Innate Immunology Flashcards
cardinal signs of inflammation
redness, swelling, heat, pain, loss of function
initial components of innate system (0-4 hours)
mechanical barriers (skin, mucosal, microflora) and chemical barriers (complement and defensins)
later components of innate system (after 4 hours)
cellular (neutrophils, macrophages, mast cells, etc.) and cytokines (IL-1, TNF-alpha, IL-6)
classical pathway
antigen-antibody complexes activate C3 convertase (C4bC2a) and C5 convertase (C4b2a3b)
lectin pathway
MBL-MASP complexes activate C3 convertase (C4bC2a) and C5 convertase (C4b2a3b)
alternative pathway
spontaneous C3 hydrolysis
C3b
amplification and opsonization
C5b
helps form MAC
C3a and C5a
inflammation via anaphylatoxins (recruit neutrophils and monocytes)
defensins
small, amphipathic peptides that are expressed by epithelial cells in select locations to prevent bacterial colonization
defensins are expressed by _
neutrophils to contribute to killing of microbes after phagocytosis
lysozymes
can eat the peptidoglycans on gram-negative bacteria
receptors on innate cells
pattern recognition receptors (PRRs)
PRRs recognize _
PAMPs and DAMPs
PAMPs (pattern associated molecular patterns)
expressed by viruses (DNA, RNA), bacteria (LPS, flagellin), parasites (PIs), and fungi (mannan)
DAMPs (damage associated molecular patterns)
expressed by dying cells (ATP, mitoDNA, uric acid)
prototypical PRR’s
toll-like receptors
TLR’s are found _
predominantly on dendritic cells and macrophages
TLR5
recognizes protein
TLR7-9, TLR3
recognizes nucleic acids
PRR locations
can be secreted, on cell surface, endosomal, cytosolic
TLR4
lipids
consequence of PRR activation
enhance host resistance, minimize tissue damage, and promote resolution
inflammasome
cleave pro-IL-1beta into active IL-1beta
TNF-alpha
induces blood vessels to be more permeable, enabling cells, fluid, and soluble effectors to enter infected tissue
IL-6
induces fat and muscle cells to metabolize, generate heat, and raise temp in affected tissue
acute phase response
cytokine release due to PRR –> activation of liver –> acute phase response
cytokines that activate acute phase response
IL-1, IL-6, and TNF-alpha (stimulate CRP, complement, and fibrinogen)
eosinophil function
combat parasitic infections via IgE mediated response
basophil function
influence development of adaptive immunity by releasing IL-4 which stimulates Th2, causing class switch to IgE (parasitic and allergic responses)
neutrophil function
phagocytic cells that are able to ingest and kill microbes but are short lived and the most numerous
macrophages
phagocytose and then digest pathogens
classical activation of macrophages
LPS, IFN-gamma, TNF-alpha
classical macrophages cause _
antibacterial activity; they are cytotoxic and have high iNOS
alternative activation of macrophages
IL-4, IL-13, IL-10, TGF-beta
alternative macrophages cause _
tissue repair; immunosuppressive and have high ARG1 expression
mature DC’s will express _
co-stimulatory molecules
function of dendritic cells
sense pathogen, phagocytose pathogen, migrate to lymph node, and increase surface expression of MHC-II and MHC-I and enhance expression of CD80, CD86, CD40, release cytokines to polarize T cells
How do dendritic cells stimulate T cells?
immature DC’s will recognize PAMPs to become activated –> TLR signaling induces CCR7 and enhances processing of antigens –> migration to lymph node via CCR7 –> present peptide via MHC complex to T cells in lymph node
innate viral responses are performed by _
plasmacytoid DCs (make IFN-1) and NK cells
plasmacytoid DCs
synthesize type I IFNs to direct antiviral effects, activate NK cells, and essential for antibody responses; significant source of IL-12 during early response
actions of type I IFN
inhibition of translation, mRNA degradation, transcriptional inhibition
NK cells
kill virus-infected cells, produce IFN-gamma, and are activated by macrophage-derived cytokines
innate cells for virus
NK cells and pDCs
level I cytokines for virus
type I IFNs
T cells for viruses
CD8’s
level 2 cytokines for viruses
IFN-gamma
antibodies for viruses
IgG for neutralization
intracellular bacteria innate cells
macrophages
level 1 cytokines for IC bacteria
IL-12, TNF-alpha, and IL-1
T cells for IC bacteria
CD4 Th1
level 2 cytokines for IC bacteria
IFN-gamma
antibodies for IC bacteria
IgG for opsonization
innate cells for EC bacteria and fungi
macrophages and neutrophils
level I cytokines for EC bacteria/fungi
IL-23, IL-1, IL-6
T cells for EC bacteria/fungi
CD4 Th17
antibodies for EC bacteria/fungi
IgG and IgA for help at mucosal sites
innate cells for parasites
eosinophils, basophils
level I cytokines for parasites
IL-4
T cells for parasites
CD4 Th2
level 2 cytokines for parasites
IL-4 elicits IgE
level 2 cytokines for EC bacteria/fungi
IL-17 recruits PMNs
antibodies for parasites
IgE to help eosinophils
