OxyFile #450

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.