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OPHTH Immunology > T lymphocytes and antigen recognition > Flashcards

T lymphocytes and antigen recognition Flashcards

1
Q

What is most likely to determine an individual subject’s HLA type?

A

inheritance from parents

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2
Q

How many alleles in total are inherited from parents for HLA determinants?

A

12:
* MHC I: 2 each of HLA A, B, C
* MHC II: 2 each of DP, DQ, DR

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3
Q

What are the 3 HLA classes which are major determinants of the HLA phenotype?

A

A, B DR

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4
Q

What are the 2 key functions of T lymphocytes?

A
  1. destroy intracellular pathogens
  2. TCR recognises small peptide fragment of antigen presented by MHC molecules on the surface of host infected cell
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5
Q

What is the T cell receptor analogous to in B cells?

A

membrane-bound Fab portion of antibody

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6
Q

Where are the variable and constant regions of T cell receptors?

A

variable = towards N terminus
constant = towards the membrane

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7
Q

How does the TCR influence intracellular signalling?

A

cytoplasmic tail too short for signalling; polypeptides associate with CD3 polypeptides with longer cytoplasmic domains (gamma, delta, episolon and zeta CD3 subsets)

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8
Q

What are the 2 major populations of T cells and their roles?

A
  • CD4+: T helper cells, see peptides on MHC class II (class II restricted)
  • CD8+: cytotoxic cells, see peptides on MHC class I (class I restricted)
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9
Q

What process increases the avidity of T cell target cell interaction?

A

co-receptor molecules bind to the relevant MGC

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10
Q

What are 3 functions of CD8 T cells?

A
  1. cytotoxic, kill target cells
  2. secrete cytokines
  3. induce apoptosis in the target cell
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11
Q

What are 5 overall functions of T helper cells (CD4)?

A
  1. secrete cytokines
  2. Recruit effector cells of innate immunity
  3. help activate macrophages
  4. Amplify and help Tc and B cell responses
  5. MHC molecules present antigen fragments at cell surface
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12
Q

What are 2 key types of T helper cells (CD4) and their respective roles?

A
  1. CD4 Th1: activate macrophages
  2. CD4 Th2: amplify antigen-specific B cell response
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13
Q

What are T cell precursors called and how do they develop?

A

progenitor cells: develop in bone marrow then migrate towards the thymus in the circulation; once mature leave thymus travel around body in the circulation

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14
Q

Where in the thymus does T cell maturation occur?

A

from cortex to medulla

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15
Q

How do T cell progenitors develop to CD4 and CD8 T cells?

A
  • initially express neither (CD4 or 8) i.e. double negative; in the cortex, T cells express a TCR precursor (pre TCR; β + “surrogate” αTCR).
  • then become double positive -express both CD4 and CD8
  • in the medulla, many different αβTCR’s created by gene rearrangement
  • generated TCRs express either CD4 or 8 - single positive
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16
Q

How does DNA get rearranged to develop the TCR protein?

A

germline DNA coding alpha and beta separately undergo rearrangement and recombination

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17
Q

What maintains the selection process of T cells in the thymus meaning only useful cells leave the thymus?

A

Checkpoints - occurs during interactino with macrophages and dendritic cells within the thymus

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18
Q

What are the 2 checkpoints in the thymus that ensure selection of T cells?

A
  1. Pre-TCR checkpoint: is new β chain functional? no -> apoptosis
  2. Post-TCR checkpoint: is αβ TCR functional? Is it dangerous/autoreactive? no; / yes -> apoptosis
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19
Q

What is negative selection?

A

T cells which see “self”, i.e. host molecules – receive signal to die by apoptosis

20
Q

What is positive selection?

A

T cell receptor binds weakly to MHC molecule – receive signal to survive

21
Q

What proportion of thymocytes survive selection?

A

5%

22
Q

What is the function of MHC molecules?

A

present antigens to T lymphocytes

23
Q

What is the structure of the MHC class I molecule?

