Flashcards in IAHI [Week 2] Deck (44):
What are 3 characteristics of germ line encoded receptors and give 2 examples?
1. Heritable, set order, and the same in each cell.
2. PRRs (TLR) and MHC
What TFs are activated from a PAMP binding a PRR, what cytokines get released, and what is the body's response?
1. NFκB or IRF3
2. TNFα, IL-1, and IL-6
3. Activate neutrophils and initiate fever
What secretes G-CSF and GM-CSF?
Macrophages and T Helper
What is the effect of G-CSF and GM-CSF?
Induce proliferation in bone marrow and the egress of PMNs
What cells secrete IL-8 and what is its function?
1. Macrophages, endothelial cells, airway smooth muscle cells
2. Help pull PMNs out of circulation to site of infection (chemotaxis)
What are the main 4 signaling molecules that control neutrophil influx?
G-CSF, GM-CSF, IL-8 and chemokines
What cells secrete chemokines and what are their effects?
1. Macrophages, DC, endothelial cells, T lymphocytes, fibroblasts, and platelets
2. Promote migration of neutrophils to infected site via a gradient, activate integrin so PMNs form stable adhesions
Do chemokines function in a cell contact dependent or independent manner?
Cell contact independent
What are 3 characteristics of receptors produced by genetic recombination and what are two examples?
1. Inherit segments, Pre "clonal expansion" each cells have different arrangements, not necessarily the same as parents.
2. TCR and Ig
How are chemokines classified?
By their biochemical structure - location of Cys residues
In concert with TNFα and IL-1, what else promotes the 4 stages of PMN extravasation?
Is T cell activation cell contact dependent or independent?
Cell contact dependent
After T cell activation what 3 things result from the signaling pathway?
1. CD40L expression -> B cell Ig class switching
2. IL-2 and IL-2R expression - proliferation
3. DNA synthesis - division
IL-2 is a cytokine that provides ____________, cell contact independent, ____________________ feedback to the T helper cell producing it.
What is the 2nd signal required for T cell activation?
Interaction of CD28 and B7
What are two "CD" names for B7?
CD80 and CD86
What is the function of CTLA-4?
It inhibits T cell proliferation by competing with B7 to provide a "stop" signal thru CD28
What are 3 examples of APC derived signals and what type of T cell do they promote?
1. IL-12 - Th1 (Via Th expression of IFNγ)
2. TGFβ - Treg (suppresses Th1 & Th2)
3. IL-10 - Promotes Treg
What happens if the APC doesn't provide a cytokine?
Default to Th2 cell
What three autocrine signals are released by Th cells?
What is the effect of Th released IFNγ?
1. Promotes Th1- more IFNγ
2. Activates macrophages
3. Class switch IgG
4. Suppresses Th2 devleopment
What is the effect of Th released TGFβ and IL-10?
Furthers Treg development
What 2 cytokines do Th2 cells release and what is their effect?
1. IL-4: Class switch IgG1, IgE; suppress Th1
2. IL-5: Class switch IfA; promote eosinophilia
What 3 cytokines direct Th17 development?
TGFβ, IL-6, and IL-23
TGFβ is primarily considered an anti-inflammatory cytokine, what is the exception?
In combination with IL-6 and IL-23 it promotes the inflammatory Th17 subset
What is overabundance of Th17 associated with? Deficiency?
2. Susceptibility to bacterial infection
Cytokines associated with Th1, Th2, Treg, and Th17 development activate distinct intracellular signaling pathways that lead to the activation of ____________________.
IFNγ and IL-12 signal thru _____ to yield _______.
IL-4 signals thru __________ to yield _________.
TGFβ, IL-6, IL-23 signal thru _______ to yield _______.
TGFβ (alone or with IL-10) signal thru _______ to yield ______.
How does Alum function?
Promotes APCs to express IL-4 --> Th2 development and antibody production
B cells are activated by CD40 engagement and __________.
What is the default antibody secreted?
IgM complement activation
What antibody gets secreted with Th1, producing IFNγ?
IgG (IgG1, IgG3)
Fc receptor dependent phagocyte responses, complement activation, neonatal immunity
What antibody gets secreted with Th2, producing IL-4?
IgE - mast cell degranulation
What antibody gets secreted by Tregs in the periphery producing TGFβ and/or BAFF?
IgA (mucosal immunity)
transport IgA thru epithelia
FcεRI regulates ______________ in a cell-contact ____________ manner in response to ____________________.
*allergens can activate this in a cell contact-independent manner
FcγRI and FcγRIIA:IgG regulate ____________ via _________________.
2. Macrophages, neutrophils, eosinophils
FcγRIIIA:IgG results in _________ thru _________ cells.
1. Antibody-dependent cellular toxicity
2. NK cells
What gets released during degranulation?
1. Histamine - inc. vascular permeability & contraction of SM
2. Prostaglandins (mast cells) - vasodilation, bronchoconstriction, PMN chemotaxis
What cytokine is associated with macrophage activation and what cell secretes it?
NK cells, T lymphocytes
What cytokines are associated with CD8 T cell cytotoxicity?
DCs and Mφ secrete IFNα
Fibroblasts secrete IFNβ
Increase MHC I expression in all cells and activate NK cells