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Immunology > MHC, Antigen Presentation & T - cell activation > Flashcards

MHC, Antigen Presentation & T - cell activation Flashcards

1
Q

Organization & Inheritance of MHC

What can Class 1 MHC be found?
And which cell are they presenting antigen to?

A

Nearly all nucleated cells

Tc cells

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2
Q

Organization & Inheritance of MHC

Where can Class 2 MHC be found?
And what cells are they presenting antigen to?

A

APC ( Antigen - presenting cells )
e.g. Macrophages, dendritic cells & B cells

Th cells

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3
Q

What is MHC referred to in humans and mice?

A

Human
-> HLA complex ( human leukocyte antigen )

Mice
-> H-2 complex

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4
Q

Organization & Inheritance of MHC

Can a mouse with MHC haplotype of b/b donate skin to its k/k parent?
Can the same mouse donate skin to its b/b parent?

Can a mouse with MHC haplotype of b/k donate skin to its k/k, b/b parents?

A

No
Yes

No

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5
Q

MHC molecules / distribution & interaction with peptide

Which of the following antigen will interacts with MHC?

Peptide
Polypeptide
Protein
Glycoprotein

A

Peptide

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6
Q

MHC molecules / distribution & interaction with peptide

What are the 2 components that make up MHC - 1 distal domain?

A

Alpha 1 & Alpha 2

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7
Q

MHC molecules / distribution & interaction with peptide

What are the 2 components that make up MHC - 1 proximal domains?

A

alpha 3 & beta 2 - microglobulin

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8
Q

MHC molecules / distribution & interaction with peptide

Is alpha 1, 2 ,3 part of the same chain?

A

Yes

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9
Q

What is the meaning of polymorphic?
Which parts of MHC - 1 are polymorphic?

A

Polymorphic :
Diverse within a population since your parents determines your allele
It adds diversity to a population

Alpha chain is polymorphic

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10
Q

MHC molecules / distribution & interaction with peptide

Where is the peptide - binding cleft located in MHC 1?
Peptide - binding cleft will bind to peptide with how many a.a.?

A

Between alpha 1 & alpha 2
8 - 10 a.a.

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11
Q

MHC molecules / distribution & interaction with peptide

Is beta 2 - microglobulin encoded by a MHC gene ?

A

Nope

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12
Q

MHC molecules / distribution & interaction with peptide

What is the 2 components that make up the MHC - 2 distal domains?

A

Alpha 1 & Beta 1

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13
Q

MHC molecules / distribution & interaction with peptide

What is the 2 components that make up the MHC - 2 proximal parts?

A

Alpha 2 & Beta 2

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14
Q

MHC molecules / distribution & interaction with peptide

Where is the peptide - binding site located in MHC - 2?
Peptide - binding site will bind to peptide with how many a.a.?

A

Between alpha 1 & beta 1
13 - 18 a.a.

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15
Q

MHC molecules / distribution & interaction with peptide

Which superfamily is MHC - 1 / 2 classified in?

A

Ig superfamily

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16
Q

MHC molecules / distribution & interaction with peptide

Which part of MHC - 2 is polymorphic?

A

alpha 1 & beta 1

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17
Q

MHC molecules / distribution & interaction with peptide

Why is there no genetic rearrangement in production of MHC compared to antibodies production in B cell?

A

Polymorphic

  • MHC varies between individual
    -> But one individual produces only one kind of MHC
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18
Q

MHC molecules / distribution & interaction with peptide

How do you calculate the MHC - 1 diversity for an individual?

A

Since MHC - 1 is solely dependent on alpha chain

Mother MHC - 1 alleles + Father MHC - 1 alleles

E.g.
Mother MHC - 1 alleles : K^k / D^k / L^k
Father MHC - 1 alleles : K^d / D^d / L^d

Kid : Mother + Father = K^k / D^k / L^k / K^d / D^d / L^d

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19
Q

MHC molecules / distribution & interaction with peptide

How do you calculate MHC - 2 diversity for an individual?

A

Since MHC - 2 diversity depends on an alpha chain & a beta chain

( Mother MHC - 2 alleles + Father MHC - 2 alleles ) x2

E.g.
Mother MHC - 2 alleles : IA a^k b^k / IE a^k b^k
Father MHC - 2 alleles : IA a^d b^d / IE a^k b^d

Kid : ( Mother + Father ) x2
-> IA a^k b^k / IA a^d b^d / IA a^k b^d / IA a^d b^k
-> IE a^k b^k / IE a^d b^d / IE a^k b^d / IE a^d b^k

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20
Q

MHC molecules / distribution & interaction with peptide

Which cell has the highest level of MHC - 1?

