Lecture 10 - MHCs Flashcards

1
Q

What type of molecules are MHC receptors

A

glycoproteins

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2
Q

an antigen fragment can trigger immune response only if it is

A

bound to an MHC molecule

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3
Q

What consequence does MHC control of antigen presenting have

A

determines animal’s susceptibility to infectious or autoimmune diseases

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4
Q

three classes of MHC gene loci

A

I, II, III

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5
Q

Genes in class I codes for

A

MHC I molecules that are present on all nucleated cells

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6
Q

Genes in class II codes for

A

MHC II molecules that are restricted to professional APCs

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7
Q

Genes in class III codes for

A

a diverse mixture of proteins, many of which are
important in innate immunity, such as complement proteins

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8
Q

MHC I distribution

A

most nucleated cells except mammalian red cells, gametes, neurons, trophoblast cells

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9
Q

MHC II distribution

A

B cells, macrophages, DC

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10
Q

MHC I function

A

present antigen to cytotoxic T cells

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11
Q

MHC II function

A

present antigen to T helper cells

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12
Q

MHC I result

A

T cell mediated toxicity

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13
Q

MHC II result

A

T cell mediated help

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14
Q

HLA

A

human leukocyte antigen

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15
Q

DLA

A

dog leukocyte antigen

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16
Q

BoLA

A

bovine leukocyte antigen

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17
Q

ELA

A

equine leukocyte antigen

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18
Q

H-2

A

mouse leukocyte antigen

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19
Q

B

A

chicken leukocyte antigen

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20
Q

MHC Class Ia

A

Expressed on most nucleated cells. Only polymorphic class I molecules

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21
Q

MHC Class Ib

A

Reduced expression and tissue distribution compared
with class Ia molecules. These bind to a limited range of ligands. Receptors for PAMPs

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22
Q

MHC Class Ic

A

MICA and MICB, involved in signaling to NK cells but do not bind antigenic peptides

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23
Q

MHC Class Id

A

bind to PAMPs

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24
Q

Structure of MHC class Ia molecule

A

2 long chains

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25
Q

MHC class Ia 2 chains

A
  1. long heavy a chain
  2. short B2-microglobulin chain
26
Q

long heavy a chain

A

three extracellular domains; a transmembrane domain; a cytoplasmic domain

27
Q

short β2-microglobulin chain

A

attached to the extracellular region of the heavy α chain

28
Q

Where do small peptides bind on long heavy a chain

A

groove, antigen binding site formed by a1 and a2 domains

29
Q

Heavy a chain is ____ while B2-microglobulin chain is ____

A

polymorphic; monomorphic

30
Q

B2 microglobulin chain serves to

A

stabilize the structure

31
Q

Peptides that bind to MHC I are

A

8-10 amino acids long; anchored at both ends and fit completely within the binding groove

32
Q

The amino acids at each end of peptide must conform to

A

particular motif

33
Q

Why can AA in middle of peptide be variable

A

do not interact with AA within the groove

34
Q

MHC I molecules present _____ which are derived from proteins manufactured by or within the cell

A

endogenous peptides

35
Q

Endogenous peptides can be

A

normal proteins or viral proteins if the virus is replicating inside the cell

36
Q

Steps of the endogenous pathway of MHC I
1. ____ binds to the cytoplasmic protein and targets it to ____
2. ____ is a cellular organelle that is a hollow cylinder and ___ proteins into short peptides
3. _____ bind cytosoloic peptides from the proteasome and transport them to the _____ of the ____
4. Peptide is trimmed to 9 aa by the ____ and binds to an empty ____ in the ER
5. ____ move to Golgi and transported in ____ to cell surface. _____ available for recognition by ______ cell

A
  1. Ubiquitin, proteasome
  2. Proteasome; degrades
  3. Transporter for Antigen processing (TAP); lumen; ER
  4. ER resident aminopeptidase (ERAP), MHC I
  5. MHC I + peptide; exocytic vesicle; Antigen MHC I; CD8+ T cell
37
Q

A normal cell displays about ____ loaded MHC I on its cell surface at any one time

A

100,000

38
Q

Because of ____, different ___ of MHC are displayed at any one time

A

polymorphism; alleles

39
Q

Why can MHC I on cell surface display samples of all endogenous proteins manufactured

A

each allele binds to a different peptide

40
Q

MHC class II present only on

A

APCs

41
Q

MHC II 2 chains

A

a and B chain

42
Q

MHC II a chain

A

three domains - extracellular α1 and α2, a transmembrane domain and a cytosolic domain

43
Q

MHC II B chain

A

three domains - extracellular β1 and β2, a transmembrane domain and a cytosolic domain

44
Q

What chains form peptide binding groove on MHC class II

A

a1 and B1 chains

45
Q

Peptides binding to MHC II
1. ____ of MHC II molecule is open
2. A peptide of 13-20 aa can be presented, with 9 aa ___ and rest ____
3. Around __ MHC II alleles must present ___; they are not very ____
4. They have broad aa requirements based on _____

A
  1. Peptide groove
  2. inside groove; protruding on sides
  3. 12; all antigens; specific
  4. charge, hydrophobicity
46
Q

EXOGENOUS PATHWAY OF MHC II
1. ___ internalizes the antigen via ___ or ___.
2. ____ digest the antigen into short peptides.
3. MHC molecule is synthesized in the _____
4. _____ of MHC II come together and form a ___.
5. ____ fill the peptide groove while the MHC II is transported through the ___.
6. ____ of the RER fuses with the _____ containing the antigen peptides.
7. The ____ is partially digested leaving a small peptide ____.
8. CLIP is removed by ____, a peptide exchanger molecule, and antigen peptide binds to the ____.
9. MHC II with ____ is transported to membrane and presented.

A
  1. APCs; phagocytosis; endocytosis
  2. Lysozomal enzymes
  3. RER
  4. a and B chains; groove
  5. Invariant; golgi
  6. Exocytic vesicle; endosomephagolysosome
  7. invariant chain; CLIP (class II associate Ii peptide)
  8. DM; MHC II groove
  9. antigen in groove
47
Q

What is MHC restriction

A

Only antigen fragments that can bind in the groove of a MHC molecule can trigger an immune response.

48
Q

A foreign molecule that cannot bind to at least one MHC molecule will not

A

trigger an adaptive immune response

49
Q

What determines susceptibility to infectious and autoimmune diseases

A

specific MHC alleles

50
Q

MHC heterozygotes are at an advantage because

A

they can respond to a greater range of antigens

51
Q

Why are there not more than 6 different MHC I and 12 different MHC II in an individual

A

increases risk that MHC molecules could bind and present more self antigens

52
Q

No single MHC haplotype confers

A

major survival advantages on individual animals

53
Q

BoLA-Aw7 linked to

A

resistance to bovine leukosis (bovine leukemia virus)

54
Q

BoLA-A*16 linked to

A

resistance to mastitis

55
Q

BoLA DR locus linked to

A

resistance to Dermatophilus sp.

56
Q

ELA-A9 linked to

A

susceptibility to equine recurrent uveitis

57
Q

ELA-A3, ELA-A15, ELA-Dw13 linked to

A

development of sarcoid tumors (likely induced by bovine papilloma virus)

58
Q

Class I MHC present endogenous antigens

A

to CD8+ T cells

59
Q

Class II MHC molecules present exogenous antigens

A

to CD4+ T cells

60
Q

Class I MHC molecules present ___ antigens

A

endogenous