Τόμος 9 (1991) – Τεύχος 4 – Άρθρο 1 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 9 (1991) – Issue 4 – Article 1 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

9: 199-218 (1991)

PHARMAKON-Press: Epitheorese Klin. Farmakol. Farmakokinet.

9: 199-218 (1991)

Non-specific defence systems, skin, mucous membranes, phagocytosis, complement, interferons

The body possesses a number of non-specific defence mechanisms, including skin and mucous membranes, phagocytosis, the complement system and interferons, which are operative at all times against potentially pathogenic microorganisms. Prior contact with the infectious agent has no intrinsic effect on these systems. The intact skin is virtually impregnable to microorganisms and only when damage occurs can invasion take place. Fur­thermore, many microorganisms fail to survive on the skin surface, due to the inhibitory effects of fatty acids and lactic acid in sweat and sebaceous secretions. Mucous, secreted by the membranes lining the inner surfaces of the body, acts as a protective barrier by trapping microorganisms and other foreign particles, subsequently removed by ciliary action linked, in the case of the respiratory tract, with coughing and sneezing. Many body secretions contain substances that exert a bactericidal action, such as the lysozyme, an enzyme found in tears, nasal secretions and saliva, the gastric acid which results in a low pH, and basic proteins, including p.ex. spermine found in semen. The microorganism initially adheres to the surface of the polymorph or macrophage and this is then followed by the engulfment of the particle so it lies within a vacuole (phago­some) within the cell. Lysosomal granules within the phagocyte fuse with the vacuole to form a phagolysosome. These granules contain a variety of bactericidal components which destroy the ingested microorganism by systems that are oxygen dependent or oxygen independent. When a microorganism breeches the initial barriers and enters the body tissues, the phagocytes form a formidable defence barrier which would be greatly enhanced if there was some system whereby the phagocytic cells could “home-in” on the organism. Evolution has achieved this system by the development of complement system.

Complement is a constituent of all normal plasma. It consists of an activatable system of proteins reacting with one another in a set sequence. There are 2 activation pathways: the classical, comprising the components C₁, C₄ and C₂ and the alternative, comprising factors B, D and properdin. Both pathways merge in that they lead to the formation of C₃-activating enzymes, thus entering the common final reaction sequen­ce in which C₅, C₆, C₇, C₈ and C₉ yield mem­branolytic complexes. Since unbalanced com­plement activation would be deleterious to the organism, the system is well controlled by inhibitors directed against activated C₁, C₄, C₃ and factor B.

Complement fulfills the following four fun­ctions: (1) The release of anaphylatoxins which cause degranulation of Mast cells and basophil granulocytes, and hence release of their in­flammation inducing agents. (2) Action as chemotactic factor (C3_a), attracting neutrophils and eosinophils to the site of the immune reaction. (3) Opsonization of IgG antibodies via C3_b, which binds the immune complex to the membranes of some cells (immune adhesion), in particular neutrophils, eosinophils, macro­phages and B-lymphocytes. This therefore leads to an increased phagocytosis of the immune complex. (4) Activation of the com­plete system leads to membrane damage and lysis of cells recognized as foreign, especially those of invading microorganisms. Thus a deficit in individual components of the comple­ment system can lead to a predisposition to bacterial infection.

Interferons are a group of substances produced by the body and released in response to certain aggressive stimuli (e.g., viruses, bacteria, allergens). They have a signal function, that is they activate other cells. They increase the capacity for response by the immune system, inasmuch as they induce an increase in the number of receptors on im­mune cells, thereby making these more ef­fective. Interferons have in regard to rapid protection against viral infections much the same role as lysosome has in respect of defence against bacteria. Interferons provide resistance against viruses in that they induce those cells prone to infection to produce a protein which blocks the transcription of viral mRNA and hence viral replication.

1. M.I. Χατζηγιαννάκης: Κλινική Ανοσολoγiα. Ιατρικές Εκδό­σεις Π.X. Πασχαλiδης, Αθήνα, 1989
2. Η.Η. Fudenberg, D.Ρ. Stites, J. Caldwell, J.V. Wells (eds): Basic and Clinical Immunology, Appleton and Lange, California, 1987
3. B.N. Fields, D.N. Knipe (eds): Fundamental Virology, Raven Press. New York, 1986
4. Furr, J.R.: Fundamentals of immunology. In: Pharmaceu­tical Microbiology (W.B. Hugo, A.D. Russell, eds), p. 275, 3rd Ed., Blackwell Scientific Publications, Oxford, 1984
5. Rodwell, V.W.: Enzymes: Kinetics. In: Harper’s Biochemi­stry (R.K. Murray, D.K. Granner. P.A. Mayes, V.W. Rodwell, eds), 21st Ed., p. 61, Lange, Norwalk, 1988