific defences have defeated the nasty bacteria, however, the splinter, now surrounded by interstitial fluid and pus, is sore. The pressure of the fluid around it, combined with a little squeezing from you, force the splinter from the wound site. Platelets respond to repair the wound again and hopefully, no further pathogens got in this time. If they did, the process starts again.

Now you’re sitting on your veranda with a sore foot and hand but you are starting to get better, however, by now your body is responding to the flu virus you inhaled. When your friend coughed at you many of the virus particles landed on your skin and face. As they didn’t reach the host tissues they didn’t infect you. It was the particles you breathed in that have caused the problem. Influenza virus, or the flu as I’m going to call it from now on, infects the epithelial cells of the respiratory tract (the surface cells). The mucus lining of the respiratory tract provides some form of protection as a barrier both physical and chemical. And in this mucus will lurk IgA B cells, ready to respond to known pathogens. Unfortunately for us, the flu mutates rapidly and regularly changing its external surface markers so it is not immediately recognised by our lymphocytes and further, the flu virus diffuses rapidly through this mucus to the epithelial cells beneath. Once it has reached the target cells, the flu, an RNA virus, injects its genetic instruction into the cell. Here it is integrated into the cell’s genetic instructions, hijacking the cells organelles causing them to make many, many copies of this virus. Eventually the cell will lyse spreading the virus to neighbouring cells and, via coughing and sneezing, to people around us. In response to the invading virus, the cells produce interferon and cytokines. This works to interrupt viral replication, ‘warn’ neighbouring cells and attract NK cells to the area. I’ve explained the role of NK cells earlier but in a nutshell they use a one-two chemical combo to force the infected cells to undergo apoptosis. While you get a fever when battling the flu, this is not a non-specific response, rather, fever as well as muscle aches, tiredness and general feelings of crappiness result from the effects of interferon.

The infected cell also fights back by placing viral antigens on its surface. Cytotoxic T cells recognise these foreign non-self antigens on the surface of a self cell and respond by producing proteins that punch holes in the infected cells membrane. While this doesn’t necessarily kill the virus, it interrupts its life cycle preventing further spread. By now, your body has begun to defeat the flu and is rapidly producing antibodies and creating memory cells for future infections. Your antibody defences are relatively limited in response to a new virus, however, it is very effective in response to future infection by the same virus.

So, your ankle, hand and respiratory system have healed themselves. Your body has responded with generic and specific defences, some chemical, some cellular, and it has added these new pathogens to its biological database for quick and efficient response next time. After a couple of days in bed, feeling a fair bit better you limp to the restaurant to finally get something to eat and hear everybody else’s tales of jungle encounters . Unfortunately, the cook didn’t wash his hands properly and the bacteria Salmonella sp has now entered your system and is starting to multiply in your gut...

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Disclaimer: The Danum Valley is a magical place and your chances of getting sick there are probably significantly less than in Melbourne. I have never been to a place before that has filled me with such awe. Pygmy elephants, orang utans, hornbills, so many types of primate and reptile... And the food is amazing and the cooks DO wash their hands! If you ever get the chance, visit. But bring leech socks.

Immunoglobulins - Ig

Immunoglobulins are Y shaped glycoproteins that bond with antigens. We referred to these as antibodies in previous essays. The difference in terminology is this: immunogloblins that are on the surface of lymphocytes are called immunoglobulins, those that are secreted into the blood by plasma cells are called antibodies. It’s all about location. They are made of four polypeptide chains – two ‘heavy’ chains and two ‘light’ chains with a hinge in the neck region to allow easier coupling with antibodies. The binding sites on these molecules are at the tips of the Y arms. Have a look at this picture I pinched off the internet: 

There are five types of heavy chain peptides used to construct these molecules, resulting in five different classes of immunoglobulins or antibodies. We abbreviate immunoglobulin to Ig and the types of immunoglobulins are called IgA, IgD, IgE, IgG, and IgM. Due to their different structures they have different properties when it comes to battling antigens.

In alphabetical order the general roles of the different classes of immunoglobulins are:

• Ig A – these occur on surface tissues that are likely to be infected such as the lung and the gut lining. They are also found in tears and sweat. These work in conjunction with barriers to prevent infection.
• Ig D – Discovered in 1965 but what it does is still a mystery – potential PhD thesis for some budding young scientist?
• Ig E – These activate mast cells and get them to release histamine
• Ig G – These kick start macrophages and the complementary protein system into action. They primarily attack bacteria and viruses
• Ig M – These are the most numerous on the immunoglobulins and Ig M's are the first class of immunoglobulins to be produced during an antibody response. The role of these is very similar to that of Ig G and at this level, that’s all you need to know.

Here's a 3D model showing protein structure:

Remember: that these are broad classes of immunoglobulins and specific antibodies within these groups target specific, individual pathogens/antigens.

Lymphatic System

Blood circulates through the blood in a closed but leaky series of tubes. Leaving the heart these are the arteries which branch into smaller arterioles which again branch into tiny capillaries. The capillaries then come together to form larger tubes called venuoles and then finally return to the heart as veins. It is as capillaries that these vessels exchange gases, minerals, sugars and other substances with the interstitial fluid. Cells are bathed in this interstitial fluid and get the materials they require and release their wastes into this fluid via diffusion, osmosis and active transport. Cells and chemicals involved in the body’s immune response also reach the body's cells in a similar manner.

Also involved with our circulatory system is another system called the Lymphatic System. This system comprising Lymph Vessels and Lymph Nodes has three main roles, two of which I’ll discuss in some detail. One thing the lymphatic system does is aid in the absorption of lipids from the intestine. That’s all I’m saying about that role. The other two jobs the lymphatic system does is to clean ‘plasma’ and return it to the circulatory system via the vena cava near the heart, and, the most important for this topic, the lymphatic system helps fight infection. Lymph vessels are thin walled and located throughout the body. They carry a clear liquid called lymph which is comprised of water, ions, proteins, fats and leukocytes (white blood cells). Lymphatic circulation transports material from tissues towards the heart. Fluid is forced from capillaries due to pressure and accumulates in the interstitial tissue, which is then reabsorbed by the lymphatic capillaries. This is due to pressure in the interstitial fluid and the thin walled (highly permeable) nature of lymph vessels. This fluid contains cellular wastes as well as pathogens. At intervals along the lymph vessels are lymph nodes sometimes incorrectly referred to as glands. These nodes are small masses of lymph tissue, up to 25mm long. Lymph nodes house phagocytes and T and B lymphocytes and, as lymph travels through the nodes, phagocytes filter out foreign matter. T & B cells respond to foreign antigens and multiply rapidly initiating antibody mediated responses previously mentioned.

When fighting a pathogen, lymph nodes swell (particularly in the neck). We often refer to these as swollen glands. Remember that these are not glands, but lymphatic tissue. Tonsils are masses of lymph tissue and sometimes the pathogens they are fighting manage to infect the cells of lymph nodes themselves. This is what tonsillitis is.

There are other masses of lymph tissue in the body including the thymus and spleen. The thymus is the site of maturing T-lymphocytes and produces a hormone which stimulates T-cell synthesis and maturation. We discussed this briefly in the Specific Immunity essay. The spleen is the largest mass of lymph tissue in the body. It is an important reservoir of lymphocytes  and also regulates the removal of old red blood cells and platelets from circulation and their replacement with newly synthesised cells.

