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Block 6 Week 1 > Hudig: Antigen Recognition and Effects of T Cells > Flashcards

Hudig: Antigen Recognition and Effects of T Cells Flashcards

1
Q

What are the two flavors of T cells receptors?

A

alpha-beta

delta-gamma

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2
Q

This is found on ALL T cells

A

CD3

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3
Q

What must T cells do before they are able to mediate functions?

A

come in contact with antigen and PROLIFERATE

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4
Q

How long do memory T cells last? What must happen before they are able to mediate functions?

A

They last a lifetime; must be re-stimulated by antigen and PROLIFERATE

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5
Q

What do T follicular helper cells secrete?

A

IFN gamma, IL2, IL4, IL5

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6
Q

What do T helper 1 cells secrete?

A

IFN gamma

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7
Q

What do T helper 2 cells secrete?

A

IL4

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8
Q

What do T helper 17 cells secrete?

A

IL17

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9
Q

What do T follicular helper cells do?

A

produce growth factors, specifically IL2, for ALL T and B cells

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10
Q

What do TH1 cells do?

A

increase cytotoxic T cell activity

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11
Q

What do TH2 cells do?

A

increase antibody production, switch to IgE

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12
Q

What do TH17 cells do?

A

bring neutrophils to the site

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13
Q

What do CD4 T regs do?

A

regulate proliferation of normal T and B cell response, suppress autoimmunity

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14
Q

What do CD8 cytotoxic T cells do?

A

kill cells infected with viruses

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15
Q

What marker is used to recognize T cells in the blood?

A

CD25

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16
Q

What can a lack of CD4 T helpers lead to?

A

AIDS

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17
Q

When a resting naive T cell with a specific T cell receptor comes in contact with its antigen via an antigen presenting cell, what does it do?

A

DIVIDES before it becomes effective, produces IL2

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18
Q

What types of cells are found in Peyer’s patches?

A

both T and B cells

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19
Q

How do T helper 1 and T helper 2 cells differ?

A

T helper 1 cells produce interferon gamma, while T helper 2 cells produce IL4. TH1s activate macrophages, help promote antibody production by B cells, and cause cytotoxic T cells to produce cytotoxic granules. TH2s are more involved in promoting Ab production and isotype switching.

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20
Q

Which T helper cell, 1 or 2, activates infected macrophages and provides help to B cells for Ab production?

A

T1

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21
Q

Which T helper cell, 1 or 2, provides help to B cells for antibody production, specifically switching to IgE?

A

T2

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22
Q

TH1 and TH2 cells can polarize immune responses. TH1 responses drive which type of immune response? TH2 responses drive which type of immune response?

A

cellular - TH1 cell releases IFNg and IL2 which causes cytotoxic T cells to produce cytotoxic granules; humoral - TH2 cell releases IL2, IL4, and IL5 which binds to B cells and causes antibody production

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23
Q

What cytokine directs a T helper 0 cell to become a TH1 cell?

A

IL12

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24
Q

What cytokine directs a T helper 0 cell to become a TH2 cell?

A

IL4 from activated mast cells and TH2 cells

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25
Q

What type of T helper cell helps control intracellular Mycobacterium tuberculosis which causes TB?

A

TH1 T cell

*TH1s control intracellular bacterial clearance. If TB infects your macrophages and lies dormant in vacuoles, you need your TH1s to be working hard!

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26
Q

What do T helper 1 cells use to tell macrophages to kill bacteria inside of them?

A

interferon gamma

**macrophage eats up the TB bacteria, then when the CD$TH1 cell encounters an MHC class II molecule with a TB peptide antigen, it secretes IFNg, which turns on a whole set of genes and ultimately kills the bacteria with toxic agents like NO

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27
Q

So, again, what is released from TH1 T cells to help deal with a TB bacterial infection?

A

IFNgamma

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28
Q

What cells mediate delayed type hypersensitivity?

A

TH1 cells

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29
Q

Can infected macrophages kill their bacteria themselves? How?

A

yes, they MUST be activated by an antigen-specific CD4+ memory TH1 cell in order to kill

30
Q

What is required to expand the TH1 numbers to an effective number to see a delayed type hypersensitivity response?

