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BDS2 PMI > PMI02-2026 > Flashcards

PMI02-2026 Flashcards

1
Q

What is the cell lineage of a T cell?

A

Pluripotent haematopoietic stem cell

Common lymphoid progenitor

Pre-T cell (to thymus)

T cell

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2
Q

What are the three main types of T cell?

A

Helper T cells

Cytotoxic T cells

Regulatory T cells

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3
Q

What is the general function of helper T cells?

A

Regulate adaptive immune response including activation of immune cells via cytokines

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4
Q

What is the general function of cytotoxic T cells?

A

Recognise cells infected by intracellular pathogens and induce apoptosis

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5
Q

What is the general function of cytokines?

A

Bind to specific receptors on target cells and initiate cell signalling

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6
Q

What are the three mechanisms by which cytotoxic T cells act?

A

Secrete TNF which bind to TNF receptors

Secrete perforin and granzymes

Fas ligand (TNF homologue) binds to Fas (TNF receptor homologue)

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7
Q

What type of enzyme is essential in apoptosis induction by cytotoxic T cells?

A

Caspase proteases

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8
Q

Where is TCR expressed?

A

On the cell surface of all T cells

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9
Q

Describe the TCR.

A

Formed by 2 polypeptides (either α, β or γ, δ), each with 2 immunoglobulin domains

Membrane distal domains form a single antigen-binding domain

Unique specificity

Binds fragments of antigens presented on MHC proteins

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10
Q

Which TCR is most common?

A

α, β (>90%)

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11
Q

Describe the structure of MHC class II.

A

2 similarly sized polypeptides (α and β), both anchored to cell membrane

β-sheets form a flat base for a groove formed by 2 α-helices = peptide-binding site

(Similar structure to TCR)

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12
Q

Describe the structure of MHC class I.

A

α and β(-microglobulin) chains but only α-chain is anchored to membrane

α-chain is larger and forms the complete peptide-binding domain

β-microglobulin has a single domain and supports the peptide-binding domain

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13
Q

How do helper T cells bind to MHC?

A

Antigen-binding domain of TCR is in contact with antigen and α-helices of MHC class II

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14
Q

Describe the CD4 glycoprotein.

A

Part of TCR complex of helper T cells

4 immunoglobulin-like domains

Binds MHC class II proteins

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15
Q

What is the function of the CD4 glycoprotein?

A

Stronger attachment

Transmission of part of the activating signal to the helper T cell

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16
Q

Describe CD3.

A

Complex of 6 transmembrane proteins surrounding the TCR

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17
Q

What is the function of CD3?

A

Transmits part of the activation signal to helper T cell

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18
Q

Which MHC class do helper T cells bind to?

A

MHC class II

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19
Q

Which MHC class do cytotoxic T cells bind to?

A

MHC class I

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20
Q

Describe the CD8 glycoprotein.

A

Dimer

Each monomer consists of 1 immunoglobulin-like domain on a long stalk

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21
Q

What is the function of CD8?

A

Stronger attachment

Transmission of part of the activating signal to cytotoxic T cell

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22
Q

Which CD glycoproteins are associated with helper T cell receptors?

A

CD4

CD3

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23
Q

Which CD glycoproteins are associated with cytotoxic T cell receptors?

A

CD8

CD3

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24
Q

Which cells express MHC class I?

A

All nucleated cells

25
Q

Which cells express MHC class II?

A

Cells involved in the immune response (dendritic, macrophage, B and T cells)

26
Q

What do MHC class I and II proteins have in common?

A

Highly polymorphic

3 gene loci each on chromosome 6

27
Q

What is a benefit of MHC and TCR binding?

A

Ensures T cells are in close proximity to target cells to allow more precise targeting of soluble factors (eg cytokines)

28
Q

What is antigen processing?

A

Process by which antigens are broken down into peptides which may be bound by MHC proteins and transported to the cell surface

29
Q

What are the peptides presented by MHC class I derived from?

A

Intracellular pathogens that synthesis or release proteins in the cytosol

30
Q

What are the peptides presented by MHC class II derived from?

A

Proteins of extracellular pathogens that are endocytosed by antigen-presenting cells

31
Q

Describe the antigen processing and presentation pathway associated with MHC class I.

A
  1. Proteosomes break down cytosolic proteins into peptides
  2. Peptides taken up into ER by TAP (Transporter associated with Antigen Processing)
  3. In ER, some peptides bind to newly synthesised MHC class I protein
  4. MHC class I/peptide complex transported to cell surface via vesicles
  5. Recognition of non-self antigens by CD8+ cytotoxic T cells triggers apoptosis
32
Q

Describe the antigen processing and presentation pathway associated with MHC class II.

A
  1. Endocytosis of extracellular protein
  2. Digestion in endosomes/lysosomes into peptides
  3. Fusion of endolysosome with ER membrane vesicles containing newly synthesised MHC class II proteins with invariant chain
  4. Proteases digest invariant chain to allow complex formation
  5. Transport of complex to cell surface
  6. Complex recognised by CD4+ helper T cells
33
Q

What are three differences between MHC class I and II processing?

