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Flashcards in Immunology 6 Deck (45)
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1
Q

Describe the TCR

A
  1. Short cytoplasmic tail
  2. Alpha and beta components (minority have gamma and delta chains)
  3. Diversity in variable region comes from VDJ recombination
  4. TCR is member of Ig superfamily
  5. CD3 IS A CONSTANT PART OF THE TCR
2
Q

What are the CD3 polypeptides?

DEGZ

A

Delta
Epsilon
Gamma
Zeta

3
Q

What are CD3 important for?

A

Delivering signal to T lymphocyte once antigen is recognised

CD3 has much longer cytoplasmic tails

Useful as a marker - present on all T cells

4
Q

What do CD3 tails have?

A

Motifs with Tyrosine residues

5
Q

Charged residues of the transmembrane Alpha and beta chain interact with oppositely charged residues in the transmembrane residues of CD3

A

T

6
Q

What happens when the TCR meets its antigen?

A

Tyrosine phosphorylated

Triggers other chemical cascades

7
Q

What is ITAM

A

Immunoreceptor Tyrosine-based Activation Motif

8
Q

What are the 2 major populations of T cells?

A

CD4 - MHC Class 2

CD8 - MHC Class 1

9
Q

What does binding of the co-receptors (CD4/8) to the relevant MHC achieve?

A

Increased avidity of T cell-target cell interaction

Important in signalling

10
Q

What do CD4 - T helper cells do?

A
  1. Secrete cytokines
  2. Recruit effector cells - activate macrophages
  3. Help/activate CTL and B cell responses
11
Q

What do CD8 - Cytotoxic T lymphocyte do?

A
  1. Kill target cells

2. Induce apoptosis in target cells

12
Q

Where do CD4 / CD8 bind?

A

TO THE SIDE OF THE MHC MOLECULE.

TCR BINDS TO THE ANTIGEN PRESENTED BY THE MHC

13
Q

CD8+ = viral infected cells and viral proteins. MHC CLASS 1.

A

T

14
Q

Describe CD4+ Th1.

A
  1. Activates inflammatory responses.

2. Activates macrophages

15
Q

Describe CD4+ Th2.

A
  1. Important in B cell response activation

Captures antigen on BCR - takes up antigen.

Antigen processed. Fragments presented on MHC Class 2.

Th2 binds and activates B cell - initiates response.

16
Q

Describe mature thymocyte production.

A
  1. Progenitor cells move from bone marrow to thymus (NO CO RECEPTORS OR ANTIGEN SPECIFIC RECEPTORS AT THIS POINT).
  2. Initially immature thymocytes in cortex
  3. As the immature thymocytes develop, they move to the medulla - become mature thymocytes.
17
Q

What determines if the thymocyte becomes CD4+ OR CD8+?

A

Depending on the type of MHC they recognise.

CD4 - MHC 2

CD8 - MHC 1

18
Q

Describe thymocyte development in relation to the TCR.

A

B chain rearranged.

A chain rearranged.

Proper alpha-beta TCR formed

19
Q

Describe Alpha / Beta chain rearrangement in TCR.

A
  1. BETA chain rearranged first. (VDJ)

2. Alpha chain rearranged second (VJ)

20
Q

Talk to me about selection of T lymphocytes.

A

Checkpoint 1

  • is the new beta chain functional?
  • YES = survival and development to CD4/8, a/b TCR
  • NO = DEATH BY APOPTOSIS

Checkpoint 2

  • Is the a/b TCR functional? Is it auto reactive?
  • If useful then proceed

Checkpoint 3

  • Does TCR recognise self-MHC?
  • Not recognising MHC is useless
  • If it binds too tightly to MHC without antigen, then it is dangerous
  • Want something in between

ONLY 5% OF THYMOCYTES SURVIVE SELECTION

21
Q

Whats special about thymus epithelial cells?

A

Express both types of MHC molecule

22
Q

What are the most important genes in controlling graft rejection?

A

MHC

23
Q

What is MHC?

A
  1. Group of tightly packed genes

2. Important in specific immune responses

24
Q

Describe MHC Class 1 structure.

