Ozone & The Immune System - Part 3 A.J. Lanigan I will stop here to say that this will wrap up the overview of the "non-specific" immune system. All the aforementioned and this message deals with our first line of immune system defense. As this material flows, you are encouraged to download, save, print, blowup (whatever) to tie these various soldiers of the "immune army" together. Some cells are highly specialized and some are highly versatile. Most depend on the others to up-regulate, down- regulate, lone ranger approaches and team efforts. This array of different "tactics" rely upon the communications between the various groups of cells & individual cells within any one group. One of the major, if not the greatest value of a proper ozone therapy is the way O3 "keys" certain communications. have a happy day, a.j Monocytes circulate in the peripheral blood prior to emigration into the tissues. Within certain organs they have special names, e.g. in liver they are known as Kupfer cells, in brain as microglia, in kidney as mesangial cells, and in bone as osteoclasts. Elsewhere they are referred to as tissue macrophages. Neutrophils, or neutrophil polymorphonuclear leucocytes, respond to chemotactic signals and leave capillaries by a complex process, involving margination (flowing nearer to the endothelial lining of blood vessels), rolling and then attaching (margination), following which they emigrate between the endothelial cells (extravasation, or diapedesis). Several mediators are involved. They include substances produced by micro-organisms, and by the cells participating in the inflammatory process. One such is a substance called interleukin-1 (IL-1), which is released by macrophages as a result of infection or tissue injury. Another is histamine, released by circulating basophils, tissue mast cells, and blood platelets. It causes capillary and venular dilatation. C3a and C5a produced during complement activation, are chemotactic for phagocytic cells. Another group of substances produced are the acute phase proteins. As a consequence of tissue damage, the liver produces a substance called C-reactive protein (CRP), which is so called on account of its ability to attach to the C-polysaccharide component of the cell wall of bacteria and fungi. This activates the complement system by the classical pathway, and as a result C3a is formed and coats the organism, facilitating its phagocytosis. Neutrophils are our body's first line of defense against bacterial infections. These cells can recognize certain chemicals and move to the source of these "chemoattractants" by migrating up the chemical concentration gradient or "toward the smell". The above neutrophils were placed in a gradient of fMLP (n formyl methionine- leucine- phenylalanine), a peptide chain produced by some bacteria that is used by the neutrophils to find infecting organisms. The cells charge out like a "posse" after the bad guys. There are no bacteria in this sequence, but if there were, the neutrophils would eat and kill them. The complement system plays an essential role in host defence against infectious agents and in the inflammatory process. It consists of about twenty plasma proteins that function either as enzymes or as binding proteins. In addition to these plasma proteins, the complement system includes multiple distinct cell- surface receptors that exhibit specificity for the physiological fragments of complement proteins and that occur on inflammatory cells and cells of the immune system. There are also several regulatory membrane proteins that function to prevent autologous complement activation and protect host cells from accidental complement attack. The role of complement in host defence has been established through genetic deficiencies of certain complement components, which may result in life-threatening recurrent bacterial infections or immune complex diseases. The role of complement in inflammation and tissue injury has become apparent through clinical investigations and discoveries that the pathogenesis of certain experimental inflammatory diseases is complement-dependent. The complement system can be activated by two different pathways: the classical complement pathway and the alternative complement pathway. The classical pathway is activated by the binding of antibody molecules (specifically IgM and IgG1, 2 and 3) to a foreign particle. This pathway is antibody-dependent. The alternative pathway seems to be of major importance in host defense against bacterial infection because, unlike the classical pathway, it is activated by invading micro-organisms and does not require antibody. This pathway is antibody-independent. The alternative pathway constitutes a humoral component of natural defense against infections, which can operate without antibodies. The six proteins C3, B, D, H, I, and P together perform the functions of initiation, recognition and activation of this pathway which results in the formation of activator-bound C3/C5 convertase. The classical pathway functions to mediate the specific antibody response. It is as elaborately controlled as the alternative pathway, although it does lack the spontaneous initiation ability; i.e. the antibody independent recognition function, and the feedback amplification mechanism. Both activation pathways contain an initial enzyme that catalyses the formation of the target cell bound C3 convertase which in turn generates the C5 convertase. This results in the cleavage and activation of C5 and, therefore, in the assembly of the membrane attack complex (MAC). The MAC is assembled from five hydrophilic precursor proteins: C5, C6, C7, C8, and C9. Activation of the MAC is a consequence of the activity of either the classical or the alternative pathway on the surface of a cell. Through its metastable membrane binding site, the forming MAC binds firmly to target membranes owing to hydrophobic interactions with the lipid bilayer. The final events are the unfolding, the oligomerisation, or the polymerisation of C9, which causes the weakening of membrane structure, and the formation of transmembrane channels thus leading to osmotic lysis of the cell. MAC assembly is regulated by the S protein of plasma, and by homologous restriction factors of host cell membranes. Complement mediated lysis occurs in many kinds of cells: erythrocytes, platelets, bacteria, viruses possessing a lipoprotein envelope, and lymphocytes.