A

MHC class I = normal process of protein turnover which doesn’t discriminate between self or non-self

MHC class II = usually longer peptides formed, MHC class II synthesised with invariant chain

34
Q

What is the function of the invariant chain synthesised with MHC class II proteins?

A

Occupies antigen-binding site so it cannot be occupied by intracellular proteins (prevents autoimmunity)

35
Q

What allows the MHC-peptide binding to be so highly promiscuous?

A

Few residues in peptide are critical for binding (often types of amino acid necessary)

All other positions can vary

36
Q

What length of peptides do MHC class I typically bind to and how many residues actually contribute?

A

8-10 residues long with only 1/2 residues contributing

37
Q

What length of peptides do MHC class II typically bind to and how many residues actually contribute?

A

12-17 residues long with only 2/3 residues contributing

38
Q

What is the different about γ, δ TCRs compared to α, β TCRs?

A

Derived from different gene loci (γ, δ has fewer V segments)

γ, δ TCRs recognise bacterial metabolites or lipids displayed on MHC class I-like receptors

No processing required

39
Q

Where does most T cell activation occur?

A

Lymph nodes

40
Q

What are the three signals required to activate helper T cells?

A

TCR/CD3/CD4 binding to MHC class II/antigen complex

CD28 binding to CD80/86 (costimulatory molecule)

Cytokines secreted from dendritic cells

41
Q

What does TCR/CD3/CD4 binding to MHC class II/antigen complex cause?

A

Activation of protein kinase that phosphorylates CD3 which results in recruitment of more kinases to transmit a signal

42
Q

What does CD28 binding to CD80/86 cause?

A

Induction of IL-2 secretion which acts in an autokine manner to activate T cell

43
Q

What role do cytokines secreted from dendritic cells have in helper T cell activation?

A

Stimulate and control proliferation and differentiation of T cell into effector and memory cells

44
Q

What three signals are required to activate cytotoxic T cells?

A

TCR/CD3/CD8 binding to MHC class I/antigen complex

CD28 binding to CD80/86 (costimulatory molecule)

Helper T cell secretion of IL-2 (likely to have been activated by same APC)

45
Q

How does helper T cells help activate cytotoxic T cells?

A

IL-2 secretion induces proliferation

APC is stimulated to express more costimulatory molecules (eg CD40 which will bind CD154 on Tc cell)

46
Q

What determines the type of helper T cell response?

A

Cytokines secreted by activated dendritic cells/APCs (ultimately by type of pathogen which will activate different receptors on APCs)

47
Q

What three helper T cell responses are possible and what type of pathogen will cause them?

A

Th1 = intracellular pathogens

Th2 = extracellular parasites

Th17 = extracellular pathogens

48
Q

What cytokines will result in a Th1 response?

A

Interferon-γ

IL-12

49
Q

What cytokine will result in a Th2 response?

A

IL-4

50
Q

What cytokines will result in a Th17 response?

A

IL-6

TGF-β

51
Q

Describe how the diversity of the TCR is generated.

A

TCR α-chain = 55V and 61J possible gene segments (on chromosome 14)

TCR β-chain = 52V, 2D and 13J possible gene segments

Recombination of segments required to form functional exons

At each site cut by endonucleases, extra nucleotides are added to the 3’ end in a non-template-directed manner

52
Q

What is the total diversity of TCRs?

A

~10^18 possible combos

53
Q

What does the J segment code for in the TCR α-chain?

A

Most of the C terminal part => most of antigen-binding domain

54
Q

Which gene segments mostly contribute to the C terminal loop of the TCR β-chain?

A

DJ segment

C terminal loop makes most contact with antigen

55
Q

What issues can arise from having such a high diversity of TCRs?

A

TCR may not bind to MHC complex

TCR may bind to self-antigen MHC complexes

56
Q

What are the two processes that give rise to the great TCR diversity?

A

Recombination of gene segments

Nucleotide additions

57
Q

Describe the selection processes of T cells.

A

Positive selection in thymus cortex

  • double positive T cells (express CD8 and CD4) are exposed to cortical thymic epithelial cells and dendritic cells expressing MHC (I and II)
  • those which can bind to MHC receive a survival signal and become single positive cells
  • those which cannot bind = apoptosis (~90% of cells)

Negative selection in thymus medulla

  • exposure to medullary thymic epithelial cells and dendritic cells with MHC/self-antigen complexes
  • those which bind with low affinity survive
  • those binding with high affinity either undergo apoptosis or become Treg cells
58
Q

What happens to T cells after they have been selected in the thymus?

A

Migrate to peripheral tissues to protect against infection

59
Q

What is the general function of Treg cells?

A

Inhibit/downregulate immune responses in an antigen-specific manner

BDS2 PMI (21 decks)

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