BIOL 435 Ch. 10 p.1 (T-cell Activation and more)

Question 1

event that triggers an adapative response

Answer 1

-interaction between a naive T-cell and an activated APC

>activated APC will migrate to secondary lymphoid organs

Question 2

secondary lymphoid organs

Answer 2

• Peyer’s patches
• draining lymph nodes
• spleen

Question 3

T-cell activation

Answer 3

• requires 2 signals
  1. Ag presentation (MHC/Ag-TCR)
  2. Costimulation (CD80/86 and CD28)

Question 4

T-cell differentiation

Answer 4

-requires a 3rd signal to differentiate into effector forms
>CD8+: killer T cells
>CD4+: several subsets

Question 5

CD80/86

Answer 5

-only on APC

>only cells who can give the second signal

Question 6

CD28

Answer 6

-on T cell

Question 7

successful T-cell APC interactions

Answer 7

-organize signalling molecules into an immunological synapse

Question 8

cSMAC

Answer 8

• central supramolecular activating complex

- TRC/MHC-peptide complexes and co-receptors (CD28 and CD80/86)

Question 9

pSMAC

Answer 9

• peripheral supramolecular activating complex
• adhesion molecules/bound ligands
• LFA with ICAM or CD2
• bring cells close together so synapse can form

Question 10

T-cell activation multiple pathways

Answer 10

-ITAMs phosphorylated on CD3
>become docking sites for ZAP-70
*leads to activation of gene for survival, proliferation and effector function

Question 11

positive costimulatory

Answer 11

• facilitate activation

ex. CD28 on T-cell with CD80/86 on pAPCs

Question 12

negative costimulatory (coinhibitory)

Answer 12

-help turn activation off
-ex. CTLA-4 on T-cell and CD80/86 on pAPC
>negative regulation of immune response

Question 13

clonal anergy results if

Answer 13

• costimulatory signal 2 is absent or inhibitory

* helps provide tolerance (especially in periphery)

Question 14

1 signal received

Answer 14

• cell is rendered non-responsive

- might happen if a T-cell isn’t screened against a peripheral self-Ag during development

Question 15

cells with costimulatory properties

Answer 15

• dendritc cells
• macrophages
• B cells
• can provide both signals to activate T-cells

Question 16

super antigens

Answer 16

• a special class of T-cell activators
• viral/bacterial proteins that bind to specific variable beta (Vb) regions of TCRs and alpha chain of class II MHC molecules
• ‘short circuits’ need for costimulation

Question 17

super anitgens produce

Answer 17

-dramatic cytokine secretion by large portion of inappropriately activated T-cells

Question 18

exogenous superantigens

Answer 18

-soluble proteins secreted by bacteria

Question 19

endogneous superantigens

Answer 19

-cell membrane proteins generated by viral genes integrated into mammalian genomes

Question 20

superantigens bind

Answer 20

-outside Ag-binding cleft

>only T-cell expressing V-beta sequence will be activated

Question 21

activation due to superantigen

Answer 21

-is polyclonal
-can result in massive T-cell activation
>overproduction of TH cell cytokines and systemic cytotoxicity

Question 22

examples of superantigens

Answer 22

-toxic shock syndrmoe toxin
-streptococcal pyrogenic exotoxins
>rheumatic fever and shock

Question 23

cytokines provide signal 3

Answer 23

• differentiation of activated T-cells

- different outcomes occur depending on cytokines present

Question 24

IL-2

Answer 24

• example of an autocrine type of cytokine response system
• T-cells produce IL-2 and IL-2 receptor
• binding of ligand induces a very strong proliferation signal during activation stages

Question 25

polarizing cytokines

Answer 25

• can send the T-cell down different subset development pathways
• regulate differentiation of T helper cell subsets

Question 26

initial activation signals 1 and 2 induce

Answer 26

-upregulation of pro-survival genes (eg. Bcl-2)
-transcription of IL-2 and IL-2R genes
*outcome is activation and robust proliferation
>production of memory cells and effector clonal cells

Question 27

IL-2R alpha chain

Answer 27

-only expressed in activation T-cells

Question 28

APCs may bind PAMPs via PRRs

Answer 28

• induces cytokine secretion

- different PRR=different cytokines produced

Question 29

viruses stimulate

Answer 29

-IL-12 to induce TH1 subsets

Question 30

worms stimulate

Answer 30

-IL-4 to induce TH2 subsets

Question 31

effector T helper subsets

Answer 31

• are distinguished by 3 properties
  1. A distinct polarizing cytokine set that induces expression of
  2. A mastor gene regulator that regulates expression of
  3. A signature set of efffector cytokines produced by that subset