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Cell and molecular biology of the immune system > Lecture 1-3 BCR, TCR and MHC > Flashcards

Lecture 1-3 BCR, TCR and MHC Flashcards

1
Q

Clonal deletion

A

removal of potentially self reactive immature lymphocytes

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2
Q

Which regions form the antigen binding site on antibody?

A

Paired variable regions- one heavy and one light chain

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3
Q

What bonds hold together the heavy and light chains on an antibody?

A

Covalent and non-covalent bonds.

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4
Q

What are 3 examples of effector cells which have FcRs that FC regions on antibodies can bind to?

A

Macrophages, neutrophiles, NK cells

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5
Q

General structure of antibody domains.

A

110 amino acids, 2 beta sheets held together by disulphide bonds. Domains are paired.

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6
Q

What is another name for hyper variable regions on antibodies?

A

Complementary-determining regions (CDRs)

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7
Q

What type of bond is between antibody and antigen?

A

non-covalent

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8
Q

Epitopes on antigens bind to what region of the antibody?

A

Bind to the amino acids in the hyper variable regions (CDRs).

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9
Q

What are the two types of light chains?

A

Lamda and kappa

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10
Q

TCRs do not recognise free antigens. What do they recognise?

A

Peptides on MHC molecules.

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11
Q

How many Ig-like domains do TCRs have?

A

4 domains. 2 variable and 2 constant. alpha and beta chains.

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12
Q

How many hypervariable regions in antibodies and TCRs?

A

antibody- 12 (3 from each variable domain).
TCRs- 6 (3 from each variable domain).

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13
Q

What is the most common T cell?

A

T cells which express alpha and beta TCRs. Less common express gamma and delta TCRs.

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14
Q

How were MHC molecules first identified?

A

Transplant rejection

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15
Q

What are MHC class 1 molecules made up of?

A

Alpha 1,2 and 3 and B2 microglobulin

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16
Q

What are MHC class 2 molecules made up of ?

A

B1 and B2, A1 and A2

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17
Q

What are the 3 different MHC class 1 molecules in humans?

A

Human leukocyte antigens - HLA-A, HLA-B, HLA-C

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18
Q

In MHC class 1, which domains are Ig-like?

A

Alpha 3 and B2 micro globulin.

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19
Q

In MHC class 2, which domains are Ig-like?

A

Alpha 2 and beta 2

20
Q

Which MHC molecules bind smaller peptides?

A

class 1 - peptides with 8-10 amino acids.

21
Q

What are the 3 different MHC 2 molecules in humans?

A

HLA-DQ, HLA-DR, HLA-DP

22
Q

What 3 gene segments encode the variable regions in Heavy chains (antibodies) and TCR beta?

A

V, D and J

23
Q

Which 2 gene segments encode the variable regions in Light Chains and TCR alpha?

A

V and J

24
Q

What is Non-homologous End Joining (NHEJ) recombination?

A

When the DNA containing the Ig segments is deliberately broken and then the segments are rearranged and joined together to form functional Ig genes.

25
Q

What is the order of Ig rearrangement in B cell development?

A

Heavy chains rearrange first, then light chains. Kappa light chains rearrange first, and if unsuccessful then lambda rearranges.

26
Q

What is Ig gene segment rearrangement of B cells guided by?

A

Recombination signal sequences (RSS).

27
Q

What enzyme is involved in Ig gene segment rearrangement in B cells?

A

V(D)J recombinase

28
Q

What does RAG stand for ?

A

recombination activating genes

29
Q

What is allelic exclusion?

A

In each individual B cell, only 1 rearranged H chain and 1 rearranged light chain is expressed. Light chain can only express either kappa or lambda.

30
Q

Somatic hypermutation leads to further diversity of antibodies. What enzyme is involved?

A

Activation-induced deaminase (AID).

31
Q

What is the role of AID in somatic hypermutation?

A

Activation-induced deaminase acts on DNA to de-aminate cytosine to uracil. Uracil is then recognised by error prone DNA repair pathways leading to mutations. These mutations lead to further diversity of antibodies.

32
Q

Where does somatic hypermutation occur and when ?

A

Germinal Centres. It occurs following the binding of Ag and activation of B cell.

33
Q

How is isotope switching and Ig rearrangement linked?

A

Antibody isotopes switching is due to heavy chain constant regions. There are 5 different constant region gene segments which produce the 5 different antibody isotopes. Isotope switching is caused by “looping out” of heavy chain constant regions.

34
Q

What is the first antibody isotope produced?

A

IgM

35
Q

Does somatic hypermutation occur in both antibody and TCR development?

A

NO! SHM only occurs in antibody development

36
Q

Where does rearrangement of gene segments occur in antibodies and TCRs?

A

Antibodies- bone marrow
TCRs- thymus

37
Q

what chromosome are all MHC molecules from ?

A

Chromosome 6

38
Q

How many MHC class 1 molecules can a person express if they are heterozygous?

A

as there are 3 MHC class 1 ( HLA-A, HLA-B, HLA-C) then a person can express 6 MHC class 1 molecules if heterozygous.

39
Q

How many MHC class 2 molecules can a person express if heterozygous?

A

6, as there are 3 different MHC class 2 molecules.

40
Q

An individual can express up to 12 different MHC molecules, so how are MHC molecules able to bind to every pathogen ever produced?

A

There are many polymorphisms in the peptide binding groove.

41
Q

What are the problems with highly polymorphic MHC molecules?

A

Risk of autoimmune diseases and reduces pool of available donors for transplants.

42
Q

Do MHC class 1 molecules present endogenous (inside) or exogenous (outside) peptides?

A

ENDOGENOUS

43
Q

What are the steps of antigen processing and presentation of MHC class 1?

A
  1. Antigen synthesised in the cytoplasm (endogenous) is processed into peptide by proteasome. LMP is part of the proteasome.
  2. Peptide enters ER through TAP transporter.
  3. Peptides inside ER bind to MHC class 1.
  4. MHC1/peptide complex transported to cell surface in vesicles.
44
Q

TAP is a transporter involved in processing and presentation of antigens on MHC class 1. What two proteins are associated with TAP?

A

Tapasin and Calreticulin

45
Q

what are the steps of antigen processing and presentation on MHC class 2?

A
  1. Exogenous antigen (can be self or pathogen) is endocytosed into intracellular vesicles inside cell.
  2. Ag is cleaved into peptides by acid proteases in vesicle.
  3. MHC class 2 molecules leave ER in vesicle and enters endocytic pathway.
  4. The 2 vesicles fuse and peptides bind to MHC class 2.
  5. MHC class2/peptide complex transported to cell surface in vesicles.
46
Q

Invariant chain is involved with MHC class 2. Describe the process of removal of invariant chain and what it is used for in the first place.

A

In the ER, invariant chains bind to MHC class 2 molecules to stop incorrect peptides binding. When MHC class 2 enter endocytic pathway, lysosomal enzymes degrade the invariant chain, leaving CLIP protein associated with the binding groove. HLA-DM bindings to MHC 2, releasing CLIP, allowing peptides to bind.

Cell and molecular biology of the immune system (5 decks)

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