There is no pump to move the lymph through the lymph system. The circulatory system has the heart to pump blood around but movement of lymph through these vessels relies on muscle movement. The more active you are the more the faster the lymph moves through the vessels. Snakes inject their venom into the skin and muscles where it moves from the cells and tissues into the interstitial fluid, ending in the lymphatic vessels where it is transported. This is why if someone gets bitten by a snake you tightly bandage the limb and limit their movement. Unless you don’t like them.

Who says nothing exciting happens in South Australia?

For hundreds of millions of years life on Earth was prokaryotic. Bacteria thrived and was the only form of life. The environment was relatively stable. Until one day a 5 kilometre wide asteroid hit South Australia creating a crater 90km in diameter with an impact of an estimated 5,200,000 megatonnes of TNT. This asteroid, named the Acraman Asteroid, and the soil and dust ejected as a result had an extreme impact upon atmosphere and the biosphere, changing the global environmental status quo. This change has been argued recently to be the major selective pressure that triggered the Cambrian explosion and all ‘higher’ life – eukaryotes and ultimately us – to evolve.

So as I said in the title, who says nothing exciting happens in South Australia?

Article

And on a completely unrelated topic there was an awesome doco on last night on the Pygmy Elephants of Borneo.  It was filmed exactly where I saw a herd of 30 just on 6 months ago. What an amazing trip that was!

Specific Immunity

The non-specific immune responses of animals provide a versatile system of defence, able to respond to pathogens in many ways simultaneously. While the non-specific immune system responds to pathogens and allergens such as pollen, it does this by recognising them as not being part of the host and attacks them in several generic ways.

Once the barriers have fallen and the non-specific defences overcome, the third line of defence involves special white blood cells, called lymphocytes. The specific immune system recognises the individual pathogens and responds directly to them. It is able to not only tell that the pathogen is foreign, it is able to recognise the specific, individual pathogen. It does this through the surface markers and receptors on the invading cells. Further, it is able to remember these pathogens and respond quicker to future infections.

Lymphocytes, Antigens and Antibodies

The lymphocytes involved in the specific response are T cells and B cells, sometimes called T lymphocytes and B lymphocytes, and they have distinctly different roles in the immune response which will be the main focus of this essay. In very general terms these cells either produce antibodies which bind with antigens and inhibit their function or remember specific antigens and initiate a rapid response to any future invasion.

I’ve just used two terms, antigen and antibody, that I haven’t introduced yet. I’ll give a brief definition that I will expand on later. An antigen is a substance, usually a protein or glycoprotein, that when recognized as non-self by the immune system stimulates the production of an antibody that specifically reacts with it. An antibody is a specific protein produced by animals in response to antigens. Antibodies recognise and bind to the specific antigen that induced its production. Seem a circular definition? Think of it this way. Antigens are receptors on the pathogen that identify it. Antibodies block these receptors stopping it from infecting the host. These are shape specific and I will discuss in more detail in a second. First watch this.

Before I go any further I want to talk about the recognition of self and non-self. This is done via a series of proteins that protrude from the cells membranes and like any receptors shape is extremely important in how they function.  We call these Major Histocompatibility (MHC) markers, and these are like an individual’s unique barcode. They come in two varieties MHC Class 1 markers which are found on all cells within the human body except red blood cells, and MHC Class 2 markers which are found on T & B cells and some macrophages along with MHC Class 1 markers. We first came across MHC markers in my essay on pheromones. These are the things you ‘smell’ when assessing the reproductive value of a potential partner. You are attracted to someone who has MHC markers on their pheromones that are most different to your own. Back to immunity, B & T Cells ignore cells with the same MHC markers. It is when MHC markers of a foreign body are recognised that they react.

Antigens receptors on B & T cells that recognise non-self molecules/cells are called immunoglobulins. Immunoglobulins have a specific nature and recognise only one antigen. Like the lock and key of enzymes they are shape specific. During development in the bone marrow variations occur producing literally millions of B cells with different immunoglobulins on the surface. Some of these are genetically encoded, some of these as a result of previous exposure to a pathogen, some as a result of mutation.

Humoral Immunity - B Cells

Develop and mature in the bone marrow. Once mature they leave the marrow and migrate where they are found in the blood, tissue and lymph nodes (lymphatic system will be in one or two essays time). While there may be millions of different types of immunoglobulins on millions of different B cell, the numbers of these individuals are low. For example, there may be millions of B cell but only a handful with a particular receptor. When one of these comes in contact with a specific antigen a series of responses are triggered. The B cell under goes rapid clonal division, it makes many, many copies of itself. These then differentiate into plasma cells that have the role of producing and releasing antibodies into the body’s fluids.  The antibodies bind with the antigens on the pathogen preventing it from infecting the body further and making it easier for macrophages to come along and eat them. Some of the B cells become what is called B memory cells and hang around in the blood for years waiting for that pathogen to invade again. Initially, the B cell response to a pathogen is slow due to the fact that they have to undergo clonal division before they can be effective. The presence of B memory cells insures that future infections by this pathogen are responded to much faster.

A response that involves the production of antibodies is called a Humoral Response or Humoral Immunity.
B Lymphocyte rave

Cellular Immunity - T Cells and Phagocytes

While Humoral Immunity referred to an immune response involving antibodies and therefore B cell, Cellular Immunity is the term for a response that involves T cells and some phagocytes. Immature T cells leave the bone marrow and move to the thymus where they mature. T cells are the second type of cell involved in specific immunity. When discussing macrophages a blog or two ago I said that they had a role in the specific immune response. When they phagocytise a cell they take the MHC markers from that pathogen and stick them to their own cell wall alongside their MHC Class 1 markers. Like this. Specialised T cells, called T helper cells recognise these foreign class 2 markers on the phagocytes, this causes them to initiate a clonal response and production of antibodies in B cells, not the T cells. They help the B cells respond. In fact this type of B cell only responds to stimulation from a T cell. T Helper cells

Another important type of T cell are the Cytotoxic  T cells. Cells infected by a virus display the viral antigen on the surface of the membrane as well as its own MHC markers. The cytotoxic T cell recognises the infected cell by the presence of the foreign antigen and responds by producing proteins that cause holes in the membrane of the infected cell, destroying it.Cytotoxic T cells

Evolution and why we get the flu year after year

To a pathogen living in a Darwinian world, our immune system is a powerful selective pressure. Heritable variations and mutations that provide a pathogen an advantage lead to an evolutionary ‘arms race’ between it and the host. One strategy evolved by viruses, bacteria and protozoans to avoid the body’s defences involves constant change in the three-dimensional structure of these markers on their surface. Regular mutations in the antigen genes create different variant of the MHC markers allowing these pathogens to dodge our immune system – at least over the short term. Our body also produces millions of different variant immunoglobulins on the B cells and some of these can and do match up with the antigens eventually. The problem for us lies in how well these organisms evolve and change. The HIV virus is a master of this. I could spend an hour raving about this one virus. Instead, I’m going to end here after a brief recap.

Recap

• ·         Specific Immunity involves two main cell types T cells and B cells. Both of these are lymphocytes
• ·         B cells respond to antigens (receptors) on the pathogen by rapidly cloning themselves and producing antibodies
• ·         Antibodies bond with the antigens rendering them useless and encouraging phagocytes to come and eat them
• ·         Some B cells become memory cells so future invasions by the same pathogen are responded to quicker
• ·         T helper cells recognise foreign MHC marker on the body’s phagocytes after they ingest pathogens. They then kick start the B cells
• ·         Other T cells called Cytotoxic T cells recognise virus receptors on the surface of infected cells. This causes them to destroy these cells with a protein arsenal

UPDATE: Just noticed I didn't include many of the cells mentioned in non-specific immunity again here as I earlier promised. And I'm not going to. I'm tired and this is more than enough depth for Yr12

Natural Killer and Mast Cells

These are two cells that I should have mentioned in the last essay but I should also include in the next. Instead, I’ll write about them here and leave them in limbo between the two articles.

