Antigen processing, presentation, and co-stimulation (Stiner-jones) Flashcards

1
Q

What is the general flow of how lymphocytes are activated?

A
  1. Microbe infects the host
  2. Antigen presenting cell engulfs microbe
  3. APC exits circulation and enters a lymph node
  4. Naive T and B cells are schooled by APC
  5. Schooled T and B cells exit lymphatic circulation and head to infection site
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2
Q

What is an effector T-cell?

A

It is an armed T-cell that is ready to destroy

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3
Q

CD8+ T cells are _____ restricted and recognize _____ _____.

A

MHC I

cytosolic proteins

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4
Q

CD4+ T cells are _____ restricted and recognize _____ and ______ ______.

A

MHC II

Extracellular and intravesicular pathogens

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5
Q

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

A

Antigen presentation

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6
Q

T-cells _____ and B-cells _____ _____.

A

Kill

produce antibodies

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7
Q

Antigen presentation is modulated by what?

A

Co-stimulatory molecules

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8
Q

The most common antigen presenting cell is the what?

A

Dendritic cell

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9
Q

Which cell is the professional APC?

A

Dendritic cells

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10
Q

Macrophages must be activated by _____ before presenting antigens.

A

Phagocytoses

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11
Q

Are APC’s limited to dendritic cells, macrophages, and B cells?

A

Nope

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12
Q

What other cells can be APC’s?

A

All nucleated cells can present endogenous antigens in association with MHC I molecules

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13
Q

What happens in pathway 1 of antigen processing?

A

Pathway 1: exogenous antigens are taken into the cell (8-13 amino acids) and are presented to T helper cells together with MHC II molecule

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14
Q

What happens in pathway 2 of antigen processing?

A

Pathway 2: for endogenous antigens- they are digested to small peptides (13-18 amino acids) and presented to CD8+ T cells

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15
Q

What is the pathway of degradation for intracellular proteins?

A

Cytoplasmic proteins are degraded by proteosomes into peptides. Exopeptidase turns the peptides into amino acids

Endocytic proteins are degraded in the lysosome into peptides. Exopeptidase turns the peptides into amino acids

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16
Q

Endogenous antigens- the cytosolic pathway: how does it work?

A
  1. Proteins that need to be degraded are tagged for degradation by ubiquitin
  2. Degradation of ubiquitin-protein complex occurs within the central channel of the proteosome
  3. Peptides generated via degradation are transported to the lumen of the RER by the TAP protein
  4. Newly synthesized MHC I within the RER membrane binds to the antigen peptide
  5. Antigen-MHC I complex is released and transported to the cell surface
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17
Q

Where are MHC I and MHC II made?

A

Endoplasmic reticulum

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18
Q

Exogenous antigens- the endocytic pathway: how does it work?

A
  1. Antigens are internalized in endosomes
  2. Antigens are digested first in the endosomes and then further in the lysosomes to 13-18 amino acids
  3. Class II molecules are produced in the RER
  4. MHC II molecules are associated with the invariant chain protein, which prevents their binding to endogenous antigens.
  5. Class II-invariant chain complex moves into endocytic compartments
  6. Invariant chain protein will be digested to a short fragment (CLIP)
  7. HLA-DM triggers the exchange of CLEP and the antigen peptide
  8. HLA-DO blocks the activity of HLA-DM
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19
Q

What three things can the MHC haplotype influence?

A

How an individual responds to certain pathogens
Susceptibility to certain diseases
Transplant success

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20
Q

T/F MHC genes are highly polymorphic?

A

True

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21
Q

MHC genes are the most polymorphic genes in the human genome- what implications does this have?

A

Difficulty finding transplant donors that match, even among first degree relatives

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22
Q

The set of MHC alleles on an individual chromosome is termed what?

A

The MHC haplotype

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23
Q

What combination of MHC and antigen does the T-cell recognize?

A

Self MHC + foreign antigen

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24
Q

T/F- MHC is expressed or its expression can be induced on almost every nucleated cell in the body?

A

True

25
Q

When a nucleated cell is virally infected, what happens?

A

MHC I functions to alert the CD8+ T cells

26
Q

MHC expression tells the immune system that the cell is a ____ cell.

A

Self

27
Q

T/F MHC is a key factor in determining tissue matching for transplant donors and recipients.

A

Trooth

28
Q

Many or few (choose one) peptides can bind within the MHC binding cleft?

A

Many

29
Q

Peptides associated with MHC have a ____ on and a ____ off rate.

A

Slow

Slow

30
Q

Do MHC molecules discriminate between self and foreign peptides?

