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Immunology > Lecture 9: MHC and Antigen Presentation > Flashcards

Lecture 9: MHC and Antigen Presentation Flashcards

1
Q

Antigen processing

A

Generation of peptides from proteins

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2
Q

Antigen presentation

A

Display of processed peptide on cell surface via MHC molecules

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3
Q

What are the three types of professional APC’s

A

Dendritic cells, macrophages and B cells

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4
Q

What do MHC I molecules present on

A

All nucleated cells

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5
Q

What do MHC II molecules present on

A

Antigen presenting cells

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6
Q

What type of T cell do dendritic cells present to and what is the response

A

Naive T cells and results in clonal differentiation and proliferation of effector T cells

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7
Q

What type of T cell do macrophages present to and what is the response

A

Present to effector T cells and results in activation of macrophages- cell mediated immunity

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8
Q

What type of T cells do B cells present to and what is the response

A

Present to effector T cells and result in B cell activation and antibody production-humoral immunity

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9
Q

Where are cytosolic pathogens degraded

A

Cytosol

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10
Q

What do cytosolic pathogens bind to

A

MHC I

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11
Q

What are cytosolic presented to

A

CD8+ T cells

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12
Q

What is the effect of presenting cytosolic pathogens to CD8+ T cells

A

Cell death

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13
Q

What are intravesicular pathogens

A

Pathogens that can survive and replicate inside a phagosome and/or phagolysosome

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14
Q

Where are intravesicular pathogens degraded

A

Endocytotic vesicles with low PH

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15
Q

What do intravesicular pathogens bind to

A

MHC II

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16
Q

Where are intravesicular pathogens presented

A

CD4+ T cells

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17
Q

What is the effect of presenting intravesicular pathogens to CD4+ T cells

A

Activation to kill intravesicular bacteria

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18
Q

What are extracellular pathogens

A

Bacteria growing outside of cell, viruses not yet in target cell. They can be bound by BCR and endocytosed

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19
Q

Where are extracellular pathogens degraded

A

Endocytotic vesicle with low Ph

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20
Q

What do extracellular pathogens bind to

A

MHC II

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21
Q

Where are extracellular pathogens presented

A

CD4+ T cells

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22
Q

What is the effect on presenting extracellular pathogens to CD4+ T cells

A

Activation of B cells to secrete Ig to eliminate bacteria/toxins

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23
Q

What is the messenger between innate and adaptive immunity

A

Dendritic cell

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24
Q

How do dendritic cells sample environment

A

TLR’s

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25
Q

When dendritic cells bind an antigen what is unregulated and for what purpose

A

Upregulate CD molecules to initiate T cell binding- differentiates CD8+-Tc and CD4+-Th

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26
Q

What are the variable regions on MHC I molecule

A

Alpha-1 and alpha-2

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27
Q

What are the components of MHC I structure

A

Alpha-1, alpha-2, B2-microglobulin

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28
Q

Where are the variable regions on MHC II

A

Beta-1

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29
Q

What is the structure of MHC II molecule

A

Alpha-1, alpha-2, beta-1, beta-2

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30
Q

All MHC molecules must be bound to a peptide to be ______

A

Expressed on the cell surface, when not bound will be broken down empty MHC molecule not on surface

31
Q

Any ___ processed into a peptide can bind into the ____ and be presented to a T cell

A

Any protein- self or non-self
MHC groove

32
Q

MHC restricted T cells respond mainly to lipids, carbohydrates, sugars, or proteins

A

Proteins broken down into peptides

33
Q

If T cell binds high affinity with MHC + peptide then what happens

A

T cell activation

34
Q

What type of peptides do MHC I molecules bind and what type of T cell do they present to

A

Bind endogenous peptides and present to CD8+ T cells

35
Q

What type of peptides do MHC II molecules bind and what type of T cell do they present to

A

exogenous and CD4+ T cells

36
Q

Where are MHC I molecules translated to and fold

A

ER, they don’t see antigens in cytosol

37
Q

What protein is responsible for carrying in amino acid strands to MHC I

A

Transporter proteins (TAP)

38
Q

What is a proteasome

A

Degrades proteins into peptides

39
Q

What increases the rate of proteolysis

A

INF-gamma

40
Q

The increase rate of proteolysis ____likelihood that antigenic peptides escape this processing

A

Increases

41
Q

___transports peptides to TAP

A

Chaperones

42
Q

Describe the steps in the MHC I Antigenic Peptide Generation

A

Partly folded MHC I alpha chain will bind calnexin while waiting for B2m

Alpha-B2m binds and releases calnexin and binds chaperones and TAP via tapasin

Cytosolic proteins and defective ribosomal products are degraded into peptides via proteasome. TAP delivers peptides to ER