Natural Killer Cells

Natural Killer (NK) cells are involved in hunting down and killing the host’s own cells that are either infected by a virus or are cancerous. Like T-cells and B-cells which we shall discuss in specific immunity, NK cells are lymphocytes, and all three of these cells arise due to the differentiation on a cell called a lymphoblast. While many of the cues other cells previously discussed used to find pathogens are chemical, NK cells look at differences in the surface of host cells to determine which are infected or tumorous. A cell that is infected by a viral pathogen release stress molecules, called cytokines, and the NK cells will zero in on these via chemotaxis. Both cytokines and interferons trigger NK cells into activation. Tumour cells signal the NK cells in a different manner. The tumour cells produce less Class 1 MHC markers than regular cells (we’ll get to MHC when we look at Specific Immunity) and in response to these low levels of MHC markers the cell is attacked.

So how do NK cells destroy virally infected and tumorous cells, you ask? They do this chemically in a two-step process. NK cells are granular and contain several types of chemicals in these vesicles. When they come in close contact to one of these dodgy cells they first release perforin. This creates pores in the cell membrane by which the second chemical, protease, enters the cell. Protease is an enzyme that causes protein catabolism (breaks down proteins). We call these protease enzymes collectively granzymes. As opposed to most of the other cell death discussed in this blog so far they do not cause cell lysis. Lysis would spread the virus further. Instead they trigger apoptosis, cell death. The cell and all the virus particles within die.

Mast Cells

Mast cells are large cells found in connective tissue and are responsible for histamine release in response to injury and allergic reactions. They are similar to basophils in role and function. While basophils leave the bone marrow completely differentiated, mast cells leave the marrow and migrate to tissues where they mature. There are two types of mast cells, connective tissue mast cells and mucosal mast cells which I’ll discuss in specific immunity. In response to injury and chemical signals produced by and because of pathogens mast cells release chemicals, primarily histamine, which trigger the inflammatory response. Mast cells can take on the antibodies released by lymphocytes and place them on their membrane. Then when they come across an antigen act a little like a landmine.

Both mast and NK cells have roles in both specific and non-specific immunity.

White blood cells involved in non-specific immunity

This essay shall focus on the cellular components of the non-specific immune system as well as the role of some chemical responses such as histamine. Some of the cellular components of the non-specific system also have a role in the specific immune response and I will revisit them when we look at specific responses, antibodies etc.

Once I’ve completed Specific Immunity and the Lymphatic System, I’ll tie all this together using the example of a bacterial pathogen invading a cut. It will all make sense then.

In response to an emailed request, I’m going to end with a brief summary/recap similar to the one I did for non-specific immunity.

Cellular components

White blood cells are the cells involved in immune responses and are called leukocytes (leuko means white, cyto means ‘a hollow, receptacle or basket’ and refers to cells). There are many different types of leukocytes but, as general rule, all leukocytes are nucleated cells (have a nucleus, red blood cells don’t), originate in the bone marrow where they differentiate from stem cells, have a role in the body’s immune system and (this is pretty cool) are capable of independent movement. Yep, they creep around in a very similar manner to amoebas, through blood and tissue.

Some of these cells are termed phagocytes. Phage means ‘to eat or digest’, so a phagocyte is a cell that eats or digests stuff. This is a good little summary of how they work in general: phagocytes The two main phagocytic cells are neutrophils and macrophages, both of these I’ll get to later.

Leukocytes are broadly grouped into two main groups based on morphology. There are Granular Leukocytes, which have visible granules in their cytoplasm and a nucleus that is irregularly shaped, and Agranular Leukocytes, which as the name suggests, does not have granules in the cytoplasm. The agranular leukocytes also have a more typical round nucleus.

Granular Leukocytes

These are your ‘phils. Neutrophils, Eosinophils and Basophils. The ‘phils are named because the ‘like’ stuff; ie they are phillic for different things.

Neutrophils are the most numerous of the leukocytes comprising between 33 – 75% of all white blood cells in the blood depending on the species of mammal examined. Neutrophils are the first cells to respond to a pathogen, and after about 6 hours are gradually replaced by macrophages at the site of the infection until, after about 48 hours, they are completely replaced. The name neutrophil (neutro means neutral, phil means loving) comes from the fact that granules found within their cytoplasm are pH neutral. Neutrophils primarily hunt down invading bacteria and fungi and engulf these cells, attacking them with a diverse and powerful chemical arsenal contained within those granulated vesicles. The process they use to find these pathogens is called chemotaxis. Chemotaxis is the directed movement of a cell along a chemical concentration gradient. They sniff them out in a similar way that a male moth finds a female (read the Pheromones essay). They are primarily active in tissues, not the blood. Neutrophils grow from stem cells within the bone marrow and once mature do not differentiate again or divide. They have about a two week life span and most neutrophils don’t leave the bone marrow but are held back as an ‘in case of emergency’ supply. When they die within tissues at the end of their two week life span they release compounds that act as powerful fungicides.

Eosinophils

Eosin is a dye used to stain cells. Eosinophils respond well to this stain and are therefore named after their ‘love’ of this stain. Like all the cells discussed in this essay they differentiate from stem cells in the bone marrow then spend the rest of their ‘life’ in the blood or gut lining. Their primary role is to defend against parasitic organisms such as worms. These comprise about 1-3% of the body’s leukocytes. Again, it’s the chemicals contained within the granulated vesicles that are used to attack the parasites. When abnormal levels of eosinophils occur in the blood they can have an adverse effect on the body. Conditions such as asthma are triggered by eosinophils.

Basophils

Basophils are quite rare in the leukocyte population, comprising less than 1% of the total number. Basophils are transported by the circulatory system and are found in blood and tissue. They are poorly understood when compared to other leukocytes, however, we know they are responsible for the release of histamine and herapin, two chemicals I will get to later.

Agranular Leukocytes

There are two types of agranular leukocytes: monocytes and lymphocytes. Lymphocytes are primarily involved in the specific immune response so I will talk about them in the Specific Immunity essay. For the next little while, I’m going to rave about monocytes.

Monocytes aka Macrophages

Like the ‘phils monocytes originate in the bone marrow. They enter the blood stream and then migrate into different tissues where they differentiate into what we call macrophages. There are several different types of macrophages that do slightly different things, but primarily these are large phagocytes involved in the ingestion and destruction of pathogens. They are also involved in wound-cleaning (the attack of pathogens entering a wound), inflammation, have a regulatory role in insulin production. But for Yr12 and for non-specific immunity, you need to know that they are large phagocytes that are found in the blood and tissue.

As you can see, several of these cells have a role in both specific and non-specific immunity. Both specific and non-specific responses occur in reaction to a pathogen, usually simultaneously. I will revisit several of these leukocytes when discussing specific immune responses.

Non-cellular Components

Platelets

Platelets are cellular fragments that are found floating in the blood. They have two main roles: they aid in blood clotting at the site of a wound and they release histamine. When exposed to air at the site of a wound, platelets break apart releasing a series of chemicals. One of these helps form thread-like fibrin, which in turn forms a net-like mesh that inhibits blood flow. This hardens into a scab, preventing blood loss and creating a barrier.

