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

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

(59 cards)

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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

Study These Flashcards
A

MHC class-I and MHC class-II

• both have peptide binding cleft

25
MHC-I presents antigen to
cytotoxic T cells (CD8+)
26
MHC-II presents antigen to
helper T cells (CD4+)
27
MHC-I chains
α2 α1 | α3 β2* (microglobulin)
28
MHC-II chains
β1 α1 | β2 α2
29
CD4+ helper T cells recognize
MHC-II + peptide on antigen-presenting cells
30
CD8+ cytotoxic T cells recognize
MHC-I + peptide on antigen-presenting cells
31
Peptide binding by MHC Class-I and MHC Class-II
* both have a peptide binding cleft or groove * Class I: α2 and α1 * Class II: β1 and α1
32
Binding of peptide to MHC-I
closed off = shorter peptides
33
Binding of peptide to MHC-II
longer peptides because ends are open
34
Peptide binding to MHC molecules is promiscuous
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
Peptide binding to MHC molecules
• 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
MHC molecules with different peptides bind
distinct collections of peptides | • different pockets accommodate different repertoire
37
Peptide binding to MHC class I
* 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
Peptide binding to MHC class II
* 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
Role of MHC-I
to sample intracellular antigen (within cell) • recognition by CD8 T cells peptides generated --> groove
40
Role of MHC-II
to sample extracellular antigen | • antigen taken up
41
2 properties of MHC genes maximize the repertoire of peptides that can be bound
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
Polygenic MHC genes
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
Polymorphic MHC genes
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
Polymorphism is a barrier to
organ transplantation | • different MHC molecules on the graft are recognized as foreign and tissue rejected due to immune response
45
The polygenic and polymorphic of MHC genes ensures
multiple different MHC molecules expressed, increasing the repertoire that can be presented
46
MHC restriction
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
T cell receptors recognize
a combination of antigen peptides
48
For most antigens, T cells must
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
T cell recognition
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
T cells recognize antigen using the
T cell receptor (TCR)
51
In each T cell, the TCR consists of
2 chains • αβ or γδ which are generated in the thymus by chromosomal recombination (--> diversity) [Somatic DNA recombination]
52
The TCR complex recognizes
a combination of antigen + MHC displayed on antigen presenting cells - MHC restriction
53
TCR stimulation by the appropriate
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
MHC-I presents antigen to
CD8+ cytotoxic T cells
55
MHC-II presents antigen to
CD4+ helper T cells
56
MHC-I presents
intracellular cytosolic antigen
57
MHC-II presents
extracellular antigen
58
MHC binds antigen in a
peptide binding groove | • this groove allows many different peptides to bind
59
The MHC is
polygenic and polymorphic, allowing a broad range of antigens to be presented for T cell recognition

Basic Immunology (15 decks)

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