7 Anitgen recognition by T cells Flashcards

1
Q

what are T cells

A

WBC

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2
Q

what do T cells do

A

play a central role in cell-mediated immunity

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3
Q

how are lymphocytes distinguished

A

can be distinguished from other lymphocytes (B cells), by the presence of a T-cell receptor (TCR) on the cell surface

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4
Q

what does a T cell receptor look like

A

very similar to antibody molecule

T cell receptor structure almost identical to one arm of antibody, and always transmembrane

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5
Q

what do T cells recognise

A

recognise epitopes presented by Antigen Presenting Cells (APC) bearing an MHC molecule, but cannot recognise the peptide alone

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6
Q

what do T cell require

A

requires breakdown of antigens

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7
Q

what do immunoglobulins

A

recognises epitopes on molecules in the blood or lymph or on surface of a pathogen

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8
Q

what is TCR for

A

ONLY for antigen recognition - then sends signal to T-cell

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9
Q

what type of molecule is immunoglobulin

A

effector molecule

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10
Q

what is MHC

A

antigen recognition molecule

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11
Q

what does MHC encode

A

Large number of genes which encode class I and class II molecules (called antigen presenting molecules) + associated molecules

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12
Q

what are MHC evolved for

A

for antigen presentation to T-cells

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13
Q

what does MHC class 1 present to

A

CD8+ cytotoxic cells

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14
Q

what does MHC class 2 present to

A

CD4+ helper cells

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15
Q

what are cytotoxic cells function

A

kill virally infected cells

- MHC is on every cell of our body (as every cell could be infected by a virus)

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16
Q

MHC class 1 structure

A

Only 1 alpha chain, with transmembrane region (3 domains)
Peptide binding cleft is part of that alpha chain
Beta 2 microglobulin is a separate molecule which stabilizes structure

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17
Q

MHC class 2 structure

A

Difference is that there are 2 molecules that form cleft

- Beta peptide and an alpha peptide

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18
Q

how do T cells recognise peptides

A

T-Cell receptor binds to peptides when they are presented on the surface of the Antigen Presenting Cell – monospecific

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19
Q

what molecules are monospecific

A

T cells

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20
Q

what molecules are polyspecific

A

MHC

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21
Q

what is polyspecific

A

able to have many peptides bind, can present many peptides in there

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22
Q

what are the classes of MHC class 1

A

3 class I α (A,B and C)

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23
Q

what are the pairs of MHC class 2

A

3 pairs of Class II α and β (DR, DP, and DQ) but can end up with 4 class II groups (in DR can have alpha was beta I or alpha with beta II)

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24
Q

what is polygenic

A

there are several different genes for class I and II

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25
Q

what is polymorphic

A

many alleles for each gene-one of the most polymorphic genes known
MANY peptides can be presented to T-cell

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26
Q

how many of each MHC class does an individual present

A

Each individual will present 3 sets of class I molecules and 4 class II

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27
Q

which MHC are polymorphic

A

All MHC products polymorphic except DR-α-reason unknown

28
Q

what will a typical human express - MHC

A

6 different Class I molecules
8 different Class II
For class II α and β chains can combine from different chromosomes

29
Q

what is gene conversion

A

misalignment in meiosis means copied from a different allele

30
Q

what is gene recombination

A

Exchange of DNA segments from different chromosomes

31
Q

what is the effects of polymorphism

A

Variability of peptide expression-allows many thousands of sequences to be presented
Rare that a protein has no peptide that can be bound by MHC
BOTH peptide MHC complex is recognised by TCR

32
Q

where is the variation between MHC allotypes concentrated

A
  • peptide binding groove where they affect peptide recognition
  • alpha helices forming walls where affect TCR recognition
33
Q

peptide specificity

A

Alleles of MHC confer some specificity on the peptide bound

34
Q

where is peptide specificity

A

2-3 residues that form the ANCHOR sequence

35
Q

length of class 1

A

only 8-10aa long

36
Q

length of class 2

A

variable length

37
Q

Class I and II present Ag to different cell types

A

This is achieved by molecular interactions between the CD4 and CD8 glycoproteins and their respective MHC molecules

38
Q

what are MHC class 1 and 2 known as

A

coreceptors

39
Q

what do CD4 and CD8 do

A
  • Stabilise/strengthen TCR/MHC interaction

- Transduce signal to T cell

40
Q

affinity of TCR

A

Affinity of TCR is weak-needs other interactions to strengthen binding

41
Q

cytokine effect on MHC expression

A

Cytokines increase the expression of MHC molecules-particularly IFN gamma

42
Q

MHC class 1 expression meaning

A

Class 1 indicates cell is infected by a pathogen so any nucleated cell can express it, make lots of MHC = to be killed

43
Q

MHC class 2 expression meaning

A

Class II presents peptides to T helper cells so tends to be expressed by professional APCs-macrophages, dendritic cells and B cells

44
Q

How do Peptides get into MHC class 1 molecules

A

Class I binds molecules come from intracellular viruses and bacteria

45
Q

How do Peptides get into MHC class 2 molecules

A

Class II can come from intracellular pathogens OR from an extra-cellular source

46
Q

what do MHC have to have when no infection

A

MHC molecules-HAVE to have a peptide bound in absence of infection-may be self

47
Q

what is the cell divided into 2 compartments

A

1 Nucleus and cytosol – intracellular

2 Vesicular system (secretory part) -ER, golgi, endocytic vesicles

48
Q

what is the cell in contact with

A

extracellular fluid

49
Q

what expresses peptides

A
  • Class I are endogenous-intracellular

- Class II exogenous-extracellular

50
Q

where are class 1 degraded

A

cytocol

51
Q

where are class 2 degraded

A

endocytic vesicles

52
Q

mononuclear phagocytes and antigen presentation

A

phagocytosis, present fragment

53
Q

B cell and antigen presentation

A

B cells brought through surface Ig

54
Q

dendritic cells and antigen presentation

A

brought through by pinocytosis

55
Q

Class II and extracellular molecule movement

A

Class II translocated to ER on way to surface

56
Q

what is done to prevent premature binding of peptides and effect

A

To prevent premature binding of other peptides the invariant chain binds (also on MHC)
also helps MHC get to the low pH endosome where proteins are degraded
MHC and endosome fuse, invariant chain cleaved and replaced by peptide

57
Q

why is HLA DM important

A

needed for T cell activation

58
Q

what is required for MHC class 1

A

Intracellular peptides require processing

59
Q

where are the antigen processing genes for class 1

A

in the MHC

60
Q

what is located in the MHC locus

A

LMP

TAP

61
Q

what forms a proteosome

A

two LMP units

62
Q

what does the proteosome do

A

continuously degrades proteins to peptides-from the cytosol including those from pathogens

63
Q

what is proteosome expression induced by

A

IFN

64
Q

what do TAP 1 and 2 form

A

complex that selects the peptides that can be transported into the ER

65
Q

where are peptides made

A

cytosol

66
Q

where are peptides transported

A

ER