Immune Activation, Helper cells and regulation Flashcards
Exogeneous Class 2 MHC (HLA-DP,DQ,DR)
Found on __ cells and ___
________
Polymorphic
Present ___ to ____ T cells
___ and __ chains
Found on B cells and APC’s
Co-dominant
Polymorphic
Present peptides to CD4 T cellns
alpha and beta chais
Endogeneous Class 1 MHC (HLA-A,B,C)
note immune recognition of only foreign peptides in these and not regular peptides is due to context.
Found on virtually all _____ ____
Co-dominant
_______
Present ____ to ____ T cells
____ chain and ____ _____
Found on virtually all nucleated cells
Co-dominant
Polymorphic
Present peptides to CD8 T cells
alpha chain and beta2 microglobulin
T cell antigen recognition
MHC 1: Bind to _ ___ ______ with help of ____ binding to area on _______. ___ activated following binding. T ____ cells.
MHC 2: Bind to ____ on ____ cell with aid of ___ binding to area on ______. ___ transduces signal to say binding has occurred.
MHC 1: Bind to T cell receptor with help of CD8 binding to area on HLA-a,b or c. CD3 activated following binding. T killer cells.
MHC 2: Bind to TCR on helper cell with aid of CD4 binding to area on HLA DP,DQ or DR. CD3 transduces signal to say binding has occurred.
Summary of patient with defect in TAP genes
A transporter gene involved in moving class 1 HLA to surface (endogenous path)
Defect means low HLA-A,B or C expression, low CD8 T cells, normal CD4. Recurrent resp viral infections. Meaning HLA 1 needed for CD8 T cell development.
Two types of adhesion molecules
extra*
______: ___ interactions, direct cell traffic around the body. Like velcro. Low ____, and rapid dissociation form these. Often up regulated during ____ response
_____: ____ cell adhesion, hold cells in tissues together, hold _____ together for activation. Site specific addressins.
Cadherins: embryogenesis, tissue developmen
Selectins: Weak interactions, direct cell traffic around the body. Like velcro. Low affinity, and rapid dissociation form these. Often up regulated during innate response
Integrins: Strong cell adhesion, hold cells in tissues together, hold lymphocytes together for activation. Site specific addressins.
Cadherins: embryogenesis, tissue development.
What do integrins stick to?
Immunoglobulin superfamily molecules.
Contain Ig like domains.
Selectins will bind causing production of these ligands which bind to the integrins, causing cell migration for example.
Will also bind a lymphocyte to an APC, causing activation
1st step of lymphocyte activation
Binding through IgSF (APC) and integrin (lymphocyte) to hold these in close contact.
2nd step of lymphocyte activation
Antigen recogntion and binding of TCR with HLA 2 with CD4 for example.
Upon biding does T cell respond imediately or not? Might not want to because self antigen.
This is modulated by co-stimulators/checkpoint regulators.
Examples of co-stimulators and how are they expressed
B7(APC) and CD28 (T cell)
CD40 (B cell) and CD40L (T cell)
Expressed transiently and modulate immune activation process
How co-modulators are expressed
Example of ____, takes up bacteria and expresses antigen on _____
PAMPs, a danger signal cause expression of this ___ co-stimulator molecule on the ___. When binds to ___ T cell, interacts with ___ so a second signal
APC has ___ antigen, no danger signal, no ___ up regulated. Signal 1 from ___ recognition, but no ____ signal. Causes T cell ____ (can not respond again)
Example of APC, takes up bacteria and expresses antigen on HLA2
PAMPs, a danger signal cause expression of this B7 co-stimulator molecule on the APC. When binds to CD4 T cell, interacts with CD28 so a second signal
APC has self antigen, no danger signal, no B7 up regulated. Signal 1 from TCR recognition, but no second signal. Causes T cell anergy (can not respond again)
B cell antigen presentation
(B cell activation requires antigen specific recognition and co stimulator interactions)
Antigen binds to ___
Pinocytoses antigen Ig complex
Breaks it down internally
Gets associated with _____
Now B cell with HLA2 with antigen as well as ____. Binds to __ cell through ___ and causes expression of ____. Binds to ___, which in turn causes expression of __. __ then will stimulate ____ on TH cell and cause ___ release, activating the _ cell
Antigen binds to sIg
Pinocytoses antigen Ig complex
Breaks it down internally
Gets associated with HLA 2
Now B cell with HLA2 with antigen as well as CD40. Binds to TH cell through CD4 and causes expression of CD40L. Binds to CD40, which in turn causes expression of B7. B7 then will stimulate CD28 on TH cell and cause cytokine release, activating the B cell
CD4 T cell clonal activation
Peptide exposed via HLA2, cytokines and co stimulators needed to promote activation.
Divide into more Th cells that secrete cytokines and a memory population