Other chemicals released by the breakdown of platelets include histamine which I shall discuss now.

Histamine

Histamine is a protein based chemical that is involved in the inflammation response by causing vasodilation, increasing blood flow to the site of infection and causing the blood vessels to become permeable. This allows more leukocytes to reach the invading pathogens. Leukocytes are also attracted to the site because of the chemotaxic effect this chemical has. Histamine is released by many of the cells already mentioned and some you are yet to meet. Sometimes these cells attack things like pollen causing a massive release of histamine leading to hayfever. It is histamine that makes a mosquito bite red , swollen and itchy. We then take antihistamines. I’ll talk about this later.

Putting it all together

• ·         There are many types of leukocytes, some eat pathogens some, attack them with chemicals, some release chemicals such as histamine that increase blood flow and attract more leukocytes to the site of the infection.
• ·         Many leukocytes have a role in the non-specific and specific immune responses
• ·         There are chemical responses, such as histamine release, which also help fight infection but can itself become a problem

Hope this helps!

Non-specific Immunity

Over the past three blogs I’ve briefly spoken about the things that can make us sick and some of the issues arising from our treatment of these diseases. This essay is going to briefly look at the generic types of defences the human body has against invading pathogens. Next week I’ll start looking at specific defences and responses to pathogens. In vertebrates, non-specific immunity includes physical barriers, physiological mechanisms, chemical mechanisms, phagocytes and inflammation.

First line of defence

Barriers, physical and chemical

The first line of defence our body has against the hoard of invading pathogens is barriers. Our major barrier is the skin. The immediate layer of cells exposed to the external environment are dead. Pathogens need to get past these dead cells to the living cells beneath. This provides a physical obstruction and prevents pathogens entering our bodies. On the surface of our skin are many, many naturally occurring, beneficial bacteria. These also help by occupying all the available space on you skin’s surface so when a nasty little pathogenic microbe lands on our skin it is out-competed by the good guys. All available resources, including space, are taken. These natural non-pathogenic bacteria are also found in the gut and vagina as well as on the external surface. When a cut becomes infected, this is because there is a break in the skin barrier allowing a pathogen to enter. Our skin is generally acidic and has a coating of oils, lipids, that help create an environment unsuitable to many potential pathogens.

Other barriers include the mucus lining of your nose and throat, lungs and gut and this provide an obstacle to pathogens inhaled or ingested. Another powerful barrier is stomach acid, which destroys many pathogenic organisms you may have swallowed. Chemical barriers also exist. Your tears contain the enzyme lysozyme, which is also found in sweat and in many of your body’s tissues. This enzyme causes lysis in invading pathogens, destroying them.

Second Line of Defence

When we talk about second line of defence it is not a list of things that happen in a certain order. These usually happen at the same time and often one response makes another more effective.

Fever

Despite our best efforts, a pathogen manages to get past our barriers. There are then a series of non-specific responses our bodies go through to try and fight off disease. Fever is one of these. In response to the pathogen, macrophages – which we shall learn about in a while – release chemicals that cause the hypothalamus to reset the body’s thermostat to an elevated temperature. This aids recovery by killing some pathogens, facilitating the death of infected cells and increasing the activity of some lymphocytes and phagocytes – which we will also learn about in a bit. Fever can also be triggered by toxic by products of some bacteria such as pyrogens, however, the effects of elevated temperature on the bacteria is similar.

Protein based responses

Let’s say that the pathogen that invaded you was viral and has invaded your cells in the manner described in previous blogs. Another non-specific response your body undertakes is the release of antiviral proteins called Interferons. Interferons, as the name suggests interferes with stuff. In this case interferons interfere with virus replication and stimulate macrophages to come along and eat the infected cells. One other incredibly beneficial thing they do is they make non-infected cells more resistant to viral infection. Again, we’ll talk about this in a future blog.

I’m going to stick with proteins and talk about Complimentary Proteins. There are about twenty of these originally synthesised in your liver and are found floating around in your blood in an inert state. They become active when they come into direct contact with a pathogen. Another trigger for their activation is when antibodies and antigens combine (future blog). They defend us against pathogens in four main ways. They cause cell lysis in pathogens – our immune system really likes lysis as a response ; they can coat the pathogen which makes it easier for phagocytes to recognise and engulf them; they attract a type of cell called leukocytes to the area of infection to attack the pathogen; and, finally, they trigger the release of a chemical called histamine, which we will soon get to, and is involved in the inflammatory response. Complimentary Proteins are also involved in Specific Immunity and will be discussed later.

Cellular components: white blood cells and stuff

White blood cells, or phagocytic leucocytes, are a group of cells that engulf, ingest and destroy invading pathogens. They eat them!  Before we go any further, watch this: Phagocytosis

I’m going to talk about the cellular components of our non-specific immune response before returning to some more physiological and chemical responses.  I’ve mentioned phagocytes, macrophages and leukocytes so far. There are many more including: Lymphocytes, Basophils, Neutrophils,  Mast Cells & Natural Killer (NK) Cells. I’ll write a short essay about all these dudes plus a few more later. What you need to know now is that phagocytic cells originate in bone marrow and destroy pathogenic cells by eating them. I will expand on this in future essays. Pinky promise.

Inflammatory Response

Inflammation is when there is swelling and usually a localised temperature rise in an area of infection. The term for this is edema. This happens because enzymes and hormones such as serotonin are released as a response to a pathogen (I keep saying this but it will be in the next essay!). These compounds cause the arterioles to dilate and become ‘leaky’. There is increased blood flow to the site of infection transporting a greater number of defensive cells and compounds and as these arterioles become permeable (leaky), these cells and compounds move out of the blood and into the interstitial fluid to the site of infection where they attack the pathogen.

One of the compounds that cause the permeability and dilation of the blood vessels is histamine. We will look at where this comes from and exactly what it does in the next essay. (I’m building this next essay up. Hope it’s good!)
Inflammatory Response 

A quick recap

Our first line of defence is barriers, both physical and chemical. If these barriers are breached we have a second line of defence. This creates a hostile environment for the pathogen (fever) causes the release of chemicals that inhibit the pathogen’s functioning and cause phagocytic cells to eat them. The second line of defence also changes conditions within the body to increase blood flow to the site of infection, which in turn brings defensive cells and chemicals to the area.

The next blog will cover: the cells involved in our non-specific immunity including platelets and the role and production of histamine. I’ll put it all together and discuss our response to a pathogen infecting a small cut.

Until then, here is some Dave Graney for you

Vectors

A vector is something that transmits a pathogen but isn’t itself a pathogen. The classic example of a vector is the mosquito. Later we will look at vectors as things used to transmit genetic information from one organism to another in genetic engineering but when discussing disease a vector transmits a pathogen.

A mosquito itself is merely annoying. It buzzes in your ear just when you are on the point of sleep waking you and maybe, if you don’t notice, lands on you and draws some blood. Or rather, she does, leaving a small, itchy bump. It is the female mosquito that feeds on humans and other mammals as she needs the nutrients from blood to develop her eggs. Males and non-pregnant females are actually vegetarians! Generally, a mosquito is nothing other than irritating. Unless of course she happens to be a vector for a disease such as Malaria, or Ross River Fever, or Dengue Fever or Yellow Fever, or Japanese Encephalitis or... Mosquitoes are vectors for many, many diseases. Malaria is spread by the mosquito vector but is actually the protozoan, Plasmodium, that causes the disease. I’m not going to discuss the life cycle of plasmodium or what it does to the human body, this can be found in most textbooks. However, I will mention that according to WHO in 2008 there was almost a quarter of a billion (247 million) cases of malaria globally resulting in approximately a million deaths. Most of these deaths were in African children.

