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Immunology > MHC > Flashcards

MHC Flashcards

1
Q

What are cogenic strains of MHC?

A

strains in which the endogenous MHC is replaced by an entire MHC locus form another strain

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2
Q

What are recombinant strains of MHC?

A

strains in which only a portion of the endogenous MHC complex has been relplaced by MHC of another haplotype (breeding from 1 strain into another)

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3
Q

Which cells express MHC I?

A

all cells in body (except RBCs)

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4
Q

Which cells express MHC II?

A

APCs (antigen presenting cells): activated T cells, B cells, macrophages, dendritic (other APC), thymic epithelium

NB: neurons do NOT express Class II but brain microglia (of monocyte/macrophage lineage) do express class II

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5
Q

How do T cells recognize viral antigens in virus infected cells?

A

only as complex with MHC antigens

[For both Cytotoxic T cells and T helper cells: the ability of T cells to recognize a particular MHC as self depends on the MHC haplotype(s) present in the thymus in which they matured]

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6
Q

Which T cells express CD4?

A

Helper T

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7
Q

Which T cells express CD8?

A

Cytotoxic T

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8
Q

Which T cell marker is on all T cells?

A

CD3?

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9
Q

Which MHC class interacts with CD4?

A

II

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10
Q

Which MHC class interacts with CD8?

A

I

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11
Q

Single mutations in T cells alter MHC . Which mutation (in B6 mice) alters Class I? Class II?

A

bm1: Class I
bm12: Class II

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12
Q

Name the MHC class that presnet antigens that originate within the cell. (like viruses and tumor antigens)

A

MHC Class I

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13
Q

Name the MHC class that present antigens that originate outside the cell.

A

MHC Class II

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14
Q

Can antigens be presented on both class I and class II MHC?

A

yes: “cross” pathways
eg: a virus that ends up in endosomes

Result: leads to two different types of immune rxns

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15
Q

How are most bacteria handled?

A

Most are extracellular:
T cell help –> Ab production –> processed for Class II presentation

TH cells recognize exogenous antigen which is phagocytosed and presented by Class II

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16
Q

How are most viruses handled?

A

Most are inside cell: require CTL (cytotoxic T cell) to kill infected cell

CTL recognize antigen synthesized inside cell, which is presented by class I

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17
Q

Steps of Class I MHC Presentation

A

1) Proteosome cleaves antigens into fragments
2) TAP system transports them to lumen of RER
3) Newly made fragments bind to newly-made Class I MHC and get shipped in vesicle to fuse with PM
4) CTL receptor binds Class I MHC + antigen fragment

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18
Q

Steps of Class II MHC Presentation

A

1) Antigen phagocytosed by APC
2) Proteolytic cleavage within endosome
3) Binding to Class II MHC in endosome
4) export of antigen/MHC complexes to PM
5) TH receptor binds to Class II MHC + antigen fragment

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19
Q

Answer for Class I molecules:

  • peptide binding domain?
  • nature of peptide-binding cleft? (open/closed)
  • size of peptides (# of AAs)
  • anchor residue motifs (where on peptide?)
  • nature of bound peptide?
A
  • peptide binding domain? alpha 1/alpha2
  • nature of peptide-binding cleft? closed at both ends
  • size of peptides: 8-10 AAs
  • anchor residue motifs: STRONG motifs; anchors at both ends of peptide; generally hydrophobic
  • nature of bound peptide? extended structure with both ends interacting with MHC cleft but middle arches up away from MHC
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20
Q

Answer for Class II molecules:

  • peptide binding domain?
  • nature of peptide-binding cleft? (open/closed)
  • size of peptides (# of AAs)
  • anchor residue motifs (where on peptide?)
  • nature of bound peptide?
A
  • peptide binding domain? alpha 1/BETA1
  • nature of peptide-binding cleft? OPEN at both ends
  • size of peptides: 13-18 AAs
  • anchor residue motifs: WEAK motifs; anchors residues distributed along the length of the peptide
  • nature of bound peptide? extended structure that is held at constant elevation above MHC
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21
Q

What is the fate of an antigen-presenting cell with no B7?

A

anergy of TH cell

22
Q

What are the two types of CD4+ cells (T helper)

A

Th1 (inflammatory);

Th2 (helper)

23
Q

What is the function of Th1 cells?

A

(inflammatory)

B-cell proliferation; 
polyclonal Ig secretion; 
*cytotoxcity; 
*suppression of Ig secretion;
*delayed-type hypersenstivity (DTH)

Note: * means unique to this cell

24
Q

What is the function of Th2cells?

A

(Helper)

B-cell proliferation;
polyclonal Ig secretion;
*HELP FOR SPECIFIC Ab!

Note: * means unique to this cell

25
Q

What cytokines are released from Th1 cells?

