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Sp 15-Micro Final > Antigen Processing, Presentation and Co-Stimulation > Flashcards

Antigen Processing, Presentation and Co-Stimulation Flashcards

1
Q

What does MHC stand for?

A

Major Histo-Compatibility Complex

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2
Q

What does APC stand for?

A

Antigen Presenting Cell

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3
Q

List the basic steps in Lymphocyte activation:

A
  • Microbe infects host
  • Microbe is taken up by APC at the site of infection
  • APC enters lymph circulation toward Lymph node (LN)
  • Naive T and B cells enter LN from circulation
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4
Q

After activation of naive lymphocytes, what happens next?

A

Clonal Expansion and Differentiation into effector and memory lymphocytes

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5
Q

Which lymphocyte will take up residence in tissues and secondary lymphoid organs?

A

memory lymphocytes

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6
Q

Which type of lymphocytes are faster at responding?

A

memory lymphocytes are much quicker than effector lymphocytes in the case of a future infection

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7
Q

Which T cells are MHC I restricted and recognize cytosolic proteins?

A

CD8+

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8
Q

Which T cells are MHC II restricted and recognize extracellular (and intravesicular) pathogens?

A

CD4+

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9
Q

______ _______ is central to the development of immune response (the bridge between antigen recognition and initiation of immune response).

A

Antigen Presentation

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10
Q

Antigen presentation enables ______-mediated killing or enables antibody production by _______.

A

T cell

B cells

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11
Q

Antigen recognition WITHOUT antigen presentation can result in _______ and a minimized chance of autoimmune activity.

A

tolerance

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12
Q

A series of molecular interactions takes place to present small fragments of ____ ________ to T cells.

A

Protein antigens

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13
Q

Antigen presentation is modulated by ________ molecules.

A

Co-stimulatory

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14
Q

Successful antigen presentation results in activation of ____.

A

T Cells

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15
Q

Which APCs are most effective for initial T cell activation (priming).

A

Dendritic Cells

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16
Q

What is “initial T cell activation” also known as?

A

Priming

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17
Q

Which APCs must be activated by phagocytosis before presenting antigens?

A

Macrophages

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18
Q

Which APCs are the major type for secondary immune response?

A

B Cells

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19
Q

All _______ cells can present endogenous antigens in association with MHC ___ molecules.

A

nucleated

MHC I

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20
Q

What are three important monocyte derivatives?

A

Macrophages (tissue)
Microglia (brain)
Kupffer Cells (liver)

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21
Q

Which two APCs are inducible for Class II expression

[negative to Positive expression]?

A
  1. Lymphocytes

2. Facultative Antigen Presenting Cells

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22
Q

Which APCs are inducible for Class II expression [Positive to Greatly Positive]?

A

Phagocytes (monocyte lineage)

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23
Q

What is “the process by which antigens are digested and placed on the cell surface with correct MHC molecules”?

A

Antigen Processing

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24
Q

In the two pathways for antigen presentation: Pathway 1 is used for _____ antigens, whereas Pathway 2 is used for ______antigens.

A

1 EXogenous

2 ENDogenous

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25
Q

In Pathway 1, exogenous antigens are taken into the cell and then small peptide antigens are presented to ____cells together with MHC class ____.

A

T Helper Cells

Class II

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26
Q

In Pathway 2, endogenous antigens are taken into the cell and then small peptide antigens are presented to ________ cells.

A

CD8+ T Cells

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27
Q

Cytoplasmic Proteins are broken into peptides via ______ and then the peptides are broken down into amino acids via exopeptidase.

A

Proteasome

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28
Q

Endocytic Proteins are broken into peptides via ______. Then the peptides are broken down to amino acids via exopeptidase.

A

Lysosome

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29
Q

Degradation of intracellular proteins into peptides occurs through enzymatic action.
Proteasome breaks down _________
Lysosome breaks down __________.

A 
Pro= cytoplasmic proteins
Lys= endocytic proteins
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30
Q

__________ breaks down peptides into amino acids.

A

Exopeptidase

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31
Q

The “Cytosolic Pathway” is used for ________ antigens.

A

ENDogenous

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32
Q

In the cytosolic pathway, proteins are tagged with _______ for breakdown into peptides.

A

Ubiquitin

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33
Q

Describe the steps in the cytosolic pathway that is used for endogenous antigens.

