|The immune system and its functions
[Translated into English by Karin Sandbergen, 2012.]
By Lies Klösters, 2012.
(Re-printed with permission).
The following description of the immune system is not complete, a lot more can be said about it. Furthermore, new things about the immune system are being discovered regularly. In this article I have restricted myself to a concise explanation of the way this comprehensive system functions.
Nearly all living creatures have an immune system, otherwise known as a defence system. Bacteria and single cells can defend themselves from outside attacks, but they do not have an immune system such as multiple cell organisms have. An immune system functions through the cooperation of several kinds of cells, which together mount an attack on an intruder.
The immune system sees to it that you do not get ill, or that you get better quickly if you are ill. Some individuals have an immune system that functions better than others and in some cases one can help the immune system function better. The immune system can be enhanced by vaccinations but also by a healthy lifestyle: healthy food, plenty of rest and a life without stress.
Defence against foreign substances
If the immune system reacts adequately to a pathogen, the body has become immune to that specific disease. 'Being immune' to a disease is not the same as 'being resistant' to. The body becomes immune because it learns to defend itself to a pathogen, but cannot pass this feature on to possible descendants. Resistance to a disease starts because a mutation occurs at cell division. Because of this, the one who this happens to has a greater chance of survival than others of his kind, who do not have this mutation. This resistance can be passed on to the next generation through inheritance of the mutated gene.
The immune system protects the body from foreign substances such as pathogens (bacteria, viruses and fungi), or cells that have entered the body through a blood transfusion or an organ donation. Poisons and diseased cells such as cancer cells are also destroyed by the immune system.
The immune system recognises the foreign cells by the foreign proteins. These foreign proteins are called antigens. There are millions of different kinds of antigens. The immune system is a very complex system, which should be able to react adequately to every kind of antigen.
Sometimes the immune system is mistaken and the body's own substances are no longer recognised. When that happens the immune system attacks its own body. This happens, amongst others, to people who suffer from psoriasis, rheumatoid arthritis, diabetes mellitus type I, multiple sclerosis. These are auto-immune diseases.
If the immune system does not work or does not work adequately, this is called immune deficiency. This happens to people who suffer from AIDS (Acquired Immuno-Deficiency Syndrome), but also to people who have to take medication to suppress rejection of a new organ after they have undergone an organ transplant.
Innate/non-specific and adaptive/specific immunity
The immune system works in different ways: innate and adaptive immunity. Both types of immune system consist of cellular (or cell-mediated) and humoral components.
Cellular components are the cells which work for the immune system, such as macrophages and lymphocytes. Macrophages and lymphocytes are white blood cells. All blood cells are produced in the bone marrow. Lymphocytes mature in the lymphoid organs (lymph nodes, bone marrow, spleen and thymus gland). The function of the lymphocytes consists mostly of recognising foreign antigens. Macrophages absorb foreign cells and consequently demolish them.
Humoral components are enzymes and specialised proteins (immunoglobulins, also known as immune bodies or antibodies) which are present in the body fluids. The humoral components slow the pathogen down or they stimulate other enzymes or cells to destroy the pathogen.
The cooperation between these different types of immune system sees to it that every antigen can be removed. In addition, the components also keep each other in balance: if one of the components becomes very active, the activity of the other component decreases.
- Innate or non-specific immunity:
The non-specific defence is part of the immune system which can stop or destroy several kinds of pathogens. This form of immunity is active directly after birth, but in its functioning not as specific as adaptive immunity. The defence against a possible pathogen is therefore not at its maximum.
The non-specific defence can be divided into two lines of defence:
1st line: The physical barrier: for example the skin, tonsils, mucous membranes and the intestinal wall. This barrier sees to it that pathogens cannot enter the body. Saliva and gastric juices are also part of the physical barrier. They kill bacteria, so they will not get a chance to infect the body.
- Cellular (or cell-mediated) component: The presence of white blood cells in the bloodstream. For the non-specific defence these are the macrophages and the natural killer cells (lymphocytes). They kill everything they encounter and that is foreign to the body. In some cases too many pathogens have entered the body (as can happen in case of a wound) and there are not enough macrophages and natural killer cells available, so they cannot combat the pathogen.
