Review Initial differentiation s thymic maturation Initial differentiation

Review…

Initial differentiation… ='s “thymic maturation”

Initial differentiation… c-Kit (receptor for stem cell growth factor) CD 44 (an adhesion molecule) CD 25 ( chain of IL-2 receptor)

Fundamental notion: Positive selection of thymocytes bearing receptors capable of binding self-MHC molecules which results in MHC restriction. Negative selection by elimination of thymocytes bearing high -affinity receptors for self-MHC molecules alone or self-antigen presented by self-MHC, which results in selftolerance.

Another fundamental notion… There are first “double negatives” (DN’s)… Then there are “double positives” (DP’s)…. DN and DP refer to the presence of CD 4 and CD 8

The effect Note what’s happening and where

Evidence for Positive selection & Negative selection

Activation… in the periphery… some key events:

“Overview” (!)

Some common themes in signal transduction… • The involvement of receptors • The generation of second messengers • The action of protein kinases and phosphatases • The induced assembly of critical components of a signal transduction pathway • Cascades • The involvement of large and small G proteins • The default setting for signal transduction is OFF

The co-stimulatory signal

Co-Stimulatory Differences among Antigen Presenting Cells (APC’s)