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Genetics and Human Disease > MHC Genetics and Disease > Flashcards

MHC Genetics and Disease Flashcards

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1
Q

What is the MHC?

A

MAJOR HISTOCOMPATIBILITY COMPLEX

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2
Q

What is the HLA?

A

Human Leukocyte Antigen Complex

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3
Q

Where is the MHC?

A

Located on Chromosome 6

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4
Q

What does the MHC consist of?

A

Transmembrane glycoproteins

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5
Q

What is the main role of the HMC?

A

Present antigens on the cell surface

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6
Q

What genes code for the MHC?

A

Highly polymorphic genes

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7
Q

How is the MHC inherited?

A

As haplotypes from parents.

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8
Q

What does the MHC locus contain?

A

2 types of highly polymorphic genes Class I and II

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9
Q

What is the difference between class i and class ii MHC?

A

Different but homologous

Different tissue distribution

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10
Q

Where are the glycoproteins expressed for class 1 of MHC?

A

All nucleated cells

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11
Q

What is the structure of MHC class 1?

A

MHC-encoded α-chain of 45kDa

α-chain anchored to the cell membrane

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12
Q

What elements are associated with the MHC Class 1 but are not covalently bonded?

A

β2-microglobulin, 12kDa, non-MHC encoded, non-transmembrane.

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13
Q

How is the shape of MHC class 1 formed?

A

Peptide antigen in a groove formed from a pair of α-helicies on a floor of anti-parallel β-strands

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14
Q

Where are the glycoproteins of MHC class 2 expressed?

A

Glycoprotein expression restricted to APCs

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15
Q

What is APCs?

A

Macrophages

Dendritic cells

B cells

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16
Q

How heavy is the alpha chain of the class 2 MHC?

A

34kDa

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17
Q

How heavy is the beta chain of the class 2 MHC?

A

29kDa

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18
Q

What is the structure of MHC class 2?

A

Both α and β chains anchored to the cell membrane

Peptide antigen in a groove formed from a pair of a-helicies on a floor of anti-parallel b strands

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19
Q

When was a full MHC sequence complete?

A

1999

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20
Q

Where do the polymorphisms occur on MHC?

A

Binding cleft

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21
Q

What is the peptide binding cleft?

A

Highly specialised grooves for antigen presentation, form
stable complexes with antigens

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22
Q

What size peptides do class 1 MHC accommodate for?

A

8-10

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23
Q

What size peptides do class 1 MHC accommodate for?

A

13-18

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24
Q

Which if the MHC classes binding cleft has an open structure?

A

Class 2

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25
Q

What does MHC bind to?

A

Antigen fragments produced by infected cells

Fragments from the proteolysis of foreign material.

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26
Q

How does the MHC interact with T cells?

A

MHC moves to surface to present antigen for T cell recognition.

27
Q

What happens when antigens presented on surface aren’t MHC bound?

A

T cell won’t recognise it

28
Q

Which T cell type does class 1 MHC interact with?

A

CD8 t cell

29
Q

Which T cell type does class 2 MHC interact with?

A

CD4 t cell

30
Q

Which MHC class deals with the endogenous pathway?

A

1

31
Q

Which MHC class deals with the exogenous pathway?

A

2

32
Q

What are the 2 laws of inheritance the MHC follows?

A

Polygeny

Polymorphism

33
Q

What does it mean that the MHC is polygenic?

A

Codominance, combination of α and β for MHCII and from both parents

34
Q

What does it mean that the MHC is polymorphic?

A

Have changes to the peptide binding groove.

35
Q

Does the MHC change over time?

A

The type and variant MHC molecules do not vary in the lifetime of the individual

36
Q

What are the variations in class 1 MHC?

A

A B and C

37
Q

What are the variations in class 2 MHC?

A

DP DQ and DR, but each can be alpha and beta so 6.

38
Q

Which gene can be had more than one of?

A

DR beta

39
Q

What does it mean if when an individual is heterozygous MHC?

A

The more variety the more antigens presented.

40
Q

What about cleft polymorphisms in MHC suggest the presence of polymorphism?

A

Replacement substitutions (non-synonymous) occur at a greater rate than silent substitutions.

41
Q

What is the effect of MHC on disease susceptibility?

A

Certain MHC alleles can increase susceptibility to disease

Certain MHC alleles can be protective in relation to disease

42
Q

What is the problem with studying MHC disease Loci?

A

High gene density

Extreme polymorphism

Strong linkage disequilibrium of MHC

Which makes it hard to study individual loci.

43
Q

Which gene in the MHC was found to be associated with Ankylosing Spondylitis?

A

HLA-B*27

44
Q

What is Ankylosing Spondylosis?

A

AS is a heritable chronic disease; form of inflammatory arthritis frequently affecting the spine?

45
Q

Which gene of the MHC is associated with type 1 diabetes?

A

HLA-DR-DQ haplotype

46
Q

Why is this HLA coded gene linked to diabetes 1?

A

Due to specific amino acid at position 57 of the HLA-DQ β chain

47
Q

What kinds of drugs do MHC bind?

A

Small molecules drugs

48
Q

Why is MHC binding drugs a problem?

A

Can pose a risk and cause adverse reactions

49
Q

What is AHS?

A

ABACAVIR HYPERSENSITIVITY

50
Q

What is Abacavir?

A

Anti-retroviral used to treat HIV-1

51
Q

What percentage of patients have AHS?

A

5-8%

52
Q

How was AHS avoided?

A

The implementation of HLA-B*57:01 screening prior

53
Q

What underpins selection at the MHC?

A
  1. Parasite-mediated selection and MHC evolution
  2. MHC-dependent sexual selection
54
Q

What is parasite-mediated selection for a rare allele advantage ?

A

New allele, then MHC advantage allele increases selection will favour pathogenic strains that are not recognised by this allele and than this pathogen will increase in frequency until recognised by a new novel MHC allele.

55
Q

What is parasite-mediated selection for a heterozygous advantage?

A

Immune competence could be
substantially enhanced by heterozygosity at MHC loci, as
heterozygotes recognise a wider variety of antigens derived from
multiple pathogens.

56
Q

What is sexual selection?

A

The advantage that certain individuals have over other individuals of the same sex and species, in exclusive relation to reproduction.

57
Q

What are the 2 mechanisms of sexual selection?

A

Male competition (intrasexual selection)

Female choice (intersexual selection)

58
Q

What is female choice?

A

To evolve it must confer a benefit in terms of reproductive success.

59
Q

What are the 2 benefits of female choice?

A

1)Females directly improve their own RS due to choice (fecundity).

2) Genetic benefits for offspring: females improve the RS of their offspring

60
Q

What is Zahavi’s handicap principle?

A

The handicap is costly therefore the individual must be of sufficient quality to afford such as costly handicap.

61
Q

Why are humans a bad example of sexual selection?

A

Too complex, with too many developed background requirements for mates along with genetics.

62
Q

What is the consequence of MHC similarity?

A

Lower successful birth rate.

63
Q
A

Genetics and Human Disease (16 decks)

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