Antigen processing, presentation & Co- stimulation Flashcards
CD8+ T cells are _______ restricted and recognize ________ proteins.
MHC I
Cytosolic
CD4+ T cells are _______ restricted and recognize _______ and _______ pathogens.
MHC II
Extracellular & Intravesicular
What are the 4 steps of lymphocyte activation?
- Microbe infects host
- microbe is taken up by APC (antigen presenting cell) at site of infection
- APC enters lymph circulation and into Lymph node
- Naive T and B cells enter Lymph node from circulation.
_______ is central to the development of immune response.
Antigen presentation
What is Antigen presentation?
It is the bridge between recognition and full blown immune response.
- Enables T cell-mediated killing, or augments antibody production by B cells.
True or false, antigen presentation is context dependent?
True! deploys different immune responses under different circumstances.
Antigen presentation is modulated by _________.
Co-stimulatory molecules
Successful antigen presentation results in what?
Activation of T cells
What are the most effective Antigen presenting cells for initial T cell activation?
Dendritic cells
_________ must be activated by phagocytes before presenting antigens.
Macrophages
_______ may be the major type of antigen presenting cell for secondary immune response.
B cells
What can happen if antigen recognition occurs without antigen presentation?
Tolerance = not good!
What is the “professional” APC?
dendritic cell
True or false, Dendritic cells, B & T cells are the only APC’s.
False!
- All nucleated cells can present endogenous antigen in association with MHC I molecules.
What are the two pathways of antigen presentation?
Pathway 1 = Exogenous antigens presented to T helper cells.
Pathway 2 = Endogenous antigens presented to CD8+ T cells
Define antigen processing…
process of antigens being digested and placed of surface with correct MHC molecules.
What are the steps of the Endogenous antigen Cytosolic pathway?
- Proteins to be degraded are tagged by ubiquitin
- Degradation of ubiquitin-protein complexes occur within the central channel or proteasome.
- Peptides generated are transported into the Lumen of RER by TAP’s
- Newly synthesized MHC within RER membrane binds to antigen peptide.
- Antigen-MHC I complex released and transported to the cell.
What are the steps of the Exogenous antigen Endocytic pathway?
- Antigens are internalized in endosomes
- They are digested first in the endosomes, then in lysosomes to 13-18 aa peptides.
- Class II molecules are produced at RER
- They are associated with the invariant chain protein, preventing their binding to endogenous antigens.
- Class II-Ii complex move into endocytic compartments
- Ii will be digested to a short fragment (CLIP)
- HLA-DM triggers the exchange of CLIP and antigen peptide.
- HLA-DO block the activity of HLA-DM
_____ is two distinct polypeptides, an alpha and a beta.
MHC II
______ is one alpha peptide.
MHC I
What is a haplotype and what does it influence?
a cluster of alternative form of same gene, closely linked on same chromosome. Influences:
- How individual responds to pathogens
- Susceptibility to certain diseases
- Transplant success
MHC genes are highly polymorphic…. what does this mean?
- Hundreds of alleys in humans apron. 10^13 combinations (This is why its hard to match ppl for transplants, even 1st relatives often differ.)
MHC alleles are _______ expressed.
concomitantly
Self MHC + foreign AG = ?
T cell response
Self MHC + Self Ag = ?
No response
MHC expression can be induced on almost every nucleated cell in the body….True or False?
True
______ is a key factor in determining tissue matching for a transplant donor and recipients.
MHC
True or false, MHC molecules have very limited specificity.
False, its very broad!
MHC molecules have a ______ on/off rate.
slow
True or false, MHC molecules discriminate self from foreign peptides.
False, it does not!
What determines which peptides bind and how they bind?
The MHC haplotype of an individual
What is MHC Restriction?
Allows individual cells to recognize foreign Ag displayed on the surface of an individual APC.
*Allows T cells to distinguish between self and non-self & prevents destruction of Non-self.
What is the basic definition of Antigen presentation?
Process by which MHC-antigen interact with T helper or T cells.
What are the steps of Antigen Presentation?
- MHC-peptide complex binds to the T cell receptor (TCR)
- CD4 interacts with both MHC II on APC and TCR on T cell to strengthen antigen-TCR interaction.
- CD8 interacts with both MHC I on target cell and TCR on T cells.
- Co-stimulatory molecules B7 on APC binds to its T cell ligand CD28.
- Adhesion molecule ICAM-1 on the APC binds to its T cell ligand LFA-1.
Expression of the ______, _______ and _______ are required for antigen recognition and signaling.
TCR, CD3 and “the squiggly line”
CTLA-4 can competitively inhibit ______ binding to _____.
CD28 to CD28
CTLA-4 when bound to B7 will actively block signals from the _____ and from _____.
TCR and CD28
What happens during the absence of a antigen-TCR interaction?
T cell will not be stimulated.
What happens during absence of co-stimulatory molecules?
T cells will not be stimulated.
T-cells need the Co-reception of what two signal to become activated?
- Co-stimulatory molecules
2. Antigen-TCR interaction
What happens (to CD28) at the the termination of the Immune response
CD28 is replaced by CTLA-4 and down regulates T-cell function.
What 6 things happen after antigen presentation?
- activation of tyrosine kinases associated with TCR/CD4(8) complex.
- Activated Tk phosphorylate cytoplasmic tails of the clustered receptors.
- Atctivation of kinase cascade follows.
- Activation of Transcripton factors.
- Induction of IL-2 and IL2R.
- Cell division after IL-2 ligation to IL-2R.
What role does the IL-2 receptor (IL-2R) have in T cell response?
It amplifies the T-cell response.
Before activation the T cells express what?
Beta, gamma IL-2R
After activation the T cells, IL-2R takes what form and does what?
Alpha, beta, gamma IL-2R
and enhances the affinity of T-cells by 1000 fold.
IL-12 drives the development of ____.
Th1 cells
IL-4 drives the development of _____.
Th2 cells
Th1 cells do what?
Provide help for cell mediated immune responses.
What are 2 of the most important Th1 cytokines?
IFN-gamma & IL-4
What do Th2 cells do?
Provide help for humoral immune responses
What structure is responsible for the fixation of avian limb structures in a lipid saturated carbohydrate membrane?
The KFC
