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Module 3 > Nature of alloresponse and major histocompatibility antigens > Flashcards

Nature of alloresponse and major histocompatibility antigens Flashcards

1
Q

What is the extracellular domain of the TCR resemble?

A

Ig Fab fragment

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2
Q

What binds the chains of the TCR?

A

disulphide bonds

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3
Q

What is found in the transmembrane region of the TCr?

A

positively charged amino acids

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4
Q

What is the antigen binding site of hte TCR composed of?

A

juxtaposed Va and Vb regions

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5
Q

What 2 properties of MHC make it difficult for pathogens to evade the strong immune pressure that MHC presentation exerts?

A

polygenic- each individual has a set of several MHC class I and II genes which form different molcules with a range of peptide binding sepcificities; polymorphic- multiple variants of each gene within the population as a whole

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6
Q

Which chromosome is the MHC region loacted on in humans?

A

6

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7
Q

Which chromosome is the mHC region located on in mice?

A

17

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8
Q

What genes are found in the MHC-II region that aren’t genes for the MHC-II?

A

genes for LMP-immunoproteasome; TAP; tapasin-antigen presentation; DM-catalyses binding peptide binding to MHC-II; DO-regulatory molecule

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9
Q

What is the difference in stimulation with type 1 IFNs and IFNy?

A

type I IFNs stimulate MHC-I expression whereas IFNy increase MHC-II expression

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10
Q

What is the MHC haplotype?

A

the particular combination of MHC alleles foudn on a single chromosome

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11
Q

What disease is caused by defects in Fas?

A

autoimmune lymphoproliferative syndrome

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12
Q

What is the sequence motif?

A

the set of anchor residues on a peptide that allows binding to a given isoform of an MHC-I or II

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13
Q

What do the specific anchor residues on peptides bind to on MHC>

A

peptide binding pockets in the peptide binding groove

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14
Q

What is unusual about HLA-DR?

A

the alpha chain is essentially invariant and only the beta chain shows significant polymorphism

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15
Q

What was the first clue to antigen presentation on MHC?

A

inbred animals failing to respond to simple antigens called immune response defects- now known because the processing of the protein did not generate any peptides with a sequence motif for binding to any of the MHC moelcuels expressed by the animal;;;only evidence was genetic, mice of one MHC genotype could respond to a particular antigen whereas mice of a different MHC genotype could not

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16
Q

Why are Ir gene defects common in inbred mice?

A

mice are homozygous at all their MHC gene loci which limits the range of peptides they can present to T cells

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17
Q

What were the first experiments to describe MHC restriction?

A

T cells could be activated only by macrophages or B cells that shared MHC alleles with the mouse in which the T cell originated

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18
Q

What experiments carried out by Doherty and Zinkernagel deomnstratewd MHC restriction
?

A

demonstrated that when mice are infected with virus, T cells kill cells infected with that virus, but not uninfected cells or cells infected with another virus–virus specifc CTLs, also that the CTLs would only kill cells with the same MHC genotype, even if other cells were also infected iwth the same virus

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19
Q

How many amino acids do proteins encoded by polymorphic genes normally differ by and what is the difference in MHC?

A

usually only by one or a few aa but the allelic variants of MHC differ by upto 20 aa

20
Q

Give an example of where polymorphism has been shown to be important?

A

small isolated populations in china and papua new guinea have 60% people carrying the same HLA-A allele, EBV has mutated so that its peptide no longer binds so can no longer be recognised by that alleles restricted T cells

21
Q

Give an example of where pathogens have selected for MHC alleles?

A

HLA-B53 allele is very common in west africa- assocaited with recovery from a lethal form of malaria

22
Q

Why is there a limited number of MHC loci?

A

each time a MHC molecule is added to the repertoire, all T cells that can respond to self peptide bound to that MHC molecules have to be removed to maintain self tolerance- balance

23
Q

What is required aside from the alpha and beta chains of the TCR to form a complete and functional receptor?

A

CD3 complex

24
Q

Which cells express MHC II?

A

DCs; B cells; macrophages; thymic epithelium

25
Q

When can MHC-II be induced on cells that don’t normally express it?

A

under proinflammatory conditions

26
Q

What genes are found in the class III MHC locus?

A

complement proteins; cytokines

27
Q

What HLA is asssociated with SLE?

A

HLA-DRB3

28
Q

What HLA is associated with ank spon?

A

HLA-B27

29
Q

What are the 2 types of allogenic response?

A

graft rejection and GvHD

30
Q

What is the direct allorecognition pathway?

A

recipient T cells recognise antigenic peptides presented on the donors APC

31
Q

What rejections is the direct pathway of allorecognition responsible for?

A

hyperacute and acute

32
Q

What is the indirect pathway of allorecognition?

A

allogeneic MHC molecule is processed and presented as a peptide by host APC

33
Q

What type of rejection is indirect involved in?

A

chronic rejection

34
Q

How can the allogenic repsonse associated with transplantation be overcome?

A

immunosuppression; inducing immunological tolerance

35
Q

What is muromonab?

A

humanised natibody against CD3

36
Q

What is muromonab used for?

A

reversing acute transplant rejection and prophylaxis; treatment of GvHD

37
Q

What is abatacept?

A

CTLA4 domain fused to IgG1Fc region

38
Q

How does abatacept work?

A

binds to CD80/86 with higher affinity than CD28

39
Q

What is the difference between abatacept and belatacept?

A

belatacept binds with even higher affinity to CD80

40
Q

What diseases is abatacept used in?

A

psoriasis and RA

41
Q

What is belatacept used for?

A

RA- better than methotrexate; prophylaxis for graft rejection in renal transplants

42
Q

What is basiliximab?

A

huamnised anti-CD25

43
Q

What is basiliximab used for?

A

to prevent acute transplant rejection

44
Q

What is etanercept?

A

soluble TNFa receptor mimic to block TNFa effect

45
Q

What is etanercept used for?

A

RA and ank spon

46
Q

What is infiliximab?

A

chimeric monoclonal antibody against TNFa receptor

47
Q

What diseases is infiliximab used in?

A

RA and IBD

Module 3 (33 decks)

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