What is a human's biggest defence against disease? Doctors? Food? Sanitation? Or your own body's immune system? Without your immune system it is unlikely that you'd have survived long enough to be sitting at a computer reading h2g2

Briefly the immune system consists of barriers to stop infections gettting in, the complement system, neutrophils, macrophages, B cells producing antibodies, T cells of various sorts and Natural Killer cells.

Knowing the enemy

Things that attack you..

Bacteria

Bacteria were living on this planet long before we did, in a way they are our ancestors. A bacterium is a special form of unicellular organism, it does not have a cell nucleus¹, and has a significantly different chemistry, which is part of the strategy behind anti-bacterial drugs. It's just a few micrometers in diameter, making it about 10 times smaller than one of our cells. Like other cells, a bacterium reproduce by cell-division - it duplicates itself. In addition to that, bacteria can also exchange genetic information with other bacteria,², this allowed mutations which increase an individual bacterium's chance of survival and thus the chances of the strain of bacteria becoming widespread, so bacteria can evolve to become drug resistant

Most bacteria are completely harmless- most surfaces, including your skin are covered by them.

Virus

A virus is about hundred times smaller than a bacterium (10-100nm) so you can't see it under a common microscope. It is composed of genetic information and a protein coat. This particle, before it has infected a cell is sometimes also called a virion. The virus' genes encode the proteins needed to form the protein coat, and some proteins that enhance its replication. A virus cannot live on its own - in order to replicate it has to attach itself to one of your cells and hijacks its the protein making equipment. The cell is normally ruined after that, as it is producing viral proteins and not doing the job it's supposed to in your body. Usually a virus kills its h1ost cell once it's used it for its own purposes, by bursting it.

- Sneaky

All Viruses attack cells, but virus attack a specic type of cell, though some are more versitle than others, for instance the HIV virus often, but not always attacks T cells, part of your immune system. Others known as bacteriophages always attack specfic types of bacteria.

There are other things that attack you such as prions³, fungi, and parasites, but the majority of the work your immune system does is fighting bacteria and viruses.

In this entry bacteria and viruses are referred to as pathogens⁴ each pathogen has antigens, which are specific feature, usually a protein on it's surface, which the immune system responds to, these features are called antigens..

First of all they have to get in the body

The best way to not get infected by bacteria or a virus is to prevent it entering your body in the first place. This is the one of the most important jobs of your skin. You may not have thought that your skin is helping your immune system in such an efficient way. You'll have noticed that a cut, if you don't keep it clean, will go "all gunky" the gunk is very often due to an infection. People who loose large parts of their skin because of burns for example will very often get severe infections where the skin in broken.

However broken skin isn't the only route of entry for a persistent pathogen. If a pathogen can't get in through the skin it will have to find another way in. Many can be found in food, although most can be killed if you cook your food thoroughly but some will be on your hand when you eat it, or on your plate or knife and fork.

There are many defences in your gut against pathogens in your food. Firstly the entire gut is covered by a mucosal layer, secondly your stomach contains very strong acid that kills some of them. The bowel is lined with harmless bacteria, because of these it is difficult for the harmful bacteria to start to reproduce there.

If your body has a good reason to believe that the food you have eaten might be infected with something, such as a small amount of harmful bacteria, then it tries to get the contents of the gut out of you as quickly as possible. You're sick and you have diarrhoea, then you take a few days off work with "food poisoning".

Another way of stopping things getting in is to keep a layer of fluid flowing over a surface that pathogens might colonise. This happens in the lungs where the goblet cells produce a layer of mucus and the ciliated cells keep it flowing upwards, towards your mouth where you swallow it, or cough it up without thinking about it. If you do have infection in you lungs and nose, then you will produce much more mucus than usual, giving you a cough or a runny nose.

If you are designing a human being⁵ you don't want to have unnecessary holes in them, that would lead to more infection. Women do need to have an opening for sperm to get into when they are likely to conceive, but they don't need an opening when there is not much chance of conception occurring. So for this reason when a woman is not ovulating there is a mucus plug over the opening of her womb, when she is ovulating the a different type of mucus, one that lets sperm through is produced.

