(From Dr. Cain’s handout, 1 Sept 2000, by Brian Buschman)
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The compliment system is made up of three pathways. It can be activated by either the classic or the alternative pathways and will ultimately end up on the common pathway.
The alternative pathway uses factors B, D and P in the process of activating C3 to C3b. The alternative pathway can be activated by exposure to an Ag on the first exposure. It does not require the presence of Abs made from a previous exposure.
The classic pathway involves the activation of compliments C1, C2 and C3. C1 is activated to C1b which activates C2 to C2b which cleaves C3 to C3a and C3b. C3a is an anaphylatoxin but C3b goes on to initiate the final common pathway.
The common pathway has C3b cleaving C4 to C4a and C4b. C4b cleaves C5 to C5a and C5b. Both C4a and C5a join C3a and are all anaphylatoxins. C5b will lead to the membrane attack complex C5b678 which works to insert C9 pieces into the plasma membrane of a cell to cause osmolysis. It is also a chemotactic agent.
The complement system is tightly regulated so that it does not function excessively. The most important regulating factors are:
Others include decay-activating factor, vitronectin, homologous restriction factor and compliment receptor-1.
1) Nephron factor is an antibody to C3bBb which stabilizes C3bBb and leads to uncontrolled membrane attack complex.
2) Heredity angioedema causes defective C1 inhibitor.
3) Component factor deficiency.
All of these cause unregulated osmolysis except for the compliment deficiency.
MHC is a tissue indicator that helps cells recognize self from non-self. When APCs grab and digest a piece of antigen they complex it with MHC I or MHC II while they show it to the T-cell. There are three MHC classes.
MHC I is found on the surface of all nucleated cells except sperm and is on platelets but not erythrocytes. It is made of a and b chains which hold an Ag fragment. The a chain is transmembrane but the b chain is not. They interact with cytotoxic T-cells and function in homograft rejection. It come in HLA-A, HLA-B and HLA-C.
MHC II is found on the surface of APCs (like macrophages and such). They bind to T-helper cells (CD4 cells). They are HLA-D.
MHC III genes code for inflammation products like TNF and do not function in antigen presentation.
These patients have HLA-B27.
It is very important for the HLA types to match with the tissue when doing a transplant or else the recipient will not recognize the donor tissue as self. There are three main types of transplants:
1) Autograft – from another part of the same person (like skin grafts).
2) Xenograft – from another species.
3) Allograft – from another individual of the same species.
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