BLG 307 Lecture Notes - Mecha, Ctla-4, Ptpn6

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28 Jan 2013
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IMMUNOLOGY
LYMPHOCYTE ACTIVATION
all immune system responses begin with NAÏVE T CELL ACTIVATION
features of T-cell activation that are distinct from other receptor-ligand processes
requires MHC-presentation
small proportion of T cells can respond to ANY antigen
many different MHC-peptide combinations are presented by a single APC
self-reactivity is a concern
Naive T-cell activation causes their DIFFERENTIATION
CD8+ cells respond to MHC class I indicates viral infection (cytosolic protein)
activation causes diffentiation into CYTOTOXIC T CELLS (kill infected host cell)
CD4+ cells respond to MHC class II indicates microbial infection (replicating intracellular
vesicles)
-activation causes differentiation into TH1 or TH2 cells
TH1 – inflammatory response (macrophage mediated)
TH2 – antigenic response (B-cell mediated)
T CELL COSTIMULATION –
signal 1 = antigen-MHC
signal 2 = antigen independent costimulatory signal (CD28 on T cell an B7 on APC)
**ensures that only APC’s can cause T-cell differentiation**
**signal 1 without costimulationANERGY**
APC’s:
DC’s – MOST important activator of T-cells; presents viral antigens (good for innate immunity)
Macrophages – present bacterial antigens (scavengers) (B7 inducible by microbial products)
B cells (B7 inducible by microbial products (LPS) (good for low level circulating Ag) bind through
Ab
(Raymond removed a table describing antigen uptake, MHC expression, costimulation, antigen
presentation, and location characteristics of B cells, macrophages, and dendritic cells.)
NOTE: DIFFERENTIATED, EFFECTOR T CELLS STIMULATED BY SIGNAL ONE ALONE!
STAGES OF T-
CELL ACTIVATION
1st Stage: T cell encounters antigen/MHC complex on APCupregulate IL-2 and IL2R
2nd Stage: T cells proliferate as a result of autocrine growth stimulation by IL-2 and acquire effector
functions
INITIAL ENCOUNTER WITH APC’s(lymph nodes, Peyer’s Patches, spleen) – SIGNAL 1
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