T Cell receptors and MHC Complex-Diebel Flashcards
CD-28 from T cell binds with ?
B7 (CD80-86) on APC
Th1’s are polarized by?
IL-12, IL-18, IFN-gama
Cytokines produced by Th1’s:
IFN-gama (most important), TNF
INF-gama does what?
induces ANGRY macrophages
induces more Th1s
pro-inflammatory agent
Angry macrophages produce which cytokines?
TNF-a
IL-1
Th17 polarized by ?
TGF-beta, IL-1, IL-6, and IL-23
Cytokines produced by Th17’s ?
IL-17, IL-22
Main job of Th17 ?
Inflammation
integrity of mucosal surfaces
Th2’s polarized by ?
IL-4
Cytokines produced by Th2’s ?
What do they do?
IL-4
IL-5
IL-13
Activate M2 Macs—-healing and debris removal
What other type of leukocyte is IL-4 a chemotactic factor for?
eosinophils
Tfh’s are polarized by?
IL-6
IL-21
Cytokines produced by Thf’s and what do they do?
IL-4, IL-21
cells migrate to lymph node follicles and encourage differentiation of B-cells depending on where they are located and which Ig’s are needed
Treg’s are polarized by?
IL-2, TGF-beta
Treg’s produce which cytokines and what do they do?
IL-10, TGF-beta
turn off other Th’s
1 Treg can suppress 1,000 other Th cells
Transcriptional regulator T-bet –> ?
Th1
Transcriptional regulator GATA3 –> ?
Th2
Transcriptional regulator RORgamat –> ?
Th17
Transcriptional regulator Bcl-6 –> ?
Tfh
Transcriptional regulator FOXP3 –> ?
Treg
What are the players in the “kiss of death” from CD8’s?
Fas (CD95) on infected cell and FAS ligand (CD95L) on CD8 —> leads to apoptosis of target cell
**CTL’s also kill by release of lytic granules (perlorins and granzymes)
CTL’s (CD8+) are activated where and how?
Lymph nodes
contact with antigen-bearing DC’s and help from Th1’s via IL-2 and INF-gama
What does “antigen specific and MHC-restricted” mean?
T-cell only recognized genetically identical (self) MHC’s
What is meant by “cross presentation” on dendritic cells?
Some phagocytized antigen is allowed to leak into the intrinsic pathway and be presented on MHC 1 as well as the normal MHC 2 presentation at the same time
What needs to happen for Macrophages to express MHC II?
Must be activated by phagocytosis
**Dendrites constituitively express high levels of MHC II.
**B-cells also constitutively express MHC II
TCR is structurally reminiscent of ?
Fab region of an antibody
have 1 C and 1 V region, alpha/beta or gama/delta for both domains
Genetic make up of TCRs?
Where does this happen?
receptors are made out of V, D, and J regions of both T-cell genes
Happens in the thymus
That actual signal that turns a T cell on is transmitted through?
CD3
Co-factors in the TCR-MHC interaction:
T-cell APC
CD28 ——— B7 (CD80/86)
LFA-1 ————- ICAM-1
CD2 —————- LFA-3
V, J encodes for which chain of the TCR?
alpha chain
V, D, J encodes for which chain of the TCR?
Beta chain
Somatic mutations are present in TCR gene rearrangement, what enzymes are involved?
TdT adding up to 6 nucleotides at junctions between V-D-J junctions
***NO hypermutation in TCRs
once they leave the thymus they are locked in
More diversity in MHC I’s or II’s?
**review the PPT (DP, DQ, DR)
II’s
I’s have a constant Beta chain
HLA-B27 increases __________ risk by 90%.
ankylosing spondylitis
HLA-DR2 linked to :
narcolepsy
MS
hay fever
SLE
HLA-A3/B14 linked to :
hemochromatosis
HLA-DQ2/GQ8 linked to :
Celiac disease
HLA-DR3 linked to :
DM1, Grave’s Disease
HLA-DR4 linked to :
RA, DM1
HLA-B53 linked to :
protection against childhood malaria
Each cell can produce how many different MHC I’s?
6
Each cell can produce how many different MHC II’s?
12