B and T Cell Activation and Regulation Flashcards
(33 cards)
What 2 things must happen for T cells to be activated by an APC?
Signal 1 = recognition of Ag bound to MHC I or MHC II via T cell’s TCR
Signal 2 = costimulatory ligand
What is signal 2?
Co-stimulatory molecules and cytokines
The TCR recognizes antigen bound to MHC but it cannot transmit that signal to the interior of the cell to produce a response. What other molecules are part of the TCR complex that lead to this respone?
CD4 –> binds to MHC II Beta 2 region and stabilizes interaction –> activates kinase that phosphorylates CD3 and zeta chain intracellular effector regions –> signal transduction and activation of Ras and MAPK pathways
For a T cell, what is signal 1?
The TCR complex (TCR + CD 4/8 + CD3 etc.)
What is signal 2 that is needed for interaction between dendritic cells and T cells in lymph nodes?
Dendritic cell expresses B7, which is the ligand for receptor (CD28) on T cells
Describe the process of dendritic cell maturation to express signal 2.
What are the downstream effects of activation of a t cell by signal 1 and signal 2?
Cell survival
Cell proliferation
Differentiation into effector and memory cells
Describe how activation by signal 1 and signal 2 leads to proliferation.
Signal 1 + signal 2 leads to T cell secreting IL-2, which leads to clonal expansion of that activated T cell
Activated T cells upregulate CD40 ligand. CD40 ligand binds to CD40 receptor on several cell types. Describe what happens when CD40 Ligand on the activated T cell binds to CD40 receptor on:
- A dendritic cell that is activating the T cell?
- B cells?
- Macrophages?
Intracellular microbes activate dendritic cells to secrete ______ which activates T cells to become Th# cells.
IL-12
Th1
Intracellular microbes trigger NK cells to secrete _____ which activates Th cells to differentiate into Th# cells.
INF-gamma
1
Secretion of IL-# in response to helminths causes Th cells to differentiate into Th# cells.
IL-4
Th2
Th cells are triggered to differentiate into Th17 cells in response to _______ pathogens.
Extracellular
Th 1 Differentiation
- Induced by what 2 cytokines?
- What cytokine is secreted by Th1 cells?
- What is the function of Th1 cells?
- IL-12 and INF-gamma
- INF-gamma
- Promotes killing of phagocytosed microbes and inhibits development of Th2 or Th17 differentiation
Th2 Differentiation
- What 2 cytokines induce differentiation?
- What cells induce differentiation?
- Cells that induce differentiation do so in response to what?
- What cytokines do Th2 cells secrete?
- What is the function of Th2 cells?
- IL-4 and IL-25
- Mast cells and eosinophils
- Helminths and allergens
- IL-4 and IL-5
Th 17 Differentiation
- What cytokines induce differentiation into Th17 cells?
- What cytokines to Th17 cells secrete?
- What is the function of Th17 cells?
- IL-1 and IL-6 from dendritic cells
- IL-17 and IL-22
- recruit neutrophils and monocytes to site of infection and cause inflammation
How are CD8+ T cells activated?
Require signals 1 (Ag) and 2 (B7 = ligand for CD28) to come from either APCs that are infected with an intracellular microbe or from an APC that is displaying cross-presentation.
What are 2 ways in which CD4+ cells can activate CD8+ cells?
Once activated, what do CD8+ cells do?
Same mechanisms as NK cells
Mature, naive B cells express what 2 Abs on their surface?
IgM and IgD
What happens to a B cell after it has been activated by microbe/Ag binding to its cellular receptors (IgM or IgD)?
Describe T-independent B cell activation (3 possible mechanisms)
- Multivalent Ag binds to surface IgM or IgD on B cell. Nearby Ig alpha and beta are co-stimulated and lead to effector response of activation
- Ag on surface of microbe binds to IgM or IgD. Microbe is bound by C3d of complement cascade. Binds to co-receptor CR2, which transmits effector signal to B cell to activate
- Ag on surface of microbe binds to IgM or IgD and a PAMP from the microbe binds to TLR.
What is the end resut of T-independent B cell activation?
Productin of low-affinity IgM Ab
Describe the process of T-dependent B cell differentiation.
Signal 1 - IgM or IgD bind to Ag, B cell endocytoses Ag, processes Ag via phagolysosome and presents peptide on MHC II.
Signal 2 - Dendritic cell presents Ag to Th cell to activate Th cell –> upregulation of CD40L –> activated T cell migrates toward follicle in lymph node where interacts with B cell –> B cell CD40 receptor binds CD40L on T cell to activate B cell and stimulate proliferation and differentiation.