- Humoral component: This form of defence consists of complement proteins. This is a group of proteins which - after they are activated - form a chain reaction. They take care of it that the blood vessels, where the infection is present, expand, and as a result of which, more fluid (containing antibodies) can flow to the affected site. Besides which, because of the expansion of the blood vessels, the large macrophages can flow more easily through the capillaries to the infection. Furthermore, the chain reaction sees to it that the proteins draw the macrophages towards the pathogen. Also, the proteins produce an enzyme that creates holes in the cell wall of the pathogen, as a result of which the pathogen can be destroyed more easily by the macrophages.
- Adaptive immunity or specific defence:
Some bacteria or viruses are able to multiply very rapidly. In a situation such as that the non-specific defence cannot control the attack by the pathogens and the specific defence will be activated. The specific defence can generate an immune reaction, which produces a great number of antibodies and memory cells especially against that one specific pathogen. This is the part of the immune system that is activated at the moment someone is vaccinated against a disease.
This specific defence is acquired through the years by the body. The fight against diseases is not always picked up that easily by the immune system. An infection with measles will lead to a good defence against that disease in almost all cases; almost
no-one gets measles twice. However, the same person can suffer repeatedly from a disease such as malaria. Resistance against malaria does not provide an immunological memory, as a result of which one can never be infected with it again.
- Cellular (or cell-mediated) component: The cells which are used for this defence strategy are known as T-lymphocytes or T-cells (T-helper cells give off substances which regulate subsequent processes. Killer T-cells see to it that pathogens are rendered innocuous. T-memory cells are produced when first infected with a pathogen. During subsequent infections these cells recognise the antigen and the immune reaction will begin more rapidly. Regulatory T-cells slow down the immune reaction, so it does not get out of hand and the body's own cells will not be attacked). T-cells mature in the thymus gland. The thymus gland (also known as thymus) is an organ which is relatively large in new-borns. Young animals are subjected to their first contacts with pathogens and the thymus is the most active in this period. As soon as an animal gets older and has been infected by (almost) all pathogens, the necessity for the thymus becomes less and the organ decreases in size.
- Humoral component: Antibodies and B-lymphocytes together are responsible for the humoral functioning of the specific defence. B-lymphocytes produce antibodies (immunoglobulins IgA, IgG and IgM) and B-memory cells, as soon as they come into contact with an antigen. These antibodies only function against that one specific pathogen for which they are produced. It takes a while after the first infection, before sufficient antibodies are produced, but during a subsequent infection the production of antibodies will begin much faster. The body still remembers the pathogen (because of the
B-memory cells) and can therefore much more rapidly and much more specifically mount an attack against it. Immunity has been developed against that disease.
(IgA is mostly present in the stomach, intestines, saliva and in mother's milk. IgM is mostly and initially produced during a new infection. IgG is produced during a second encounter with the same pathogen. IgG is transferred during pregnancy to the foetus by the placenta.)
Passive and active immunisation
- Passive immunisation:
The individual gets its antibodies from someone else. The immune system itself does not generate antibodies and, furthermore, no memory cells are formed. During a subsequent infection, the immune system will not be able to react rapidly. It will react as if this is the first time the body comes into contact with that specific pathogen. For example, passive immunisation is the defence a descendant gets from its mother. Or the receiving of a serum with antibodies from another individual.
- Active immunisation:
The body produces its own antibodies and memory cells are generated. Active immunisation occurs when someone is infected with a pathogen and subsequently produces their own antibodies against that specific pathogen. Or one can be vaccinated against pathogens. Because of this, someone hardly gets ill or does not get ill at all, but it is seen to that someone produces antibodies and memory cells themselves.
When animals are still very young, they are dependent on the defence they have received through their mother (maternal immunity). Mammals provide their descendants with antibodies in the womb and through mother's milk. Birds give maternal immunity to their chicks through the egg yolk.
- Diaplacentary maternal immunity:
A young animal receives the first defence from their mother through the placenta, this is called diaplacentary maternal immunity. The mother and the foetus have separate blood circulations. Therefore, there is no exchange of blood between mother and child. But in the placenta - through the tissues between the two blood circulations - an exchange of substances does take place. The foetus gives waste products to the mother and the mother provides the foetus with antibodies. The distance between the blood circulations of mother and child is determined by the thickness of the tissues and the number of layers of tissue between the two blood circulations. This distance differs with every animal species. The greater the distance between the two blood circulations, the less possibility there is to exchange substances between mother and child. A number of animal species has no possibilities at all for exchange of substances, because the placenta is impenetrable because the distance between the two blood circulations is too big. As a consequence, the young of these animal species are born without any form of defence.