A
  • 2 non-covalently associated polypeptide chains
  • Heavy: α1, α2¸ α3 – these are transmembrane
    polypeptides with a peptide binding, immunoglobulin like
    and cytoplasmic region
  • Light: β2-microglobulin – this only consists of an
    immunoglobulin like region
  • α1 and α2 are joined by PEPTIDE BINDING GROOVE
24
Q

What are the 2 chains and their associated regions forming MHC I?

A
  • heavy chain: alpha 1-3 polypeptides
  • light chain: beta-2 microglobulin
25
Q

Whcih polypeptides of MHC class I are joined by the peptide binding groove?

A

alpha 1+2

26
Q

Which part of MHC class I does CD8 interact with?

A

the alpha-3 domain

27
Q

What is the structure of MHC class II molecules?

A

2 transmembrane polypeptides of equal length, alpha and beta, each with 2 domains, alpha 1+2, beta 1+2

28
Q

Which part of the MHC class II molecule does CD4 interact with?

A

beta 2

29
Q

What are 3 characteristics of peptides accommodated by MHC class I?

A
  1. peptides of 8-10 amino acids
  2. peptides are buried within the structure
  3. peptides all same length
30
Q

What are 2 characteristics of peptides accommodated by MHC class II?

A
  1. peptides >13 amino acids
  2. peptides stick out from MHC molecule
31
Q

How do MHC molecules overcome there being relatively few MHC but needing to present many peptides?

A

they present subsets of peptides using binding motifs

32
Q

What is abinding pocket?

A

certain residues (anchor residues) are directly associated with the peptide due to their specific sequence; useful to predict which peptides will be presented

33
Q

How many functional genes code for HLAs?

A

128 (only 40% immune related)

34
Q

What is meant by the term co-dominant when referring to expression of MHC genes?

A

both materna and patern MHC is expressed

35
Q

Which cells express MHC class I?

A

all nucleated cells, levels may be altered during infection or by cytokines

36
Q

Which cells express MHC class II?

A

only professional APC (B lymphocytes, macrophages, dendritic cells), may be regulated by cytokines

37
Q

What is meant by polymorphism in reference to MHC molecules?

A

large nuber of alternative different versions of the same gene within the population, termed an allele

38
Q

What does an MHC haplotype refer to?

A

each group of MHC alleles linked on one chromosome

39
Q

What are the most polymorphic HLA forms in each class of MHC (I and II)?

A
  • I: B
  • II: DR β
40
Q

In what form do T lymphocytes recognise antigens?

A

only processed antigens that are presented on cell surfaces by MHC molecules

41
Q

How is endogenous antigen dealt with?

A

processed is antigen synthesised within the APC; is taken to CD8

42
Q

How is exogenous antigen dealt with?

A

synthesised outside the APC, can be taken up by macrophage etc, taken to CD4

43
Q

What are 4 stages of producing class I MHC?

A
  1. antigen is cleved by proteasome, taken into rough endoplasmic reticulum by Transporter Associated with antigen Presenting (TAP)
  2. Binds with MHC class I
  3. chaperones e.g. calnexin help protein polding
  4. then trafficked by golgi to the surface
44
Q

What are 6 stages of producing MHC class II?

A
  1. antigen endocytosed
  2. cleaved by proteases
  3. MHC II migrates into rough endoplasmic reticulum and associates with the invariant chain
  4. the MHC II-invariant complex is migrated into the golgi in the endosome
  5. invariant chain is digested by CLIP (class II associated invariant chain peptide)
  6. CLIP is then exchanged for the antigenic peptide, which is then presented at the surface
45
Q

What is a Gamma delta (γδ) T cells?

A

small subset of CD3-positive T cells in the peripheral blood but occur at increased frequency in mucosal tissues - have TCR composed of gamma and delta chains, don’t require MHC to present antigen peptide, exist in epithelium peripherally

46
Q

What type of antigenic material is presented by MHC class I?

A

intracellular

47
Q

What type of antigenic material is presented by MHC class II?

A

extracellular

OPHTH Immunology (8 decks)

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