T Cell Receptors and the Major histocompatibility Complex Flashcards
Memory T Cells
After a response to antigen with its rapid expansion of the relevant T cell clones, the number of T cells quickly declines, until perhaps 5% of the maximum amount are left a couple of weeks after infection or immunization. These are memory cells, which have some of the attributes of stem cells, in that they replace themselves, as well as rapidly differentiating into effector cells when re-exposed to low antigen concentrations.
T cell differentiation
Helper T cells are so called because they ‘help’ other cells do things. Most helpers begin as an undifferentiated precursor (Th0). When their correct antigen is brought to them by dendritic cells (DC), they begin to divide and differentiate, becoming either Th1, Th17, Th2, Tfh, or Treg cells.
The previous experience of the DC—the conditions in the periphery when it was stimulated, what TLR were engaged, what cytokines and chemokines predominated—is the main determinant of the precursor T cell’s ultimate progeny (many details about this are still being investigated). For most antigens, you end up with some of each T cell type but the proportions of each T cell type can vary by antigen.
Th1 Cells
Induced by IL-12 and IFN-α.
After this T cell has been activated and has proliferated in the lymph node, some of the daughters leave and circulate around the body. When they encounter antigen, say at the infection site, they secrete lymphokines.
The most important lymphokine secreted by Th1 is interferon gamma (IFNγ) which is pro-inflammatory and a chemotactic agent for blood monocytes and tissue macrophages. These cells move in large numbers into the area where the Th1 is recognizing antigen. They are also activated by IFNγ, becoming classically-activated M1 (angry) macrophages which avidly ingest and kill bacteria or other foreign invaders.
The macrophages release their own cytokines that can intensify inflammation. These cytokines include tumor-necrosis factor alpha (TNFα) and IL-1.
The division of labor is efficient. The T cell recognizes, the macrophage removes. However this system can damage local tissues. Get a good stimulator of Th1 cells on your skin—poison ivy is excellent—and you’ll see. This is called “contact sensitivity”.