One of the most important ways to stop the spread of diseases such as malaria isn’t to target the plasmodium, instead it is to control the mosquito. Remove the vector and the disease’s spread is contained. This is the main focus of global anti-malarial programmes.

The mosquito is not the only vector though. There is a huge catalogue of animal vectors that include insect, mollusc and vertebrate. Bubonic plague is spread by fleas, bats are vectors for the Hendra virus, dogs, monkeys and other mammals can spread rabies but the example I would like to finish with is a case that occurred in Sydney last year (2010). I don’t know what the inspiration was, maybe alcohol, Jack Ass movies or a combination of both, but boys being boys one mate dared another to eat a slug. Unfortunately for the slug-eater, this slug was a vector of a rat lungworm, a nematode that causes a rare type of meningitis. It left him fighting for his life with doctors hoping his immune system would fight it off.
Malaria Life Cycle 1
Malaria Life Cycle 2 

We're in serious trouble

We’ve only been able to treat bacterial infections for the past 70 years or so. Other than our natural defences, which will be the subject of my next blog, we had no means to fight off these infections. None of our medicines were effective against bacteria. Then came the discovery and use of penicillin, first widely used by Allied troops during WW2. This discovery led to a class of drugs we refer to as antibiotics and these have revolutionised how we treat disease. Before this, what we see as minor, easily treated infections could often be fatal.

Penicillin and antibiotics were seen as a panacea. Until chinks began to appear in our medical armour. Let me start this with the story of syphilis. That is syphilis the sexually transmitted infection, not Sisyphus, the man from Greek mythology. Apart from sounding similar these two have a lot in common as we shall soon see. Bear with me. Soon after the use of penicillin to treat syphilis in hospitals, doctors noticed a strain of syphilis had emerged that was resistant to treatment by penicillin. The new uber-medicine was not as effective as thought. Now, not all bacteria were as susceptible as when treatment with penicillin was first used. Why? Bacteria reproduce rapidly via binary fission. One becomes two, then four, then eight. Like this. You get the picture. And due to binary fission they are all clones. Except for the occasional, rare, genetic mutant. As we will discover in Unit 4, which is just around the corner, often these mutations lead to death or suboptimal functioning but sometimes the mutation causes the organism to have an advantage. The competitive edge in the case of this bacterium was resistance to penicillin. When hit with a dose that killed all its non-mutant siblings, this bacterium survived. And reproduced passing that trait for resistance on to its daughter cells. And soon a strain had evolved that was resistant to treatment. But here comes the interesting part. While bacteria reproduce asexually, they also perform an incredible evolutionary act, they swap genes in an act called conjunction. Two bacterium can come together and exchange genetic information. It’s like a brunette going up to a red-head and taking a copy of the red-head’s gene for hair colour, while the donating a gene for lactose tolerance. The brunette now expresses the red-hair phenotype and the red head can now tolerate lactose. A resistant bacterium could, did and still does come in contact with non-resistant bacteria and swap genetic information, passing on this gene for resistance. New mutations can rapidly spread throughout populations. The drugs we use became less effective, so we would use a different antibiotic. Successfully at first, then, over time, less so. Hmmmm, a strain now resistant to two treatments. That’s OK, we have another drug...

Then humans come along and start over using and misusing antibiotics. Prescribing antibiotics for viral infections, using them at the wrong dosage level, or not for long enough. Placing antibiotics into the food we give farm animals. How many of you have started a course of antibiotics and not finished them? Every time you do this you are establishing the perfect evolutionary pressures for drug resistance to evolve. And it has. Rapidly. Each year nearly 500,000 cases of multi-drug resistant tuberculosis are diagnosed. Half a million cases that are resistant to all known treatments. 150,000 fatalities occur as a result. According to WHO extensively drug-resistant tuberculosis has been reported in 64 countries to date.
Many articles in the mainstream media refer to the 'superbug NDM-1'. A bacteria that is resistant to all of our medicines. This is pretty scary but it is also wrong. NDM-1 isn't a bacterium, it's a gene. And this gene is readily passed from one species of bacteria to another, through bacterial conjunction termed horizontal gene transfer (the passing of genetic information to an organism that is not a decendant). The media do have it right about one thing though. Bacteria that have the NDM-1 gene are resistant to all treatments we have available.

But it is not just bacteria. Plasmodium, the protozoan that causes malaria, is also developing resistance to many forms of treatment. Areas of Thailand, Burma, Laos and Cambodia now have malaria with resistance to some of the most effective treatments and preventatives. As do other regions in the world.

Anti-viral treatments for disease such as HIV/AIDS have been shown to be losing their efficacy as these viral strains evolve into new types as a direct response to the drug treatment. In a recent article I read, which I have attached, the idea of a world in the not-too-distant future where disease is resistant to our treatments is suggested by WHO. We will potentially be in a situation where ‘minor’ disease become fatal again. Scary shit.

I mentioned a Greek guy at the start with a name similar to a sexually transmitted disease, Sisyphus. Sisyphus was cursed to spend his life pushing a bolder up a hill and just when he would near the top the bolder would roll to the bottom and he would be back where he started. As we look at drug resistant syphilis taking us back to where we were 70 years ago I think syphilis and Sisyphus have more in common than similar sounding names.

http://www.abc.net.au/news/stories/2011/04/07/3185138.htm

UPDATE 15/5:
Todays's RadioTherapy program on 3RRR had an interesting discussion on NDM-1 and other bacterial infections. Listen to it here while studying

Agents of disease - stuff that makes you sick

I hate feeling sick. I’m one of those whingy blokes that always feels worse than symptoms may suggest. Yes, I’m a firm believer in the man-flu.

Disease is a condition an organism has or contracts that causes it to function at a less than optimal level. This disease causes a negative change in an organism’s state of health. Disease can be placed into two broad categories; infectious and non-infectious. An infectious disease is something that can be caught or transmitted, while, by definition a non-infectious disease cannot be transmitted. Non-infectious disease includes things like some cancers and genetic disorders. I will discuss non-infectious genetic disease or disorders during Unit 4. Remember that some cancers can be transmitted and are infectious, such as the Human Papillomavirus (HPV) that can lead to cervical cancer, and this is why it is important for everyone, guys and girls, to have the HPV vaccine. Why guys? What is the point of immunising everyone for this disease except for the carriers?

This rant will focus on agents of disease – the things that make you sick. The term for something that causes an infectious disease is pathogen. These are usually living, such as bacteria, but can be non-living, such as prions. I’m not going to get into the ‘are viruses living or non-living debate’ here.  I believe they are living but that is for another day and another blog. I’m going to divide pathogens up in this blog into micro-organisms, including bacteria, protists and fungi, macro-organisms, such as arthropods, annelids and nematodes, and non-cellular agents that will include viruses, viroids and prions.

