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Basic Immunology > Lecture 3 ((4) - Week 2A) > Flashcards

Lecture 3 ((4) - Week 2A) Flashcards

1
Q

Cells of the innate and adaptive immune systems recognize

A

self and non-self in different ways

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2
Q

Cells of the innate immune system

A
  • NK cells
  • manocytes/macrophages
  • dendritic cells
  • granulocytes (eg neutrophils)

• a limited number of common microbial structures can be recognized: PAMPs

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3
Q

Cells of the adaptive immune system

A
  • T cells
  • B cells

• millions+ of antigens recognized

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4
Q

T cells recognize antigen using a

A

T cell receptor (TCR)

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5
Q

Antigen recognized by T cells

A
  • linear (peptide) antigens recognized
  • antigen represented by an antigen presenting cell (APC) - eg dendritic cell, macrophage, B cell
  • very different to antigen recognition by B cells
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6
Q

In T cells, antigens are presented by

A

an antigen presenting cell
• display antigen on surface
• dendritic cell, macrophage, B cell

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7
Q

The APC presents antigen to the T cell using a

A

major histocompatability complex (MHC) molecue

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8
Q

The structure of the T cell receptor

A
  • have 2 chains - α and β chains, or γ and δ
  • variable region out further - has CDR1, CDR2, and CDR3
  • constant region near membrane
  • stalk segment (disulfide bond) followed by a transmembrane region, then a cytoplasmic tail
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9
Q

CDR

A

complementarity-determining regions

• highly variable, make contact with ligand

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10
Q

These structural elements allow the TCR to interact with

A 
the major histocompatability complex 
(MHC) + peptide
V domain:
• TCR binds to MHC (at CDR2)
• TCR binds to antigen (at CDR3)
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11
Q

The T cell receptor comes in 2 forms

A
  • αβ T cell receptor: 90-99% of T cells
  • γδ T cell receptor: 1-10% of T cells
  • structurally similar; different antigen recognition properties
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12
Q

T cells first express the TCR

A

as they develop in the thymus

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13
Q

There are 2 major types of T cells

A
  • CD4+ cells = helper T cells

* CD8+ cells = cytotoxic T cells

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14
Q

The T cell receptor complex includes various CD3 molecules

A
  • αβ TCR binds antigen: MHC but cannot signal to the cell
  • CD3 complex transmits signal
  • CD3 components also required for cell surface expression of αβ chains
  • sequence motifs called ITAMs essential for signalling
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15
Q

ITAM

A

immunoreceptor tyrosine based activation motif

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16
Q

CD3

A

forms complex with T cell receptor
• signal - say which type of antigen
(T cell doesn’t signal, not right cytoplasmic cell)
• CD3 enables T cell receptor to get to cell surface

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17
Q

The TCR complex signals

A

to the cell nucleus
• from CD3 to Lck and Fyn, to ZAP70
–> signal to nucleus
• Lck and Fyn phosphorylate ITAM motifs (ITAM activated) –> recruit ZAP70 (phosphorylated and activated) –> cascade of events
• activation of transcription factors, gene transcription, proliferation and differentiation

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18
Q

The generation of T cell receptors

A

• a gene for each each receptor?
-no - would require more genes than present in the entire genome
• there’s only 4 genes: αβγδ
• instead, gene rearrangement by somatic DNA recombination
(like Ig gene rearrangements in B cells)

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19
Q

TCR gene rearrangement takes place in

A

the thymus
• each chain has genes for variable, joining, and constant regions
• the β also has genes for diversity regions

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20
Q

TCR recombination and the generation of diversity

A

TCRlocus
germline
1. D to J rearrangement
2. V to DJ rearrangement
3. transcription (mRNA)
4. mRNA splicing and translation (TCRβ protein)
• RAG = recombination activating genes encode recombination enzymes
• TCRβ rearranges first, then TCRα (several attempts possible)
• allelic exclusion operates

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21
Q

Somatic mutation

A

does not occur in T cells

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22
Q

Recombination of TCR genes

A

is random
• can generate receptors that recognize MHC + self peptide
• self reactive T cells must be removed or controlled
• junctional diversity
• thymus also makes self-reactive receptors

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23
Q

MHC

A

major histocompatability complex
• the major genetic region that determines compatability of tissues transplanted between individuals
• HLA (man): human leukocyte antigens
• H-2 (mosue)

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24
Q

There are 2 types of MHC

A

MHC class-I and MHC class-II

• both have peptide binding cleft

25
Q

MHC-I presents antigen to

A

cytotoxic T cells (CD8+)

26
Q

MHC-II presents antigen to

A

helper T cells (CD4+)

27
Q

MHC-I chains

A

α2 α1

α3 β2* (microglobulin)

