MHC and Ag Presentation to T Cells (Lec 7) Flashcards

1
Q

Cell-mediated immunity is due to the direct action of what?

A

T cells

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2
Q

T cells have evolved to protect us against intracellular microbes such as?

A

viruses and some bacteria

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3
Q

True or False?

T cells can directly recognize unprocessed Ags and bind to microbes

A

False; T cells cannot directly recognize unprocessed Ags or bind to microbes

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4
Q

Ags in host cells are broken up into linear peptides and displayed by what?

A

MHC molecules expressed on their cell surface

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5
Q

The T cell antigen receptor (TCR) only recognizes linear antigens (peptides) bound to what?

A

MHC molecules

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6
Q

True or False?

Each T cell can recognize various foreign peptides

A

False; each T cell recognizes only one specific-foreign peptide but there is a large TCR repertoire generated in the body

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7
Q

CD4 T helper cells recognized what class of MHC molecules? What cells express these molecules?

A

MHC class II; dendritic cells, macrophages, and B cells

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8
Q

CD8 cytotoxic T cells recognize peptides associated with MHC molecules?

A

MHC class I

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9
Q

The differential requirement CD4 and CD8 relates to the fact that CD4 and CD8 attach to the ____ part of the MHC class II and MHC class I molecules, respectively

A

non-polymorphic

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10
Q

True or False?

T cells do not have to be activated in order for them to carry out their functions

A

false; they do need to be activated

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11
Q

Is recognition of the peptide Ag by the TCR sufficient enough to activate the cells?

A

no

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12
Q

T cell activation leads to production of ___ which controls clonal expansion of the specific T cells

A

IL-2

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13
Q

Th1 cells help mast cells to get rid of intracellular microbes and help the development of what type of cells?

A

cytotoxic T cells

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14
Q

IFN gamma produced by Th1 cells activate what?

A

macrophages

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15
Q

True or False?

Th2 cells are mainly involved in helping B cells to develop into memory cells and plasma cells

A

true

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16
Q

IL-4 produced by Th2 cells is important for what?

A

B cell proliferation

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17
Q

The TCR for Ag is only found where?

A

T cell membrane

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18
Q

The genes coding for TCR polypeptide chains are members of what?

A

the Ig superfamily

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19
Q

True or false?

Unlike Abs, TCRs do not recognize native antigen, but can only bind processed Ag presented in MHC molecules

A

True

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20
Q

The TCR is associated with CD3. What is CD3?

A

a signaling complex

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21
Q

In regards to MHC properties, what is the significance of co-dominant expression: both parental alleles of each MHC gene being expressed

A

increases number of different MHC molecules that can present peptides to T cells

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22
Q

In regards to MHC properties, what is the significance of polymorphic genes: many different alleles are present in the population

A

ensures that different individuals are able to present and respond to different microbial peptides

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23
Q

What are the MHC class II -expressing cell types?

A

dendritic cells, macrophages, and B cells

CD4 helper T cells interact with these cells

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24
Q

What are MHC class I - expressing cell types?

A

all nucleated cells

CD8 CTLs can kill any virus-infected cell

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25
Q

Class I genes (HLA-A, -B, -C) encode what?

A

a polymorphic heavy chain which combines with B2-microglobulin and is expressed on the surfaces of all nucleated cells

26
Q

In regards to MHC molecule structure, the heavy chain has a “___ ____” for peptides to be recognized by T cells

A

binding groove

27
Q

Class II genes (HLA-D) encode what?

A

molecules (HLA-DP, -DR, and -DQ) composed of dissimilar polymorphic polypeptide chains, both of which contribute to the peptide-binding groove

28
Q

In regards to MHC molecule structure, the polymorphic regions of MHC class I and class II are the peptide-binding domains of these molecules and bind peptides ranging from how many amino acids?

A

8-10 and 10-20 respectively

29
Q

Class I MHC molecules are composed of a polymorphic alpha chain covalently attached to what?

A

non-polymorphic Beta2-microglobulin

30
Q

These residues on the peptides bind to residues in the MHC class I and II grooves and vary for different MHC alleles

A

anchor residues

31
Q

Class II MHC molecules are composed of a polymorphic alpha chain covalently attached to what?

A

polymorphic Beta chain

32
Q

Where are the polymorphic residues of class I and class II MHC molecules located?

