- Describe the immune response to microbial infections
- Split into innate and adaptive immunity
- Innate Immunity
- Inflammation
- RECOGNITION → RECRUITEMENT → ELIMINATION → RESOLUTION
- Macrophages and Dendritic cells engulf and detect microbial organisms through Pattern Recognition Receptors
- Activation of NF-kB signalling pathway causes the release of inflammatory cytokines TNF and IL-1
- TNF and IL-1 activate the endothelial to promote neutrophil adhesion and transmigration
- Neutrophils arrive at the site of inflammation in hours, followed by an influx of monocytes
- TNF causes the degranulation of neutrophils, releasing elastases, Cathepsin G, Proteinases and Neutrophil Extracellular Traps containing histones that damage host tissue and cells
- Macrophages phagocytose microbes and neutrophils, degrading them using proteases and antimicrobial peptides
- Lipoxins, protectins and resolvins send anti-inflammatory signals that promote resolution and repair. Lipoxins stop neutrophil influx and promote uptake of apoptotic neutrophils and recruitment of additional monocytes
- Macrophages, neutrophils, and epithelial cells produced Secretory Leukocyte protease inhibitor (SLPI) that activates the proteases released from neutrophil granules, and this pushed the inflammatory response towards resolution.
- Complement activation
- Teichoic acids, Lipoteichoic acids, and LPS activate the alternative complement cascade
- Mannose activates the mannose binding lectin pathway
- C3b attaches to the cell membrane causing opsonisation
- C5a liberated act to cause neutrophil chemotaxis
- C5b-C9 form the Membrane Attack Complex (MAC) causing ultimate lysis of the bacteria
- Phagocytosis
- Mannose receptors, Scavenger receptors, Fc receptors, and complement receptors on the surface of phagocytic macrophages, neutrophils, and dendritic cells facilitate phagocytosis of microbes
- Once inside the cell the phagosome fuses with the lysosome forming the phagolysosome that mediates oxidative killing of the microbes via lysozyme and the oxidative burst
- Inflammation
- Cellular adaptive Immunity
- Macrophages present antigen to CD4+ T-cell via MHC II, B7 and CD28, Secreting IL-12 which activates the CD4+ cell to Th1 Subtype
- Th1 cell secretes IFN-y, activating the macrophage into a classical M1 type causing phagolysosome maturation, Production of NO via inducibe NOS, Autophagy and release of defensin
- Activated M1 macrophages complete killing of microbes
- CD8+ T-cells detect Microbial products displayed on host cells via MHC I, causing apoptosis of infected cells via granzyme and perforin, and FASL binding to FASDR on the host cells
- Humoral Adaptive Immunity
- B-cells phagocytose and present Microbes to activated T-CD4+ Cells via MHC II, CD40L and CD40. T-cell differentiates into Th2 phenotype stimulating cytokine production that causes B-cell class switching and affinity maturation
- Antibodies produced by Plasma cells neutralize microbes, opsonize microbes, and activate complement on the surface of the microbe via the classical pathway
- What determines the effector response elicited against infections
- Site of entry
- Route of spread
- Tissue specificity
- Transmission
- What key events occur during an infection
- Entry → Invasion → Colonization of host tissue → Evasion of host immunity → Tissue injury AND OR Functional impairment