28
Q

MHC-II chains

A

β1 α1

β2 α2

29
Q

CD4+ helper T cells recognize

A

MHC-II + peptide on antigen-presenting cells

30
Q

CD8+ cytotoxic T cells recognize

A

MHC-I + peptide on antigen-presenting cells

31
Q

Peptide binding by MHC Class-I and MHC Class-II

A
  • both have a peptide binding cleft or groove
  • Class I: α2 and α1
  • Class II: β1 and α1
32
Q

Binding of peptide to MHC-I

A

closed off = shorter peptides

33
Q

Binding of peptide to MHC-II

A

longer peptides because ends are open

34
Q

Peptide binding to MHC molecules is promiscuous

A

an MHC molecule can bind many different (but not all) peptides
• therefore, we don’t need a different MHC molecule for every possible peptide

35
Q

Peptide binding to MHC molecules

A

• the fit between amino acid side chains in the peptide and pockets in the grove of the MHC molecule determine binding
(amino acid side chains fit into pocket - but not that specific)

36
Q

MHC molecules with different peptides bind

A

distinct collections of peptides

• different pockets accommodate different repertoire

37
Q

Peptide binding to MHC class I

A
  • peptides 8-10 amino acids (short)
  • bound at each end (peptide bound by H bond)
  • additional anchor residues
  • different MHC class I molecules
  • peptides which bind to 2 different MHC class I molecules
38
Q

Peptide binding to MHC class II

A
  • peptides 13+ (-17) amino acids (longer)
  • not bound at end
  • interactions along peptide with pockets on MHC - anchors less defined
  • common core, different lengths
39
Q

Role of MHC-I

A

to sample intracellular antigen (within cell)
• recognition by CD8 T cells
peptides generated –> groove

40
Q

Role of MHC-II

A

to sample extracellular antigen

• antigen taken up

41
Q

2 properties of MHC genes maximize the repertoire of peptides that can be bound

A

MHC genes are
1. polygenic
2. polymorphic
• in the evolutionary battle with pathogens, these counteract the strong selective pressure in favor of pathogens that mutate to escape peptide binding to MHC

42
Q

Polygenic MHC genes

A

individual has several different MHC-I and MHC-II molecules encoded by genes in the MHC

Phenotype influenced by more than 1 gene

  • MHC-I and MHC-II each make 3 gene products
  • tend to be inherited together as a halotype
43
Q

Polymorphic MHC genes

A

there are multiple variants (alleles) of each gene in the population
• multiple alleles in the population means that most individuals are heterozygotes
• MHC genes are the most polymorphic genes known in the human genome
• estimated 4x10^19 different combinations of human MHC class I and class II genes

44
Q

Polymorphism is a barrier to

A

organ transplantation

• different MHC molecules on the graft are recognized as foreign and tissue rejected due to immune response

45
Q

The polygenic and polymorphic of MHC genes ensures

A

multiple different MHC molecules expressed, increasing the repertoire that can be presented

46
Q

MHC restriction

A

co-recognition of both MHC and peptide
MHC restricts the ability of T cells to recognize antigen
• directly: TCR-MHC interactions
• indirectly: by effecting which peptides bind

47
Q

T cell receptors recognize

A

a combination of antigen peptides

48
Q

For most antigens, T cells must

A

provide “help” to B to cells in order for antibody production to occur
• involves recognition of the antigen by both B and T cells

49
Q

T cell recognition

A

involves recognition of the antigen by both B and T cells
1. B cell binds virus
2. virus particle is internalized and degraded
3. peptides from internal proteins of the virus are presented to the T cell, which activates the B cell
• helper T cell armed by prior stimulation by Ag on DC
• re-encounters same Ag/MHC on B cell
• T cell cytokines and surface molecules aid B cell activation and differentiation
• linked recognition

50
Q

T cells recognize antigen using the

A

T cell receptor (TCR)

51
Q

In each T cell, the TCR consists of

A

2 chains
• αβ or γδ
which are generated in the thymus by chromosomal recombination (–> diversity)
[Somatic DNA recombination]

52
Q

The TCR complex recognizes

A

a combination of antigen + MHC displayed on antigen presenting cells - MHC restriction

53
Q

TCR stimulation by the appropriate

A

MHC + antigen signal
activates signalling pathways that induce gene expression in the cell nucleus
• engage with correct peptide –> cascade of events to behave differently

54
Q

MHC-I presents antigen to

A

CD8+ cytotoxic T cells

55
Q

MHC-II presents antigen to

A

CD4+ helper T cells

56
Q

MHC-I presents

A

intracellular cytosolic antigen

57
Q

MHC-II presents

A

extracellular antigen

58
Q

MHC binds antigen in a

A

peptide binding groove

• this groove allows many different peptides to bind

59
Q

The MHC is

A

polygenic and polymorphic, allowing a broad range of antigens to be presented for T cell recognition

Basic Immunology (15 decks)

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