The ability of the immune system to respond to an antigen exists before it ever encounters that antigen. The immune system relies on the prior formation of an incredibly diverse population of:
- B cells (B lymphocytes) each with its surface covered with thousands of identical copies of a receptor for antigen (the B-cell receptor for antigen = BCR)
- T cells (T lymphocytes) each with its surface covered with thousands of identical copies of a T-cell receptor for antigen (TCR)
The above figure illustrates the activation of the one B cell in a pool of B cells whose BCR is specific for an epitope (small dark spheres) on the antigen. This phenomenon is called clonal selection because it is antigen that selects particular lymphocytes for clonal expansion. Clonal selection leads to the eventual production of:
- A pool of antibody-secreting plasma cells. Plasma cells are B-cells that have tooled up (e.g., forming a large endoplasmic reticulum) for massive synthesis and secretion of an antibody. The antibody is the secreted version of the BCR. (For clarity, each BCR is shown with a single binding site for the epitope; actually, the BCRs are IgM and each has 10 identical binding sites.
- A pool of "memory" cells. These are B lymphocytes with receptors of the same specificity as those on the original activated B cell.
How B cells and T cells meet antigens
Fig.18.104.22.168 Postcapillary venule
What is the probability that those few lymphocytes able to bind to a particular epitope will actually encounter the antigen carrying that epitope?
Surprisingly, it is quite high because both B cells and T cells migrate in and out of lymph nodes and the spleen. Lymph nodes serve as lymph filters, trapping foreign matter that gains access to the tissues. It has been shown that as much as 99% of the bacteria entering a node are removed by it. Similarly, the spleen traps antigens that gain access to the blood. Even if an invader fails to enter either lymphatic or blood vessels, its antigens can still reach lymph nodes and spleen carried there by dendritic cells that
- engulf the antigen in the tissues
- migrate in the lymphatic vessels to nearby lymph nodes or spleen
- process the antigen and "present" it to T cells and also B cells
Graft rejection is a form of cell-mediated immunity. If a piece of skin from a mouse of one strain (B) is grafted onto the flank of a mouse of a second strain (A), the graft does well at first. Blood vessels from the host grow into it, and it functions normally. After some 10–14 days, however, the blood supply to the graft breaks down and the graft degenerates. Finally it is sloughed off like an old scab. This is called a first-set rejection. That the graft rejection is an immune response is demonstrated by now grafting the mouse with two pieces of skin a repeat of skin from strain B and skin from another strain (C)
The results are quite different.
- The B skin may not even survive long enough to acquire a blood supply. It is rejected in a much shorter period (less than a week). This "second-set" phenomenon is the T-cell equivalent of the secondary "memory" response of B cells. Its specificity and memory is shown by the fact that
- The graft of C skin is rejected in the normal "first-set" period.