A

Lymphocytes

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21
Q

MHC molecules / distribution & interaction with peptide

Which is anchor residues and the purpose of it?
Which numbers of a.a. are anchor residues?
Which number of a.a. has the highest affinity?

A

a.a. that are complementary with binding cleft
-> creates a bulge
that looks like this -../.

Anchor residues : 2, 3 ,9
9 ( nomameric peptides ) bind to MHC-1 100-1000 fold higher affinity

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22
Q

MHC molecules / distribution & interaction with peptide

Where does MHC - 1 molecules bind peptides come from?

A

Endogenous intracellular protein
-> digest in cytosol

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23
Q

MHC molecules / distribution & interaction with peptide

Where does MHC - 2 molecules bind peptide come from?

A

Exogenous protein
-> Degraded within endocytic processing pathway

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24
Q

MHC molecules / distribution & interaction with peptide

Does both MHC - 1 & 2 bind peptide have anchor residues?

A

Only MHC - 1 bind peptide anchor residues

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25
Q

Self - MHC restriction of T cell

Can Tc cells kill target cells with different haplotype of MHC - 1?

A

NOPE

26
Q

Self - MHC restriction of T cell

What does“ Self MHC, Foreign peptide “ mean?

A

TCR will only bind with cells with self MHC
TCR will only bind with non self peptide

27
Q

Antigen - presenting cells & presentation pathways

What is antigen processing & antigen presentation?

A

Antigen processing :
-> Metabolic process
- -> Degrade protein antigen into peptides

Antigen presentation :
-> Peptide - MHC complexes
- -> Transported to membrane

28
Q

Antigen - presenting cells & presentation pathways

Which of the following is the most effective APCs?

Dendritic cells
Macrophages
B cells

A

Dendritic cells

29
Q

Antigen - presenting cells & presentation pathways

Which of the following must be activated before they become APC?
How are they activated and what do they express after they are activated?

Dendritic cells
Macrophages
B cells

A

Macrophages
-> Phagocytosis
- -> MHC - 2
- -> B7

B cells
-> Ag - mIg activation
- -> B7

30
Q

Antigen - presenting cells & presentation pathways

What are the 4 steps in MHC - 1 endogenous pathway?

A

Degradation of endogenous antigen by proteasome
Peptide -> RER via TAP channel
Binding of peptide & MHC - 1
Peptide - MHC complex [ RER -> Golgi -> Membrane ]

31
Q

Antigen - presenting cells & presentation pathways

What are the 6 steps of MHC - 2 exogenous pathway?

A

Invariant chain binds onto MHC - 2 alpha & beta
-> blocks binding of endogenous antigen

MHC complex -> Golgi -> Endocytic pathway compartments

Degradation of Invariant chain
-> leaving CLIP fragment on MHC complex

Exogenous antigen is degraded -> Endocytic pathway compartments

HLA-DM exchanges CLIP for antigenic peptide

Peptide - MHC complex -> membrane

32
Q

Antigen - presenting cells & presentation pathways

What molecules presents non protein antigens ( e.g. glycolipid )?

A

CD1

33
Q

T - cell receptor complex : structure & role

What molecule is responsible for signal transduction and membrane expression of TCR?

A

CD3

34
Q

T - cell receptor complex : structure & role

What are 2 molecules that recognize peptide - MHC complex and are responsible for signal transduction?

A

CD4 & CD8

35
Q

T - cell receptor complex : structure & role

Which cell has CD4 & which cell has CD8?

A

CD4 : Th cell
CD8 : Tc cell

36
Q

T - cell receptor complex : structure & role

What does CD4 bind to & what does CD8 bind to?

A

CD4 : MHC - 2
CD8 : MHC - 1

37
Q

T - cell receptor complex : structure & role

Are all TCR made up of alpha& beta chain?

A

Nope

38
Q

T - cell receptor complex : structure & role

What are TCR made up of if not alpha & beta?

A

gamma & delta

39
Q

T - cell receptor complex : structure & role

What does gamma delta T cells TCR bind to?

A

Microbial phospholipid

40
Q

T - cell receptor complex : structure & role

What molecule is used to present antigen captured by gamma delta T cell?

