How are immune cells activated?

By | February 1, 2015

The most important immune cells for adaptive immunity are the lymphocytes.

T cells

  1. An antigen presenting cell (APC), such as a dendritic cell, binds an a peptide from a pathogen on either a pattern recognition receptor (PRR), a complement receptor (CR), or a Fc antibody receptor (FcR). It can also uptake a pathogen through macropinocytosis.
  2. The APC presents the peptide from the pathogen to a naive T cell using MHC molecules. A Class I MHC is used in the case of intraceullular pathogen and a Class II MHC is used in the case of extracelullar or intravesicular pathogens. If Class I is used, then the associated CD8 molecule on the T cell is also part of this binding. Conversely, CD4 is used with Class II MHC.
  3. Additionally, an important binding element is the B7-CD28 adhesion (B7 on the APC, CD28 on the T cell).
  4. These binding steps leads to the influx of Ca2+, which activates calmodulin, which activates calcineurin, which activates transcription factor NFAT. NFAT leads to the release of IL-2 and IL-2R alpha.
  5. IL-2R (the receptor for IL-2 on the T cell) now has high affinity for IL-2, and so IL-2 that was just released binds to itself. This activates mTOR which leads to proliferation/differentiation/activation.

To summarize, when a CD4 T cell is activated, it results in more IL-2, IL-2R alpha, CD-40L, CTLA-4 (competes with CD28 and hence downregulates CD4 T cell activation), Class II MHC (relatively unknown why this is - thought to also be immunosuppresive just like CTLA-4), cytokine secretion, and memory T cell development.

B cells

  1. A B cell is an antigen presenting cell (APC), so it can uptake pathogens as a dendritic cell can (however it uses a B cell receptor and optionally a B cell co-receptor consisting of CD19, CD21, and CD81). It first acquires a peptide from a pathogen and presents it on its surface.
  2. Th1 or Th2 CD4 T helper cell binds to the Class II MHC molecule on the B cell and the CD40 on the B cell binds to the CD40L on the T cell.
  3. The T cell then releases cytokines to activate the B cell.

This process takes place at the edge of the primary follicle and the paracortical space in a lymph node. Note that the B cell and T cell both must have acquired a peptide from the same pathogen for this process to complete.

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