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YEAR 2 HUMAN BIOCHEMISTRY > T-Cell biochemistry > Flashcards

T-Cell biochemistry Flashcards

1
Q

Downsides of antibodies:

There are things that antibodies cannot be used to combat effectively, what are these things?

A
  • Intracellular pathogens
  • Bacteria and Viruses
  • Tumours
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2
Q

Downsides of antibodies:

As antibodies cannot be used to combat everything, what else does the immune system need?

A

The T-cell

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3
Q

The T-cell receptor (TCR):

Approximately how many T-Cell receptors are on the surface of the the T-Cell?

A

10^5

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4
Q

The T-cell receptor (TCR):

What does the TCR consist of?

A
  • 2 polypeptide chains
  • Majority - ⍺β T-cells
  • Minority - 𝛾δ T-cells
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5
Q

Differences between the TCR and Fab:

C⍺:
Half of the domain, what does that closest to the β chain form?

A
  • Forms a β-sheet
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6
Q

Differences between the TCR and Fab:

C⍺:
What is the other half made up of?

A
  • The other half is made up of loosely packed strand and a short stretch of ⍺-helix
  • Held to one of the strands of the β-domain to this helix
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7
Q

Differences between the TCR and Fab:

What are the interactions between C⍺ and Cβ assisted by?

A
  • Carbohydrates
  • Carbohydrate on C⍺ forming hydrogen bonds with the amino acids of Cβ.
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8
Q

Differences between the TCR and Fab:

CDR loops: what are they fairly similar to?

A

Fairly similar between an antibody and the TCR, some displacement

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9
Q

Differences between the TCR and Fab:

What do TCRs have a 4th of? and where is it found?

A
  • TCRs have a 4th hypervariable region
  • Away from the antibody binding site
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10
Q

T-cell receptor gene rearrangement:

TCR⍺ is similar to what chain? and why?

A
  • The Immunoglobulin light chain
  • V and J segments
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11
Q

T-cell receptor gene rearrangement:

TCRβ is similar to what chain? and why?

A
  • The immunoglobulin heavy chain
  • V, D, and J segments
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12
Q

T-cell receptor gene rearrangement:

When do the genes rearrange and where does the process happen?
What is this process similar to?

A
  • The genes rearrange during T-cell development
  • In the thymus
  • In a process similar to the Germinal Centre Reaction for B-cells
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13
Q

T-cell Receptors don’t bind antigen directly:

Where do antibodies bind antigen?

A
  • Antibodies bind antigen in the circulation
  • Whether that be free flowing or on the surface of the pathogen
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14
Q

T-cell Receptors don’t bind antigen directly:

What do T cells bind to?

A
  • T-cell bind to an antigen-protein complex
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15
Q

MHC-I and MHC-II:

What is MHC?

A

MHC= Major histocompatibility complex

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16
Q

T-cell Receptors don’t bind antigen directly:

What is an antigen-protein complex?

A
  • Short, continuous amino acid sequences from an unfolded protein

-Presented as part of a protein complex on the surface of an antigen presenting cell

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17
Q

MHC-I and MHC-II:

The 2 are closely related in overall structure and function, but what do they differ in?

A
  • Differ in their protein subunits
  • 2 paired domains nearest the membrane resemble an immunoglobulin
  • 2 domains furthest from the membrane produce a peptide-binding cleft
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18
Q

MHC-I and MHC-II:

What does MHC-I consist of?

A
  • 2 Polypeptide chains
  • The ⍺-chain, which makes up 3 domains of the protein and crosses the membrane and forms the entire peptide binding cleft
  • Β2-microglobulin associates with the ⍺3 domain
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19
Q

MHC-I and MHC-II:

What does MHC-II consist of?

A
  • 2 polypeptide chains
  • Both the ⍺ and the β chain cross the membrane
  • The peptide binding cleft is made up of both the ⍺ and the β chain
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20
Q

MHC-I and MHC-II:

What do MHCs need to be able to do in order to stimulate T-Cells?

A
  • MHCs need to be able to bind a large variety of peptides
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21
Q

MHC-I and MHC-II:

When are MHC proteins unstable?

A
  • MHC proteins are unstable when not bound to a peptide
22
Q

MHC-I and MHC-II:

What length of amino acids to MHC-I and MHC-II bind peptides to?

A
  • MHC-I binds peptides 8-10 amino acids in length
  • MHC-II can bind peptides of any length
23
Q

MHC-I and MHC-II:

MHC-I binds and presents intracellular peptides that reside where?

A
  • In the cytosol
24
Q

MHC-I and MHC-II:

Where do some pathogenic bacteria and some protozoa reside?

A
  • Reside inside vacuoles once inside the cell and peptides are presented on MHC-II
25
Q

MHC-I and MHC-II:

Extracellular pathogens go through what process? and where are peptides then presented?

A
  • Extracellular pathogens are phagocytosed
  • Peptides are presented on MHC-II
26
Q

MHC-I and MHC-II:

What is cross presentation?

