Antigen Processing, Presentation, Co-stimulation Flashcards
In general, once an antigen presenting cell (APC) contacts an antigen (Ag) at the site of infection it will move into the ______
lymph circulation/ lymph node
CD8+ T cells are _______ restricted and recognize cytosolic proteins
MHC I
CD4+ T cells are _____ restricted and recognize extracellular and intravesicular pathogens
MHC II
What are naive B and T cells
inactivated B and T cells floating in the circulation
when would naive B and T cells move from the circulation into a lymph node ?
when a APC engulfs an antigen and transports it to the lymph node
What does it mean when saying antigen presentation is context dependant
Different immune responses under different conditions
Example : MHC I or MHC II
Antigen presentation acts as a bridge b/w Ag recognition and what ?
the full blown immune response
Is Ag recognition part of the innate or adaptive immune response
adaptive immune response
Successful Ag presentation results in ?
Activation of naive B and T cells
What are the 3 “professional” APC
- Dendritic cells (Best)
- Macrophages
- B cells (rare)
- These are majority, but more exist*
What can ALL nucleated cells do with regards to Ag presentation ?
Present endogenous Ag tagged with MHC I
Degradation/break down of cytoplasmic proteins occurs within ?
proteasome
Degradation/break down of endocytic proteins occurs within ?
lysosome
There are 2 main pathways in Ag presentation. One processes exogenous Ag with aid of _______ molecule, and the other processes endogenous Ag tagged w/________
MHC II (CD4) MHC I (CD8)
What are the names of the 2 pathways of Ag presentation, and what type of Ag do the recognize ?
Cytosolic Pathway - Endogenous Ag
Endocytic Pathway - Exogenous Ag
Explain the Cytosolic pathway of Ag presentation starting from the labeling of proteins via ubiquitin.
1 - Ubiquitin tags proteins(Ag) for degradation
2 - degradation (of Ag) occurs in proteasome
3 - TAP transports digested Ag peptides to lumen RER
4 - MHC I binds to Ag peptides
5 - Ag-MHC I complex transport to surface for interaction w/lyphmocytes
What are TAP’s
proteins that transport digested fragments of Ag protein into lumen of RER
MHC I and MHC II are both synthesized where ?
RER
What is the diff. b/w HLA-DM and HLA-DO
HLA-DM loads Ag in endocytic pathway
HLA-DO inhibits the loading of Ag (by blocking HLA-DM)
clatherin coated pits are used to engulf/vesiclize Ag in what Ag presentation pathway
Endocytic Pathway (Exogenous Ag)
Explain the Endocytic pathway of Ag presentation starting w/ Ag binding to cell surface
1 - Ag binds and internalized via endosomes
2 - digested in lysomes in Ag peptides
3 - HLA-DM triggers loading of Ag to MHC II
what is the role of the invariant chain in the endocytic pathway
When bound to MHC II, it keeps MHC II from binding endogenous Ag
what triggers the exchange from CLIP (Class II associated invariant chain peptide) to an Ag on the MHC II molecule
HLA-DM (loads the Ag)
what is a haplotype
clusters of alternative forms of the same gene closely linked on the same chromosome
What 3 things does the MHC haplotype influence
- how individual responds to pathogens
- susceptibility to disease
- transplant success
The MHC genes are highly polymorphic, what does this mean ?
10^13 different allele combinations (broad response) E
-reason why we can recognize so many different specific types of Ag’s
A self MHC + a foreign Ag will elicit ___________ whereas a self MHC + self Ag will elicit ______
T cell response
NO T cell response
All nucleated cells in the body can alert either CD4 or CD8 T cells, which is it ?
CD8 T cells via MHC I
What results in a positive selection in MHC restriction and what results in a negative selection
Ag + MHC = positive selection
self + MHC = negative selection
In order to get activation of a T cell, there are 2 signals needed in the immunological synapse, what are they ?
1 - MHC-Ag complex binds to TCR (T cell receptor)
2 - Co-stimulatory signal (engagement of CD28 w/B7 molecule)
NEEDS BOTH SIGNALS to ACTIVATE
what is the role of CTLA-4 on co-stimulatory molecules
Acts as an “OFF” switch for immune response activation of Tcells by binding to B7 (co-stimulatory molecule)
what are the 2 ways CTLA-4 can downregulate the immune response
1 - competively inhibit (co-stimulatory molecule) CD28 from binding to B7
2 - Bind to B7 which actively blocks
CD28 and CTLA-4 both can bind to B7, what is the difference in signals if either bind
If CD28 binds to B7 = stimulate T cell activation
If CTLA-4 binds to B7 = inhibit T cell activation
What is the difference b/w TH1 and TH2 helper T cells
TH1 - involved in cell mediated immunity, pro-inflammatory
TH2 - humoral immunity, anti-inflammatory
What is the main generic role of cytokine IL-2
induces T cell proliferation/differentiation
After antigen presentation, in order to amplify the T cell response a signal cascade will occurs to activate ______ which will induce IL-2
transcription factors NF-AT and NF-KB
IL-2 is a cytokine that amplifies the T cell response by how much
1000 fold
IL-2 once produced can cause 3 effects, what are they ?
1 - T cell proliferation
2 - Regulatory T cell development
3- -NK cell proliferation
naive T cells can develop into Th1 or Th2 helper t cells, what drives the development of each
IL-12 drives dev. of Th1
IL-4 drives dev. of Th2
what is the most important cytokine produced in response to Th1
IFN-gamma
what is the most important cytokine produced in response to Th2
IL-4