A

(pro-inflammatory)

IL-2,* 
IL-3;
GM-CSF;
*IFN-gamma, *TNF-Beta
TNF-alpha

Note: * means unique to this cell

26
Q

What cytokines are released from Th2 cells?

A

IL-3;
*IL- 4, 5, 6, 10;
GM-CSF;
TNF-alpha

27
Q

Which cytokines are released from any/all CD4+ cells?

A

IL3, GM-CSF; TNF-alpha

28
Q

What is the role of the thymus for T cells?

A

maturation and selection

29
Q

What is negative selection of T cells?

A

Round II of selection:

T cells that recognize self-antigens are not allowed to exit the thymus and are eleminated

Removes Tcells that show dangerously high reactivity to self

30
Q

What is positive selection of T cells?

A

Round I of selection:

ONLY cells with TCR that match self with MHC (with at least some affinity) are allowed to mature

Purpose: weed T cells with TCRs that don’t match a self-MHC (bc it is useless)

31
Q

What is “round III” of selection? (immune response creation)

A

takes place after T cells mature:

Match self MHC + foreign peptide well?
Y: survive and divide –> create immune response
N: die

the set of foreign antigens encountered determines which immature T cells will make immune responses, proliferate, and give rise to long-lived descendants

32
Q

Which class of MHC activates the immune system?

A

MHC II

33
Q

Which class of MHC responds to virally infected cells?

A

MHC I

34
Q

What is TAPASIN?

A

protein that fxns as bridge btwn TAP and MHC-I in the presentation pathway (MHC-I)
-edits the peptide repertoire, making sure only high affinity peptides are presented

35
Q

What is ERAP?

A

MHC-I presentation pathway

ER aminopeptidase: trims peptides in ER prior to binding to MHC class I. Creates peptides that are the correct size

36
Q

What is the “invariant chain” in the MHC-II pathway?

A

binds to MHC-II in ER and facilitates transport from ER to endosomes; portion of chain is bond in class II peptide groove

37
Q

What is DM’s role in the MHC-II pathway?

A

edits peptide repertoire, making sure only high affinity peptides are presented

38
Q

What do Myeloid dendritic cells (mDC):

  • produce?
  • express?
A
  • produce: IL-12
  • express: TLR 2, 4

effective in antigen presentation

39
Q

What do plasmacytoid dendritic cells (mDC):

-express?

A

express: TLR 7, 9; high levels of IFN-alpha (impt in viral infections)

lymphoid origin?

40
Q

How are antigens captured?

A
  • passing epithelium of skin, GI tract, resp tract
  • lymph node collects antigen from epithelium and CT
  • blood borne antigens are captured by APCs in spleen
41
Q

What (receptors/molecules) do immature dendritic cells produce?

A

purpose: antigen capture

Express Fc receptors and mannose receptors (help them capture things)

  • low expression of T cell activating molecules (B7; ICAM-1; IL-12)
  • short half-life of MHC-II molecules
42
Q

What (receptors/molecules) do mature dendritic cells produce?

A

(Purpose: antigen presentation to T cells)

-high expression of molecules involved in Tcell activation (B7, ICAM-1, IL-12)

  • no expression of Fc receptors or mannose receptors
  • longer half life (>100hr)
  • 7x amt of surface molecules compared to immature DCs
43
Q

What is responsible for immature to mature DC conversion?

A

TLR ligation (when DC eat pathogen and receives TLR ligation

44
Q

What MHCs do APCs express?

A

Class I and Class II

45
Q

How do DCs present antigens, and what’s the response?

A

*NATIVE T CELL ACTIVATION

Present with costimulator (B7) to CD28 of native T cell to activate the Native T cell toward differentiation to effector T cells and clonal expansion

46
Q

How do macrophages present antigens, and what’s the response?

A

EFFECTOR T CELL ACTIVATION (AND activation of macrophages: cell-mediated immunity)

Macrophage presents antigen to Effector T cell which then results in killed microbe

47
Q

How do B cells present antigens, and what’s the response?

A

EFFECTOR T CELL ACTIVATION (AND B cell activation and Ab production –> humoral immunity)

B cells present antigen to effector T cells –> Abs

48
Q

What process allows for viral peptides to be bound to MHC I molecules?

A

DCs can ingest viral infected cells and display peptides bound to MHC I –> cross presentation provides way for naive CD8 T cells to get activated

49
Q

What type of peptides are on the majority of class I and class II?

A

self-peptides (but no reaction bc tolerance has been established; unless autoimmunity)

50
Q

Where are most of the genes for MHC I and II?

A

MHC is POLYGENIC (and polymorphic) –> variation

HLA Genetic Region:
Class I: A, B, C
Class II: DP, DQ, DR

Note: genes for invariant chain and Beta2m are on other chromosomes

51
Q

Where do most of the polymorphisms lie in MHC?

A

in peptide binding groove

Immunology (8 decks)

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