Immuno - Lymphocytes (T cells & Lymphocyte activation) Flashcards
Pg. 200-202 in First Aid 2014 Pg. 195-197 in First Aid 2013 Sections include: -Differentiation of T cells -T and B cell activation -Helper T cells -Cytotoxic T cells -Regulatory T cells
What are the sites of T cell differentiation, and what major events occur at each site?
(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
Where does positive selection occur? What T cells survive it?
Thymic cortex; T cells expressing TCRs capable of binding surface self MHC molecules survive
Where does negative selection occur? What T cells undergo apoptosis?
Medulla; T cells expressing TCRs with high affinity for self antigens undergo apoptosis
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?
IL-12 => Th1; IL-4 -> Th2; TGF-Beta + IL-6 => Th17 cell; TGF-Beta => T reg cell
What kinds of cells do cytotoxic T cells kill?
Kills virus-infected, neoplastic, and donor graft cells
What are the antigen presenting cells (APCs) involved in T and B cell activation?
(1) Dendritic cell (only APC that can activate naive T cell) (2) Macrophage (3) B cell
What is required for T cell activation and/or B cell activation and class switching?
Two signals are required for T cell activation and B cell activation and class switching
What are the 4 major steps involved in naive T cell activation?
(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.
What is the only APC that can activate naive T cells?
Dendritic cell
What are the 4 major steps involved in B cell activation and class switching?
(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.
What is the “costimulatory signal” for T cell activation?
“Costimulatory signal” is given by interaction of B7 (dendritic cell) and CD28 (T cells) = Signal 2
What is “signal 2” for B cell activation and class switching?
CD40 receptor on B cell binds CD40 ligand on Th cell (signal 2)
What determines class switching of B cells? Besides class switching, what are 2 other major events that occur after a B cell activates?
Th cell secretes cytokines that determine Ig class switching of B cell. B cell activates and undergoes class switching, affinity maturation, and antibody production.
What is the difference between Th1 and Th2 cells in terms of cytokines secreted?
Th1 - Secretes IFN-gamma; Th2 - Secretes IL-4, IL-5, IL-6, IL-13, IL-10
What is the difference between Th1 and Th2 cells in terms of function/purpose?
Th1 - Activates macrophages and cytotoxic T lymphocytes (CTLs); Th2 - Recruits eosinophils for parasite defense and promotes IgE production by B cells
What is the difference between Th1 and Th2 cells in terms of their inhibitors?
Th1 - Inhibited by IL-4 and IL-10 (from Th2 cell); Th2 - Inhibited by IFN-gamma (from Th1 cell)
What is the “macrophage-lymphocyte interaction”?
Macrophages release IL-12, which stimulates T cells to differentiate into Th1 cells. Th1 cells release IFN-gamma to stimulate macrophages.
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?
Helper T cells have CD4, which binds to MHC II on APCs
What function do cytotoxic T cells serve, and how in general?
Kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis
How exactly do cytotoxic T cells induce apoptosis? Be specific.
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
What is perforin, and what function does it serve?
One of the preformed proteins released in the cytotoxic granules of killer T cells; helps to deliver the content of granules into target cells
What is granzyme, and what function does it serve?
One of the preformed proteins released in the cytotoxic granules of killer T cells; a serine protease, activates apoptosis inside target cell
What is granulysin, and what function does it serve?
One of the preformed proteins released in the cytotoxic granules of killer T cells; antimicrobial, induces apoptosis
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?
Cytotoxic T cells have CD8, which binds to MHC 1 on virus-infected cells
What function do Regulatory T cells serve, and how in general?
Help maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions
What cell surface markers do Regulatory T cells express? What transcription factor do they express?
Express CD3, CD4, CD25 (alpha chain of IL-2 receptor) cell surface markers, and transcription factor FOXP3
What cytokines do activated regulatory T cells produce?
Activated regulatory T cells produce anti-inflammatory cytokines like IL-10 and TGF-beta
