Rhl

At this stage, the interactive avidity of T cells with antigen presenting cells also includes the interaction of CD8 and CD4 with class I and class II MHC, respectively. Negative selection within the medulla is accordingly more finely-tuned than in the cortex, with multiple high avidity interactions, including TCR, CD4 (CD8) and class II (class I) MHC products all playing prominent roles.

Mature naive T cells

T cells exit the thymus as naive T cells, seeding secondary lymphoid tissues or entering the pool of recirculating lymphocytes.

Transport of Lymphocytes from Primary to Secondary Lymphoid Tissues

Blood and lymph vessels serve as highways for the movement of lymphocytes throughout the body. Lymphocytes leave their maturation sites in the blood, and either seed the secondary lymphoid tissues, or recirculate in immunosurveillance (Fig. 7.12). Migration of naive lymphocytes from the blood into lymph nodes occurs at specialized postcapillary venules, termed high endothelial venules (HEV) (Fig. 7.13). These cuboidal shaped endothelial cells feature a prominent filamentous layer (glycocalyx) on their luminal surface that traps molecules (Fig. 7.14). In addition, HEV express molecules that bind circulating lymphocytes.

Extravasation of naive lymphocytes into tissues at HEV requires: (i) interaction of L-selectin on lymphocytes with its ligand on endothelial cells to induce lymphocyte rolling; (ii) activation of integrins, (e.g., LFA-1) present on the lymphocytes, increasing their adhesiveness and allowing stable binding to HEV; (iii) lymphocyte secretion of matrix metalloproteinases that proteolytically degrade collagen to generate channels in the subendothelial basement membrane; and (iv) transendothelial migration of lymphocytes into the tissue.

If naive lymphocytes do not encounter antigen in the lymph nodes, they continue their immunosurveillance in the lymphatics (Figs. 7.12, 7.13). One cycle through the body takes approximately one to two days.

Summary

Alpha/beta T cell express a unique T-cell receptor (TCR) which consists of a variable region and a constant region. Gene segments termed "variable (V), diversity (D), and joining (J) regions, are randomly recombined in a process termed somatic recombination to encode variable genes. The recombined segments, along with the DNA encoding the constant regions, encode the TCRa and TCRp polypeptides. Somatic recombination of the V, (D), or J segments is random and leads to the expression of TCRs that are potentially autoreactive, or ineffective. During a screening process in the thymus, cells expressing autoreactive TCRs are eliminated. T cells expressing TCRs that are not autoreactive are positively selected and undergo clonal expansion. Selection is based on the interactive avidity of the developing thymocyte with cells displaying a self-antigen/self MHC complex on their

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