(11) T-cell II

Question 1

(T cell differentiation in the thymus)

1. CD4 and CD8 are proteins on T cells that are associated with what?
2. What is a protein associated with the TCR and provides the singals to the T cell when TCR binds to MHC-ag complex?
3. How many T cells are lost in thymus?

Answer 1

1. The TCR
2. CD3
3. 95%

Question 2

• Which chain of TCR rearranges first?
• mature T cells leave the thymus via what?
• does t-cell production occur constitutively?

Answer 2

• the beta chain, then alpha
• the blood
• yes

Question 3

(T cell trafficking)

2. Once T cells enter the lymph tissue - what can they encounter?
3. What happens if they don’t?
4. What happens to T cells that do encounter their Ag?
5. Once activated, where do they go?
6. does t-cell receptor rearrange completely independent of antigens?

Answer 3

2. Ag presenting cells
3. reenter circulation via lymphatics
4. activated to proliferate and differentiate into armed effector cells
5. leave via lymphatics and circulate to other lymphoid organs, and tissues depending on what cytokines and chemokines they encounter
6. yes (part of development, not activation)

Question 4

just read this and get general idea (on ipad)

Question 5

(T cell maturation in the periphery)

1. Adaptive immune response starts by co-mingling of different cell types where and where?
2. What brings antigen to the lymph nodes?
3. What can it do there?
4. What are also present than interact with expanding T cells?
5. To become activated, T cell must receive multiple signal from what?
6. What are these signals?

Answer 5

1. draining lymph nodes and other secondary lymphoid organs
2. APC (dendritic cells)
3. can attract T cells via chemokine production (T cells will sample the presented antigens on the surface of the APC)
4. B cells
5. The APC
6. TCR must be engaged, co-stimulatory receptor-ligand interactions must occur, and cytokines must stimulate T cell

Question 6

T helper cells exist in functionally distinct suspopulations:

1. What do Th1 do?
2. Th2?
3. Th17?

Answer 6

1. activate phagocytes and amplify innate immune responses
2. activate B cells and amplify humoral immune responses
3. activate neutrophils

Question 7

just read this…

Answer 7

Question 8

(Th Cell Subpopulations)

1. Are CD4 cells leaving the thymus naive?
2. During activation in the lymph node they can become what of four types?
3. They exit the thymus as what? proliferate in response to what? then differentiate into what?
4. Pathway is controlled by what?

IL-12 and IFN-gamma causes what?

TGF-beta and IL-23 and IL-6?

IL-10 and IL-4?

5. Each Th cell subpopulation has different role in what?

Answer 8

1. no
2. Th1, Th2, Th17 (or Treg cells)
3. uncommitted Th0 cells; ag presentation; one of the subpopulations
4. cytokines

TH1

TH17

TH2

5. adaptive immunity

Question 9

(Th Cell Differentiation)

1. How can the pathogen influence which T cell population differentiates?
2. Viruses and some bacteria induce what secretion by dendritic cells? produce what?
3. Worms induce what? Cause what?

Answer 9

1. by influencing the cytokines produced (during the inital interaction with non-specific immune cells)
2. IL-12 and IFN-gamma ; Th1
3. IL-4; TH2

Question 10

(Th1 Cells)

1. What is the principal function of Th1 cells?
2. Secrete cytokines that augment what?
3. Secrete factors that inhibit what?

Answer 10

1. macrophage activation
2. augment non-specific immune responses
3. Th2 differentiation

(just look at list)

GC-CSF promotes granulocyte and macrophage production in bone

Question 11

remember these functions and factors that promote them - don’t kill yourself over it though - main thing to remember is that Th1 make “macrophages” happy

Answer 11

Question 12

1. What is the primary activity of Th2 cells?
2. Efficient activators of macrophages?
3. Secrete factors that regulate isotype switching? if so which ones?
4. Secrete factors that inhibit what? what specifi factors accomplish this?

Answer 12

1. to activate and differentiate B cells
2. no
3. yes, IL-4 and IL-5
4. inhibit Th1 differentiation; IL-4 and IL-5

Question 13

(Th2 cells influence IgE class switch)

1. IgE class switching in B cells is initiated by what cells? these develop in the presence of what?
2. The presence of what regulates isotype expression?
3. What is the first signal sent to Th0 cell through? second? third?
4. Do we always understand what drives production of certain cytokines? In some cases, the same pathogen can induce different responses (cytokines) depending on form or anatomic location

Answer 13

1. Th2, IL-4
2. cytokines
3. TCR MHC molecule, co-stimulatory molecules, cytokines
4. no

Question 14

(Th17 cells)

1. What cytokine is produced by Th17 cells? is it pro or anti-inflammatory? Play an important role in what?

Answer 14

1. IL-17; pro-inflammatory; against extracellular microbes and promoting neutrophil recruitment (to target extracellular bacteria)

Question 15

(Cytotoxic T Cells (Tc or CTL))

1. Do Tc interact with target cells bearing a specific antigen? Do they use the same receptor system as CD4? What is the only difference?
2. These are particularly important fighting what?
3. Will they kill surrounding cells of host?
4. Do they have rearranged TCR like Th cells do?

Answer 15

1. yes; yes; CD4 molecule replaced by CD8 homodimer
2. viral infections and intracellular bacteria
3. no
4. yes

Question 16

(Tc Cells)

1. What are the three cytotoxins the Tc granules release to kill cells?

Answer 16

1. perforin, granzymes, and lymphotoxin-alpha (LT-a)

Question 17

(Tc)

1. What does perforin do?
2. What do granzymes do?
3. What do lympotoxin-alpha do?

Answer 17

1. polymerizes on cell membrane to form pore
2. serine proteases which cleave proteins on target cell membrane
3. induces cell death via apoptosis (cell death by cleaving host DNA)

Question 18

(Tc Cells)

1. Are neighboring cells damaged when Tc cells kill stuff? What account for this specificity? Does this process damage Tc cells themselves?
2. How do Th cells augment Tc cells?
3. What do CD8+ cells secrete what that cna block viral replication?
4. do apoptotic cells trigger further inflammation?
5. Granzymes activate what in target cells to start apoptosis?
6. Do cytotoxic T-cells make cytokines that make target cells more susceptible to apoptois?

Answer 18

1. no; polar release of the cytolytic granules (release contents only in the space between the Tc cell and target); no (they can go to another cell)
2. secretion of IL-2 and by increasing MHC class 1 gene expression
3. IFN-a
4. no
5. capases
6. yes

Question 19

(Memory T cells)

1. After an immune response, the number of T cells responsive to the antigen increase how many times? These live a long time and are called what? Does this occur for both CD4 and CD8? How are they distinguished?
2. Do memory T cells hang out in one place like most memory B cells do (in the bone marrow)?

Answer 19

1. 100x; Memory T cells; yes; by surface proteins
2. nope - some produce cytokines and enter inflamed tissue - some express CCR7 and hang out in lymph nodes (don’t really need to remember these protein names)

Question 20

1. Are memory T cells like naive T cells? what’s the difference?
2. What are some benefits of some of the proteins that memory T cells express?

Answer 20

1. no, alot easier to activate memory T cells
2. gives you stronger receptor signalling, prolonged survival, or trafficking to certain tissues

Question 21

(understand this)

1. Are Th cells required to make and activate memory T cells?
   - the thing on the next page shows this in experimental form

Answer 21

1. yes