A

need primary exposure or immunization in order to proliferate TH1 numbers and see a delayed type hypersensitivity

31
Q

What antigen is used in a skin TB test? What cells are required to elicit a response to the test?

A

PPD - purified protein derivative
memory DTH CD4 T cells that recognize the PPD peptides are required to evoke a macrophage inflammatory response, which kills the bacteria and causes a skin inflammation

**so, if you have been infected with TB, you will have memory DTH CD4 T cells that recognize the peptide, and when you receive the skin test, you will develop a skin reaction. This is a positive TB skin test.

32
Q

Why does it take ~48 hours for a TB skin test to work?

A

It takes time for the 2 cell types to activate - resting memory TH1 cells must induce mRNA and make IFNg and macrophages must be primed, too

33
Q

What do T helper 2 cells secrete? What does this do?

A

secrete IL4, which drives B cells to switch to IgE

34
Q

What cytokines are critical in controlling helminths (worms classified as parasites)?

A

IL3 and IL9

35
Q

What do Thelper17 cells do? What do they secrete?

A

secrete IL17, which activates resident fibroblasts and other cells which induce inflammation and brings in neutrophils to the site of infection.

36
Q

What causes T helper 0 cells to become Thelper17 cells?

37
Q

Neutrophils migrate into tissues and kill bacteria. How could you identify a neutrophil?

A

multi-lobed nucleus

38
Q

What do Tregs do? What do they secrete to aid in this process?

A

Tregs recognize both foreign and self peptides. They release TGFbeta and IL10 to suppress T helper cells so that they ultimately create less cytokines and stop dividing!

39
Q

Tregs are released from the thymus as (blank) T cells.

A

CD4+CD25+

*all other T cells are CD25-

40
Q

What would happen without T cell regulation?

A

T cells would keep proliferating and keep producing cytokines and you would have swollen lymph nodes and a swollen spleen. You need tight regulation!

41
Q

List 7 types of lymphocytes that divide in response to specific antigens

A 
T follicular cell
CD4 Thelper 1 cell
CD4 Thelper 2 cell
CD4 Thelper 17 cell
CD4 T reg
CD8 cytotoxic T cell
B cells
42
Q

What does overproduction of Tregs in TB lead to?

A

clinical anergy

  • *Tregs produce IL10 which shuts off IFNg production
  • *TGFbeta turns off all proliferative responses
  • *Pts are unable to respond to TB skin test, candida tests, new antigens, etc
43
Q

To summarize, list the cytokine secreted and the main function of each of the following:

T follicular helper cell
CD4 TH1 cell
CD4 TH2 cell
CD4 TH17 cell
CD4 T reg
A

TFH cell: IFNg, IL2, IL4, IL5; helps B cells switch to IgE Ab production
CD4TH1: IFNg; activates infected macrophages, helps B cells to produce Ab
CD4TH2: IL4; helps B cells produce Ab and switch to IgE
CD4TH17: IL17; enhances neutrophil response, promotes barrier integrity
CD4 T reg: IL10, TGFbeta; suppress T cell response

44
Q

CD8 cytotoxic T cells are introduced to antigen, proliferate, and release cytokines in order to become cytotoxic. What are some cytokines they produce?

A

IL2, IL15, IL21, IFNg

45
Q

What must CD8 cytotoxic T cells have in order to kill?

A

they need cytotoxic granules with perforin OR they must have membrane molecules of the TNF receptor family (ex: FasL)

46
Q

Again, which class of MHC molecules do CD8 T cells associate with?

A

MHC class I

47
Q

What are two ways in which cytotoxic T lymphocytes can prevent viral replication?

A
  1. use IFNgamma to induce the infected cell to degrade viral mRNA
  2. kill the infected cell via necrosis or apoptosis
48
Q

Cytotoxic T cells can kill viruses via necrosis or apoptosis. What is the difference?

A

necrosis involves damage from outside the cell - the plasma membrane is irreversibly damaged
apoptosis involves damage from the inside, like cellular suicide. The plasma membrane usu remains intact.

