Integrating Immune Responses Flashcards
Exam 2
How do both innate and adaptive immunity work for effective clearance
-mild infections can be cleared by innate alone
-most adaptive responses require innate immunity
Why is activating all immune cells bad
-wasteful
-damaging (non infected tissue)
-not tailored for pathogen
What is Type 1 immunity
-intracellular bacteria, viruses, and protozoa
What is Type 2 immunity
parasitic worms, venom, and allergies
What is Type 3 immunity
extracellular bacteria and fungi
How does PAMP-(and DAMP-) sensing activate different responses
-which response will be activated depends on
-what PAMP’s are recognized
-where the PAMP’s are recognized (inside or outside)
-which cytokines are produced
What induces Type 1 response
-induced by IL-12 (really built around macrophages and dendritic cells)
-can be induced by LPS, Protozoa, and viral DNA (inside cell)
-sensed by TLR (leads to IL-12 release and still requires other pro-inflammatory signals from other cells dead from pathogen)
Describe role of IL-12 in Type 1 response
1)NK activation and differentiation
2)Th1 differentiation
3)Class switch to IgG
4)proliferation of progenitor cells in bone marrow
In type 1, how is CD8 T-cells activated (2 ways)
-cytotoxic T lymphocytes (CTL)- activated Tc cells
-bystander effect (doesn’t involve TCR at all , only signaling role)
-signaling/sense IL-12 + make IFN-gamma
-anti-viral pathway
-activate macrophages
How does IFN-gamma acts as positive feedback in type 1
-both Th1 and CD8 secretes IFN-gama
-IFN-gamma activates macrophages/NK cells
-IFN-gamma drives Th1 differentiation
-IFN-gamma also increase IL-12 release
-Ensures a robust response (positive feedback to make a ton of Th1
What is the role of innate lymphoid cell 1 in signaling role in type 1 immunity
-ILC1 # matches immunity type
-main role: IFN-gamma secretion
1)sense IL-12
2)release IFN-gamma
Name the 6 roles Th1 cells play in type 1
1)activate MI so can better kill bacteria inside
2)can induce apoptosis if macrophage can’t kill whats inside
3)T cells specifically CD8+ creation b/c important for killing viruses
4)goes to bone marrow and increases monocytes
5) Th1 increases monocyte differentiation into macrophages
6) secrete chemokines to the infection site
What is the main cause of allergies (pollinosis)
type 2 immunity
What is Damage Associated Molecular Patterns
-DAMPs
-Associated with tissue damage
-for type 2 immunity, epithelial damage from helminth
-example: when you get vaccine, puncture itself triggers type 2
What can epithelial damage trigger
-ILC2 secretion of IL-4 and IL-13 (and DC activation)
-IL are key cytokines, activate mast cells basophils eosinophils
What are tuft cells
-cell type that lines intestine w/ taste receptors (same on tongue) test for parasites
Explain how IL-4 induces Th2 differentiation
-produced by eosinophils, basophils, mast, and Th2 cells (positive feedback) drives differentiation of more Th2 and more IL-4 then too
-Induces IgE class-switching (good for granule release)
-Inhibitys Th1 differentiation (IFN-gamma inhibited)
-AGAIN, not the only one involved
Give a sumar of how Th2 plays a key role in helminth (worm) expulsion
1) wound repair
2)increases mucus to get rid of worm + protect cells
3)increase M2 (wound repair)
4)activate eosinophils
5) activate mast cells
What is arginie key role in M2 respiratory burst
-Arginase-1
-generates ornithine and polyamines
-used for type 2 immunity
-M2 macrophages express Arg-1
-M1 macrophages express Arg-2
What do Arg1 products do
trap helminth larve
How can antibodies help localize cytotoxic cells to the helminth organism
-Ab binding localizes/ bring eosinophils/neutrophils/basophils to worm which then secrete toxic mix to kills the worm
-Ab in type 2 IgE specific to worms, IgG, IgA in mucus for expulsion
How is type 3 immunity induces
-activated by TLRs sensing flagellin and fungal cell wall components
-requires other inflammation signals (prevents attack of microbiome)
-mediated by Th17 cells
How does IL-6 and IL-23 play the key role in Th17 differentiation
-ILC-3 synthesize IL-1B and IL-23
-release by APC’s
Give summary of how Th17 plays multiple roles in responding to extracellular bacteria/fungi
1) release IL to make epithelial cells secrete AMPS (b/ outside cell)
2)increases epithelial cell turnover to prevent colonization and increases mucus
3)IL-17 more neutrophil differentiation
4) recruit via chemokines neutrophiles and Th17 to infection site
What do you do after the infectious ion cleared
-clonal contraction removes all the unneeded effector cells
Explain the generation of immunological memory
-generation of immunological memory
-quick generation of a response to an already encountered antigen
-longterm considered life-long b/c memory cells last so long
Multiple exposures lead to what
-more IgG vs IgM AND higher affinity
-higher affinity b/c of somatic hypermutation
Membor B-cells have a higher level of what compared to naive B-cells
Higher levels of MHCII and B7.1 than naive B-cells
Explain what Central memory Tcm is
-migratory
-blood to secondary lymph organ to blood (naive T-cells)
Explain what effector memory Tem is
-migratory
-blood to peripheral tissues to lymph system to blood
-localize to inflamed tissues
Explain what Tissue-resident memory Trm is
-non-migratory
-found in tissues
What are the 3-types of memory T-cells
-Central memory Tcm
-Effector memory Tem
-tissue-resident memory Trm
Why do secondary responses appear to be mostly through memory cells
-memory cells become activated quicker than naive cells
-upo memory cell activation, naive activation appears to be suppressed