A

2 different chains, Alpha (HEAVY) and B2-microglobulin (light).

3x Alpha chains.
1x B2-microglobulin chain

Alpha is polymorphic but B2-microglobulin chain is the same in everyone

Light chain (B2-microglobulin) binds non-covalently with Alpha chain.

B2-microglobulin is NOT TRANSMEMBRANE

25
Q

Describe MHC Class 2 structure.

A

2x Alpha chains
2x Beta chains

Peptides bind between a1 and b1.

26
Q

Which MHC Molecule presents shorter chain peptides (8-10 aa long)

A

MHC Class 1

27
Q

What length does MHC Class 2 present?

A

13+ aa (longer peptides)

28
Q

Describe how peptides bind to MHC.

A
  1. MHC has binding pockets.
  2. In the peptide, certain positions tend to have the same amino acid,
  3. This is known as a binding motif, whereby certain positions are a particular aa, other positions can be anything else.
  4. So MHC presents a substantial of peptides with some things in common where characteristics are conserved.
29
Q

What is HLA?

A

Human Leukocyte Antigen., on Chromosome 6

HLA genes encode polypeptides that make up MHC molecules.

HLA Class 1 has 3 types; A, B, C.

HLA Class 2 has 3 types; DP, DQ, DR

In class 1, only the heavy chain is encoded by the HLA. (B2-Microglobulin is encoded on a different chromosome)

We are diploid, so we can have upto 6 different class 1 and class 2 molecules.

HUMAN VERSION OF MHC

30
Q

MHC is polygenic and co-dominant. What is meant by this?

A
  1. Several Class 1 and Class 2 loci.

2. Maternal and paternal genes both expressed

31
Q

Which type of MHC is expressed in nearly all cells?

A

MHC Class 1

Expression varies during infection or cytokines

32
Q

Which type of MHC is expressed only in professional APCs?

A

MHC Class 2

Regulated by cytokines

33
Q

What is the most polymorphic gene in the human genome?

A

MHC

34
Q

What causes different immune responsiveness to different infections?

A

MHC is polymorphic.

We have 2 MHC haplotypes (We are diploid)

35
Q

Which MHC Class is linked to autoimmune diseases?

A

MHC Class 2

36
Q

There are over 4200 HLA genes

A

T

37
Q

Are MHC haplotypes randomly distributed?

A

NO

38
Q

Define exogenous

A

Captured from the outside (e.g. phagocytosis)

39
Q

Define Endogenous

A

synthesised within cells (e.g. virus)

40
Q

Which MHC class is endogenous?

A

MHC Class 1

41
Q

Which MHC Class is exogenous?

A

MHC Class 2

42
Q

How are endogenous antigens presented?

A

Via MHC Class 1 to CD8+ T cells

43
Q

How are exogenous antigens presented?

A

Via MHC Class 2 to CD4+ T cells

44
Q

Explain endogenous antigen presentation via MHC Class 1

A
  1. Viral proteins in cytoplasm are processed by proteasome
  2. Peptides move into ER via TAP (Transporter associated with Antigen Processing)
  3. Newly synthesised MHC Class 1 moves into ER
  4. MHC Associates with chaperone proteins which aids its folding
  5. Class 1 heavy chain binds with peptide and B2-microglobulin
  6. All chains correctly folded. Then goes via golgi to cell surface. Awaits possible recognition by CD8 positive T cells
45
Q

Explain exogenous antigen presentation via MHC Class 2.

A
  1. Proteins endocytosed and processed - peptides now in endocytic vesicles.
  2. Class 2 molecules enter ER.
  3. In the ER, Class 2 associates with INVARIANT chain. (iNVARIANT because not polymorphic - binds to all MHC Class 2).
  4. Invariant chain has targeting signal sequence which triggers molecules to go to the Golgi
  5. Invariant chain is chopped up and a small fragment remains - CLIP peptide.
  6. Finally, CLIP peptide swapped for peptide derived from antigen.
  7. MHC Class 2 then moves to cell surface for CD4+ T cell recognition