Immuno - Lymphocytes (T cells & Lymphocyte activation)

Question 1

What are the sites of T cell differentiation, and what major events occur at each site?

Answer 1

(1) BONE MARROW - T-cell precursor (2) THYMUS - Positive selection (cortex) –> CD4+CD8+ T cell & Negative selection (medulla) –> CD4+ vs. CD8+ T cell (3) LYMPH NODE - cytotoxic vs. helper T cell & helper T cell –> Th1 vs. Th2

Question 2

Where does positive selection occur? What T cells survive it?

Answer 2

Thymic cortex; T cells expressing TCRs capable of binding surface self MHC molecules survive

Question 3

Where does negative selection occur? What T cells undergo apoptosis?

Answer 3

Medulla; T cells expressing TCRs with high affinity for self antigens undergo apoptosis

Question 4

Which cytokines differentiate a CD4+ helper T cell into Th1 versus Th2? What are 2 other classes into which helper T cells can differentiate? What cytokines promote differentiation into each?

Answer 4

IL-12 => Th1; IL-4 -> Th2; TGF-Beta + IL-6 => Th17 cell; TGF-Beta => T reg cell

Question 5

What kinds of cells do cytotoxic T cells kill?

Answer 5

Kills virus-infected, neoplastic, and donor graft cells

Question 6

What are the antigen presenting cells (APCs) involved in T and B cell activation?

Answer 6

(1) Dendritic cell (only APC that can activate naive T cell) (2) Macrophage (3) B cell

Question 7

What is required for T cell activation and/or B cell activation and class switching?

Answer 7

Two signals are required for T cell activation and B cell activation and class switching

Question 8

What are the 4 major steps involved in naive T cell activation?

Answer 8

(1) Foreign body is phagocytosed by dendritic cell (2) Signal 1: Foreign antigen is presented on MHC II and recognized by TCR on Th (helper) cell. Antigen is presented on MHC I to Tc (cytotoxic) cells.
(3) Signal 2: “Costimulatory signal” is given by interaction of B7 and CD28.
(4) Th cell activates and produces cytokines. Tc cell activates and is able to recognize and kill virus-infected cell.

Question 9

What is the only APC that can activate naive T cells?

Answer 9

Dendritic cell

Question 10

What are the 4 major steps involved in B cell activation and class switching?

Answer 10

(1) Helper T cell activation (as in previous card)
(2) Signal 1: B cell receptor-mediated endocytosis; foreign antigen is presented on MHC II and recognized by TCR on Th cell.
(3) Signal 2: CD40 receptor on B cell binds CD40 ligand on T cell.
(4) Th cell secretes cytokines that determine Ig class switching of B cell. B cell activates and undergoes class switching, affinity maturation, and antibody production.

Question 11

What is the “costimulatory signal” for T cell activation?

Answer 11

“Costimulatory signal” is given by interaction of B7 (dendritic cell) and CD28 (T cells) = Signal 2

Question 12

What is “signal 2” for B cell activation and class switching?

Answer 12

CD40 receptor on B cell binds CD40 ligand on Th cell (signal 2)

Question 13

What determines class switching of B cells? Besides class switching, what are 2 other major events that occur after a B cell activates?

Answer 13

Th cell secretes cytokines that determine Ig class switching of B cell. B cell activates and undergoes class switching, affinity maturation, and antibody production.

Question 14

What is the difference between Th1 and Th2 cells in terms of cytokines secreted?

Answer 14

Th1 - Secretes IFN-gamma; Th2 - Secretes IL-4, IL-5, IL-6, IL-13, IL-10

Question 15

What is the difference between Th1 and Th2 cells in terms of function/purpose?

Answer 15

Th1 - Activates macrophages and cytotoxic T lymphocytes (CTLs); Th2 - Recruits eosinophils for parasite defense and promotes IgE production by B cells

Question 16

What is the difference between Th1 and Th2 cells in terms of their inhibitors?

Answer 16

Th1 - Inhibited by IL-4 and IL-10 (from Th2 cell); Th2 - Inhibited by IFN-gamma (from Th1 cell)

Question 17

What is the “macrophage-lymphocyte interaction”?

Answer 17

Macrophages release IL-12, which stimulates T cells to differentiate into Th1 cells. Th1 cells release IFN-gamma to stimulate macrophages.

Question 18

What kind of CD do T helper cells have? What kind of MHC does it bind, and on what kinds of cells is that MHC found?

Answer 18

Helper T cells have CD4, which binds to MHC II on APCs

Question 19

What function do cytotoxic T cells serve, and how in general?

Answer 19

Kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis

Question 20

How exactly do cytotoxic T cells induce apoptosis? Be specific.

Answer 20

Release cytotoxic granules containing preformed proteins; Preformed proteins include (1) Perforin - helps to deliver the content of granules into target cells (2) Granzyme - a serine protease, activates apoptosis inside target cell (3) Granulysin - antimicrobial, induces apoptosis

Question 21

What is perforin, and what function does it serve?

Answer 21

One of the preformed proteins released in the cytotoxic granules of killer T cells; helps to deliver the content of granules into target cells

Question 22

What is granzyme, and what function does it serve?

Answer 22

One of the preformed proteins released in the cytotoxic granules of killer T cells; a serine protease, activates apoptosis inside target cell

Question 23

What is granulysin, and what function does it serve?

Answer 23

One of the preformed proteins released in the cytotoxic granules of killer T cells; antimicrobial, induces apoptosis

Question 24

What kind of CD do cytotoxic T cells have? What kind of MHC do they bind, and on what kind of cells do they bind these MHC?

Answer 24

Cytotoxic T cells have CD8, which binds to MHC 1 on virus-infected cells

Question 25

What function do Regulatory T cells serve, and how in general?

Answer 25

Help maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions

Question 26

What cell surface markers do Regulatory T cells express? What transcription factor do they express?

Answer 26

Express CD3, CD4, CD25 (alpha chain of IL-2 receptor) cell surface markers, and transcription factor FOXP3

Question 27

What cytokines do activated regulatory T cells produce?

Answer 27

Activated regulatory T cells produce anti-inflammatory cytokines like IL-10 and TGF-beta