A

in peptide-binding clefts and the alpha helices around the clefts

33
Q

How do peptides lie in the clefts of MHC class I molecules compared to class II

A

The cleft of class I molecule is closed

The cleft of class II molecule is open

note: open cleft allows class II molecules to accommodate longer peptides

34
Q

Expression of MHC class I or II molecules is modulated by what?

A

cytokines

35
Q

What occurs after naive T cells are activated?

A

clonal expansion and differentiation into effector T cells

36
Q

The effector T cell response: macrophage activation relates to what type of immunity

A

cell-mediated

37
Q

The effector T cell response: B cell activation and antibody production relates to what type of immunity

A

humoral

38
Q

Class II MHC expression increases in dendritic cells with what?

A

increases with maturation and by IFN gamma

39
Q

What are costimulators of dendritic cells

A

inducible by TLR ligands, IFN gamma, and T cells (CD40-CD40L interactions)

40
Q

What is the principal function of dendritic cells?

A

initiation of T cell responses to protein ags

41
Q

What is expression of Class II MHC inducible by in macrophages?

A

IFN gamma

42
Q

What are costimulators of macrophages?

A

inducible by TLR ligands; IFN gamma, and T cells (CD40-CD40L interactions)

43
Q

What is the principal function of macrophages?

A

effector phase of cell-mediated immune response

44
Q

What increases Class II MHC expression on B lymphocytes?

A

IL-4

45
Q

What are costimulators of B lymphocytes?

A

induced by T cells (CD40-CD40L interactions), antigen receptor cross-linking

46
Q

What is the principal function of B lymphocytes?

A

antigen presentation to CD4 helper T cells in humoral immune responses (T cell - B cell interactions)

47
Q

Microbial antigens commonly enter though the skin, GI, and respiratory tracts, where they are captured by what? and transported where?

A

captured by dendritic cells

transported to regional lymph nodes

48
Q

Antigens that enter the blood stream are captured by what?

A

APC’s in the spleen

49
Q

What is the function of Tissue resident dendritic cells compared to activated dendritic cells?

A

tissue resident dendritic cell: antigen capture

activated dendritic cell: antigen presentation to T cells

50
Q

NK cells, during immune reactions to microbes or by T cells during adaptive immune reactions, produce what?

A

IFN gamma

51
Q

IFN gamma stimulates what type of expression?

A

Class II MHC expression on APCs and thus enhances the activation of CD4 T cells

52
Q
True or False?
IFN gamma and type I interferons have very different effects on the expression of class I MHC molecules and the activation of CD8 T cells
A

False; similar effect

53
Q

Why do alphabeta T cells recognize cell-associated and not soluble Ags?

A

MHC stably bound peptides stably and complexes are located on cell surface

54
Q

True or false?

CD4 T cells recognize extracellular Ags. CD8 T cells recognize intracellular Ags.

A

true

55
Q

What is the series of events in the class I MHC pathway for Ag processing?

A

production of proteins in the cytosol -> proteolytic degradation of proteins -> transport of peptides from cytosol to ER -> assembly of peptide-class I complexes in ER -> surface expression of peptide-class I complexes

56
Q

What is the series of events in the class II MHC pathway for Ag processing?

A

uptake of extracellular proteins into vesicular compartments of APC -> processing of internalized proteins in endosomal/lysosomal vesicles -> biosynthesis and transport of class II MHC molecules to endosomes -> association of processed peptides with class II MHC molecules in vesicles -> expression of peptide-MHC complexes on cell surface

57
Q

The HLA-DM editing mechanism works to ensure what?

A

the presentation of only the protein fragments most relevant for eliciting an immune response

58
Q

What are the three major functions of the HLA-DM?

A

causes dissociation of CLIP from the peptide binding groove of MHC II

stabilizes and prevents degradation of the empty MHC II

facilitates the binding of antigen fragments to the open, stabilized binding groove

59
Q

What is the series of events that take place in the HLA-DM mechanism?

A

synthesis of class II MHC in ER -> transport of class II MHC and Ii to vesicle -> binding of processed peptides to class II MHC -> transport of peptide class II MHC complex to cell surface -> expression of peptide-MHC complex on cell surface

60
Q

Are DC’s able to present extracelluar Ags by the class I pathway?

A

yes; cells infected with intracellular microbes are ingested by DCs and Ags of the infected microbes are transported into the cytosol and presented in association with class I MHC molecules to CD8 T cells

61
Q

Immunodominant peptides are obtained by what?

A

proteases available in cells