A
  • Some pathogens will not infect phagocytic antigen presenting cells (such as dendritic cells). eg the epithelium
  • So the antigen presenting cell will express MHC-I presenting peptide antigens from the infected cell
27
Q

T-cell Co-receptors:

What are the 2 T-cell co receptors and what are their functions?

A
  1. CD4+:
    - T-helper cells
    - Recognises MHC-II
  2. CD8+
    - Cytotoxic T-cells
    - Recognises MHC-I
28
Q

T-cell Co-receptors:

How do co-receptors work?

A
  • TCR binds directly to the MHC peptide binding cleft
  • CD4 and CD8 bind to an invariant site away from the peptide binding cleft
29
Q

TCR signal transduction:

Why is the CD3 complex needed and what does it consist of?

A
  • Needed as the TCR⍺β heterodimer, along with either CD4 or CD8 is not sufficient to initiate activation of the T-cell.

CD3 complex:
CD3𝛾
CD3δ
CD3ε

30
Q

TCR signal transduction:

What is signalling initiated by in this process?

A
  • Signalling is initiated by ITAMs in the 𝛾, δ, ε, and ζ chains
  • ITAMs = Immunoreceptor Tyrosine-based Activation Motifs
31
Q

How many ITAMs does each of the following have?

1.CD3𝛾
2. δ
3. ε
4. ζ chain

A

1.CD3𝛾 =1
2. δ =1
3. ε =1
4. ζ chain =3

32
Q

TCR signal transduction:

What does each ITAM have?

A
  • Each ITAM has 2 Tyrosine residues
33
Q

TCR signal transduction:

What does the phosphorylation of the tyrosine residues lead to?

A
  • Phosphorylation leads to the recruitment of Zap70
34
Q

TCR signal transduction:

Zap70 phosphorylates LAT (Linker for Activated T-cells). What does this then lead to?

A
  • Leads to the recruitment of PI 3-kinase
35
Q

TCR signal transduction:

After Zap70 phosphorylates LAT, What happens from here?

A
  • From here the T-cell signal branches into distinct modules
  • leading to the activation of different transcription factors with different effects
36
Q

TCR signal transduction:

What are the effects of the following transcription factors?

  1. NFκB
  2. AP-1
  3. NFAT
A
  1. NFκB: the master inflammatory transcription factor
  2. AP-1: differentiation, proliferation, and apoptosis
  3. NFAT:
    - Requires Calcium influx
    - Family of 5 proteins differentially expressed in different tissues
    - For T-cells, NFAT is important for activation and the production of specific signalling molecules
37
Q

T-cell maturation:

Where are T-cells derived from? and where does all of the development of them happen?

A
  • Derived from the bone marrow
  • All the development happens in the thymus
38
Q

T-cell maturation:

What are the similarities of T and B cell maturation?

A
  • Gene re-arrangement
  • Testing of the new receptor
  • Release of the new T-cell or cell death
39
Q

T-cell maturation:

There is a round of positive and negative selection, what is this dependent on?

A

Dependent on Notch signalling

40
Q

T-Cell subsets:

CD4+ T-cell produces different subtypes depending on the signal from other parts of the immune system, What are they? (6 answers)

A
  1. Tfh
  2. Th1
  3. Th2
  4. Th17
  5. Treg
  6. CD4 CTL? (Unclear if this actually exists yet)
41
Q

T-Cell subsets:

What is the function of Tfh?

A

Tfh= B-cell formation

42
Q

T-Cell subsets:

What is the function of Th1?

A

Th1:
- Type 1 response
- Autoimmunity
- Intracellular bacteria, protozoa and viruses

43
Q

T-Cell subsets:

What is the function of Th2?

A

Th2:
- Type 2 response
- Allergy and asthma
- Extracellular helminths and venoms

44
Q

T-Cell subsets:

What is the function of Th17?

A

Th17:
- Type 3 response
- Autoimmunity
- Extracellular bacteria and fungi

45
Q

T-Cell subsets:

What is the function of Treg?

A

Treg:
- Immune tolerance
- Immune regulation

46
Q

T-Cell subsets:

What is the suggested function of CD4 CTL?

A

CD4 CTL:
- MHC II- dependent killing

47
Q

CD8 Cytotoxic T-cells:

How do they kill cells?

A
  • By inducing cell death by either:
  1. Intrinsic pathway of apoptosis
  2. Extrinsic pathway of apoptosis
48
Q

CD8 Cytotoxic T-cells:

What do both intrinsic and extrinsic pathways of apoptosis require?

A

Both require capase enzymes:

  • Proteases
  • Initiator capases
  • Effector capases
49
Q

CD8 Cytotoxic T-cells:

Explain how initiator and effector capases work.

A
  1. Initiator capases:
    - Promote apoptosis by cleaving and activating other caspases
    - Intrinsic = Caspase 9
    - Extrinsic = Caspase 8 and 10
  2. Effector Caspases:
    - Initiate the cellular changes associated with apoptosis
    - Both pathways use Caspase 3, 6, and 7
50
Q

CD8 Cytotoxic T-cells:

Why is cytochrome C important?

A

Important for electron transport chain

YEAR 2 HUMAN BIOCHEMISTRY (12 decks)

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