Clonal Development and Immunity
Immune networks evolve quickly in each person by generating recognition molecules that specify a large number of potential antigens. T cell antigen receptors consist of two polypeptide chains that are unique on each lymphocyte clone because of gene rearrangements during development. The genes are shuffled in different combinations to produce an array of T-cell receptor and immunoglobulin molecules. The idea is that new lymphocytes are created everyday with new possibilities of interaction with new antigens. An enzyme, B lymphocyte nuclease, creates double-strand breaks at various locations in the genome that are repaired by an error-prone polymerase.
New lymphocytes must proliferate and wander through the body looking for an antigen that fits their receptor. If an antigen is found, the lymphocytes are stimulated to proliferate, establishing a clone that is likely to persist for some time. Not all antigen recognition is accurate or stable over time. Some lymphocytes that display the wrong receptors are eliminated, other cells correct faulty receptors by further recombination of their DNA. The idea is that if a receptor interacts with a cell target that is normal in the body, it should eliminated. Auto-reactivity clone elimination is very active before birth so that, in the best case, an infant does not have lymphocytes who will attack self. In adults some form of receptor editing remains.
T-cells belong to distinct subgroups. Memory cells have a long life span and a high proliferative capacity. Effector cells have a short lifespan and respond to signals that activate voluntary cell death. The size of the T-cell population is maintained by the proliferation of long-lived progenitor cells. There are also a small number of long-lived quiescent T cells that act as a reservoir of progenitor cells.
Killer T-Lymphocytes (NKT) act directly to attack cells expressing non-self antigens along with the proteins of the major histocompatability complex (MCH 1). Controller T-cells fall into groups that suppress immune response (supressor T-cells), and opposing groups that enhance immune response (helper T-cells). T-cells deliver stop, caution, and go signals, regulating traffic flow in the system, acting as controllers or modulators of the antibody producing cells, the B-Lymphocytes.
T helper 1 (Th1) cells, are often the first type of lymphocytes that respond to antigen challenge by proliferating and releasing Th1-type cytokines that activate other immune cells. Inhibiting the Th1 cells will reduce or prevent an immune response, creating immune tolerance. In the investigation of immune tolerance, researches have discovered specific signals that turn off Th1 cells. For example, T-cell immunoglobulin mucin 3 is a specific molecular signal that inhibits Th1 cells. According to Kotz: T-helper lymphocytes (Thp) are directed toward either the Th1 or Th2 pathway by two cytokines:
Interferon-? (IFN?) favors Th1
Interleukin-4 (IL-4) favors the Th2 pathway.
Kotz stated: "How these signals are coordinated with T-cell receptor (TCR) activation is not known. Immunological synapses are clusters of signaling molecules at the point of contact between T cells and antigen presenting cells… results suggest a mechanism in which a Th1-promoting complex is assembled at the immunological synapse in the absence of an IL-4 inhibitory signal." NK cells are capable of spontaneously killing target cells, but may be stopped by if inhibitory receptors on the NK cell surface recognize MHC class I molecules on the target cell. Cells that lack self markers such as tumor cells or transplanted cells prone to this form of killing.