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This article discusses the benefits of a two-tiered immune system, the different groups of pathogens, and the two phases of the innate immune response. It also explores the role of epithelial barriers, complement activation, and the recognition of pathogens by phagocytes.
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Innate Immunity: The Immediate Response April 6, 2009 10:00-11:00
Figure 8-1 BENEFITS OF A TWO-TIERED IMMUNE SYSTEM Innate Immunity is a pre-requisite for adaptive immunity
LOCATION, LOCATION……. The site(s) at which a pathogen enters and resides direct the immune response
Immediate Response Induced Response TWO PHASES OF INNATE IMMUNE RESPONSE Cells and proteins involved reside at sites of pathogen entry Proteins produced during the immediate response recruit help. Cells do not reside at the site, but rather respond to the cry for assistance
THE FIRST STEPS IN INFECTION The pathogen must breech an epithelial surface, interior or exterior In order to be successful, the micro-organism must establish an initial focus or colony.
Figure 8-6 EPITHELIUM IS AN ACTIVE BARRIER
Figure 8-7 RESIDENT MICROFLORA PROTECT AGAINST PATHOGENS
COMPLEMENT IS ACTIVATED BY PATHOGENS THAT BREECH THE EPITHELIUM
Figure 8-9 ACTIVATION OF COMPLEMENT VIA THE ALTERNATIVE PATHWAY Functional C3b on the microbial surface bind factors B and D As a result…more C3b is generated as well as C3a C3b acts on macrophages C3a acts on endothelial cells
Figure 8-10 FATE OF C3b DEPENDS ON THE CELL SURFACE
Figure 8-11 HOST PROTEINS BLOCK ACTION OF MICROBIAL PROTEASES Serpins a-Macroglobulin
INNATE IMMUNE EFFECTOR CELLS Short lived and not present in healthy tissue Long lived macrophages are always present in tissue Function: kill virally infected targets Functions: phagocytosis, secretion of enzymes and cytokines, antigen presentation Functions: phagocytosis cytokine production First cellular defenders
RECOGNITION OF PATHOGENS Danger: Pathogens cause tissue damage thereby alerting the immune system Stranger: Pathogens have distinguishing membrane “patterns”, a.k.a. PAMPs Innate immune cells have receptors that recognize the patterns
PHAGOCYTE PATHOGEN RECOGNITION RECEPTORS Complement Receptors: CR3 a.k.a. Cd11 and CR4 Pattern Recognition Receptors LPS, mannose, glycan, scavenger receptors recognize bacterial carbs. PAMP stimulate phagocytosis
THE ACTIVATED MACROPHAGE INGESTS PATHOGENS 1. Recognition 2. Engulfment 3. Phagosome forms • Phagosome fuses • with lysozome • Acidification of • phagolysozome • Release of toxic • substances
* ANTIMICROBIAL PRODUCTS OF PHAGOCYTES *NADPH oxidase in lysozomes generate toxic oxygen species in the RESPIRATORY BURST Chronic Granulomatous Disease: absence of NADPH; recurrent infections
Figure 8-13 TOLL RECEPTORS ARE INVOLVED IN PATHOGEN RECOGNITION
TOLL RECEPTOR RECOGNITION IS INDIRECT TLR-4 DOES NOT DIRECTLY BIND LPS
Figure 8-14 TOLL RECEPTORS ACTIVATE A SIGNAL TRANSDUCTION CASCADE