Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
43 Cards in this Set
- Front
- Back
|
Do T cells undergo isotype switching? Why or why not?
|
No. Immunoglobulins serve as both binding proteins AND effector molecules (Fc). T cell receptors are binding only.
|
|
|
What are the two chains of a T cell receptor. Are they analagous to anything? Why?
|
Alpha and beta. Alpha is like light chain (VJ) while beta is like the heavy chain of an immunoglobulin (VDJ).
|
|
|
How many hypervariable regions are on the binding site of a TCR?
|
6. 3 from the alpha chain and 3 from the beta chain.
|
|
|
Multipoint attachment
|
A single T cell encountering a single APC will bind to multiple MHC-peptide complexes with multiple TCRs.
|
|
|
REVIEW: Cellular mechanisms PRE B cell activation, and POST
|
PRE: Genetic rearrangement to form the V region of a membrane-bound immunoglobulin.
POST: Somatic hypermutation leading to affinity maturation, C-region (isotype) switching, mRNA splicing to make soluble immunoglobulin. |
|
|
Location of the TCR chain loci. How many constant regions does alpha have? How many for beta?
|
alpha is on 14, while beta is on 7. alpha has one C, while beta has 2 (no functional difference)
|
|
|
Where does TCR genetic rearrangement take place?
|
The thymus
|
|
|
SCID and cause.
|
Severe Combined Immunodeficiency. One or more RAG genes are unexpressed.
|
|
|
Omenn syndrome and cause.
|
Missense mutations that cause partial RAG function. More fatal than SCID.
|
|
|
Where do the alpha and beta chains link up?
|
In the ER. Early CATOS review.
|
|
|
How many signaling association proteins does a functional TCR require?
|
4. 3 homologous from chromosome 11, 1 from 1 called Xi. Naturally a deficient CD3 delta or epsilon result in impaired receptor binding to the cell membrane, and thus immunodeficiency.
|
|
|
Wait. What is a gamma-delta receptor?
|
A special kind of TCR. The gamma has high jxn diversity while th delta can incorporate extra D segments. It's a mad mad world. The gamma-delts are found in epi and do not require peptide-MHC presentation.
|
|
|
Do we know what the gamma-delts do?
|
Not really.
|
|
|
Take home message on TCR structure as it relates to TCR function
|
It is only a binding molecule that relays signals via it's 4 signaling associated proteins. Therefore, it does not have an Fc nor does it undergo post-activation changes.
|
|
|
Antigen processing
|
A required intracellular digestion to present peptides via the MHC to T cells.
|
|
|
Broad pathogenic division
|
Extra (bacteria) and intracellular (virii). There are two types of T cells as a result.
|
|
|
The T cell that fights intracellular infection
|
Expresses CD8, is cytotoxic. Killer.
|
|
|
The T cell that fights extracellular infection
|
Expresses CD4, there are two subclasses.
|
|
|
Primary function of TH2 cells
|
Stimulate antibody production in B cells
|
|
|
Primary function of TH1 cells
|
Activate macrophages to phagocytose and propogate immune response via cytokines.
|
|
|
Possible rationales for additional J segments in TCR loci?
|
Compensate for lack of post-activation changes, to encourage additional diversity.
|
|
|
Structure of CD4
|
4 ig-like domains with a hinge between D2 and D3 (like an arm with an elbow)
|
|
|
Structure of CD8
|
Two stalk-like a-b chains with iG-like domains. (pussywillows, seriously)
|
|
|
What does MHC I present? Why?
|
antigens of intracellular orgiin to CD8. MHC I and CD8 can communicate.
|
|
|
What does MHC II present? Why?
|
Antigens of extracellular origin to CD4. MHC II and CD4 can communicate.
|
|
|
Why do we care about glycoproteins CD4 and CD8, apart from their categorization?
|
They aid in antigen recognition, and are therefore coreceptors.
|
|
|
Structure of MHC I
|
1 3-alpha segment heavy chain, peptide binding 1-2: coupled with a B2-microglobulin.
|
|
|
Structure of MHC II
|
Two chains, alpha-beta, each contributing one domain to the binding site and one domain to the membrane linking.
|
|
|
What's the point of the immunoglobulin-like domains of the MHCs?
|
They bind to CD4 and CD8 respectively.
|
|
|
Degenerate binding specificity
|
Ability of MHC to bind multiple kinds of peptides.
|
|
|
Specifics of MHC I and II antigen binding.
|
The pocket-binding of MHC I limits peptides to approx 9 AA. The non-pocket restraint of MHC II means the peptides can be extremely variable and much longer.
|
|
|
Where does MHC I bind its peptide in the cell? MHC II?
|
ER. Endocytic/digestive vesicles.
|
|
|
3 most polymorphic MHC class I molecules in humans
|
HLA-A, HLA-B, HLA-C
|
|
|
3 most polymorphic MHC class II molecules in humans
|
HLA-DR, HLA-DP, HLA-DQ
|
|
|
Theoretical total number of MHC molecules present in humans
|
18.
|
|
|
The name for the critical amino acids in the MHC binding groove?
|
anchor residues. This is the only true constraint for MHC antigen binding (a peptide must match at LEAST these residues). For MHC I, there is still the issue of the pocket.
|
|
|
MHC polygeny
|
The presence of multiple MHC genes encoding similar proteins with similar functions.
|
|
|
MHC Polymorphism
|
The presence of multiple alleles of MHC genes.
|
|
|
Note about anchor residues
|
They vary in position per class, and can sustain some variability in binding (one hydrophobic aa for another)
|
|
|
What is TAP
|
Transporter associated with antigen processing. It moves digested peptides from the cytosol into the ER. There are 2, they can move oligopeptides, and require ATP
|
|
|
4 step process of MHC-I expression
|
1. Calnexin holds MHC-I until B2-microglob binds
2. Calreticulin and tapasin hold the MHC-I to TAP until a peptide arrives 3. Peptide arrives, MHC-I is mature 4. MHC-I is sent to cell membrane |
|
|
Bare lymphocyte syndrome
|
TAP is broken, no peptide to MHC-I, no MHC-I on cell surface.
|
|
|
Cause of autoimmunity related to MHC-I?
|
MHC-I also carries self-peptides, which shouldn't trigger an immune response but can.
|