A
  • Cell is infected
  • Proteins are tagged with Ubiquitin for proteolysis
  • Ubiquitin-Protein complex enters the proteasome
  • Complex is degraded into peptides
  • Peptides are transported into the lumen of the RER via transporters (TAP)
  • MHC I (newly synthesized) within RER membrane binds to antigen peptide
  • Antigen-MHC I Complex is released and transported to the cell surface
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34
Q

Which transporter molecule is associated with antigen processing and allows peptides to cross the RER membrane?

A

TAP

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35
Q

The “Endocytic Pathway” is used for ________ antigens.

A

EXogenous

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36
Q

Exogenous antigens that bind to the membrane surface will enter _______-______ vesicles. The vesicle will then un-coat and fuse to form an _______ which will then degrade the proteins.

A

Clathrin-Coated

Endosome

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37
Q

The endogenous pathway is used to present peptides on the surface of ________. The exogenous pathway is used to present peptides on _______.

A 
Endo = MHC I
Exo = MHC II
38
Q

Endogenous proteins are tagged with ______for degradation; exogenous proteins are ______ and degraded.

A

Ubiquitin

Endocytosed

39
Q

Describe the steps in the endocytic pathway that is used for exogenous antigens.

A
  • Antigens bind to membrane receptors and are internalized within endosomes
  • Digestion begins in the endosome, then continues within lysosomes
  • Class II molecules are produced at RER and associated with “Invariant Chain Protein”
  • Class II-Invariant Chain Protein complex moves into endocytic compartment
  • Invariant Chain Protein is digested into CLIP (fragment)
  • HLA-DM triggers the exchange of CLIP and antigen peptide
  • Peptide Class II is released to the cell surface
40
Q

The binding of Class II molecules with ________ prevents binding to endogenous antigens and initiates movement into endocytic compartments.

A

Invariant Chain Protein (li)

41
Q

Invariant Chain Protein (li) is digested into the short fragment _______ which will be exchanged for antigen peptide in the presence of HLA-____.

A

CLIP

DM

42
Q

HLA-____ blocks the activity of HLA-DM and therefore does not allow the exchange of CLIP for antigen peptide.

A

DO (off)

43
Q

Class II MHC is associated with presentation of _____ antigens to _______Lymphocytes.

A

Extracellular

CD4+ Helper T Lymphocytes

44
Q

Class I MHC is associated with presentation of _______ antigen to ________ lymphocytes.

A

Cytosolic

CD8+ Cytotoxic T Lymphocytes

45
Q

The antigen-expressing target cell is marked for direct killing when cytosolic antigen is presented to ______.

A

CD8+ Cytotoxic T Lymphocytes

46
Q

Antigen presentation to CD4+ helper T Lymphocytes will result in _______ ________ or ______ ________.

A 
Macrophage Activation (on macrophage)
Antibody Binding (on antigen-specific B cell)
47
Q

MHC I molecules are composed of a _______ noncovalently attached to a ________. MHC II molecules are composed of a _______ noncovalently attached to a ________.

A

I = Polymorphic Alpha Chain + NonPolymorphic B2 microglobulin

II = Polymorphic Alpha Chain + Polymorphic Beta Chain

48
Q

What are three influences of MHC (HLA) haplotype?

A
  1. How an individual responds to certain pathogens
  2. Susceptibility to certain diseases
  3. Transplant success
49
Q

MHC genes (mice) are equivalent to _____ in humans.

A

HLA

50
Q

MHC genes are highly _______ which is why it is difficult to find transplant donors.

A

Polymorphic

51
Q

What is “MHC haplotype”?

A

The set of MHC alleles on an individual chromosome that determines which peptides bind and how peptides bind

52
Q

T cells constantly survey for foreign antigens and _____is essential for antigen presentation to T cells.

A

MHC

53
Q

Self MHC + Foreign Ag = ________

A

T Cell Response

54
Q

Self MHC + Self Ag = ________

A

No T Cell Response

55
Q

MHC molecules have a _______ specificity for peptides.

A

Broad

56
Q

What is MHC Restriction?

A

A given T cell will recognize a peptide antigen only when it is bound to a host body’s own MHC molecule. This dual recognition system is critical to T Cell Function

57
Q

MHC restriction prevents destruction of _______.

A

Self Tissue

58
Q

Cell-cell adhesion is mediated by multiple ligand-receptor pairs. Molecular interaction occurs between _____ and ______. The interaction is mediated by T cell receptors, ligands (MHC), and _________.

A

T cells
antigen-presenting cells
intracellular adhesion molecules

59
Q

MHC-peptide complex binds to ______.

A

TCR (T-cell Receptor)

60
Q

How is the antigen-TCR interaction strengthened by CD4?

