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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Downsides of antibodies:

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

A

The T-cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

T-cell receptor gene rearrangement:

TCR⍺ is similar to what chain? and why?

A
  • The Immunoglobulin light chain
  • V and J segments
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

MHC-I and MHC-II:

What is MHC?

A

MHC= Major histocompatibility complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
MHC-I and MHC-II: Extracellular pathogens go through what process? and where are peptides then presented?
- Extracellular pathogens are phagocytosed - Peptides are presented on MHC-II
26
MHC-I and MHC-II: What is cross presentation?
- 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
T-cell Co-receptors: What are the 2 T-cell co receptors and what are their functions?
1. CD4+: - T-helper cells - Recognises MHC-II 2. CD8+ - Cytotoxic T-cells - Recognises MHC-I
28
T-cell Co-receptors: How do co-receptors work?
- TCR binds directly to the MHC peptide binding cleft - CD4 and CD8 bind to an invariant site away from the peptide binding cleft
29
TCR signal transduction: Why is the CD3 complex needed and what does it consist of?
- 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
TCR signal transduction: What is signalling initiated by in this process?
- Signalling is initiated by ITAMs in the 𝛾, δ, ε, and ζ chains - ITAMs = Immunoreceptor Tyrosine-based Activation Motifs
31
How many ITAMs does each of the following have? 1.CD3𝛾 2. δ 3. ε 4. ζ chain
1.CD3𝛾 =1 2. δ =1 3. ε =1 4. ζ chain =3
32
TCR signal transduction: What does each ITAM have?
- Each ITAM has 2 Tyrosine residues
33
TCR signal transduction: What does the phosphorylation of the tyrosine residues lead to?
- Phosphorylation leads to the recruitment of Zap70
34
TCR signal transduction: Zap70 phosphorylates LAT (Linker for Activated T-cells). What does this then lead to?
- Leads to the recruitment of PI 3-kinase
35
TCR signal transduction: After Zap70 phosphorylates LAT, What happens from here?
- From here the T-cell signal branches into distinct modules - leading to the activation of different transcription factors with different effects
36
TCR signal transduction: What are the effects of the following transcription factors? 1. NFκB 2. AP-1 3. NFAT
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
T-cell maturation: Where are T-cells derived from? and where does all of the development of them happen?
- Derived from the bone marrow - All the development happens in the thymus
38
T-cell maturation: What are the similarities of T and B cell maturation?
- Gene re-arrangement - Testing of the new receptor - Release of the new T-cell or cell death
39
T-cell maturation: There is a round of positive and negative selection, what is this dependent on?
Dependent on Notch signalling
40
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)
1. Tfh 2. Th1 3. Th2 4. Th17 5. Treg 6. CD4 CTL? (Unclear if this actually exists yet)
41
T-Cell subsets: What is the function of Tfh?
Tfh= B-cell formation
42
T-Cell subsets: What is the function of Th1?
Th1: - Type 1 response - Autoimmunity - Intracellular bacteria, protozoa and viruses
43
T-Cell subsets: What is the function of Th2?
Th2: - Type 2 response - Allergy and asthma - Extracellular helminths and venoms
44
T-Cell subsets: What is the function of Th17?
Th17: - Type 3 response - Autoimmunity - Extracellular bacteria and fungi
45
T-Cell subsets: What is the function of Treg?
Treg: - Immune tolerance - Immune regulation
46
T-Cell subsets: What is the suggested function of CD4 CTL?
CD4 CTL: - MHC II- dependent killing
47
CD8 Cytotoxic T-cells: How do they kill cells?
- By inducing cell death by either: 1. Intrinsic pathway of apoptosis 2. Extrinsic pathway of apoptosis
48
CD8 Cytotoxic T-cells: What do both intrinsic and extrinsic pathways of apoptosis require?
Both require capase enzymes: - Proteases - Initiator capases - Effector capases
49
CD8 Cytotoxic T-cells: Explain how initiator and effector capases work.
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
CD8 Cytotoxic T-cells: Why is cytochrome C important?
Important for electron transport chain