Revision sheet
Self, non-self and the markers of identity
What the immune system reads before it decides to attack, and why a graft is rejected.
Self and non-self
Every cell carries molecular markers on its surface. The set an individual carries is their self; anything bearing different markers is non-self and can trigger an immune response. An antigen is precisely that: any molecule capable of being recognised as foreign and of provoking a response.
Recognition is not global but local: antibodies and lymphocyte receptors bind a small region of the antigen called the epitope. One antigen carries several epitopes, which is why one microbe provokes several different antibodies at once.
- Antigen = recognised as foreign. Epitope = the exact part recognised.
- Immunological tolerance to self is acquired during lymphocyte maturation, not innate.
The MHC, the identity card
The major histocompatibility complex — HLA in humans — supplies the markers that define an individual's self.
It is extraordinarily polymorphic, so apart from identical twins two people almost never share the same set, and it is co-dominantly expressed: both parents' alleles appear on the cell surface.
There are two classes, and the distinction structures the entire immune response. Class I molecules are on every nucleated cell and present peptides from inside the cell — including viral ones — to CD8 T cells.
Class II molecules are only on antigen-presenting cells (macrophages, dendritic cells, B lymphocytes) and present peptides taken in from outside to CD4 T cells.
- MHC I: all nucleated cellsCD8 (cytotoxic) T cells
- MHC II: antigen-presenting cells onlyCD4 (helper) T cells
- A T lymphocyte only recognises an antigen presented on an MHC molecule — never free.
Blood groups
The ABO system is a second set of self markers, carried on the red cell membrane.
A group A individual has antigen A and naturally occurring anti-B antibodies; group B the reverse; group AB both antigens and no antibody, making them universal recipients; group O no antigen and both antibodies, making them universal donors.
The rhesus system works differently: an Rh− person has no natural anti-D and only produces it after being exposed to Rh+ blood.
Hence the classic risk — an Rh− mother carrying an Rh+ fetus can be immunised at delivery and attack a subsequent Rh+ pregnancy, which is why anti-D immunoglobulin is given.
- ABO antibodies are natural; anti-D is not, and must be induced.
- AB = universal recipient. O = universal donor.
Grafts and rejection
A graft is rejected because the recipient's T cells read the donor's MHC molecules as non-self. The closer the HLA match, the weaker the reaction — which is why donors are typed and why a sibling is often the best match.
Rejection is essentially a cell-mediated response: cytotoxic CD8 T cells destroy the graft cells. Immunosuppressive treatment blunts it, at the price of a permanently increased risk of infection and of cancer — the clearest possible demonstration that the immune system does both jobs at once.