The Complement System

The complement system is a mechanism for activating the immune system. When activated they attract phagocytic cells and increase blood supply to the damaged area.

The Complement System is made up of a number of proteins (10 or so) these are names C(for complement) and followed by a number.

When the body is alerted to the presence of a bacterial or fungal infection one of the first things that will happen is that one of these proteins, namely C3, will be cut in three specific pieces. The three pieces are called C3a, C3b and C3c - each of these has a important role in the defence against an infection.

When the body is altered to the presence of a bacterial or fungal infection one of the first things that will happen is that the protein C3 will be cut in three specific places to produce new proteins each of these has a important role in the defence against disease.

This activates Mast cells, which release chemicals that increase your chances of fighting disease. They cause blood vessels in the area around the infection to dilate, and become more permable, so it is easier for all the cells that fight disease to get to the site of infection. Some of the chemicals attract more neutrophils to the area others attract Eosinophil cells which are important in cases of infection with worms and other parasites. Some of the other chemicals break down the connective tissue making it easier for the cells of the immune system to reach the infected area.

This is one of the most important proteins in the complement system, it has a number of important roles.

• One of the main tasks of C3b is to stick to cells that it recognises as foreign, marking the target for the activated neutrophils and other phagocytic cells.

• It also induces more splitting of C3.

• Another part of C3 splits C5 into two parts C5a and C5b

• C5a attracts phagocytes and activates them when the reach the site of infection.

• C5b joins up with C6, 7, 8 and 9 to puncture holes in bacteria cell walls, it doesn't harm our cell membranes because they are made of different chemicals.

If Complement Activates all This What activates Complement?

There are two main mechanisms to activate the complement proteins: the Classical pathway, which was discovered first, and the alternative pathway which is more common. In this sense a pathway is a series of reactions that lead to C3 being cleved, this in turn leads to complement system springing into action.

The alternate pathway occurs in response to yeast fungus and bacteria cell walls, in combination with some chemicals and C3b, which is always present in blood in small amounts. The Classical Pathway occurs when the antigen combines with one of two type of antibody and some of the complement proteins. The system is incredibly complex, if you are interested in the exact chemical reactions that take place you could take a look at this site run by the University of Illinois.

The Next Line of Defence Against Bacteria..

The neutrophils are the cells in your body that kill most bacteria that live outside of your cells. Because they can only be used once and have a rather short life, they can only neutralise about 20 bacteria each. Because of this your bone marrow produces large numbers of neutrophils: approximately 150,000,000,000 a day.

Neutrophils fight bacteria that are in the tissue but outside of cells. In order to migrate to the sites of infection from your blood, they have to know that attack from bacteria is taking place. A number of singalling chemicals can "tell" neutrophils to move to the tissues. Some of these chemicals signals are produced by bacteria themselves. In addition to this the body has its own but more complex system to alert itself to pending attack.

It is also important to stop neutrophils eating cells of your own body by activating them (like priming a grenade) and telling them what they may and what they may not "eat". This is done by antibodies and the complement system.

What Happens Once Neutrophils Arrive?

A neutrophil will engulf the bacterium, ingesting it and then digesting it by injecting chemicals that will damage it. Most of those chemicals are enzymes which break down many of the chemicals that make up our and the bacterium's bodies. Neutrophils are like bumble bees in that they can only kill things a few times - about 20 - and then they start to die. Once a neutrophil has started to die, it will send out a signal of its imminent death by making characteristic signalling proteins which it displays on its surface. These proteins attract another sort of cell known as a Macrophage, which will arrive to eat the neutrophils and the remnants of the bacterium contained in the neutrophil. Most of the chemicals are recycled. If a large amount of neutrophils are dying in one place, sometimes the macrophages can't recycle them fast enough, that's why we get an abscess. An abscess is a crust of neutrophils containing a clear fluid, which consists of bacteria and dead neutrophils. It is sealed so bacteria can't get out, also neutrophils can't get in.

Macrophages too play an important role in phagocytosing bacteria themselves, as well as ingesting neutrophils that are at the end of their lives.