A

CD4 interacts with both:
MHC II on the APC
and with
TCR on the T-cell

61
Q

CD8 interacts with _____ on the target cell and ______ on the T cell.

A

MHC I

TCR

62
Q

What is the T-Cell ligand for co-stimulatory molecule B7 on APC?

A

CD28

63
Q

Adhesion Molecule ICAM-1 on the APC binds to its T Cell ligand ______.

A

LFA-1

64
Q

List the order of interactions at the immunological synapse.

A
  1. MHC I (APC) binds to TCR (T Cell)
  2. MHC I (APC) is bound by CD8 (T Cell)
  3. Co-Stimulatory Molecule B7 (APC) binds to CD28 (T Cell)
  4. Adhesion ICAM-1 (APC) binds to LFA-1 (T Cell)
65
Q

At the immunolocial synapse, which molecules are involved in adhesion?

A

ICAM-1

LFA-1

66
Q

At the immunological synapse, which molecules are involved in costimulation?

A

B7

CD28

67
Q

What is the structure of TCR?

A

Membrane-anchored heterodimer consisting of the highly variable alpha (α) and beta (β) chains expressed as part of a complex with the invariant CD3 chain molecules on each side.

68
Q

What are the two different forms of B7 Receptors?

A

Before T Cell Activation: B7–CD28 –>activation/division

At Immune Termination: B7–CTLA-4 –>inactivation

69
Q

CTLA-4 will actively block signals from the TCR and CD28 when it is bound to which molecule?

A

B7

70
Q

At the termination of the immune response, CTLA-4 replaces ________ and downregulates T cell function.

A

CD28

71
Q

Which molecule is considered to be the main activator of T cells?

A

IL-2

72
Q

Non-Self products will stimulate the expression of MHC, adhesion molecules, and _______ molecules which determines the modality of their responses.

A

Co-stimulatory

73
Q

What is the difference between Th1 and Th2 in their inflammatory action?

A 
TH1 = Pro-Inflammatory (cell mediated)
TH2 = Anti-Inflammatory (humoral/antibodies)
74
Q

TH1 is involved in ______ immunity.

A

cell-mediated

75
Q

TH2 is involved in _______ immunity.

A

Humoral

76
Q

After antigen presentation, tyrosine kinases associated with TCR/CD4(8) complex are activated. These active TK will then _______.

A

Phosphorylate cytoplasmic tails of the clustered receptors and initiate the kinase cascade

77
Q

The kinase cascade results in the induction of ____ and ____ which will lead to cell division.

A

IL-2 and IL-2R

78
Q

IL-2 ligation to IL-2R results in _____ _______.

A

Cell Division

79
Q

Which receptor is essential for amplification of the T cell response?

A

IL-2

80
Q

Interleukin-2 will act on T cells and NK cells to initiate what processes?

A

T Cells: clonal expansion, differentiation into effector and memory cells
T Cells: Regulate development, “Survival Sign”
NK Cells: cell proliferation, increased cytotoxic activity

81
Q

TH1 and TH2 regulate each other and the interleukins driving their development are different.
IL- ____ drives TH1
IL-_____ drives TH2

A

IL-12 (th1)

IL-4 (th2)

82
Q

TH1 cells will lead to activation of ______ in the presence of ____ and _____.

A

Macrophages
TNF-alpha
IFN-gamma

83
Q

TH2 cells will lead to _______ in the presence of ____ and ____.

A

B Cells
IL-4
IL-5

84
Q

Which molecules are important in regulating the complex balance of T Helper 1 and T Helper 2 cells?

A

Cytokines

85
Q

The following are a result of which helper cell activation?

  • macrophage activation
  • complement binding and opsonization
  • neutrophil activation
A

Th1

86
Q

Which cytokine is extremely important for Th1 activity?

A

IFN-gamma

87
Q

The following are a result of which helper cell activation?

  • Production of neutralizing IgG antibodies (mast cells)
  • Production of IgE
  • Eosinophil activation
  • Suppression of macrophage activation
A

Th2

88
Q

Which cytokine is extremely important for Th2 differentiation/expansion and inhibition of Th1?

A

IL-4

89
Q

Antigen recognition of MHC II results in ____ T Cell activation, clonal expansion via IL-___ and activation of ___ cells in peripheral tissue.

A

Naive CD4+
2
B

90
Q

Antigen recognition of MHC I results in ____ T Cell activation, clonal expansion via IL-___ and activation of ______ in peripheral tissue.

A

Naive CD8+
2
macrophages

Sp 15-Micro Final (12 decks)

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