The penetrability of the placenta (and therefore also the exchange of substances between mother and foetus in the womb) is good where higher primates, humans, guinea pigs, rabbits, mice and rats are concerned. Here the placenta barrier between the two blood circulations consists of 3 cell layers (Placenta hemochorialis). In dogs and cats the passing of substances through the placenta does not work as well, the placenta barrier in these animal species consists of 4 layers (Placenta endotheliochorialis). But in, for example, ruminants, horses and lower primates no exchange of substances through the placenta is possible. These species of animal have a placenta barrier of 5 or 6 cell layers (Placenta epitheliochorialis).
- Colostral maternal immunity:
The first milk a mother produces after giving birth, is colostrum. Colostrum is a deeper yellow and thicker than normal mother's milk and contains large quantities of immunoglobulin. These are large chains of proteins, which normally cannot be absorbed through the intestinal wall by the body. However, new-borns can absorb these chains of proteins through the intestinal wall, thereby strengthening their defence. This form of defence is called colostral maternal immunity.
Antibodies are absorbed the easiest the first hours after birth, the ability to absorb these large chains of proteins decreased quickly after that. One or two days after birth the intestinal wall is definitely closed off to these large proteins. Giving colostrum to a young that is a week old will therefore not do much good, the intestinal wall will probably not let the antibodies through. It is therefore important to let new-borns of all mammals drink the first mother's milk within a few hours after birth. But especially for species of animal where the placenta is impenetrable, it is of the utmost importance for the defence of the young.
- Lactogenic maternal immunity:
After each feed the mother gives, the structure of mother's milk changes more and more into 'normal' mother's milk. However, this normal mother's milk still contains antibodies. Nevertheless, these antibodies cannot be absorbed through the intestinal wall into the body of the young, because the intestinal wall has already closed itself off. These antibodies therefore stay in the intestines and there combat antigens the young get through their mouths. The antigens are rendered harmless by the mother's antibodies in the intestines of the young and therefore cannot infect the body. This is called lactogenic maternal immunity. As long as the young is still suckling, the presence of these antibodies is still renewed. As soon as the young does not drink mother's milk anymore, this protection will disappear after approximately 24 hours, when the last antibodies are excreted through the intestinal tract with the faeces.
Inducing adaptive immunity with the help of vaccinations
Animals can be vaccinated against several diseases to guarantee their health. The first vaccination takes place as soon as maternal immunity decreases. If vaccination takes place while maternal immunity is still abundantly present, the vaccine will be broken down by the maternal antibodies which are already present and the young's body will not be producing its own antibodies. That way, no memory cells will be produced and the animal will not be well-protected against the disease in future, whereas that was precisely the reason for the vaccination.
Normally, a pathogen is stopped at the physical barrier (skin, mucous membranes, tonsils, etc.). But because a vaccine is injected subcutaneously into the body, this first barrier is evaded. The pathogen can spread itself fairly rapidly through the body via the body fluids that flow under the skin. These body fluids take the pathogen to the lymphatic vessels where it finally ends up in the lymph glands. Here, the pathogen is identified and production of lymphocytes and antibodies is begun, to combat the pathogen.
The immune system is activated for the first time during the first vaccination and will react slowly, resulting in a low concentration of antibodies. The animal is not yet directly fully protected from the disease or diseases it has been vaccinated against, but only a week or two after the first vaccination. Shortly after the first vaccination, a second vaccination (booster) is given, activating the immune system for the second time. This time, the immune system will react more quickly and efficiently, because during the first vaccination memory cell have been produced, which can now come into action rapidly. The immunity of the animal will be much stronger after the booster vaccination, as opposed to it being given only the first vaccination.
Subsequently, in many cases one vaccination every 2 or 3 years will suffice.
There are two types of vaccines: inactivated (or killed) vaccines and live/attenuated vaccines. Inactivated (or killed) vaccines consist of substances the pathogen produces. The vaccinated animal will not get ill because of this, but the immune system will be stimulated to produce antibodies against the pathogen. Live vaccines consist of attenuated (rendered harmless) pathogens. With this form of vaccination the vaccinated animal can get ill. Usually, this is a slight form of the disease against which it is vaccinated (vaccine reaction).
If a vaccinated animal is infected with the pathogen against which it is vaccinated, the immune system recognises the pathogen and the right antibodies can be produced directly. Usually, vaccination with attenuated vaccines is more effective than those with inactivated vaccines and that is why vaccination with attenuated vaccines is usually preferred.