Some Sneaky Bacteria can Escape

Some bacteria, such as the ones that cause Tuberculosis and Leprosy, manage to escape by inhibiting by releasing chemicals which interfere with the killing process in some way, so inhbiting the action of the macrophage.

Hidden inside the macrophage the bacteria cannot be attacked by the immune sytem, it travels as the macrophage does through the blood or lymphatic systems, spreading the infection.

Once the Macrophage has arrived

Let us assume that the bacteria didn't inhibit the action of the macrophage, so it has done the first part of its job and the bacteria has been killed. The chances are that there will be a lot more of the same sort of bacteria around the same spot (they never come alone) so the body starts to make preparations...

The macrophage takes the proteins from the bacteria it digested, and chops them up into small pieces, which it displays on its surface in special proteins known as Major Histocompatability Complexes Type II ⁶ (or, MHC II). Sooner or later a T-helper cell will recognise the foreign protein in the MHC-II and start an immune response. The T-helper cell's job is to recognise these MCH complexes and spot other infected cells.

Hang on What's this T cell Thingamejig?

T Cells are matured in your thymus gland, which is in your chest - the T stands for thymus. There are two main sorts of T-cells, or T-lymphocytes. T helper cells, which start an immune response going and T killer cells which will be discussed later. All T cells have a receptor that recognises one particular antigen. During their maturation, or specialisation, they are drilled to recognise differently shaped receptors. These receptors are manufactured at random, and the ones that, by coincidence, would recognise a protein in a healthy cell of your body are destroyed

Each T cell has a receptor that recognises one particular antigen. When T cells are produced the receptors are manufactured at random. Some receptors will inevitably recognise parts of the body, so if a young T cell recognises a cell it comes into contact with then it is destroyed.

So What do T Helper Cells do..

They have two main roles. To help B cells start producing antibodies and to release chemicals⁷which stimulate the immune response

When a T cell that has met a macrophage that has "its antigen" in its MHC then it goes looking for a B cell that has a receptor for the same antigen as its self. B cells are produced in bone, hence the B⁸. and when they are activated by a T cell they start dividing to produce more B cells. Some of these B cells start reproducing quickly and mutating in the hope that by accident one of them will mutate to form something better at combating the B cells. This takes place in your lymph glands, which becomes swollen when you're ill. Also in your lymph glands are cells that are known as interdigitating cells, these have examples of all the self proteins in the body so that new B cells that recognise them can be quickly disposed of.

The rest of the B cells will multiply several times and eventually become plasma cells that produce antibodies.

What do These Antibodies do now you've gone to All that Effort to Get Them?

• Some antibodies block the parts of virus that get the virus into the cell.

• Most of them bind to the antigen with one end and then go on and do something with the other end. Many processes are started this way...
  
  • The complement system can also be activated this way
  • Mast cells can also be activated
  • As can Neutrophils
  • and Eosionphils, these are similar to neutrophils but they act against much bigger antigens such as worms, so they release the noxious substances onto the antigen rather than taking them into the cell it's self
  • Macrophages can also be activated by antibody and a complement protein
• Antibodies can also join antigen together to form a mat of antigen which cannot have much harmful effect.

So Does this mean the Immune system's no good against Viruses?

Viruses get inside your body and then gets inside your cells, then it hijacks your cells protein-producing machinery to make more copies of itself.

We produce antibodies against viruses as described above, they attach to the part of the viruses that is used to get into cells. You have another important mechanism of defence.

MHC I is an Important Defence against Viruses

Every cell in the body puts a sample of all the proteins that it makes on its surface using MHC I proteins. If a T helper cell recognises these then they activate T Killer cells, which kill infected cells.

Some viruses are sneaky and to avoid detection they stop the cell displaying proteins on its coat. But Natural Killer Cells kill cells that are not displaying sufficient amounts of MHC I.

Your Body can Remember Antigens

Once you have killed all the bacteria or all the virus then some of the B cells and T helper cells will remain and be on hand if the bacteria is still around. This means that the next time you are exposed they'll be able to kill a virus or bacteria much quicker. When you are immunised against a disease either a dead or inactivated form of a bacteria or viruses is injected, so having bounced a