T cell development and effector cell function (Michels) Flashcards
What type of recombination do TCR receptors undergo
VDJ
How many CDR regions are there on TCR
3 per V region, 2 V regions
Which CDR of TCR is the most hypervariabl
CDR3
What are the differences between TCR and BCR
TCR have no class switching or affinity maturation. also small population of lambda and gamma T cells instead of alpha and beta
What is the minimun number of residues that TCR recognize on MHC complex
1-3
Which interation is weaker:
Ab-Ag
or
TCR binding to peptide presented on MHC
TCR-MHC molecule is weaker
additional surface molecules are necessary
Describe the MHC Restriction
TCR must recognize MHC molecule and the presented antigen
Where is the TCR beta chain locus and components
chromosome 7
leader sequences infront of variable regions then has diveristy junctional and constant regions
describe location and components of TCR alpha chain locus
chromosome 14
leader, variable, juntional and constant region
Which enzymes mediate TCR recombination
Rag 1 and Rag2
What are the light chains of TCR
Kappa alpha and beta
Which chains of TCR have diversity regions
Heavy chain and the beta chain
During what phase of thymocyte maturation does it undergoe positive selction- describe process as well
Thymocytes are double positive at this stage still.
They need to bind MHC to recognize self- this is positive selection. Those that don’t bind are killed
During what phase in thymocyte maturation do they udnergo negative selection and describe this process
Thymocytes are single positive at this time
Negative selection is if they bind too strongly to MHC they are killed. so those that have low affinity survive
If you have a deficiency of MHC I or HLA I R what is the outcome on T cell populations
Have alot of CD4+
no CD8 CTL
predict outcome of MHCII deficiency on T cell population
have lots of CD8 or CTL
no CD4+
Cell mediated Immunity is used it what cases
Ingested microbes (phagosomes)
Viruses (non-phagocytotic cell)
All nucleated cells have what type of molecule
MHC class I or HLA class I
T cell expansion takes out long after antigen exposure
about 2 weeks
What cytokine is responsible for clonal expansion of CD4+
IL2
What is the role of effector CD4+ T cells
Activation of macrophages, B cells, other cells
What is the role of effector CD8+
Killing infected target cells; macrophage activation
All TCR must also have what complex
CD3 and epsilom
What molecule interaction assists in slowing down lymphocytes so they can interact with MHC
LFA-1 on lymphocyte. ICAM-1 on T cell
What are the T cell accessory molecules
CD3, epsilom, CD28, CTLA4
LFA1
VLA-4(endothelium)
CD4 or 8 depending on type of T cell
What T cell accessory molecules assist in signal transduction
CD28 on T cell binds to B7 on APC
CD4 or 8 depending on T cell
What is the co stimulatory molecule of T cells
and its actions?
CD28 which binds B7of APC to produce IL2
when produced it will activate CTLA-4 which will send inhibitory signals.
Activation of T cells triggers the expression of what proteins on T cels
CD40L and IL2 Receptor
CD4+ T cells produce which cytokines
IL2
IL4
IL5
IFN-gamma
TGF beta
What cytokines do CD8+ T cells produce
IL2
IFN-gmma
What is the role of IL2
proliferation and differentiation of effector and CD4+ cells
What is the role of IL4
B cell switching to IgE
What is the role of IL5
Activation of eosinpohils
What is the role of IFN-gamma
activation of macrophages— will produce IL12 to activate NK to release more IFN-gamma
Role of TGF-beta
Inhibition of T cell activation
differentiation of Tregulatory
When and what changes in ILR to make it high affinity
secretion of IL2- activation of T cells induces expression of IL2R-alpha chain which makes IL2Rabgamma complex= high affinity
Blocking CTLA-4 cases what?
When would this help?
Keeps T cells on
anti-cancer therapy but run the risk of autoimmunity
What are the subsets of CD4+ cells and what cytokines are they assoc with
Th1: IFNgamma- macrophage activation
Th2: IL4 IL5 IL13- humoral immunity
Th17: IL17- host defense and pathogenesis of autoimmune disease
T reg- suppress T cell function
What directs the development of T cell subsets?
cytokines
Describe CD4+ role in cell mediated immunity vs humoral immunity
cell-mediated: activates macrophages for killing phagocytosed material
humoral immunity: causes secretion of Ab with enhanced abilities to neutralize and eliminate Ag
What type of infections usually cause activation of Th1 subset
Intracell microbes- usually chronic because IFNgamma and TNFalpha are pretty hardcore.
What type of infection causes activation of Th2 subset
helminthic parasites and allergic diseases. usually upregulate IgE and mast cell activation
What types of infections activate the Th17 subset
Extracell bacteria and fungi causing neutrophilic, monocytic inflammation.
Usually assoc with autoimmune and inflammatory diseases
What activates the Th2 subset
TSLP thymic stromal lymphoprotein
IFNgamma secretion activates what
MAcrophages
B cells to stimulate C’ binding
Class II HLA and B7 expression on APCs
What is the main overal role of Th17 cells
maintaining gut tolerance. Increased barrier function of epithelium
What CD4 subset will be present during an asthma attack
Th2
What CD4 subset will be present in multiple sclerosis patients
Th1
Why is L selctin down regulated ater T cell activation
Don’t what the T cells stuck in lymph nodes, need to return to circulation
What T cell molecules are involved in homing native T cells and what are their complementary molecules on endothelial cells
L selectin- L selectin Ligand
LFA-1 - ICAM-1
CCR7 - CCL19 or CCL21
What T cell molecules are involved in himoning activated T cells and what are their complementary molecules on endothelial cells
E and P selctin ligands - E or P selectin
LFA-1 or VLA-4 - ICAM-1 or VCAM-1
CXCR3- CXCL10
What is the basis for delayed-type hypersensitivity reaction
DTH reaction: Macrophage activation by Th1 subset is depended on antigen-recognition on presenting cells (CD4)
The macrophage increase MHC molecules and B7 costimulators
also macrophages secrete TNF, IL1 and IL12
What is an example of delayed-type hypersensitivity reaction
PPD test for TB
What determines the outcome of intracellular infections?
Balance between Th1 and Th2 cell activation
What do Th2 cells inhibit when activated
Microbicidal activity of macrophages
Mycobacterium elicits what responses in patients
Usually Th1 and you have Tuberculoid leprosy however some patients are defective in Th1 so predominately Th2 response leading to Lepromatous leprosy
How do CTLs induce apoptosis
activation of perforin and granzymes to enter cell and iduce apoptosis
or Fas-FasL interactions
How are TCRs overall different from BCRs
they are not secreted and do not undergo somatic hypermutation
Which T Cells can do cell-mediated immunity
CD4 activate macrophages
CD8 directed kill of infected cell
Which Th subset has a response characterisitic of DTH
Th1 after secreting IFN-gamma
classical activation of macrophages