B and T Cell Activation and Regulation Flashcards
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.
What is the ultimate outcome of T-dependent B cell activation?
Initial B cell undergoes minimal isotype switching and produces low affinity Ab. It then migrates to the germinal center of follicle in lymph nodes where it undergoes isotype switching and somatic hypermutation (via AID) to affinity mature.
Do memory b cells need to see Ag again to be maintained?
No –> they are maintained by cytokines
How is B cell activation regulated?
Once sufficient Ab has been made, it will bind to a receptor (Fc receptor) on the surface of the B cell and block the effector signal from binding of microbe / Ag.
How is T-cell activation regulated (2)?
- Through action of CTLA-4, which is a receptor with high affinity for B7. CTLA-4 is expressed on Treg cells so it prevents further activation of B7.
- Contraction –> signaling from Ag declines –> no longer signaled to proliferate –> stresses T cells –> upregulation of Fas and Fas ligand –> apoptosis
What is T cell exhaustion?
Refers to inability of CD8+ cells to respond to an Ag if the Ag is presented over too long a period of time. Infected cells will express inhibitory ligand resulting in no cytotoxic effects. This can occur in chronic infections and cancer.
What antigens stimulate T-independent activation of B cells?
Polysaccharide
Lipid
Other non protein antigens
What antigens stimulate T-dependent B cell activation?
proteins