Micro-organisms
Bacteria

Bacteria are an amazing group of organisms. The majority of life on this planet is bacterial. It was here before all other life and I believe it will be the last form of life to finally die off on this planet, many billions of years into the future. Bacteria inhabit just about every conceivable niche this planet provides, from kilometres under the surface within rock, to near-boiling hotsprings, in hyper-saline solutions and environments without oxygen, from the Antarctic to inside your gut. Yes, your gut. We are just another habitat for some bacteria, and most of the time we get along in a happy symbiosis. Bacteria is so good at surviving that some astrobiologists have suggested that life on Earth originated from Martian bacteria getting to Earth in a meteor ejected by some Martian supervolcano. While there is no evidence for this - there is no evidence that life once occurred on Mars in the first place - it’s still a cool little theory. The trouble with talking about bacteria as a group is that they’re not a homogenous group. There is more diversity in what we call bacteria than is all other forms of life. In general terms they are divided by shape: spherical cocci, rod-like bacillus, and spiral-shaped spirochaetes. But this is like saying a tall people are in one group, fat people in another and a third group made up by short red-heads. These gross morphological similarities do not necessarily mean they are related. Another way they are categorised is in the composition of the cell wall and how these respond to different types of dyes and stains. Those that can be stained are called Gram Positive, those that can’t Gram Negative. The final way bacteria can be grouped is by gaseous requirements: those that require oxygen (aerobic), those that thrive in the absence of oxygen (anaerobic) and those that don’t really care either way (facultative). It is a huge group that is all clumped together. The one thing that separates them from everything else is they are all prokaryotic. Despite our near pathological fear of bacteria, most bacteria leaves us alone or is beneficial and there are relatively few bacteria that make us ill. I mean there is so much of this stuff everywhere, it’s all over our bodies, the pillows we place our heads on, the utensils we eat with, if bacteria was ‘bad’ we would be in deep, deep trouble. As a rule, bacteria becomes a problem from a human point of view when in colonises a new habitat where it normally does not occur. An example of this may be bacteria entering a cut and forming a colony within the wound, or bacteria that is normally found in the lower intestine getting into the gut, usually by drinking water contaminated by faecal matter. Or not cooking food properly. There is a bacterium called Campylobacter sp that normal occurs in the intestines of chickens and causes them no problems at all. In fact, it is beneficial for chickens. The problem for us occurs in the processing of chooks for meat. Sometimes the meat becomes contaminated and, if you don’t cook your food properly, this bacterium is introduced into your gut. Where it will make you very sick.  So how do these microscopic organisms actually make us sick? One of the key factors is the virulence of the pathogen and how quickly they reproduce. In lay terms virulence refers to how good bacteria is at spreading and making you sick. The more virulent a pathogen is the better it is at making you sick. You need to remember here that bacteria aren’t trying to make you sick, that is not their purpose. They aren’t aware of you as anything other than habitat. Some bacteria make you sick by actively invading and destroying cells. Salmonella typhimurium will do this. We get Salmonella sp from contaminated food, and refer to its effects as food poisoning. It survives the acid of our gut and enters our colon where it destroys the epithelial cells of the intestine causing diarrhoea and vomiting. Another way that bacteria can make us sick is via their waste products. Like all life, bacteria eat and produce wastes. Some of the wastes from some bacteria are toxins and these make us sick and trigger responses in our bodies such as fever. As the bacteria colony grows and multiplies, the amount of toxin produced increases exponentially causing the host to become sick.

Protozoans - amoebas and their friends

In general terms, protozoans such as amoeba make us sick in a similar way to the bacteria previously mentioned. This Kingdom, again extremely diverse, is comprised mainly of single celled eukaryotes. The two examples I will give of disease caused by these protozoans is amoebic dysentery and ciguatera poisoning. Amoebic dysentery is caused by the amoeba Entamoeba histolytica. Humans are the host of this amoeba and it is spread by drinking water or eating food contaminated by the cysts of this protozoan. It is much more common in developing nations. It is nasty, I’ve had it. Many years ago when travelling through Nepal I made the mistake of drinking from a mountain stream high in the Himalaya. The problem was this stream was contaminated by this amoeba. Nepal is a developing country and no matter where you go you will find people up to, and beyond, the snow line. There were no roads where I was, I had walked for days to get there. Needless to say there were no flushing toilets either. Human waste is transported by rain or snow melt into the streams and carry the amoeba cysts with it. And that’s how the cysts got into me. I was luckily back in Kathmandu when the cysts hatched and the amoeba multiplied. It affected me in a similar way to the Salmonella sp mentioned before, eating away at the cells lining my intestine and has the same impact on your body. I lost many kilograms over several days before I was able to crawl into a rickshaw and get to a doctor. Holidays...
To go off on a wee tangent, my favourite species name of all time belongs to an amoebia. It is called Chaos chaos.

Another protozoan that can make you sick is the dinoflagellate Gambierdiscus toxicus, which is responsible for ciguatera poisoning. Dinoflagellates are single celled marine plankton. These are ingested by small fish at the base of the food chain and here, it is not the plankton that causes illness it is the toxins produced by it. These toxins are bioaccumulative and are magnified as they are passed up the food chain; small fish is eaten by big fish which is eaten by bigger fish until you catch yourself a large snapper or coral trout for dinner. You then ingest the toxins – which are heat resistant and not destroyed by cooking and you become sick yourself.

Apicomplexans are another protozoan that causes the disease malaria. I’ll discuss this later when I talk about vectors. Maybe, time and space dependent.

Fungi

I’ve spent too long talking about stuff I wasn’t going to mention so I will keep the last of the micropathogens, fungi, to a short paragraph.  Ringworm, athlete’s foot and thrush are fungal infections they colonise the external surface and digest your dead skin cells. External environment? Thrush? Thrush often occurs in the vagina and the mouth. Technically these are external environments. Vagina, etymologically speaking, means a fold and that’s what a vagina is. It is an envagination of the skins surface. These infections occur when a colonising cell reproduces successfully and produces many thousands of daughter cells. Enough said.

I’ve just looked at the word count and hit 1,500 so I’m going to skip over macro-organisms briefly. I’ll write another short blog about multiple-host life cycles of things like tapeworms tomorrow. Pathogenic macro-organisms are things like pubic lice, ticks, tapeworms... they are varied as are the effects and the impacts. They can be internal or external parasites. I’ll leave the details to your teacher. An interesting note though is that while rates of sexually transmitted bacterial infections such as Chlamydia are rising rapidly in the community, rate of pubic lice infections have decreased. The reason suggested? The popularity of Brazilians.

Non-cellular pathogens

Finally: non-cellular agents of disease. Viruses, viroids and prions. These pathogens are all non-cellular and technically non-living – remember that cells are the smallest independently functioning unit of life. I’m not going to argue that viruses are living here.

Viruses
Viruses are comprised of nucleic acid (DNA or RNA) surrounded by a protein coat. Some of these are further covered in a modified membrane. Smallpox, herpes and warts are examples of DNA viruses, hepatitis, influenza and HIV are examples of RNA viruses. Usually DNA viruses are double stranded but can be single and RNA viruses are single stranded but can be double. Viruses are obligate intracellular parasites. This means they must infect a host cell to reproduce. As they lack ribosomes and other organelles they hijack these in the host cell and force the cell to make viruses. How they do this is pretty cool. They insert their genetic information into the host cell and this interrupts the cells normal functioning. Two things can happen: the genetic information is spliced into the host’s cells genome where it lurks until later OR it forces the cell to make many, many virus particles until the cell eventually undergoes lysis (bursts) spreading these to infect new cells. I’ll use herpes as an example. The common cold sore is caused by the herpes virus. For example, if you kiss someone with a cold sore the virus passes to you where it inserts its information into your lip’s cell’s genome where it lurks. As your lip cells under mitosis and divide, the virus is also copied. This is called a lysogenic cycle. Then as a result of some trigger, your infected cells start producing virus particles, swell and burst. This is the lytic cycle and results in cold sores.

