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[Biology A-level]: Immunity

Source taken from: http://www.s-cool.co.uk/alevel/biolo...f-defence.html

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:

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 the following diagram...

The stages of Phagocytosis

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


Phagocytosis. The neutrophil will engulf the bacteria.


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


The lysosomes will fuse with the phagosome.


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:

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

It can't deal completely with any one particular micro-organism (some pathogens will nearly always survive this attack).
It can not remember past infections.
This is why a third line of defence is needed (the next Learn-it is about the third line of defence).

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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
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:

The pathogens clumping together make them more vulnerable to phagocytes.
The antibody "tags" the bacteria when it is stuck to it, making it more easily recognisable to phagocytes.
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.

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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.

Artifical 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!

Natural immunity

If the activation of the immune system occurs naturally during an infection, this is termed natural immunity. Because in response to the antigens, Band T cells have gone into action and a memory has been produced, it is also termed active immunity. Vaccination would also be termed a form of active immunity.

However, passive immunity, which is not long term, is also a possibility. Antibodies from a mother may cross the placenta during pregnancy and remain in the infant for several months. Colostrum, the first breast milk produced for four or five days after giving birth, may also contain antibodies. These two examples could also be termed natural immunity.

Passive artificial immunity is used in the treatment of tetanus, which kills quickly, before a natural active response can occur. An injection of antitoxin is given which contains human antibodies taken from blood donors who have recently been vaccinated against tetanus. An immediate but temporary response is the result, because the antibodies would be identified as foreign and removed from the patient's body.

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Not all vaccination programs are completely successful in eradicating a disease. One that was, is the smallpox vaccine.

Eradication of smallpox

This disease was caused by the variola virus. 12-30% of sufferers died while many who recovered were often blinded. In 1967, WHO (the World Health Organisation) vaccinated more than 80% of the worlds population who were at risk and when a case was reported all possible contacts in the area were vaccinated (ring vaccination).

Eradication in rural areas proved a challenge, but the last case occurred in Somalia in 1977 and in 1980, WHO declared the world free of smallpox.

Reasons for the success of the vaccine included:

The variola virus did not mutate and change its antigens.
It was made from a live harmless strain of a similar virus, so it mimicked a natural infection, multiplying and continually presenting the immune system with a large dose of antigens.
It could be freeze-dried and kept for six months aiding distribution.
Infected people were easy to identify.
It was easy to administer and the disease did not linger in the body.
Smallpox does not infect animals.

Less successful vaccination programs have included those against measles, tuberculosis, malaria and cholera.

Measles


This disease offers the promise of eradication if worldwide surveillance was followed-up by vaccination.

However, so far it has failed because:

A poor response to the vaccine has been shown by some children, who need boosters.

High birth rates and shifting populations make following-up cases difficult.

Migrants and refugees may spread the disease.

Measles is highly infective and 95% immunity of a population is required to prevent transmission.

The vaccine only has a 95% success rate.

Tuberculosis


This disease was once thought to have been eradicated, but is actually showing a resurgence.

The reasons include:

Some TB bacteria are resistant to drugs used to treat them because they can mutate.

AIDS can allow TB to infect an individual due to their compromised immune system.

Poor housing and homelessness lowers peoples' natural resistance.

There have been breakdowns in the TB control program.

It is actually caused by two different bacteria with two different antigens, which can live inside human cells, making them hard to fight.

It can be carried in cattle.

Malaria


This is a disease caused by Plasmodium, a protoctist (eukaryotic) that has hundreds or even thousands of different antigens. It also has three different stages in its life cycle, meaning that developing a vaccine is incredibly challenging and has not yet been achieved.

Cholera


This disease is caused by Vibrio cholerae, which can live in the intestines where antibodies - produced by vaccines that are injected - cannot get to it. An oral vaccine is in development.

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These are drugs used to treat or cure infections and to be effective they must kill or disable the pathogen, leaving host cells unharmed. Most antibiotics are used to treat bacterial and fungal infections, there are very few that are effective against viruses. A few antibiotics are synthetic but most are derived from living organisms. They work by either interfering with the growth or metabolism of the bacteria or fungi. They may inhibit the synthesis of the cell wall, translation or transcription of proteins, interfere with membrane function or enzyme action.

Antibiotics need to be carefully chosen. This is done by screening them against the strain of bacterium or fungus obtained from the sufferer. The samples obtained are grown on agar plates and antibiotic discs placed on to the plate. The disc with the greatest diameter of inhibition zone, is the most effective. Broad spectrum antibiotics are effective against a wide range of bacteria, while narrow spectrum antibiotics affect only a few.


Penicillins are well known antibiotics, which work by preventing the synthesis of peptidoglycan polymer cross links in the cell walls of bacteria. They are only effective when the organism is making new cell walls, i.e. growing. Many bacteria are now resistant to penicillin as they have penicillinases (enzymes which destroy penicillin). Resistance to antibiotics, is coded for by small rings of DNA found in bacteria, called plasmids.

Some bacteria may contain up to five plasmids, each conferring resistance to a different antibiotic. DNA and therefore plasmids can be passed between members of the same species of bacteria during conjugation, or sexual reproduction. Specialised tubes or pili join one bacterium to another during conjugation.

Resistance to antibiotics is increasing and has a great impact on the treatment of a disease because it prolongs illness and increases mortality. Hospitals try and keep some antibiotics as a last resort and drug companies are continually looking for new ones.

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These are a result of an overreaction of the immune system to a harmless antigen, as in asthma, hay fever and eczema.


They are caused by allergens - for example, pollen, dust, particles of animal skin, dustmites and their faeces.

When these allergens are inhaled, the immune system recognises them as foreign and B cells produce antibodies. These antibodies coat the surface of mast cells, which line the airways, sensitising the body to the allergen.

When the allergen is encountered for a second time, it binds to the antibodies on the mast cells and stimulates them to release histamine. This enables white blood cells and fluid to leak from capillaries resulting in inflammation.

In hay fever, the inflammation occurs in the eyes, nose and throat but is not fatal and only usually occurs from May until September.

Asthma can be much more severe and over one thousand people in the UK die from it every year. During an attack, fluid and mucus collects in the airways, blocking the smaller ones. Muscles in the trachea, bronchi and bronchiole walls contract, and breathing becomes difficult. A vaccine, which will desensitise sufferers is in development, as one in seven children have asthma it could make a huge difference to lots of peoples lives.