Assignment 9 - use pictures too!

Question 1

where does a primary immune response take place?

Answer 1

secondary lymphoid tissue

Question 2

what is the main function of effector CD4+ T cells?

Answer 2

secretion of cytokines

Question 3

when are T cells considered naive (Thp)?

Answer 3

when they survive the screening process in the thymus

*note they are unable to perform their biological function without a differentiation stage

Question 4

where does the antigen-induced differentiation stage occur for naive T cells?

Answer 4

outside of the thymus

Blood –> spleen
Mucosaltissue –>MALT–>laminapropria
Lymph–>lymphnode–>whitepulp

induced by high avidity interaction with foreign peptide/class II MHC in the presence of costimulatory signals

Question 5

what 2 things can T cells differentiate into?

Answer 5

memory cells

apoptosis

Question 6

what does the subset of Thp cell activation depend on

Answer 6

the cytokines in the local environment

Question 7

what does the activation of T cells require?

Answer 7

the antigen to be displayed on the surface of APC in association with class II MHC

Question 8

what is the most efficient APC

Answer 8

dendritic cell

Question 9

why is the dendritic cells the most efficient APC

Answer 9

because it expresses both class II MHC and various costimulatory molecules (whose counter products are present on the T cell)

Question 10

what happens when a T cells interacts with a peptide/class II MHC complex in the absence of costimulatory interactions

Answer 10

the T cell becomes unresponsive = anergic

Question 11

what are the interactions that take place between a T cell and APC

Answer 11

• class II MHC peptide ——– TCR
• class II MHC ——————-CD4
• ICAM(1,2,3)———————LFA-1 (CD11a/CD18)
• CD40—————————-CD40L (CD154)
• LFA-3—————————-CD2
• CD80—————————–CD28
• CD86—————————–CD28

*all enhance the avidity of peptide/MHC interactions with TCR

Question 12

what occurs when class II MHC peptide and TCR interact?

Answer 12

Thp express IL-2 receptors and secrete cytokine, IL-2

functions in autocrine + paracrine

Question 13

what does the interaction of IL-2 with IL-2 receptor induce?

Answer 13

clonal expansion of antigen stimulated T cells = increasing the number of T cells with specificity uniquely recognizing the class II MHC peptide complex that induced the initial differentiation

Question 14

what is hte role of the CD28 and CD80/86 interaction

Answer 14

to stabilize mRNA for IL-2

if this doesn’t occur = anergic T cell

Question 15

where are the two forms of B7 (CD80 = CD86/B7-1 and B7-2) expressed and induced

Answer 15

expressed - dendritic cells + peritoneal macrophages

induced - activated B cells, monocytes, Langerhans cells

Question 16

antigen induced differentiation of Thp proceeds via a _____ intermediate to either a ___ or ___ subset

Answer 16

Th0
Th1
Th2

*defined by the cytokines they secrete

Question 17

what cytokines do Th0 cells secrete?

Answer 17

IL-4
IL-2
IFNgamma

common to both subsets

Question 18

if IFNgamma is high, what subset predominates?

Answer 18

Th1

Question 19

if IL-4 is high, what subset predominates

Answer 19

Th2

Question 20

what is hte source of IL-4 before differentiation of Thp to Th2

Answer 20

Mast cells
basophils
other non T cells
transiently—Th0

provide in early phase of response
mast cell stimulation –> Th2 development

Question 21

what produces IFNgamma?

Answer 21

Th0 cells

IL-12 activated NK cells

Question 22

what cytokines have been shown to enhance the role of IL-12 on NK cell production IFNgamma production

