Immunology 1/3

IMMUNOLOGY
1. Unspecific Defence
1.1. Barriers Against The Intrusion Of Germs
Several layers of dead cells protect our keratinised skin. It is only pierced by sweat channels and the openings of hair follicles. The slightly acid surface of our skin (pH5.5), caused by the colonisation by lactic bacteria, also creates an environment unfavourable for pathogenic (disease causing) bacteria. Mucous secretions in the respiratory tract (nose, trachea, bronchia) trap dust and bacteria, whereupon they are swept out by the cilia. Tears and mucus of nose and intestine contain the enzyme lysozyme, which can dissolve the cell walls of gram-positive bacteria (staphylo- and streptococci etc.). It is liberated when phagocytic cells disintegrate. Interferons are produced by cells infected by viruses. They are glycoproteins (sugar-protein-compounds), which inhibit the proliferation of viruses and protein synthesis in the host cells. In doing so they also inhibit the host cell's reproduction and may reduce proliferation of lymphocytes. In bacterial infections one can find so-called C-reactive protein (CRP) in the blood plasma, which can activate the complement system (see below) and also promotes agglutination and phagocytosis of bacteria. The complement system, which also plays an important role in specific defence, consists of about 20 proteins which can destroy viruses and bacteria. It builds channels into their outer membrane, leading to osmotic rupturing of the germs. Complement proteins also attract phagocytic cell. The large phagocytic cells, the macrophages, which can be found everywhere in the body, phagocytose microorganisms and disassemble them with enzymes from lysosomes. They also clear away the debris from dead cells and antigen-antibody complexes. While circulating in the blood they are called monocytes. Neutrophils (neutrophilic granulocytes, microphages) are attracted by substances released upon inflammation., e.g. by mast cells in the skin, they are also attracted by some components of the complement system. They too eat microorganisms. natural killer cells (NK-cells) can recognise cells infected by viruses and make them burst.

1.2. Unspecific Chemical Defence

1.3. Unspecific Cellular Defence

2. Specific Defence
2.1. The Components of Specific Defence
Our specific defence system mainly comprises the following components: Humoral defence by antibodies. Antibodies are proteins which have binding sites for antigens. They also have regions which are recognised by macrophages and the complement system. Antibodies can bind and inactivate soluble antigens like bacterial toxins, snake venom etc.. Larger

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objects like viruses and bacteria are "labelled" so they will be recognised and destroyed by macrophages and the complement system. Cellular Defence Killer-T-cells destroy cells invaded by viruses and cancer cells. Complement makes microbes burst and activates phagocytes. These three systems work together.

2.2. The Cell Types Involved

Lymphocytes are involved in both humoral and cellular immunity. They constantly circulate between blood and lymph. In small blood vessels they can squeeze through the wall of the vessel and leave the blood stream. They can move freely through the different tissues and collect again in the lymph vessels. In the lymph nodes different lymphocytes preferentially collect in specific areas. T-cells near the centre, B-cells towards the periphery in the germinal centres. From the lymph nodes the lymphocytes can regain the blood stream via the large lymph vessels. In our body we have a large number of passive "untouched" or "virgin" lymphocytes. On their membrane they carry receptor molecules, only one type per cell with a specific binding site. In B-cells these receptors are antibody molecules fixed to the membrane.

2.3. Activation Of Lymphocytes

If a virgin lymphocyte comes into contact with a foreign molecule which fits its binding site (i.e. an antigen), it will be activated and start to divide. Strong mitotic activity will produce a clone of cells composed of large effector cells on one hand and small memory cells on the other. Memory cells do not divide any more. They can be reactivated later upon new contact with the antigen. The systems answer to contact with the antigen consists of the selection and multiplication of lymphocytes possessing specific receptors which fit the antigen. This mechanism is therefore called clonal selection. In reality one observes, that upon invasion by foreign substances many clones are activated, because different regions of even one large molecule (e.g. a protein) can bind to several different receptors. Furthermore one structure of an antigen may bind to several receptors, albeit with different levels of precision. (A master key of the janitor fits all the locks in the school. Teacher's keys, lift keys etc. are "specific" for a major or minor "subpopulation" of locks.)

2.4. Antigen-Presentation
Macrophages phagocytose invading bacteria or viruses and disassemble them into their component molecules. They then import these molecules into their own membrane and present them to lymphocytes. B-lymphocytes can also take up antigen molecules and present them. Antigen presentation makes the immunological reaction especially effective.

2.5. Lymphocytes
2.5.1. B-Lymphocytes Effector-B-cells are also called plasma cells. Each clone can only synthesise antibodies with one type of specific antigen binding site (variable region!). These cells can however switch the class of antibody they produce. First they produce IgM, then they switch IgG. Hereby the variable region is kept and only the constant regions are changed.

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2.5.2. T-Lymphocytes Three different types of T-cells fulfil specific functions: Direct cellular defence by killing intruding foreign cells or own cells infected by viruses. The attacked cells disintegrate after being touched by Killer-T-cells. Channels are made in the target cells, leading to their bursting by osmosis On the other hand, T-cells play an important role in humoralen defence. If there are not enough Helper-T-cells, antibodies can only be produced inefficiently or not at all against many antigens. If a Helper-T-cell finds a B-cell which has bound antigen, it will attach to it and liberate substances which animate the B-cell to divide and produce a clone of mature plasma cells. Suppressor-T-cells suppress the immune reaction and are therefore involved in its regulation. They are responsible for shutting down the immune system after a successful fight against a disease. Production of further effector cells is suppressed and until a new contact with the germ only memory cells remain in readiness. T-cells are also responsible for the rejection of transplanted organs. Not only does the body of the recipient react against the grafted organ, but the also the graft against the recipient. Similar to the blood groups, molecules on the cell membrane play a role in the recognition of "foreign" cells. A careful choice of donor can therefore reduce the risk of graft rejection. By secretion of special hormone-like substances, T-cells can induce other lymphocytes to multiply, with special attractive substances they can attract macrophages to the site of an infection. There is a complex co-ordinated teamwork between the cell types involved in defence, which is far from being completely understood.

2.6. Complement
The complement system consists of a large number (about 20) of proteins circulating in the blood and the extracellular fluids. In different combinations, these may cause different reactions If the system is activated, it leads to the integration of protein channels into the membrane of the cell to be destroyed. These channels are permeable to salt and water, but not for the larger proteins. This leads to osmosis and the swelling and bursting of the target cell. There are two ways of activating the complement system. Complement recognises the constant regions of IgG and IgM molecules bound to a cell. It can also be activated directly by the polysaccharides on the cell surface of bacteria, yeasts and protozoans, allowing action even before the production of antibodies sets in. Complement proteins bound to microbes lead to phagocytosis by macrophages. Complement proteins lead to inflammatory processes which attract phagocytes to the site of inflammation Vocabulary
intrusion trachea keratinised follicle mucus mucous to disintegrate to proliferate M.Tottoli Eindringen Luftrhre verhornt Follikel, Haarbalg Schleim schleimig, Schleim zerfallen s.vermehren, wuchern to rupture to disassemble debris [' ] to comprise to regain to invade to fulfil(l) aufreissen, platzen zerlegen Trmmer beinhalten wiedererlangen eindringen in erfllen

immunology.doc /2004