Lecture 20: Immunity to Microbes Flashcards
What do acute phase proteins CRP and SAP do?
Bind C1q on bacteria and activate complement
What role do C3a and C5a have in extracellular infections
Bind receptors on mast cells and activate them to release histamine
What activates the endothelium and neutrophils in extracellular infection
Cytokines released from mast cells along with bacterial derived molecules (endotoxins)
What are two examples of potent neutrophil chemoattractants
C3a and C5a
Role of immature vs mature DCs in extracellular infections
Immature DCs engulf bacteria via PRRs, mature DCs migrate to local lymph nodes
What adhesion molecules are responsible for the adhesive interaction b/w lymphocytes and HEVs
L-selectin on lymphocytes
PNAds on HEVs
Where do activated Th cells interact with B cells to promote affinity maturation/Ig class switching
Germinal centers
Endotoxins vs exotoxins
Endotoxin- Component of bacterial cell wall
Exotoxin- Secreted by bacteria
Principal mechanisms of innate immunity to extracellular bacteria are
Complement activation
Phagocytosis
Inflammation
Peptidoglycans (Gram+) and LPS (gram-) bacteria activate which pathways
Alternative and classical pathways
What causes the cleavage of C3b and C4b that prevents them from forming active convertases
Factor I
What are the cofactors for Factor I
MCP
CR1
Factor H
C4BP
What proteins inhibit assembly of C3 convertase in classical pathway
DAF
CR1
C4BP
What proteins inhibit assembly of C3 convertase in alternate pathway
DAF
CR1
Factor H
What is the classical C3 convertase
C2aC4b
What is the alternative C3 convertase
C3bBb
What can inhibit the assembly of the MAC
MAC-Inhibitory protein CD59
Encapsulated bacteria rich in TI polysaccharide Ags are primarily eliminated by
Ab-mediated immunity
What is the role of Th17 cells when activated by extracellular Ags, and what happens if there is a genetic defect in the Th17 cells
Promote local inflammation and recruit neutrophils and monocytes to the area
-Increased susceptibility to bacterial/fungal infections, with formation of multiple skin abscesses
What is the role of Th1 cells when activated by extracellular Ag
Produce IFN-y which activates macrophages
May also stimulate production of IgG Abs
What are the principal injurious consequences of host responses to EC bacteria
Inflammation and septic shock
What causes the early phase of septic shock
Cytokines produced by macrophages
Macrophages secrete TNF-a which does what
Upregulates Tissue Factor TF and nitric oxide synthase (iNOS)
What is the role of IL-18 secreted by macrophages
Induces IFN-y which activates more macrophages
What cytokine is a global suppressor of macrophage function
IL-10
What are local effects of IFN-a in viral infections
Inhibition of viral gene replication
Up-regulation of MHC class I molecules
Activate NK cells early in infection
What is the major mechanism used by bacteria to evade humoral immunity
Variation of surface Ags
What activates NK cells at later stages of viral infections
IFN-y and IL-2 produced by Th1 cells
What are Langerhans cells
Tissue DCs in the skin which transport Ag to local lymph nodes
What molecules locally produced by macrophages and T cells have systemic effects of fever
IL-1 and TNF-a
Naïve B cells acquire viral Ags through
Attachment to surface IgM or IgD
Th1 cells recruit and stimulate virus specific CTLs by providing ____ for _____
IL-2 for proliferation of CD8+ T cells
What are the key attributes of effector Th cells and CTLs in viral infections
Virus specific TCRs
Upregulation of adhesion molecule LFA-1
Upregulation of production of cytokines
After death, viral secreted proteins are removed/neutralized by
Ab in the form of immune complex
Ab may guide Fc receptor-expressing NK cells
When pathogenic bacteria are resisting degradation by phagocytic cells, this can be overrun by NK cells producing ____. Which cells release which cytokines to stimulate the NK cells to do this
Dendritic cells and macrophages produce IL-12 and IL-15 to activate NK cells to produce IFN-y which in turn promotes killing of phagocytized bacteria by macrophage
Endogenous pathway of Ag presentation
Proteins from IC pathogens such as viruses are degraded by proteasome and the peptides are shuttled into the ER by TAP proteins and presented in MHC class I molecules
Exogenous pathway of Ag presentation
Extracellular pathogens are engulfed by phagosomes, in the phagosome, the peptides are loaded onto MHC class II molecules which activate Th cells to stimulate Ab production (some peptides from exogenous pathway can be cross presented on MHC class I molecules)
Fungi are recognized by what receptors
PRRs
The detection of _____ by _____ is important for fungal infection
B-glucan by dectin 1
What cytokines activate Th1, Th2 and Th17 cells
Th1 = IL-12 Th2 = IL-4, IL-5 Th17 = TGF-b, IL-6
In general, in fungal infections, Th1 responses do what, while Th2 responses do what
Th1 responses are required for clearance, while Th2 responses usually result in susceptibility to infection
What is Dectin-1 role in fungal infections
Expressed on Macrophages. Binds and internalizes B-glucans and mediates activation of NF-kB and subsequent secretion of proinflammatory cytokines and ROS
