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Immunology > Antigen Processing, Presentation, and Co-Stimulation > Flashcards

Antigen Processing, Presentation, and Co-Stimulation Flashcards

1
Q

Activation of naive lymphocytes leads to ___ ___ and differentiation into ___ and memory lymphocytes.

A

clonal expansion; effector

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2
Q

___ T cells and antibodies enter into tissue and eliminate antigen.

A

Effector

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3
Q

T/F. Memory lymphocytes take up residence in tissues and secondary lymphoid organs in preparation for next infection.

A

True.

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4
Q

CD8+ T cells are ___ restricted and recognize ___ proteins.

A

MHC I; cytosolic

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5
Q

CD4+ T cells are ___ restricted and recognize extracellular and ___ pathogens.

A

MHC II; intravesicular

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6
Q

What is the bridge b/w antigen recognition and the initiation of a full-blown immune response?

A

antigen presentation

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7
Q

T/F. Antigen presentation enables B cell-mediated killing, or augments antibody production by T cells.

A

False. Antigen presentation enables T cell-mediated killing, or augments antibody production by B cells.

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8
Q

Antigen recognition without antigen presentation can result in ___, this minimizes the chances of autoimmune activity.

A

tolerance

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9
Q

A series of molecular interactions takes place to present small fragments of protein antigens to ___ cells.
Antigen presentation is modulated by ___ molecules. Successful antigen presentation results in activation of T cells.

A

T; co-stimulatory; T

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10
Q

Which cells are the most effective APCs for initial T cell activation (priming)?

A

Dendritic cells

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11
Q

What cells must be activated by phagocytoses before presenting antigens?

A

Macrophages

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12
Q

___ cells may be the major type of APCs for secondary immune response.

A

B

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13
Q

T/F. All nucleated cells can present endogenous antigens in association with MHC I molecules.

A

True. Antigen presenting cells are not limited to dendritic cells, macrophages, and B cells.

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14
Q

___ antigens are taken into the cell, small peptide antigens (8-13 aa) are generated and presented to T-helper cells together with MHC ___ molecule.

A

Exogenous; II

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15
Q

For endogenous antigens,

they are digested to small peptides (13-18 aa) and presented to ___ T cells.

A

CD8+

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16
Q

Define antigen processing.

A

The processes by which antigens are digested and placed on the cell surface with correct MHC molecules.

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17
Q

Explain how the endogenous antigens are degraded in the cytosolic pathway.

A

An amino group on the lysine side chain of a protein is complexed with ubiquitin and peptides are released after interaction with a proteasome.

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18
Q

How do peptides released from the proteosome enter the RER lumen to be loaded to MHC I?

A

TAP - transporters associated with antigen processing

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19
Q

During the cytosolic pathway, how are proteins to be degraded tagged for proteolysis?

A

by ubiquitin

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20
Q

Degradation of ubiquitin-protein complexes occurs within the central channel of ___. Peptides generated are transported into the lumen of RER by ___. Newly synthesized ___ within RER membrane binds to antigen peptide. Antigen-___ complex (2 polypeptides) released and transported to the cell surface.

A

proteasome; TAPs; MHC I; MHC I

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21
Q

For the endocytic pathway, antigens are internalized in ___. They are digested first in the ___, then in ___ to 13-18 aa peptides.

A

endosomes; endosomes; lysosomes

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22
Q

Class II molecules are produced at ___. They are associated with the ___ ___ protein (Ii), preventing their binding to endogenous antigens. Class II-Ii complex move into ___ compartments.

A

RER; invariant chain; endocytic

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23
Q

Ii will be digested to a short fragment ___ . HLA-___ triggers the exchange of CLIP and antigen peptide.

A

CLIP (Class II-associated invariant chain peptide); DM

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24
Q

T/F. HLA-DM block the activity of HLA-DO.

A

False. HLA-DO block the activity of HLA-DM.

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25
Q

How are extracellular and cytosolic antigens presented to difference subsets of T cells?

A

Extracellular antigens are presented by macrophages or B lymphocytes to CD4+ helper T lymphocytes, which activate the macrophages or B cells and eliminate the extracellular antigens.
Cytosolic antigens are presented by nucleated cells to CD8+ CTLs, which kill (lyse) the antigen-expressing cells.

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26
Q

T/F. Work with skin grafts for transplantation later revealed the importance of immune responses involving protein antigens and MHC molecules.

A

True.

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27
Q

What is the human MHC loci? mice?

A

HLA (human leukocyte antigen); H-2

28
Q

Describe the structure of class I MHC.

A

Class I molecules are composed of a polymorphic alpha chain noncovalently attached to the nonpolymorphic Beta2-microglobulin.

29
Q

T/F. Class II molecules are composed of a polymorphic alpha chain noncovalently attached to a polymorphic beta chain.

A

True.

30
Q

What can the MHC haplotype influence?

A
  • how an individual responds to certain pathogens
  • susceptibility to certain diseases
  • transplant success
31
Q

MHC genes are ___ (slightly/highly) polymorphic.

A

highly
Hundreds of alleles in humans with approximately 10^13 combinations (most polymorphic genes in the human genome)
Reason why it is difficult to find transplant donors, even among 1st degree relatives

32
Q

MHC alleles are concomitantly expressed. The set of MHC alleles on an individual chromosome is termed the MHC ___.

A

haplotype

33
Q

What is essential for antigen presentation to T cells?

A

MHC

34
Q

Self MHC + self Ag =

Self MHC + foreign Ag =

A

No T cell response

T cell response

35
Q

T/F. MHC is expressed or it’s expression can be induced on almost every nucleated cell in the body.

