Immunity

The First Line of Defence

Self and non-self

On the surface of all cells are chemical markers (for example, proteins) called antigens.

Each antigen has its own unique shape. The more closely related 2 individuals are, the more antigens they have in common.

This means that you and a brother, sister or parent will have more antigens in common than you and a distant cousin.

Your body recognises the antigens on your cells as your own (self); anything with different antigens to you (non-self) stimulates an immune response.

In an immune response, your body will recognise the antigen as foreign (and therefore bad) and will attack it.

Infection and disease

Your immune system is made up of cells that work with the body’s physical and chemical barriers (see below). It helps prevent any pathogen (disease-causing organism) entering your body, and your body therefore becoming infected.

Note: Harmful bacteria is an example of a pathogen.

If the worst comes to the worst and any pathogens do get into your body, the immune system tries to stop them from causing harm.

You begin to experience the symptoms of and start suffering from the disease if the pathogens manage to multiply, produce toxins and damage your cells.

Physical and chemical barriers

The first line of defence is made up of physical and chemical barriers.

These types of barriers are non-specific (i.e. if any organism is not recognised, it is assumed to be a pathogen, and will be treated the same way).

These barriers occur at the skin or any other openings to the outside world. Here is a list of some physical and chemical barriers you should know to quote in your exams:

Physical Barriers

Skin: it is a hard outer layer that generally prevents the entry of any undesirables

Nose, throat and digestive tract: the membrane lining these secretes sticky mucus to trap microbes. Fine hairs called cilia waft the mucus away.

Chemical Barriers

Eyes: tears have lysozyme enzyme in them. This kills some bacteria.

Ear: your wax has antimicrobial properties.

Stomach: hydrochloric acid in your stomach kills bacteria.

Large intestine, urethra and vagina: resident harmless bacteria use the nutrients that any harmful microbes would need to survive (i.e. harmless bacteria out-compete the harmful bacteria).

Sweat: is an acidic liquid that contains enzymes which kills some bacteria.

The Second Line of Defence

The second line of defence is also a non-specific response (i.e. the response is the same for any pathogen).

It is a 3-pronged attack on any microbes that have survived the first line of defence;

Attack no 1: Inflammation (yes, this is good!)


Inflammation happens because cells damaged by invading pathogens and particular white blood cells release ‘alarm’ chemicals which makes blood vessels enlarge (vasodilate) and the capillaries more ‘leaky’.

This means that:

1.

More blood is coming to the site of the infection, bringing with it more white blood cells of the immune system

2.

Then, the white blood cells are let out of the blood capillaries and into the affected tissue.

This extra blood makes the area red (as more blood means that the area looks red) and swollen (more blood and liquid leaving the blood and entering the tissue fluid surrounding the body cells).

The area will also become hot (as the extra blood is also carrying heat with it) and painful (because the tissues will be swollen with the blood).

Attack no 2: Phagocytes and lymphocytes:


Inflammation attracts white blood cells to the area.

The three types of white blood cell you need to know for your exam are neutrophils, macrophages (these are both phagocytes, which are engulfing cells), and lymphocytes.

The phagocytes (for example a neutrophil), having squeezed through the capillary wall and into the infected tissue, engulf and digest offending bacteria as shown in this diagram:

The stages of Phagocytosis

1.

The bacteria will be attracted to the membrane of the neutrophil.

2.

Phagocytosis. The neutrophil will engulf the bacteria.

3.

Once in the neutrophil, lysosomes (vesicles containing digestive enzymes) will form and make their way towards the phagosome containing the bacteria.

4.

The lysosomes will fuse with the phagosome.

5.

Now the bacteria will be killed and digested by enzymes.

The lymphocytes will also kill bacteria. However, some bacteria may escape by having a protective cell wall or capsule.

(Note: A good example to remember of a bacterium with a capsule is the bacterium that causes tuberculosis)

As revolting as pus may be, it is in fact a sign that your immune system is doing what it is designed to do.

Pus is millions of dead immune cells that have previously migrated to the site of the infection and engulfed the pathogens.

Attack no 3: Macrophages and Interferon


Other than direct ‘hand-to-hand’ combat, some killing is done at a distance. Macrophages make proteins that act in two ways:

1.

They can punch holes in the bacteria and parasites so that they die

2.

or the proteins can stick to the outside of the bacteria to make them more appealing for the phagocytes to eat!

If a virus or an intracellular parasite (one that lives inside a cell) has invaded a cell, the cell will make a chemical called interferon. Interferon ultimately prevents that cell from making molecules that the pathogen would need to survive.

Although the second line of defence is very powerful, it does have a some weaknesses:

1. It can’t deal completely with any one particular micro-organism (some pathogens will nearly always survive this attack)

2. It can not remember past infections.

This is why a third line of defence is needed (the next Quick Learn is about the third line of defence)

The Third Line of Defence

Lymphocytes


The third line of defence depends on lymphocytes. There are two basic types of lymphocyte and both are made in bone marrow.

One type, the T cells, mature after having first migrated from the bone marrow to the thymus gland. The other type, B cells, migrate to and then mature in either the bone marrow or in the foetal liver or spleen.

