MCB Lecture 47 T cells Flashcards Preview

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Flashcards in MCB Lecture 47 T cells Deck (44)
0

How is diversity of BCRs generated?

Outline the steps

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

1

Which gene locus is responsible for diversity of BCRs?
Describe the structure

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

2

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

Heavy

V, D and J

3

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

Lambda
Gamma

V, J

4

Why are there both the kappa and lambda locus?

The kappa locus is used first
If this does not produce a viable BCR, lambda is used

5

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

Bone marrow stromal cells

6

What is the requirement for a pre-B cell?

It must have produced viable heavy chains

7

Describe how further diversity of antibodies is generated

Junctional diversity

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

8

How many unique antibodies does junctional diversity give rise to?

10 to the 13

9

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

TdT

10

Which enzymes mediate gene rearrangement of BRC?

TdT
Exonucleases
RAGs: recombinase activating genes

11

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

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

12

What is the outcome of isotype switching?

Different Fc
The Fab doesn't change, however

13

Describe the structure of TCRs

Two chains: alpha and beta

14

Which genes code for the TCRalpha?

V J D

15

Which genes code for the TCRbeta?

V D J C

16

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

Rapid proliferation
Removal of attractive BCR

17

Where do lymphocytes reside in the body?
Give percentages

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

18

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

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

Give a brief description of the cellular adaptive immune response

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

What are the two types of MHC?
Where are they each found?

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

What are APC?
List a few

Antigen presenting cells

Macrophages
Dendritic cells
B cells

22

What is the structure of MHC?

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

23

Describe how diversity is generated for MHC

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

Describe the specificity of MHC
Ie which MHC bind to which antigens and TCR

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

Describe how peptides come to be presented on MHC II

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

What is the medical importance of MHC? (5)

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

- Disease susceptibility
- Allergic response
- Infection potential
- Autoimmunity
- Transplantation

27

Describe how T cells become activated

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

When does isotype switching occur?

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

29

How many segments does each locus have?

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

30

Which chain rearranges first?

First the heavy chain, then the light chain

31

What is a pre-B cell?

It has, as of yet, only rearranged the heavy chain locus
Surrogate light chain bind whilst the light chains are still being produced

32

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

Junctional diversity

33

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

IgM and IgD (passed the autoreactive test)

34

What do TCRs resemble?

The Fab region of a BCR

35

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

Only BCRs can
TCR must be membrane bound

36

Describe the structure of a TCR

V-alpha
C-alpha

V-beta
C-beta

37

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

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

38

How is PRR diversity generated?

We inherit our Pattern Recognition Receptors

39

What is HLA?

The name for MHC found inhumans

40

What is beta-2 micro globin?

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

41

What are the MHC genes in humans?

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

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

42

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

MHC I: 8-11 amino acids long

MHC II: 10-30 amino acids long

43

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

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

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