Peptide binds MHC and completes folding, MHC is released from TAP and exported to cell membrane

43
Q

What are immunoevasins

A

Allow viruses to evade antigen presentation by blocking TAP functions, block antigenic peptide loading into MHC, can tag MHC molecules for degradation

44
Q

What do US6 and ICP47 do

A

They are immunoevasins that block TAP and prevent antigen from moving from cytosol to ER to bind MHC

45
Q

What is adenovirus protein E19

A

Immunoevasins that disrupts tapasin binding to MHC molecule and inhibits antigenic peptide loading

46
Q

What is Mk3

A

E3-ubiquitin ligase that targets MHC I for degradation

47
Q

What are some examples of organisms that replicate in vesicles in macrophages

A

Leishmania, mycobacterium and salmonella

48
Q

What are intravesicular bacteria not exposed to and what must then degrade proteins

A

Cytosolic proteasome so intravesicular proteases degrade proteins

49
Q

Describe steps of MHCII and intravesicular bacteria

A

Antigen is taken up from extracellular space into intravesicular vesicle

In early endosomes pH is neutral so proteases are inactive

Acidification of vesicles activates proteases to degrease peptides to proteins

Vesicles containing peptide fuse with vesicle containing MHC II

50
Q

What does the invariant chain prevent

A

Binding to self antigens

51
Q

Describe the steps of MHC II antigenic prep for endocytosed/BCR bound antigens

A

Invariant chain forms complex with MHC blocking binding of self peptides, misfolded proteins

Invariant chain is cleaved in acidified endosome and leaves short peptide called CLIP bound to MHC.

Endocytosed antigens are degrade into peptides but CLIP is still blocking their binding to MHC

HLA-DM binds to MHC II releasing CLIP and allowing other peptides to bind MHC II. MHC II then travels to cell surface

52
Q

What is the role of HLA-DM and where is it found

A

Role: catalyzes loading of antigen into MHCII binding pocket

Found: only in MHC II compartment

53
Q

Cross presentation and activation of naive CD8 T cells

A

Some dendritic cells present on their MHC I molecules

54
Q

What is the source of protein antigens in MHC II pathway?

A

Endosomal/lysosomal proteins- internalized from extracellular environment

55
Q

What is the source of protein antigens in MHC I pathway

A

Cytosolic proteins- mostly synthesized in cell

56
Q

What are the enzymes responsible for peptide generation in MHC II pathway

A

Endosomal and lysosomal proteases

57
Q

What enzymes are responsible for peptide generation in MHC I

A

Enzymatic components of cytosolic proteasome

58
Q

What is the site of peptide loading of MHC II pathway

A

Late endosomes and lysosomes

59
Q

What is the site of peptide loading in MHC I

A

Endoplasmic reticulum

60
Q

What molecules are involved in transport of peptides and loading of MHC molecules in MHC II pathway

A

Invariant chain and HLA-DM

61
Q

What molecules are involved in transport of peptides and loading of MHC molecules in MHC I pathway

A

TAP

62
Q

How are MHCs able to bind so many antigens

A

Genetic diversity with many different loci

63
Q

What are the loci in MHC I and what do they encode for

A

HLA-A, B, C and encode for alpha chain

64
Q

What are the loci in MHC II and what do they encode for

A

HLA-DP, DQ, DR and encode for alpha and beta chains

65
Q

Polymorphic

A

Multiple alleles for each gene

66
Q

What is a HLA haplotype

A

Set of MHC alleles present on each chromosome

67
Q

Each person has __ HLA haplotypes

A

2

68
Q

Professional APC’s expresses alleles of which class (es)

A

MHC I and II

69
Q

All nucleated cells express which class (es)

A

MHC I

70
Q

The diversity of MHC alleles expressed partially determines individuals susceptibility to _____

A

Infectious diseases

71
Q

Is it advantageous to be MHC heterozygote or homozygote

A

Heterozygote can respond to greater number of antigens

72
Q

There has been linkage between expression of certain DLA haplotypes and susceptibility to what diseases

A

Canine RA, I-M hemolytic anemiadiabetes mellitus

73
Q

Association between expression of certain BoLA alleles and resistance to what has been shown

A

Resistant to bovine leukosis due to infection with bovine leukemia virus

74
Q

What are superantigens

A

Toxins that encourage the aberrant binding of MHC and TCR results in long lived binding and cytokine storm

Immunology (22 decks)

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