Mhc Genetics/variation And Disease

Question 1

What do MHC bind

Answer 1

Ag epitopes

Question 2

Who do they present to

Answer 2

T cells either cd8 or cd4

Question 3

How is central self/immune tolerance achieved

Answer 3

Negative and positive selection in thymus for T cells

Negative In bm for b cells

Question 4

Which gene allows ag like insulin to be expressed in thymus to stop autoimmunity

Answer 4

Aire

Question 5

How is peripheral immune tolerance different

Answer 5

That is tolerance in lymph nodes not primary lymphoid organs

Question 6

What types of cells made in thymus damp down T cells escaping selection

Answer 6

Fox p3 tregs

Question 7

What type of ag do mhc 1 present to cd8

Answer 7

Self ag if healthy, neo ag if cancer cells, foreign material in transplantation, viral if infected

Question 8

How is peptides loaded on MHC 1 after proteasomes deg

Answer 8

Via tap enter rer and tapasin helps loading

Question 9

How are MHC 2 different

Answer 9

Only on b cells, mac and dcs

Present to CD4

Only exogenous ag

Question 10

Explain trafficking of MHC 2

Answer 10

Mhc2 with invariant chain meet ag fragments in a vesicular compartment MIIC (late endosomal) where proteases which cleaved ag cleave the invariant chain. Clip is then remaining and hla-dm exchanged this with the peptide

Move to surface via vesicles

Question 11

How are the 2 sets of hla genes inherited

Answer 11

As a haplotype

Question 12

Which chain of MHC 1 is acctually encoded by hla abc

Answer 12

A chain (b2 micro globulin is on chr 15)

Question 13

Which MHC holds smaller peptides

Answer 13

MHC 1 because closed ended (see more info on fr)

8-10 aa

Question 14

What needs to form for MHC to be in reactive and stable

Answer 14

Pmhc complex is needed. Ie usually always presenting self ag but tolerant

Question 15

What is the pMHC dependant on

Answer 15

The alleles a person inherits which is v diverse so more peptides presented

Question 16

What confounding factors affect if peptides would bind

Answer 16

Tapasin, hla-dm available and ag availability

Question 17

MHC are targets of immune evasion by pathogens. What is this

Answer 17

Where they mutate the peptides previously recognised and presented by the MHC alleles. If they mutate can’t recognise and present

Question 18

Which hla class 2 gene can actually have more than 1 copy of b chain so increasing diversity of variations

Answer 18

Hla dr

Question 19

Give 3 ways MHC genetics allows diversity

Answer 19

Polygenic (3 pairs of genes each)

Codominance of maternal and paternal alleles

Polymorphisms mainly in the binding groove

Question 20

What does codominance mean

Answer 20

Both maternal and paternal alleles are expressed Same time same cell

Ie 2 forms of hla dp alpha chain etc

Question 21

Which genotype will recognise and present more ag

Answer 21

Heterozygous

Question 22

Why are mutations in MHC likely due to selection pressures rather than random

Answer 22

Because they always cause a significant change eg in AA sequence

Question 23

Give an example of polymorphisms effects

Answer 23

Can affect peptide groove opening, tcr binding affinity , better stimulation of T cells (see fr)

Question 24

How many MHC 1 and 2 molecules expressed on cells

Answer 24

If heterozygous 6 for MHC 1 and 8 for MHC 2 given dr can have 2 copies