Viruses mutate and evolve regularly and rapidly, changing the markers on the outside of them to confuse your immune system. This is why it is hard to build immunity to some viruses such as influenza. Remember a few years ago we were worried about bird flu and SARS? Viruses can and do mutate and jump species. Fantastic evidence for evolution. It IS evolution.

Viroids are small virus-like pathogens that infect plants. That’s all I’m saying about them.

Prions

And to end this we have prions. Prions are abnormal proteins that change, denature, normal proteins by changing their shape. Eventually this leads to cell lysis which spreads the prions to infect other cells. Prions are usually found in neurons. The most well known prion disease is spongiform encephalitis. This disease causes huge holes in your brain (spongiform) and is commonly known as Mad Cow Disease, the only disease to be named after my ex-wife. This disease became a huge problem in England when infected sheep’s brains were mushed up and fed to cows, and then in turn fed to people. And you thought cows were vegetarians... Other prions disease include Kuru, a disease from PNG that came from eating the brains of dead relatives, and Creutzfeldt-Jakob disease.

Google these for more information. My pizza has arrived and I’m hungry. Hope this helps. Sorry it’s so long.
Watch a couple of these for giggles:
HIV life cycle. Pretty cool 
Bacteria 
Virus 

Pheromones

I remember hearing about a study where a group of women were asked to rank a series of photos of different men according to how attractive they found them. Once this was done, several of the photos around the median were treated with a pheromone from a boar. Not a person who talks in a monotone about the benefits of superannuation, rather, a male pig. The experiment was repeated several times with different groups of women and each time, the pheromone treated photos were ranked as more attractive than they were in the control group. Unfortunately, sitting here on a Saturday night with a beer in my hand, I have no way of checking if this study is true but for a minute let’s believe it is true and valid because I like the story. This study, if true and not an urban myth, seems to indicate that pheromones, an external signalling hormone, can affect the way we perceive another’s reproductive worth. What is even freakier is that pheromones from a pig are attractive to humans!

This shouldn’t be a shock. For years, human females have been applying pheromone extracted from the anal glands of various animals to themselves in an attempt to be found more attractive. This is where musk originated from. However, musk is a male scent originating in the male Musk Deer, and it seems that women apply this scent to themselves because they find it attractive. Why else would you consciously apply an odour to yourself?  Regardless to whether perfumes come from deer, civet or flower sources the idea behind a perfume is to make oneself more attractive by smelling nice.

Pheromones can be extremely powerful. They can cause extreme behavioural responses in incredibly tiny concentrations. Many animals communicate sexual availability via pheromones and more than just availability, their worth as a prospective partner is also assessed by smell. In humans most of this happens on a subconscious level. First let me preface this by saying that visual stimulation is incredibly important. When you see someone across the room who you  find attractive, it is not their scent that is initially appealing. It is their appearance. The limbic brain including the hypothalamus is often referred to as the emotional brain and is the region that is responsible for your libido. Have you ever wondered why when you meet someone you find attractive you can’t seem to hold a conversation and become a giggling idiot? The visual arousal causes dopamine and many other neurohormones to be released from the limbic brain causing you to feel that rush that is hard to explain but all of us have experienced. Pupils dilate, you start getting sweaty armpits and clammy palms and your body language changes – up to 55% of flirtation according to psychologists, is all in the body language.

Now while your brain is causing this rush of hormones in you, your genetic health is being actively assessed by your prospective partner. They may not realise it but they are smelling your genotype. And you are doing this too in return. Human pheromones are also released at this time of attraction. These are found in your sweat. When you find someone attractive on a pheromonal level it is because their smell is different to yours. We want genetic variation in our offspring and we literally sniff this out. We are seeking a partner who has major histocompatibility complex (MHC) genes (these are important in immunity and I will talk about in the next rant when I start disease) that are different from yours. Studies indicate that couples with different MHC markers are more satisfied in their relationships and are more likely to be faithful. Further, they tend to have less fertility issues than couples who have similar MHC markers.

The type of sweat produced in the armpits and groin is different to that produced elsewhere in the body. As well as being rich in pheromones it is thick and oily. And this is why we have hair under our arms and in our groins; it traps this sweat creating a reservoir of pheromones. This is not body odour. Body odour is caused by not washing regularly and bacteria building up and feeding on this oil sweat. It is their waste products that cause the bad smells and have the exact opposite effect of pheromones!

The genetic compatibility, which is actually genetic difference, that we are seeking in a partner (actually we are seeking this difference in the other parent of our child and often a male partner did not contribute to the genetic make up of the child it helps raise as its own – serious shit. Will rave about this in Unit 4) can be masked causing us to be attracted to a partner we actually aren’t attracted to. Huh? Let me explain. Studies suggest that women who take the oral contraceptive pill have their pheromonal responses skewed. Instead of being attracted to someone with different MHC markers, they are attracted to someone who has a similar MHC odour to themselves. Things move along well until it comes time to have a child. The woman stops taking the pill and, after a bit of time, starts looking at her partner differently, hormonally speaking. And these couples, statistically, are more likely to be unhappy in their relationships, have affairs and have fertility issues.

Actually, an interesting aside, studies have indicated that woman are attracted to different ‘types’ of males depending on where they are in their menstrual cycle. Again, hormones, and again, something I need to look up.

Let’s leave humans for a few brief paragraphs but still stick with sex. In the animal kingdom, pheromones are also used for reproductive purposes. Most of this is common knowledge and is found in all textbooks so I’m only going to talk about finding a mate and I’m going to give to insect examples. A male moth can and does respond to the pheromones of a female from kilometres away. In fact the male silkworm moth can detect a female from 11 kilometres away. I don’t know if there are others who can detect pheromones from greater distances, there most likely is, this statistic just sticks in my head. When they detect a pheromome they fly into the wind and locate the female by small, ever increasing responses of pheromones hitting those receptors on their antenna . And eventually they find the female. Let’s just hope there wasn’t another male moth closer as their mating rituals aren’t quiet as intricate as human systems. Nor are they as fussy. But what I want you to consider is just how much pheromone a female moth can produce – they’re not that big – and how powerful these molecules must be. They have such a major impact in such small quantities.

Wasps also use pheromones to find a mate. Again it is the female releasing the pheromone and the male responding. It works really well over long distances as we saw in the moth example, however, other organisms have managed to use these pheromones against the wasp. These organisms are orchids. Yep, those beautiful flowering plants. Not all orchids but some also use pheromones to have sex, however, they use wasp pheromones. When these orchards are ready to be pollinated they release a pheromone that is remarkably similar to those produced in certain wasps. Male wasps are attracted to the flowers that smell like female wasps and superficially resemble a female wasp. The wasps then try unsuccessfully to mate with the flower. In the attempt the orchid’s pollen sacs are attached to the back of the wasp. Finally the wasp gives up and flies off to find another female. Often this female is another orchid and the pollen is transferred, the plant fertilised and the male wasp remains frustrated.

So pheromones are hormones that work externally and communicate information between members of the same species. Often, the information communicated is about sex. It can also be used to communicate location of food, threats to the colony or territorial boundaries but these are relatively straight forward in concept and are easily understood by reading your textbook.

And to that woman who I am psychologically and genetically attracted to; sorry, I don’t mean to blabber, it’s my pheromones reacting to yours. Makes it sound so romantic doesn’t it?

