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MICR3305 > 7 - B and T Cell Receptors > Flashcards

7 - B and T Cell Receptors Flashcards

1
Q

Structure of B and T cell receptors

A
  • Alpha and beta chains
  • Variable region (antigen binding site, top of receptor)
  • Constant/fc region (effector function, bottom of receptor)
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2
Q

Long chains

A

Heavy chains

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3
Q

Short chains

A

Light chains

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4
Q

B-1 cells

A
  • B-1a and B-1b
  • Arise in foetal liver
  • T independent antigens
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5
Q

B-2 cells

A
  • Marginal zone and follicular
  • Arise in bone marrow
  • T dependent antigens
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6
Q

B cell classes

A
  • B-1 cells
  • B-2 cells
  • Regulatory B cell
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7
Q

What is the first antibody that appears on a developing B cell

A

IgM

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8
Q

Ig expression during B lymphocyte maturation

A
  • Mature B lymphocytes activated by antigens and other stimuli differentiate into plasmablasts and then into antibody secreting plasma cells
  • Process is accompanied by changes in pattern of Ig production
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9
Q

Changes in pattern of Ig production

A
  • Increased production of the secreted form of Ig relative to the membrane form
  • Expression of Ig heavy chain isotypes other than IgM and IgD, by heavy chain isotype (or class) switching
  • Introduction of new amino acid substitutions into the variable domains of the antibody heavy and light chains to create high-affinity antibodies (affinity maturation)
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10
Q

Antibodies/Immunoglobulins (Ig)

A
  • Secreted form of the B cell receptor
  • Consists of 2 heavy chains (H) and 2 light chains (L)
  • Light chain may be κ or ƛ
    (never both)
  • H and L chains include constant (invariant) C
    domains and variable V
    domains
  • Greatest variation in the
    antigen binding domains of H and V chains
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11
Q

HV1, 2, and 3

A

Hypervariability regions in V domains

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12
Q

Antigen-antibody complexes

A
  • An antigen can cross-link two
    antigen-binding sites to create antigen-antibody complexes
  • Possible due to flexible antibody arms
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13
Q

T cell classes

A
  • CD8 cytotoxic T cells
  • CD4 Th1 cells
  • CD4 Th2 cells
  • CD4 Th17 cells
  • Tfh cells
  • CD4 regulatory cells
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14
Q

CD8 cytotoxic T cells

A

Kill virus infected cells (some intracellular bacteria)

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15
Q

CD4 Th1 cells

A
  • Activate infected macrophages
  • Provide help to B cells for antibody production
  • Targets microbes that persist in macrophage vesicles and extracellular bacteria
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16
Q

CD4 Th2 cells

A
  • Provide help to B cells for antibody production, especially switching to IgE
  • Target helminth parasites
17
Q

CD4 Th17 cells

A
  • Enhance neutrophil response
  • Promote barrier integrity (skin, intestine)
  • Target Fungi
18
Q

Tfh cells

A
  • B cell help
  • Isotype switching
  • Antibody production
  • Target all pathogens
19
Q

CD4 regulatory T cells

A

Suppress T cell responses

20
Q

Fab fragment and TCR

A
  • Both disulphide linked heterodimer
  • Each chain contains one Ig C domain and one Ig V domain
21
Q

Ig vs TCR

A

TCR are anchored to cell membrane and are not produced in secreted form

22
Q

How to T cells see antigens

A

Unlike B cells and antibodies which can recognise antigens in their native form, T cells (via their TCR) can only see antigen as short peptides bound to MHC molecules

23
Q

Structure of ⍺β T cell receptor

A
  • The TCR heterodimer is composed of two transmembrane glycoprotein chains, ⍺ and β
  • Each chain includes a variable V region and a constant C region, a stalk,a transmembrane region and
    cytoplasmic domains
24
Q

How do CD8 T cells recognise antigen

A
  • CD8 Cytotoxic T lymphocytes recognise target cells that display peptide fragments of non self proteins bound to MHC class 1 molecules at the cell surface
  • MHC class 1 molecules are expressed by all nucleated cells in the body
  • Peptides from intracellular pathogens, especially viruses, are recognised by CTL and result in the infected cell being killed by apoptosis
25
Q

Class of MHC that CD8 recognises

A

Class 1

26
Q

Class of MHC that CD4 recognises

A

Class 2

27
Q

How do CD4 T cells recognise antigen

A

CD4 T cells recognise peptides resulting from antigen degradation within intracellular vesicles, displayed on the cell surface in the context of MHC class 2 molecules

28
Q

How are CD4 T cell subsets defined

A

On basis of the cytokines they secrete and on their functions

29
Q

MHC Class 1

A
  • MHC encoded HLA-A, -B, -C heavy chain α bound to β2-microglobulin
  • The α chain folds into 3 domains: α1, α2, α3
  • The α1 and α2 domains form the antigen binding groove
  • Peptides (8-10 aa long) are stabilised at both ends of the groove by binding to invariant sites
30
Q

MHC Class 2

A
  • Class 2 molecules (HLA-DP, DQ, DR in humans) heterodimers of α and β chain
  • No β2-microglobulin
  • Peptides are at least 13 aa long
  • Ends are not bound to groove, peptide is held in place by interactions along its length
31
Q

Human MHC genes

A
  • Highly polymorphic
  • Each MHC locus has many alleles (variant genes that occupy the same loci and encode variants of the MHC protein)
  • The expressed MHC molecule determines which peptide antigen the cell can bind and present for surveillance by CD4 and CD8 T cells
32
Q

Allelic variation in MHC molecules

A
  • Occurs at specific sites
  • variation arising from genetic polymorphism is usually in the peptide binding clefts
  • Such variation can alter the specificity of an MHC molecules for a peptide antigen
33
Q

How do CD4 T cells help activate B cells

A

Via germinal centre reaction

34
Q

γδ T cell receptor

A
  • Specialised to bind to certain ligands, including heat shock proteins and non peptide ligands such as mycobacterial lipid antigens
  • May not be restricted by classical MHC class 1 and 2 molecules
  • May bind to free antigen and/or may bind to peptides presented by non classical MHC

MICR3305 (22 decks)

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