Cell-Mediated Effector Responses
Antigen Specific Cells:
CD4+ Th1 and Th2 cells
CD8+ T cytotoxic lymphocytes (CTLs)
Antigen Non-Specific Cells:
macrophages, neutrophils, eosinophils, and natural killer cells
Activity of both of these cell types dependent upon cytokine patterns
This branch of the immune system is responsible for the clearance of intracellular pathogens, virus-infected cells, tumor cells, and foreign grafts.
Effector T cells
less stringent activation requirements
increased expression of cell-adhesion molecules
production of both membrane-bound and soluble effector molecules
These cells can respond following signal 1 (T cell receptor binding to peptide + MHC) without a requirement for the co-stimulatory signal.
Effector T cells exhibit different trafficking patterns than naive T cells.
They express increased levels of adhesion molecules allowing them to enter MALT, SALT, etc. in addition to secondary lymphoid tissues.
Effector T cells also express certain effector molecules (membrane-bound or soluble).
Membrane molecules belong to the TNF family (Fas ligand on CD8+ CTLs, TNF-b on Th1 cells, and CD40L on Th2 cells).
Soluble molecules include : cytotoxins such as the perforins and granzymes of CTLs, as well as two cytokines, IFN-g and TNF-b.
The Th1 and Th2 effector cells have non-overlapping cytokine patterns.
Th1: IL-2, TNF-b, IFN-g, GM-CSF (high)
Th2: IL-4, IL-5, IL-6, IL-10, IL-13, GM-CSF (low)
Fas ligand, perforins, and granzymes mediate target-cell destruction by the CTL cells.
Membrane-bound TNF-b and soluble IFN-g and GM-CSF promote macrophage activation by the Th1 cell.
Membrane-bound CD40ligand and soluble IL-4, IL-5, and IL-6 all play a role in B cell activation by the Th2 cell.
Direct Cytotoxic Responses:
CTL-Mediated Cytotoxicity
CTLs are generated by immune activation of Tc cells.
CTLs have lytic capability and recognize and eliminate altered self-cells or foreign grafts.
In general, CTLs are CD8+ / Class I MHC restricted.
Since essentially all nucleated cells in the body express class I MHC, CTLs can recognize and eliminate almost any altered body cell.
Two Phases:
Phase 1-Generation of CTLs
activation and differentiation of naive Tc cells into functional CTL cells.
Naive Tc cells are also termed CTL-Ps (to denote their immature state)
Required signals:
* An antigen-specific signal 1 transmitted by the TcR complex upon recognition of a peptide-MHC complex
*A co-stimulatory signal transmitted by the CD28-B7 interaction
*A signal induced by the interaction of IL-2 with the high affinity IL-2R, resulting in proliferation and differentiation of the antigen-activated CTL-P into an effector CTL.
Unactivated CTL-Ps do not express IL-2 or IL-2R, do not proliferate, and do not display cytotoxic activity.
The IL-2 most often must come from proliferating Th1 cells
The proliferation and differentiation of both antigen-activated Th cells and CTL-Ps are dependent on IL-2. In IL-2 knock-out mice, CTL activity is abolished.
Th1 cells and CTL-P cells probably do not interact directly. The nature of their interaction is not yet completely understood. May be that interdigitating dendritic cells are presenting viral peptides in association with both Class I and Class II and thus are recognized by both CD4+ and CD8+ T cells. Or...organized lymphoid tissue may just represent an anatomic niche which is rich in cytokines.
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