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human biochemistry > T cell biochemistry > Flashcards

T cell biochemistry Flashcards

1
Q

the immune system cells all start life where

A

life in the bone marrow, receiving signals from stromal cells

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2
Q

describe T cells

A

Mature in the Thymus

Regulatory and Cytotoxic

Can further differentiate depending on specific signals

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3
Q

describe B cells

A

Mature in the Bone Marrow

Produce antibodies

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4
Q

describe NK (natural killer) cells

A

Mature in the Bone Marrow, but also secondary lymphoid tissues

Cytotoxic

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5
Q

describe antibodies

A

Antibodies illicit a strong immune response, coordinating many cells of the immune system, and B-cells can develop an immune memory to help in times of further infection.

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6
Q

name some things antibodies cannot be used to combat effectively.

A

Intracellular pathogens

  • Bacteria and Viruses
  • Tumours
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7
Q

what does the immune system need to work efficiently

A

T cells

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8
Q

explain the T cell receptor

A

Approximately 105 T-Cell receptors on the surface of the T-cell

Consists of 2 polypeptide chains:
- Majority - ⍺β T-cells
- Minority - 𝛾δ T-cells

Each chain has 2 domains, V (Variable) and C (Constant), which are linked by a disulphide bond

Hydrophobic transmembrane domain and a very shot cytoplasmic tail

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9
Q

describe some differences between TCR and fab

A

Antibodies:

Broad sheets of anti-parallel β-sheets

  • Hydrophobic side chains are tightly packed between the sheets and held together with disulphide bridges
  • Alpha helix is towards the back of T cell receptor

C⍺:

Half of the domain, that closest to the β chain, forms a β-sheet

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

Additionally, the interactions between C⍺ and Cβ is assisted by carbohydrates
- Carbohydrate on C⍺ forming hydrogen bonds with the amino acids of Cβ.

CDR loops:

Fairly similar between an antibody and the TCR, some displacement

V⍺ CDR2
- At a right angle compared to the equivalent loop in the equivalent loop in an antibody.

TCRs have a 4th hypervariable region away from the antibody binding site

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10
Q

explain the T-cell receptor gene rearrangement on TCR⍺

A

similar to the Immunoglobulin light chain

V and J segments

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11
Q

explain the T-cell receptor gene rearrangement on TCRβ

A

similar to the immunoglobulin heavy chain

V, D, and J segments

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12
Q

when do genes in T cells rearrange

A

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

do T cell receptors bind antigens directly

A

no

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14
Q

antibodies bind what in the circulation
and make contact with what

A

bind antigen in the circulation, whether that be free flowing or on the surface of the pathogen

Make contact with discontinuous amino acids only brought together when the antigen is in its tertiary structure

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15
Q

what do T cells bind to

A

to an antigen-protein complex

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16
Q

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

what does MHC stand for

A

Major Histocompatibility Complex

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18
Q

how are MHC 1 and MHC 2 similar and different

A

Closely related in overall structure and function, but 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
19
Q

explain MHC 1 structure

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
20
Q

explain MHC 2 structure

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
21
Q

In order to stimulate T-cells, MHCs need to be what

A

able to bind a large variety of peptides

Unlike other peptide-binding receptors such as GPCRs
MHC proteins are unstable when not bound to a peptide
- MHC-I binds peptides 8-10 amino acids in length
- MHC-II can bind peptides of any length

22
Q

MHC-I binds and presents what

A

intracellular peptides that reside in the cytosol

23
Q

Some pathogenic bacteria, and some protozoa, reside inside vacuoles once inside the cell and peptides are presented on what

A

MHC 2

24
Q

Extracellular pathogens are phagocytosed, and peptides are presented on what

A

MHC 2

25
Q

describe cross presentation

A

Some pathogens will not infect phagocytic antigen presenting cells (such as dendritic cells), for example the epithelium

Thus, the antigen presenting cell will express MHC-I presenting peptide antigens from the infected cell

26
Q

name some T cell co receptors

A

CD4 +

CD8+

27
Q

describe the T cell co receptor CD4+

A

T-helper cells

Recognises MHC-II

28
Q

describe the T cell co receptor CD8+

A

Cytotoxic T-cells

Recognises MHC - 1

29
Q

describe T cell co receptors

A

TCR binds directly to the MHC peptide binding cleft

CD4 and CD8 bind to an invariant site away from the peptide binding cleft

30
Q

The TCR⍺β heterodimer, along with either CD4 or CD8 is not sufficient to initiate what

A

activation of the T cell

31
Q

what 2 things are needed for TCR signal transduction

A

CD3 complex

ζ-chain – zeta

32
Q

what is CD3 complex made up of

A

CD3𝛾
CD3δ - delta
CD3ε - epsilon

33
Q

TCR signal transductions signalling is initiated by what

A

initiated by ITAMs in the 𝛾, δ, ε, and ζ chains

  • Immunoreceptor Tyrosine-based Activation Motifs
  • CD3𝛾, δ, and ε all have 1 ITAM
  • ζ chain has 3
34
Q

in TCR signal transduction, Each ITAM has 2 Tyrosine residues
what happens to these

A

Become phosphorylated by tyrosine kinase Lck, which is colocalised with the CD4/CD8 coreceptor, when the receptor binds its ligand (MHC + peptide)

Phosphorylation leads to the recruitment of Zap70

35
Q

what next happens in TCR signal transduction, to Zap70

A

phosphorylates LAT (Linker for Activated T-cells), which leads to the recruitment of PI 3-kinase

36
Q

in TCR signal transduction, what happens after the recruitment of PI 3-kinase

A

the T-cell signal branches into distinct modules, leading to the activation of different transcription factors with different effects

37
Q

during TCR signal transduction different transcription factors with different affects are activated, name these and describe them

A

NFκB – the master inflammatory transcription factor

AP-1 – differentiation, proliferation, and apoptosis

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
38
Q

Derived from the bone marrow, but all the development happens where

A

in the thymus

39
Q

what happens in T cell maturation

A

Similar to B-cell maturation:
- Gene re-arrangement
- Testing of the new receptor
- Release of the new T-cell or - cell death

Round of positive and negative selection
- Dependent on Notch signalling

40
Q

CD4+ T-cell produces different subtypes depending on what

A

the signal

41
Q

what are the subtypes CD4+ T-cell produces

A

Tfh – B-cell formation

Th1 - type 1 response. intracellular bacteria, protozoa, and viruses. autoimmunity

Th2- type 2 response. extracellular helminths and venoms. allergy and asthma

Th17 - type 3 response. extracellular bacteria and fungi. autoimmunity

Treg- immune tolerance. immune regulation

CD4 CTL? - MHC2-dependent. killing

42
Q

what are CD8+ subsets

A

cytotic lymphocytes

  • MHC 1 dependent
  • killing
43
Q

explain CD8 Cytotoxic T-cells

A

Kill cells by inducing cell death by either intrinsic or extrinsic pathways of apoptosis:

  • Extrinsic – binding of Death Receptors
  • Intrinsic – Mitochondrial degradation

Both require Caspase enzymes:

  • Proteases
  • Initiator Caspases
    Promote apoptosis by cleaving and activating other caspases
    Intrinsic = Caspase 9
    Extrinsic = Caspase 8 and 10

Effector Caspases
- Initiate the cellular changes associated with apoptosis
- Both pathways use Caspase 3, 6, and 7

44
Q
A

human biochemistry (10 decks)

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