A

CD1

41
Q

T - cell receptor complex : structure & role

Are gamma delta T cell related to innate immune system?

A

Yes

42
Q

T - cell receptor complex : structure & role

What does gamma delta T cell secrete to recruit alpha beta T cell to the site of invasion?

A

Cytokines

43
Q

T cell receptor : organization & expression

In mouse, how many chromosomes are responsible for alpha, delta, beta & gamma chain DNA?

A

3 in total
-> 14 alpha & delta
-> 6 beta
-> 13 gamma

44
Q

T cell receptor : organization & expression

In mouse, do both TCR alpha chain & delta chain DNA contain V D J ?

A

Nope
-> Only delta chain DNA contain VDJ

45
Q

T cell receptor : organization & expression

In mouse, what happens in alpha delta DNA so alpha beta T cell can be produced?

A

deletion of delta chain in alpha delta DNA

46
Q

T cell receptor : organization & expression

In mouse, which of the following has VJ DNA?

alpha chain DNA
delta chain DNA
beta chain DNA
gamma chain DNA

A

alpha chain
gamma chain

47
Q

T cell receptor : organization & expression

What is the 5 mechanisms for generating diversity in TCR genes?
( Tips : 4 of them are in BCR diversity too )

A

V(D)J recombination **
Alternative joining
P - addition **
N - addition **
Junctional flexibility **

48
Q

T cell receptor : organization & expression

What is alternate joining?

A

It only occurs in D gene segments
-> Since D genes have One turn RSS on one side and Two turn RSS on another
-> They can join together to increase diversity
-> While joining 3 things can happen to further increase diversity
- -> P - addition
- -> N - addition
- -> junctional flexibility

49
Q

T cell receptor : organization & expression

Alternative joining can happen on which of the following genes?

Alpha
Delta
Beta
Gamma

A

Delta
Beta

50
Q

T cell receptor : organization & expression

How many CDRs are there in TCR?
And what are they called?

A

3

CDR1, CDR2, CDR3

51
Q

T cell receptor : organization & expression

Which CDRs in TCR has the most diverse region for antigen recognition? and why?

A

CDR3 > CDR1 & CDR2

CDR1 & CDR2 are located within V segment

CDR3 is located between the V, (D) & J where many of the diversity mechanisms were applied

52
Q

T cell receptor : organization & expression

What are the 2 reasons why T cell doesn’t generate a self - reactive response?

A

T cells who react with self - antigen - MHC are eliminated in thymus
T cells don’t undergo somatic hypermutation
-> T cells specificity don’t change after thymic selection

53
Q

T cell selection, activation & differentiation

What is the name of the two thymic selection?
What do they do?

A

Positive selection
-> Thymocytes who bind to self - MHC molecules survives
- -> Thymocytes who don’t have the capability of binding dies

Negative selection
-> Thymocytes that don’t react strongly to self antigen / self - MHC molecules survives
-> Thymocytes that binds strongly to self antigen / self - MHC molecules dies

54
Q

T cell selection, activation & differentiation

What are the estimated percentage of thymocytes survives & mature?

A

2%

55
Q

T cell selection, activation & differentiation

What are the central event in generation of both humoral and cell mediated immune responses?

A

Activatation
Clonal expansion

56
Q

T cell selection, activation & differentiation

What does CD3 in TCR - CD3 complex do?

A

It helps stabilize TCR when TCR binds to antigen MHC complex
& is responsible for signal transmission

57
Q

T cell selection, activation & differentiation

What is the 2 signals required to fully activate T cells?

A

Ag - mIg ( TCR - CD3 complex )

CD28 - B7
-> Can be suppressed by CTLA - 4 ( Cytotoxic T - Lymphocyte Associated Protein 4 ) on activated T cell

58
Q

T cell selection, activation & differentiation

which signal determines clonal anergy or clonal expansion?

A

Signal 2
-> CD28 - B7

59
Q

T cell selection, activation & differentiation

Can signal 2 be activated by external help?
(e.g.
-> Another APC reaching out with B7

A

Yes

60
Q

T cell selection, activation & differentiation

What are the 3 signal transduction products upon Th cell activation?
And when are they expressed?
( Tips : genes )

A

Immediate genes
-> Within 30 mins

Early genes
-> 1-2 hours

Late genes
-> After 2 days

Immunology (8 decks)

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