Answer 22

IL-15

IL-18

Question 23

what cells secrete IL-12

Answer 23

activated dendritic cells
macrophages

influence of IL-12 on development may be indirect

Question 24

what are type 1 cytokines

Answer 24

IL-2
TNF
IFNg

Question 25

what are type 2 cytokines

Answer 25

``` IL-4 IL-5 IL-6 IL-10 TGFbeta IL-13 ```

Question 26

what is the role of type 1 cytokines

Answer 26

support immune responses in which macrophages, NK cells and CD8+ T cells are effectors resposnbile for delayed type hypersensitivity responses that are manifestations of activated memory CD4+ Th1 cells

Question 27

what is the role of type 2 cytokiens

Answer 27

support B cell induced activation support antigen induced B cell differentiation to plasma cells support isotype switching to IgG1 and IgE humoral immunity

Question 28

what is required for isotype switching to IgE?

Answer 28

IL-4

Question 29

in general, isotype swithcing requires the contribution of both _____ and ___ cytokines

Answer 29

type 1 and type 2

Question 30

what is hte role of IL-10

Answer 30

key role in down regulation of Th1 (cells/cytokines) -- this occurs via inhibition of IL-12 secretion by APC

Question 31

what are hte mechanisms that control T cell activation

Answer 31

1. loss of T cell stimulation because the infectious agent has been eliminated so class II MHC peptide are no longer being presented to T cells 2. reciprocal regulation of cytokine secretion by Th1 and Th2 cells 3. CTLA-2/CD152 interaction 4. CD200-CD200R interaction 5. apoptosis 6. regulatory T cells (Tregs)

Question 32

what are the T cells that leave the thymus?

Answer 32

- CD4+ naïve cell (Thp) | - Precytotoxic CD8+ T cells (pCTL)

Question 33

what does an active Thp express? What does it secrete and what does the secretion lead to? what does it stimulate the dendritic cell to secrete? what does this do?

Answer 33

IL-2R secretion IL-2 - induces expansion of Th0 clones form antigen stimulated T-cells secretion of IL-12 from dendritic cell - activates NK cell to secrete IFN gamma

Question 34

what cytokines are secreted by Th0 clones?

Answer 34

IFNy --> Th1 cells (type 1 cytokines) IL-2 --> makes more Th0 clones IL-4 -> Th2 cells (type 2 cytokines)

Question 35

what triggers the secretion of IL-4?

Answer 35

mast cell

Question 36

how does T cell regulation occur in Th1?

Answer 36

CD80/CD86 ---CD152(CTLA-4) = T cell downreg | CD80/CD86 ---CD28 = T cell activation

Question 37

what is the role of IFNy?

Answer 37

its a Th1 cytokine that shuts off Th2

Question 38

what cytokines turn off Th1?

Answer 38

IL-10 IL-4 both are Th2 cytokines

Question 39

what is the role of IL-10

Answer 39

inhibits secretion of IL-12 by APC | downstream inhibits Th1 and prevents NK cells from producing IFNy

Question 40

how is pCTL (precytotoxic CD8+ T cell) activated

Answer 40

interaction with: - CD4+ T cell derived IL-2 cytokine - Target cell expressing antigen + class I MHC - CD2---LFA3 - LFA1---ICAM (1,2,3) - CD8 binds to class I MHC at separate site from where it binds to TCR

Question 41

what is the difference between the differentiation stage environments between CD4+ and CD8+ T cells

Answer 41

CD4+ need secondary lymphoid tissue | CD8+ it can do it anywhere, site of infection etc.

Question 42

what occurs in the progression from pCTL to CTL

Answer 42

- IL-2 expression - preCTL detaches from target cell expressing antigen - differentiation takes about 1 week

Question 43

what occurs when there is a delivery of lethal hit

Answer 43

-mature CTL (CD8+) conjugates with target cell -conjugate formation triggers locatization of lytic granules to membrane where two cells are attached o granules are released outward toward target cell -polarized release of granules ensures specificity of killing target cell and not self -death caused by osmotic lysis or apoptosis -CTL detaches and continues its function of immunological surveillance -as elimination of virally infected cells occurs the antigenic stimulus for specific CD8+Tcells decrease. -CTL clones that are generated with TCRs specific for the antigen will die others will become dormant (memory cells) -Memory cells will become activated immediately in the event that the antigen reappears -These cells require less costimulation than for the primary response

Question 44

how long does it take for pCTL--> CTL

Answer 44

1 week

Question 45

what does the interaction between CD200 and CD200R lead to?

Answer 45

suppression of T cell mediated immune response - immunosupressent

Question 46

CD200 is expressed on what cells?

Answer 46

T cells B cells Dendritic cells

Question 47

CD200R is expressed on what

Answer 47

myeloid lineage cells | and some T cells