49
Q

Which 2 cell types release perforin and granzymes?

A

CTLs and NK cells

50
Q

How do cytotoxic T cells kill the infected cell?

A
  1. CTL binds specifically to the infected target cell via dual recognition (to the peptide and to the MHC molecule)
  2. kills via FAS ligand OR by granule exocytosis
51
Q

What does killing by FasL require?

A

Killing by FasL requires Fas on the target cell and FasL on the killer CTL. When these interact, caspase-dependent apoptosis occurs

52
Q

Do resting CD8 memory T’s has FasL and cytotoxic granules? What do they need to induce these molecules?

A

No! They need IL2 and other cytokines to induce these molecules

53
Q

What are the contents of cytotoxic granules?

A

perforin**
granzymes**
granulysin

54
Q

How do granules cause cell death?

A

Perforin release can cause immediate necrosis because it punctures the cell.

Or

Granzymes A and B enter the target cell after perforin makes it permeable. The cell then undergoes apoptosis.

55
Q

Most CD8 T cells are anti-viral, but what component of CD8 CTLs call also kill TB bacteria?

A

granulysin

56
Q

Why are live vaccines more effective than inactivated vaccines?

A

live vaccines will present the antigen in MHC I to T cells and will boost memory CTLs to prevent disease (as opposed to just generating antibodies)

ex: shingles

57
Q

Which type of vaccines are most effective?

A

CTL-inducing vaccines in which live virus is induced and presented in MHCI

**polio vaccine has nearly wiped out polio

58
Q

What condition is this:
Defective thymus, parathyroid, and heart. Pt has low T cells, but has antibodies. Pt may be resistant to bacterial infections, but die of viral infections.

A

diGeorge Syndrome

**affects T cells, suggests that more Ab are needed to eliminate viruses

59
Q

T cell receptors have dual recognition which means that they recognize both the (blank) and the (blank)

A

peptide; MHC

60
Q

If there is no infection and no antigen peptide held in MHC, what is held in MHC?

A

self peptides

61
Q

What happens to T cells that have anti-self T cell receptors?

A

they are deleted or made unresponsive

62
Q

Which two cofactors of T cells initiate the recognition signal?

A

CD3 and CD8

63
Q

How do MHC class II proteins differ from MHC class I?

A

MHC class II proteins can bind larger peptides, hold peptides for CD4 T cells, and have an alpha-beta chain dimer; MHC class I proteins binds smaller peptides (forms a cleft to bind the peptide), hold peptides for CD8 T cells, and have a single alpha chain + a beta2microglobulin

64
Q

CD4 and CD8 are both considered (blank) for antigens

A

co-receptors

65
Q

CD4 T cells bind only to (blank) and CD8 T cells to (blank)

A

MHC II; MHC I

66
Q

What molecule presents NON-peptide antigens, such as lipid antigens, to T cells?

A

CD1

  • not an MHC protein, but similar
  • CD4negCD8neg T cells respond
67
Q

In addition to antigen, what do CD4 and CD8 T cells require to elicit a response? Give an example.

A

Both CD4 and CD8 T cells require co-stimulation.

Ex: Signal 1 for T cells in antigen
Signal 2 is B7, which interacts with CD28 on T cells
*also, you need a triggering event, like the innate IL1/TNFalpha danger signal to elicit a response

68
Q

What do T cells require as a “signal 2” after encountering antigen? What happens if they don’t receive this signal?

A

B7; they die or become anergic

69
Q

What are some similarities between T and B cells in regards to cell receptor structure and function?

A
  1. their receptors have two chains
  2. variable Ag binding regions at the end of the receptor chain
  3. receptors with short intra-cytoplasmic tails
  4. other molecules perform transmembrane signaling
70
Q

What are some differences between T and B cells in regards to cell receptor structure and function?

A

B cells have Ig receptors that recognize native antigen structures
T cell receptors recognize “processed” proteins
T cell receptors don’t undergo changes in AA sequence
B cells can later secrete proteins similar to their antigen receptor proteins
B cells undergo gene mutation for affinity maturation of the receptor and immunoglobulin

Block 6 Week 1 (13 decks)

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