Once mature, they patrol around the blood and body, hunting for foreign antigens. T cells are involved in the cell-mediated response, whilst B cells are involved in the humoral response (both described below).

Cell-mediated response (T cells)


Different T cells have different receptor molecules on their surface. When an antigen invades the body, macrophages engulf it and present it to the lymphocytes.

If an antigen is presented to a T cell with a complementary shaped receptor, the T cell is stimulated, increases in size and starts to divide.

A clone of identical T cells is formed, all with the correct shaped receptor. These T cells then differentiate to form 4 groups of specialised T cells. These are:

· killer T cells
· helper T cells
· suppressor T cells
· and memory cells.

Members of this powerful infantry (except the memory cells) then make their way to the site of infection.

Killer T cells

combine with the antigens on the surface of any invading cell and release a powerful group of chemicals called lymphokines. Some lymphokines kill the pathogens directly, others stimulate other lymphocytes to become active, and still others increase the inflammation so that there are more macrophages.

Helper T cells

co-operate with B cells in antibody production (see later about antibodies). They also activate macrophages and promote inflammation.

Suppressor T cells

keep the immune system in check so that once the antigens have been dealt with, the system is switched off

Memory T cells

remain after the pathogens have been killed to stop re-infection (see lesson 4 on memory)

Humoral response (B cells)


As with T cells, a B cell will form a clone if it comes into contact with a complementary shaped antigen. The clone contains mostly plasma cells for immediate use and some memory cells for use in the future.

Antibodies

The plasma cells are highly developed and are able to make several thousand antibody molecules every second.

Unlike the T cells, the B cells do not leave the lymph nodes – only the protein (antibody) molecules that they make move around the body. These proteins are released into the blood and carried to the area of infection.

They will be the right shape to bind with any appropriate antigen they meet but only the one that caused the stimulation of the B cell in the first place.

The antibody molecule, on the other hand, binds to the antigen in a similar way to a substrate binding with an enzyme. The fit, however is not as precise as the enzyme-substrate complex. The better the fit, the stronger the subsequent immune response will be.

By combining with the antigen labels the pathogen (which the antigen is attached to) as foreign. Often several antibodies combine with several antigens so that a complex mass is formed.

Antigen-Antibody Complex:

This action means that:

1. The pathogens clumping together make them more vulnerable to phagocytes.

2. The antibody "tags" the bacteria when it is stuck to it, making it more easily recognisable to phagocytes.

3. Any antigens acting as toxins in your body are neutralised when the antibody sticks to it i.e antibodies can act as antitoxins. In a similar way, if a virus has an antibody attached to it, it will no longer be able to attach or enter a host cell.

Tissue transplants


Unfortunately this defence system also means that recipients of organ transplants are not assured of an end to their troubles when this option is offered to save their lives.

It should be fairly obvious now that anything foreign in your body will be forcefully attacked. This means that an organ being transplanted from one person to another will be spotted as foreign (as it has different antigens) and could be destroyed.

The only way around this (unless you have an identical twin who can spare the appropriate part of the body) is to destroy the T-cells in your body using x-rays and immuno-suppressant drugs.

The downside is that with fewer T-cells patients are much more vulnerable to diseases that would not normally kill e.g. pneumonia.

Memory

Immunological memory



Plasma cells and most of T cells die after only a few days. However, the memory B cells and a few memory T cells survive.

Each plasma cell and T cell will only be programmed to only respond to the one antigen that they have already encountered. So they wait in the lymph nodes in case re-infection occurs, in which case they are ready to attack.

This way, although the first infection was dealt with in a few days to a few weeks by the primary response, the secondary response to re-infection is much quicker and much more powerful.

Because of this clever system, even if you are re-infected, you may not even know about it because no symptoms show! The infecting organism does not have the chance to cause disease. This is why many diseases can only infect you once.

This is not infallible though. There are some diseases that come in a variety of guises, for example the common cold and influenza (flu).

Although each time you get a cold you have a similar set of symptoms, each new cold is in fact caused by a slightly different virus with slightly different antigens.

This is not the worst of it though. Unfortunately, viruses have a relatively high mutation rate, which may alter their antigens. Even a slight change may mean that your memory cells do not recognise a disease you have had before.

This means then, that your response to it will be as slow as it was the first time.

Artificial immunity - vaccines



In the past, to become immune to a disease you would have had to have contracted the disease at least once.

Nowadays, this need not be the case. Immunity can be artificially induced. This is achieved by injecting a vaccine so that you will form the necessary memory cells without much (if any) suffering.

This vaccine is, in fact, small quantities of the antigen attached to the offending organism.

To reduce the risk involved when taking the vaccine, the disease itself may have been artificially weakened.

This ‘weakening is achieved by taking the disease cell and altering it (as in polio, smallpox and measles vaccines), killing it (as in whooping cough and typhoid vaccines), or by using altered toxins (as in the tetanus vaccine).

Your body will mount an attack and overcome this weakened strain of the disease quickly and easily – and memory cells will be created in the process.

This way, if you ever encounter the real disease, the memory cells are ready to be quickly stimulated and your immune system can destroy the disease before you even notice it!