A rave about hormones

Hormones don’t really do much themselves but the effects of hormones on an organism is huge. Hormones are signalling molecules. They tell a cell or group of cells it is time to do something. That’s it. They simply carry a message. Once that message is received though, the effects can be staggering. This is called signal transduction.
Homeostasis and negative feedback

Hormones are one of the mechanisms humans and other animals use to maintain homeostasis, the other being the nervous system. They are also used to initiate change such as growth and reproductive maturity. There is a narrow range that most variables within the body, such as pH of your blood and your body’s temperature, need to be kept within.  Think of enzymes. Remember them? Little worker proteins that catalyse the chemical reactions that occur inside you. What happens to them when they get too hot, or placed in a solution too acidic? They denature, change shape and stop working and you end up feeling pretty shitty at best, dying at worst. The primary mechanism that the body uses to keep things in this narrow range is called the negative feedback system. Positive feedback, while uncommon, is also used but I’m not going to go into that here. Negative feedback is often made to sound incredibly complex, and, while the body’s biochemical pathways can be very complicated, negative feedback is actually a very simple concept. Imaging you are driving, car is flying along the road and you decide to take your hands off the wheel and put them on your head. You continue driving with hands on your head and all of a sudden the car hits the gutter. This is the stimulus, if you don’t do something you’ll crash. You respond by quickly grabbing the wheel and steering the car back into your lane. And then you put your hands back on your head. And after a while the car swerves into the oncoming traffic. And you respond again to avoid crashing. This is how the body drives itself- with its hands on its head! It waits until something goes wrong and then responds. It waits until one of the many variables it is monitoring moves out of a given range, then responds to return it to within those narrow limits. Bad way to drive but seems to work in animals.
Hormones, receptors and signal transduction

You should know by now that, hormones are produced by the endocrine system and, generally, are released into the blood stream. It takes about a minute for your blood to do a lap of your body – pretty quick really when you consider the length of all those arteries, arterioles, capillaries, venuoles and veins. There are two main types of hormones: peptide (protein) and steroid (lipid). This is where you really need to recall hydrophilic and hydrophobic molecules and movements in and out of membranes. Peptide hormones are hydrophilic. Stop here and think: how will this hormone respond when secreted into blood and what will happen when it gets to the cell membrane? While you’re thinking about that, I want you to also recall how important shape is to all the biomolecules you’ve studied so far. Shape is extremely important for hormones and will continue to be important as you look at disease. You may release a hormone from one of your glands and want it to trigger a response in the testes or ovaries. How does the hormone make these cells/organs respond but leave others, say the pancreas, alone? Again it is shape. The cells that the hormone is trying to get a response from are called Target Cells, and these target cells have shape-specific receptors for these particular hormone. And they would most likely have other receptors for other hormones as well. When the right hormone connects with the receptor of the target cell a response is triggered.

Let’s get back to that question I posed a while back. A protein hormone is hydrophilic and is readily carried in the blood around the body until it reaches the target cell. As a hydrophilic molecule it is lipophobic and therefore has issues crossing the cell membrane. So the receptors for protein-based hormones are on the outside of the cell membrane. Steroid hormones, being lipid-based, are hydrophobic and need carrier proteins to help them get around, however, they easily pass through the cell membrane and the signal receptor for them is on the inside of the cell membrane. The triggering of a hormone receptor and the response it causes within a cell is referred to as signal transduction. A signal transduction pathway includes the activation of a receptor by a hormone and the series of responses it causes within the cell. This is often referred to as a cascade effect, like sneezing in the alps and triggering an avalanche. The response seems disproportionate to the stimulus. For the cell to do whatever it needs to do once stimulated by the hormone there are usually a series of steps that are amplified at each stage causing a tsunami of biochemical reactions, each one having a greater impact until the final produce molecule is synthesised or whatever was supposed to happen, happens.

Avalanche? Tsunami?  Time to move on...

Ever wondered how these molecules are removed from the blood? In a nutshell they are broken down, filtered from the blood by the kidneys and peed away. Read your textbook.
Plant hormones and tropisms

Plants also use hormones to regulate themselves and to maintain homeostasis. As they lack a nervous system, they rely on their hormonal system. One would intuitively think that by relying on this system alone, plants would have developed an intricate and complex system of hormones. They have but they only use five of them. (Six if you want to include florigen, the hormone that no one has ever found but some botanists argue must be there). They work by combination and concentration: how much of them there is and what other hormones are with them. They are transported in the phloem and also diffuse through and around cells and are responsible for everything a plant does, from bending toward the light to flowering. I’m going to rant a little about tropisms in plants, then flowering and the importance of environment in the synthesis of hormones in plants. These five hormones and their general impact on a plant would be a good think for a Yr12 student to learn, they are in all textbooks and I’m not getting into them here.

Tropisms in plants are responses in plants to certain stimuli and auxin is a very important hormone in these responses. The three main tropisms that are covered in this course are phototropism (a response to light), gravitropism (a response to gravity) and thigmotropism (a response to touch) and they way they work is relatively simple in concept, the particulars though are quite complicated but unnecessary to discuss at Yr12. Phototropism is a plants response to light. It is usually positive in that a plant will bend and grown toward the light. This occurs by auxin in the growing stem diffusing away from cells in the light and building up in concentration in the cells that are more shaded. Once in these cells they cause them to elongate. These cells grow longer taking up more area and bending the plant toward the light. What actual causes the hormone to move though? The light triggers the response however, what actually causes the auxin to move... I can’t remember. I’ll get back to this later. Gravitropism is similar. If a shoot is on its side gravity causes auxin to move to the underside, causing these cells to elongate and the shoot growing up. Gravitropism also occurs in the roots but works in the opposite way, causing the roots to grow down. I won’t go into thigmotropism but will say that this is a response to touch. It’s what causes pea to wrap those spring-like shoot around branches to give the plant support, or causes a plant to move away when crowded. Don’t worry about this too much.
Environmental stimulation of hormone production

Hormones in plants are often stimulated into production by environmental factors such as light. The example I’m going to give comes from a conversation I had many years ago in Nepal with a Dutch guy. We were sitting in a cafe looking out at a vacant block of land that was covered in wild marijuana plants. This dude started telling me how he grew marijuana hydroponically in Holland. Apparently, the parts of marijuana that drug addicts and malcontents smoke are the flowers. He told me that light prevents these plants from producing flowers and they need at least 10 hours of darkness to allow the build up of the hormone that triggers flowering. If they are exposed to any light during this dark period, the flowering hormone isn’t produced. He was telling me that he had several plants growing in a cupboard and all but on were flowering successfully. He worked out that the one plant that wasn’t flowering was getting a little bit of light through a crack on a couple of leaves. As hormones are transported around the plants even the parts of this plant that were receiving uninterrupted darkness weren’t flowering as the hormones move throughout the plant. Drugs are bad. This is just an example.
Pheromones: external communication hormones

Finally, I’m going to return to animals and pheromones. These are an interesting group of hormones as they work externally and impact primarily behaviour. They are used to communicate and the information is usually species specific. They can communicate territory. This is why dogs pee on poles. They are marking their area with their pheromones. They can communicate a food source. This is why ants will follow a trail. They are following a trail of pheromones laid down by the ants that found the food. And most importantly they can communicate sexual availability. For example a female dog in heat will attract male dogs from all around as they smell her pheromones. Male moths can smell a female moth from kilometres away. That’s how sensitive they are. I’ve got heaps to say about pheromones but I’m going to stop here. That’s about all you need to know. It’s late and I’m tired. I'll type some more about pheromones tomorrow.