Major Histocompatability Complex: Structure and Function Flashcards Preview

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Flashcards in Major Histocompatability Complex: Structure and Function Deck (23):

Passive immunization

Transferring B cells (serum antibodies) from a previously infected host to a non-infected host to transfer protection from infection to the non infected host


Why is passive immunization in humans expensive?

Gamma-globulin (IgG) injection for HIV patients has half life of about 30 days


Will the transfer of T cells protect a new host? Why or why not?

Only if the two hosts are genetically identical
T-cells always recognize foreign antigen in the context of self
New strain has different "non-self" MHC molecules presenting the antigen


MHC restriction

T-Cell receptors are specific for LCMV antigen, but are restricted by self-MHC, so they don't protect allogeneic host


What happens when tumors are transplanted from one strain of mice into same inbred and different inbred strains

Tumors flourished and killed syngeneic mice
Tumors were rejected when implanted into allogeneic mice


Tumor rejection genes are ________



Gene structure of MHC

Over 200 genes are encoded within the MHC which spans 7 million base pairs on chromosome 6



Human leukocyte angtigen (Gene of class I MHC)


Class I: three classical gene products

HLA-A, -B, -C ("heavy chains")


Class II: Six classical gene products, heterodimers

HLA-DR, -DQ, - DP, - (α and β chains)


How can T cells see the widest possible variety of antigens?

Polygenic (3 genes)
Codominant (Each gene is co-dominant)
Polymorphic (numerous identified alleles in the human population at each locus)


What type of screening is done before bone marrow transplantation?

Tissue typing for MHC class I and class II
1:4 chance of another sibling matching for all 10 products assuming no recombination between loci


Human Class I MHC molecules (6)

1) Three classical class I MHC gene products: HLA-A, HLA-B, HLA-C
2) Highly polymorphic
3) Class I MHC molecules are expressed on all nucleated cells
4) Class I MHC molecules play a major role in allograft rejection
5) Class I MHC molecules present peptide antigens to CD8 T Cells
6) Class I heavy chain forms heterodimers with a light chain, β2 microglobulin


Human Class II MHC Molecules (7)

1) Three class II MHC gene products: HLA-DR, HLA-DQ, HLA-DP
2) Highly polymorphic
3) Class II MHC molecules expressed only on specialized antigen-presenting cells
4) Class II molecules also play a major role in allograft rejection
5) Class II MHC molecules present peptide antigens to CD4 T cells
6) Heterodimers of two chains, α and β - each chain is induced by a different gene
7) The β chain is the more polymorphic gene - only type β chains are tissue typed in class II


For MHC molecules ___ helices form the groove and the __ sheets form the bed of the cleft



Polymorphisms in MHC I and MHC II

- Occur in α helices and in β sheets of the heavy chain for class I MHC
- Occur in α helices and in β sheets on the β chain for MHC II


Size limits for peptides in class I and II

Class I: 8-10 residues
Class II: 12-16 residues although they can be as long as 30+ residues


Features shared by all class I peptides

N-term, C-term, peptide backbone


Loose constraints for peptide

Certain amino acid residues are anchor residues, the rest can vary


Estimated number of distinct peptides that can bind to each class I MHC molecule



Benefits of polymorphism

Although one virus can escape efficient presentation on antigen on a given individual's 6 MHC molecules, it is hard to imagine a virus escaping presentation on all 1000 allelic variants within the population


A high percentage of people who do not respond to Hepatitis B vaccine have HLA-DR7 and HLA-DR3 - why?

Homozygotes for these two haplotypes are found almost exclusively in the non-responder (NR) population
Antigen presenting cells (APC) of NR are defective in the uptake of HBsAg and they are unable to present this AG adequately (T-cells are defective in recognizing this antigen)


Ankylosing Spondylitis

An inflammatory, possible autoimmune disease of vertebral joints
The HLA-B27 tissue type, while not causing AS, does predispose individuals with the B27 tissue type to developing AS - increases the chances by 100 fold