A

True. Viruses can infect virtually any nucleated cell so MHC I functions to alert the CD8+ T cells.

36
Q

___ expression tells the immune system that the cell is a “self” cell.

A

MHC

37
Q

What is a key factor in determining tissue matching for transplant donors and recipients?

A

MHC

38
Q

What is the on rate when peptides associated with MHC? off rate?

A

slow

slow

39
Q

T/F. MHC molecules discriminate from self and foreign peptides.

A

False. MHC molecules do not discriminate from self and foreign peptides.

40
Q

What determines which peptides bind and how peptides bind?

A

the MHC haplotype of an individual

41
Q

Define MHC restriction?

A
  1. Allows individual T cells to recognize foreign Ag displayed on the surface of an individual APC.
  2. Allows T cells to distinguish between self and non self. This prevents destruction of self tissue (autoimmunity).
42
Q

Define positive selection.

A

T cells are specific for foreign Ag + MHC in the thymus

43
Q

Define negative selection.

A

In the thymus, T cells that bind with low avidity to self peptide-MHC complexes survive and TCRs that bind with high avidity die.

44
Q

At the immunological synapse, MHC-peptide complex binds to ___. CD4 interacts with both ___ on APC and ___ on T cell to strengthen antigen-TCR interaction. ___ interacts with both MHC I on the target cell and TCR on T cells.

A

TCR; MHC II; TCR; CD8

45
Q

Co-stimulatory molecule ___ on APC binds to its T cell ligand ___. Adhesion molecule ___ on the APC binds to its T cell ligand ___.

A

B7; CD28; ICAM-1; LFA-1

46
Q

T/F. Binding through adhesion molecules is specific and non-reversible.

A

False, non-specific, reversible binding through adhesion molecules.

47
Q

T/F. Antigen-MHC-TCR binding provides specific interaction, results in prolonged cell-cell contact.

A

True.

48
Q

What does co-stimulation generate?

A

a second signal that is important for the fate of the cell.

49
Q

CD3 and ___ are non-convalently associated to the TCR.

A

zeta

50
Q

T/F. Expression of the TCR and CD3 are required for antigen recognition and signalling.

A

False, Expression of the TCR, CD3 and z chain are required for antigen recognition and signalling.

TCR recognizes Ag
CD3 and z signal

51
Q

What does B7 bind before T cell activation? after?

A

CD28; CTLA-4 (at termination of immune response)

52
Q

Explain CTLA-4 competition.

A

A. CTLA-4 can competitively inhibit binding to CD28

B. CTLA-4, when bound to B7, will actively block signals from the TCR and from CD28.

53
Q

If there is absence of co-stimulatory molecules, what will happen to the T cell? Absence of antigen-TCR interaction?

A

It will not be activated (anergy).

54
Q

At the termination of the immune response, how is the T cell function down regulated?

A

CTLA-4 replaces CD28 and down regulates T cell function

55
Q

T/F. Bacterial products cause signalling that provides T cells with “context” information that may determine the modality of their responses (e.g. tolerance, T-helper 1 or T-helper 2).

A

True.

56
Q

After antigen presentation, there is activation of ___ ___ associated with TCR/CD4(8) complex. Activated TK phosphorylate ___ tails of the clustered receptors and activation of kinase cascade follows.

A

tyrosine kinases; cytoplasmic

57
Q

Activation of transcription factors leads to the induction of ___ and ___, which causes cell division ___ ligation to ___.

A

IL-2; IL-2R; IL-2; IL-2R

58
Q

Before T cell activation, T cell express ___ ___ IL-2R. After T cell activation, IL-2R takes the form of ___ ___ ___ trimer, which enhances the affinity by ___ fold.

A

beta gamma; alpha beta gamma; 1000

59
Q

What happens once naive T cells are activated in the lymph nodes?

A

Naïve T cells enter LN from circulation and cause activation/proliferation of effector T cells. Then there is an efflux of effector cells back into circulation. They are activated at site of infection by cytokine and chemokine secretion, which eventually leads to the elimination of antigen at site of infection.

60
Q

What does interleukin-2 do?

A
  1. T cell clonal expansion, differentiation into effector and memory cells.
  2. Regulatory T cell development, survival
  3. NK cell proliferation, increased cytotoxic activity.
61
Q

What drives development of Th1 cells? Th2 cells?

A

IL-12; IL-4

62
Q

What conditions are Th1 cells needed? Th2?

A

Th1 - Delayed-type hypersensitivity, cytotoxicity, T-cell-mediated autoimmunity, graft rejection
Th2-Humoral immunity, allergy, antibody-mediated autoimmune diseases, tolerance

63
Q

T/F. Th1 cells provide help for humoral immunity.

A

False, Th1 cells provide help for cell mediated immune responses. Th2 cells provide help for humoral immune responses.

64
Q

Which cytokine is important to Th1s? Th2?

A

IFN-gamma; IL-4

65
Q

What is the role of IFN-gamma?

A
  1. macrophage activation, increased microbicidal activity
  2. isotype switching to opsonizing and complement fixing antibodies
  3. development of Th1 effector cells
  4. increased MHC expression, antigen presentation.
66
Q

What is the role of IL-4?

A
  1. isotype switching to IgE and IgG1, IgG4
  2. differentiation and expansion of Th2 cells
  3. Inhibition of differentiation of Th1 cells
67
Q

What is the sequence leading to effector functions?

A

antigen recognition, activation, clonal expansion, differentiation (all in lymphoid organs) and effector functions, which do the following:

  1. CD4 - activation of macrophages, B cells
  2. CD8 - killing of infected “target cells”, macrophage activation

Immunology (12 decks)

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