A

No

31
Q

The ___ ____ of an indiviudal determines which peptides bind and how peptides bind.

A

MHC haplotype

32
Q

What allows individual T cells to recognize foreign antigens displayed on the surface of an individual APC?

A

MHC restriction

33
Q

What allows T cells to distinguish between self and non self?

A

MHC restriction

34
Q

Where do T cells mature?

A

In the thymus

35
Q

What are the two things that can happen to a T cell in the thymus?

A
  1. T cells that are specific for foreign antigen + MHC bind self peptide-MHC with low affinity survive (positive selection) or
  2. T cells that bind with high affinity to self peptide-MHC complexes die (negative selection)
36
Q

Why do T cells undergo positive or negative selection in the thymus?

A

It prevents destruction of host tissue (autoimmunity)

37
Q

What happens at the synapse between an APC and a T cell?

A
  1. MHC-peptide complex binds to the T cell receptor
  2. CD4 + interacts with both the mHC II on the APC and the TCR on the T cell to strengthen the antigen-TCR interaction
  3. CD8 interacts with both the MHC I on the target cell and TCR on T cells
  4. Co-stimulatory molecule B7 on the APC binds to its T cell ligand CD 28 on the T cell
  5. Adhesions molecule ICAM-1 on the APC binds to its T cell ligand: LFA-1
38
Q

What is the function of CD4 when APCs and T cells meet?

A

It strengthens the antigen-TCR interation

39
Q

What is the function of CD8 when APCs and T cells meet?

A

It interacts with the MHC I on the target cell and with the TCR on T cells

40
Q

What is responsible for adhesion when APCs and T cells meet?

A

ICAM-1 (on APC) and LFA-1 (on T cell)

41
Q

When APCs and T cells bind, is it reversible?

A

Yes

42
Q

The co-stimulation during APC-T-cell interaction does what?

A

It generates a second signal that is important for the fate of the cell

43
Q

How is specific interaction achieved? What does it result in?

A

Antigen-MHC-TCR binding provides specific interaction

This results in prolonged cell-cell contact.

44
Q

Are the CD3 and squiggly line thing covalently associated to the TCR?

A

Nope

45
Q

What three things must be expressed for antigen recognition and signaling?

A

TCR
CD3
Squiggly line thing

46
Q

TCR recognizes what?

CD3 and squiggly line thing do what?

A

TCR- recognizes antigen

CD3 and squiggly signal stuff

47
Q

In the T cell-APC interaction, B7 and CD28 usually bind. What can competitively inhibit this binding and what happens when this occurs? Why would this be beneficial?

A

CTLA-4 can competitively inhibit the binding. When it is bound to B7, it will block signals from the TCR and from CD28
It would be beneficial to down regulate the T cell after the immune response is done

48
Q

What happens if the co-stimulatory molecule isn’t present during the APC-T cell interaction?

A

T cell will not be activated.

49
Q

During the APC-T cell interaction, what happens if there is no TCR-antigen interaction?

A

T cell will not be stimulated.

50
Q

During the APC-T cell interaction, are both interactions (TCR-antigen and co-stimulatory interaction) necessary?

A

Yes, co-reception of both signals activates T cells

51
Q

What does the CTLA-4 do at the termination of the immune response?

A

It replaces CD28 and down regulates T cell function.

52
Q

How is merely non-self differentiated from dangerous?

A

The expression of MHC, adhesion molecules, and co-stimulatory molecules in APCs provide the T cells with context information that let it determine what type of response to have- tolerance, T helper 1 or 2 response

53
Q

What happens after antigen presentation?

A
  1. Activation of tyrosine kinases associated with TCR/CD4(8) complex
  2. Activated TK phosphaorylate cytoplasmic tails of the clustered receptors
  3. Activation of kinase cascade follows
  4. Activation of transcription factors
  5. IL-2 and Il-2R are made
  6. Cell division occurs after IL-2 ligation to IL-2R
54
Q

What do T cell express before activation?

A

beta,gama IL-2R

55
Q

After T cell activation, IL-2R take the form of an alpha,beta,gama trimer which does what?

A

Enhances affinity 1000 fold

56
Q

Naive T cells enter the LN from circulation, activation and proliferation occurs, the now effector cells get back into circulation, then they are activated at the infection site by cytokine secretion and chemokine secretion. Then the antigen is eliminated

A

yep

57
Q

What drives the development of T helper 1 cells?

A

IL-12

58
Q

What drives the development of T helper 2 cells?

A

IL-4