CSIM 1.23 T-Cells 1 Flashcards

1
Q

How are T cells distinguished from other lymphocytes?

Where do these mature?

A

CD3 (cluster of differentiation 3) - Anything that is a CD3 positive cell is a T cell

These mature in the thymus

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2
Q

What co-receptor protein is seen on the surface of T-helper cells?

What does this cell interact with?

A

CD4

MHC class II

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3
Q

What are the T-helper (CD4+) cell responses when induced by a professional antigen-presenting cell?

A

Th1 Reaction
• Neutralises intracellular infections by activating macrophages
• IL-2, IFNƔ

Th2 Reaction
• Helps to activate B cells
• IL-4, IL-5

Th17
• Activates neutrophils to clear extracellular bacteria and fungi
• IL-17

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4
Q

What co-receptor protein is seen on the surface of T-cyototoxic cells?

What does this cell interact with?

A

CD8

MHC class I

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5
Q

What proteins are found in T-regulatory cells?

A
  • CD4 on cell surface

* FOXP3+ intracellularly

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6
Q

What are the roles of T-regulatory cells?

A

‘Policemen of the adaptive immune response’
• Helps control the immune response after initial activation ‘calms down’ activity
• Prevents auto-reactive T cells from causing damage

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7
Q

What is the role of T-cytotoxic cells?

A

Kills infected cells by apoptosis

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8
Q

How do B cell receptors and T cell receptors differ, in terms of the protein chains that make them up?

A
B cell:
  •  Bivalent (i.e. 2 of each chain)
  •  Identical to antibodies and can be secreted
  •  Heavy and light chain
  •  Light = V and J segments
  •  Heavy = V, D and J segments
T cell:
  •  Monovalent
  •  Membrane-bound and never secreted
  •  α & β chains 
  •  α = V and J segments
  •  β = V, D and J segments
  •  IMG 57
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9
Q

How does the recombination of the antigen-catching (variable) region of T and B cell receptors differ?

A

It does not differ - exactly the same process

( •  Junctional diversity/imprecision
  •  N regions (random nucleotides)
  •  RSS signal sites
  •  RAG proteins
  •  Etc.)
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10
Q

How does T and B cell receptor maturation differ?

Why is this?

A
  • There is no somatic hypermutation in T cells
    • There is no T cell class switching, constant region stays the same

T cells are the instigators of immune responses, and thus ‘orchestrate’ immunity. Thus, they cannot be allowed to mutate, as doing so may lead to autoimmunity.

(NB: Genes used to make the initial T cell receptor will never have autoimmunity, as this would produce a survival disadvantage)

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11
Q

Where is most diversity found on the T cell receptor?

A

Complementarity determining region (CDR) 3

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12
Q

What other membrane-bound protein is associated with T cell receptors to allow signal transduction?

What is found on their cytoplasmic domain? What happens to these when an antigen binds to the T cell receptor?

A

CD3 (cluster of differentiation 3)

Immunoreceptor tyrosine-based activation motifs (ITAMs).
• When TCRs bind to an antigen, they begin to cluster on the cell surface.
• This causes phosphorylation of associated ITAMs by kinase enzymes.
• This phosphorylation initates a cascade of downstream signalling to the nucleus
• Transcription factors are induced
• This leads to cytokine secretion, T cell proliferation, activation and differentiation.

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13
Q

What do the co-receptors CD4 and CD8 do?

A

They help to bind to MHC molecules on antigen-presenting cells by stabilising the interaction between TCR and MHC

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14
Q

What is expressed within an MHC molecule?

A

An antigen from an invading pathogen

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15
Q

Describe cytokine receptors and how they work when bound to by cytokines

A
  • Membrane bound receptors consisting of two separate chains
    • On the cytoplasmic domain lyes Janus kinases (JAKs)
    • These dimerise when cytokines bind, activating each other
    • This causes phosphorylation of the receptor
    • Transcription factors (STAT) bind to the phosphorylated receptors and are in turn phosphorylated by JAKs
    • Phosphorylated STATs dimerise and move to the nucleus to initiate gene transcription

IMG 58

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16
Q

Interleukins are examples of what?

A

Cytokines

17
Q

What is major histocompatibility complex (MHC)?

Which chromosome is MHC encoded on? What is the name given to the genes which make up this information?

A

A membrane glycoprotein which displays peptide antigen to T cells

Chromosome 6 - the Human Leukocyte Antigen (HLA) genes

18
Q

Describe the structure of MHC I molecules.

Which T cells interact with this molecule?

A

Contains two polypeptide chains: α and β.
• α = heavy chain, comprised of α1, α2 and α3
• β = microglobulin which stabilises
Cleft for antigen presentation is formed between α1 and α2 chains (IMG 59)

T-cytotoxic cells
• Kills infected cells by apoptosis

19
Q

Where is MHC I expressed?

A

Any cell with a nucleus (including APCs, leukocytes and thymic epithelial cells)

20
Q

Where is MHC II expressed?

A
Predominantly cells of the immune response:
  •  ACTIVATED T cells
  •  B cells
  •  APCs
  •  Thymic epithelial cells
21
Q

Why do all nucleated cells express MHC class I?

A

Because this is the MHC class that T-cytotoxic cells are specific for, and thus by expressing this protein, somatic cells are able to express antigen from viruses which may have invaded the cell, thus signalling for their destruction

22
Q

Why does it not matter if a non-nucleated cell infected by viruses does not express MHC I for self-destruction?

A

The lack of nucleus renders the cell useless to the virus anyway, and the pathology cannot continue

23
Q

How large is the antigen that can fit into MHC grooves?

A

MHC I = 8-10 amino acids

MHC II = 13-17 amino acids

24
Q

Describe the structure of MHC II molecules.

Which T cells interact with this molecule?

A

Contains two polypeptide chains: α and β.
• α is comprised of α1 and α2
• β is comprised of β1 and β2
Cleft for antigen presentation is formed between α1 and β1 chains (IMG 60). This cleft is larger than in MHC I, and so can accommodate slightly longer antigens.

T helper cells -
• Clears intracellular infections by activating macrophages (Th1)
• Helps activate B cells (Th2)
• Activates neutrophils to clear extracellular bacteria and fungi (Th17)