Chapter 8 T Cell-Mediated Immunity hapter 8: Activation of ...theory.bio.uu.nl/immbio/sheets/Chap8HandsOut.pdf · T Cell-Mediated Immunity Naive T and B cells circulate in the blood
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Dendritic cells carry antigens from sites of infection to secondary lymphoid tissues
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Dendritic cells are adept and versatile at processing antigens from pathogens
yellow = endocytic vesicles red = lysosomal protein green= MHC class II activation induces CCR7, the receptor for CCL21, which chemokine is made in secondary lymphoid tissue (results in migration to lymph node and stops further processing as a consequence dendritic cell focusses on T cell activation)
Dendritic cells use various pathways to process and present protein antigens
Activation of naive T cells on encounter with
antigen • Naive T cells first encounter antigen presented by
dendritic cells in secondary lymphoid tissues • dendritic cells enter via afferent lymp (drains from
the site of infection • Naive T cells enter the lymph node by a) squeezing through blood capillaries (high endothelial venules) and enter the cortecal region b) through the lymph from an upstream lymp node (efferent lymp)
and green dendritic/macrophage sniffing T cell that do not encounter their specific antigen leave (green) whereas the ones that do, are activated, proliferate and differentiate into effector cells
Naive T cells encounter antigen in the secondary lymphoid organs
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How the lymph network works
In any given infection only 1 in 104 to 1 in 106 of the total pool of circulating T cells is activated.
Homing of naive T cells
to secondary lymphoid tissues is determined by chemokines and cell-adhesion molecules
Naive T and B cells circulate in the blood and enter lymph nodes by crossing high endothelial venules
chemokine = CCL21 and 19 which binds to CCR7 receptor on Naive T cell
More about lymphocyte adhesion to professional antigen-presenting cells (APC)
DC-SIGN a lectin unique to activated DC
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Transient adhesive interactions between T cells and DC are stablized by specific Ag-recognition Activation of naive T cells requires a co-stimulatory signal
delivered by a professional antigen-presenting cell
signal 1 induces clonal expansion but only when signal 2 is delivered
B7.1 and 7.2 are known as costimulatory molecules
CTLA4 is expressed only on activated T cells, is similar to CD28 but binds much stronger to its ligand B7 and works as an atagonist
Activation of naive T cells on encounter with
antigen
• There is a concentration gradient of (sphingosine 1-phosfate (S1P) from the lymp/blood to the secondary lymphoid tissues
• T cells activated by Ag suppress the expression of S1P receptors for several days (makes them stay in the lymph node while they differentiate into effector cells). Later they are drawn away by the gradient of S1P