Immunity; T cells are many different types (Introduction)

by David Turell , Monday, August 28, 2017, 20:12 (2645 days ago) @ David Turell

New discoveries describe very complex ways different T cells are encoded to fight infections. The article should be viewed to appreciate how this system is designed and works:

http://www.the-scientist.com/?articles.view/articleNo/49941/title/The-Ever-Expanding-T-...

"When a pathogen enters the body and starts causing tissue damage, it triggers an inflammatory response that gets the attention of antigen-presenting cells (APCs), which monitor the environment and display bits of foreign proteins that they encounter using the major histocompatibility complex class II (MHC II) molecules located on their surfaces. Once they detect a pathogen, the APCs migrate to the spleen and lymph nodes, collectively known as secondary lymphoid organs, where naive T cells (and other T-cell types) await their call to duty.

"T-cell precursors originate from stem cells in the bone marrow, but T cells mature in the thymus—hence the name “T cells.” Every mature T cell has a cell-surface receptor (TCR) that recognizes a short, nonself peptide (those that recognize self proteins are, for the most part, eliminated), as well as one of two glycoprotein coreceptors: either CD4 or CD8. These coreceptors bind not to the peptide antigens but to MHC molecules. CD4 binds to MHC Class II receptors, found uniquely on APCs; CD8 binds to MHC Class I, found on virtually all somatic cells, including APCs.

"In the secondary lymphoid organs, APCs display their bound antigens to the CD4+ T cells via MHC Class II. These interactions, combined with signaling molecules in the cell environment, stimulate the CD4+ cells to differentiate into various T helper (Th) cells with functions specific to each pathogen type. One subset of these helper cells—T follicular helper (Tfh) cells—stimulates B cells to produce antibodies specific to the antigen in question. Naive CD8+ cells also interact with APCs, via MHC Class I receptors, triggering their differentiation into what are called cytotoxic lymphocytes (CTLs), aka killer T cells, which seek and destroy cells displaying the offending antigen.

"Once activated, both the CD8+ killer cells and the CD4+ helper cells migrate to the infected tissue. The helper cells produce cytokines and other molecules to recruit an array of immune cell types, such as neutrophils, macrophages, and mast cells, to help fight the infection, while the activated CD8+ cells bind to the pathogenic cells through the TCR and release cytotoxic enzymes into the “immunological synapse” between the T cells and their targets, inducing apoptosis in the latter.

"When the infection is under control, most of the newly activated T cells die, but some of them remain as memory cells, which stay prepared to quickly combat another infection of the same type. Whereas activation of naive T cells takes more than a week, memory T cells can respond to a secondary infection within hours.

"Memory cells, which can be either CD4+ or CD8+, come in several flavors, classified by the areas that they patrol. Effector memory cells travel throughout the tissues and the blood performing their “effector functions” in response to repeat encounters with foreign antigens: CD4+ cells act in their helper roles, while CD8+ cells carry out their cytotoxic duties. Tissue-resident memory cells act similarly, but develop at the site of an infection and stay there, rather than circulating throughout the body. Finally, central memory cells, which patrol the entire body, focus more on self-renewal (like stem cells) and less on fighting pathogens.

“'Those [functions] have been documented for CD4s as well, with the possible exception of the vascular memory,” Kedl says, referring to cells that specifically patrol the vasculature to combat returning blood infections. “But certainly all of the other ones—resident memory, effector memory, central memory, and effectors themselves—those are all part of both the CD4 and CD8 T-cell world.'”

Comment: This is a very complete system which allows cells to be coded to fight all intruders. It cannot be developed by chance or hunt and peck measures. Newborn cells are produced and taught to fight. Infectious agents appear to have been present from the start of life. Bacteria fight phages as well as each other. The survival of life depends on these defense mechanisms.