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Miscellaneous > MCB Lecture 47 T cells > Flashcards

MCB Lecture 47 T cells Flashcards

0
Q

Which gene locus is responsible for diversity of BCRs?

Describe the structure

A

Immunoglobulin gene locus

There are three loci, each on different chromosomes:
Heavy, H
Lambda
Kappa

The heavy loci contains many V, D and J genes

The lambda and kappa loci contain many J and V genes

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1
Q

How is diversity of BCRs generated?

Outline the steps

A

Immunoglobulin gene rearrangement

  1. Somatic recombination: one of the many V, D and J genes are selected
  2. Gene transcription of the recombinant gene
  3. mRNA is spliced
  4. Translation
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2
Q

Which genes code for the variably portion of the heavy chain?

A

Heavy

V, D and J

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3
Q

Which genes code for the variable portion of the light chain?

A

Lambda
Gamma

V, J

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4
Q

Why are there both the kappa and lambda locus?

A

The kappa locus is used first

If this does not produce a viable BCR, lambda is used

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5
Q

Which cells play a vital role in gene rearrangement of BCRs?

A

Bone marrow stromal cells

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6
Q

What is the requirement for a pre-B cell?

A

It must have produced viable heavy chains

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7
Q

Describe how further diversity of antibodies is generated

A

Junctional diversity

When the genes are being rearranged, extra nucleotides are added at the junctions between the V D and J regions

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8
Q

How many unique antibodies does junctional diversity give rise to?

A

10 to the 13

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9
Q

Which enzyme is required for junctional diversity (hyper variation)?

A

TdT

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10
Q

Which enzymes mediate gene rearrangement of BRC?

A

TdT
Exonucleases
RAGs: recombinase activating genes

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11
Q

How do we prevent auto reactive antibodies from causing damage in the body?

A

The BCR must pass a test to make sure they are not auto reactive before they can move out into the blood

If they fail the test, they are removed

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12
Q

What is the outcome of isotype switching?

A

Different Fc

The Fab doesn’t change, however

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13
Q

Describe the structure of TCRs

A

Two chains: alpha and beta

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14
Q

Which genes code for the TCRalpha?

A

V J D

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15
Q

Which genes code for the TCRbeta?

A

V D J C

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16
Q

Which processes follow on after gene recombination for BCR and TCRs?

A

Rapid proliferation

Removal of attractive BCR

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17
Q

Where do lymphocytes reside in the body?

Give percentages

A

50% mucosal associated lymphoid tissue
40-50% Lymph nodes
2% blood

18
Q

What are the main differences between PRR and TCR & BCRs?

A

PRR: bind to common features (PAMPs)
100-300 different types

BCR/TCR: bind to specific antigens
10 to the thirteen - 10 to the 18 receptors

19
Q

Give a brief description of the cellular adaptive immune response

A

When pathogens get into cells, BCR can not find them to bind and produce a response

We now need T lymphocytes that recognise protein coming from inside a cell to detect that a cell is infected

When T cells get activated in this way, they launch a response to kill the cell

20
Q

What are the two types of MHC?

Where are they each found?

A

Type I: all nucleated cells
Present protein that has been made inside that cell (can include virus protein)

Type II: present on antigen presenting cells
Present protein that originated outside the cell and was endocytosed

21
Q

What are APC?

List a few

A

Antigen presenting cells

Macrophages
Dendritic cells
B cells

22
Q

What is the structure of MHC?

A

A beta sheet and two alpha helices form a cleft, to which peptides bind

23
Q

Describe how diversity is generated for MHC

A

The genes for MHC are highly polymorphic
Diversity is inherited
We inherit one type from mum and one type from dad

The two alleles are codominantly expressed

24
Q

Describe the specificity of MHC

Ie which MHC bind to which antigens and TCR

A

For a peptide to be presented in an MHC molecule, it most contain the correct residues, so that it can bind to residues of the MHC cleft

Also, for the T cell receptor to bind to the peptide being presented, it must have the correct binding site

Also, the MHC and TCR must agree

25
Q

Describe how peptides come to be presented on MHC II

A

Pathogen in engulfed by a APC

Pathogen is broken down in a lysosome into peptides

Peptides bind to the cleft of the MHC

MHC inserted into membrane, with the peptide facing the outside

26
Q

What is the medical importance of MHC? (5)

A

The structure of an individual’s MHC determines many things:

  • Disease susceptibility
  • Allergic response
  • Infection potential
  • Autoimmunity
  • Transplantation
27
Q

Describe how T cells become activated

A

T cells each have a unique TCR on their surfaces

A TCR recognises and binds to its complimentary antigen, which is being presented by an MHC

The T cell now divides and proliferates

28
Q

When does isotype switching occur?

A

After a B cell has found its antigen, ie after it has been clonally selected

29
Q

How many segments does each locus have?

A

Kappa: v: 40 j: 5
Lambda: v: 30 j: 4
Heavy: v: 40 d: 25 j: 6

30
Q

Which chain rearranges first?

A

First the heavy chain, then the light chain

31
Q

What is a pre-B cell?

A

It has, as of yet, only rearranged the heavy chain locus

Surrogate light chain bind whilst the light chains are still being produced

32
Q

Which process makes the largest contribution to overall diversity of BCRs?

A

Junctional diversity

33
Q

Once in circulation, B cells express which isotypes bound to their surface?

A

IgM and IgD (passed the autoreactive test)

34
Q

What do TCRs resemble?

A

The Fab region of a BCR

35
Q

Can TCR and BCR be found unbound in plasma or tissue fluid?

A

Only BCRs can

TCR must be membrane bound

36
Q

Describe the structure of a TCR

A

V-alpha
C-alpha

V-beta
C-beta

37
Q

How many types of C-alpha and C-beta are there respectively?

A

There is only one C-alpha, but there are two C-betas

38
Q

How is PRR diversity generated?

A

We inherit our Pattern Recognition Receptors

39
Q

What is HLA?

A

The name for MHC found inhumans

40
Q

What is beta-2 micro globin?

A

It is one of the subunits making up MHC I (HLA) in humans

41
Q

What are the MHC genes in humans?

A

For MHC I:
HLA-A
HLA-B
HLA-C

For MHC II:
HLA-DR
HLA-DP
HLA-DQ

42
Q

Compare the length of the peptide presented in MHC I and MHC II

A

MHC I: 8-11 amino acids long

MHC II: 10-30 amino acids long

43
Q

Describe how different peptides may be presented in the same MHC molecules

A

Different peptides may have the same anchor side chains.

Thus they may bind to the same polymorph of the MHC which has the same binding pocket

Miscellaneous (109 decks)

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