Innate immunity Flashcards
Innate immunity
Macrophages, Dendritic cells
Natural killer cells
Complement
Cytokines
Immediate and non-specific response
Activates adaptive immunity
Innate barriers
Skin, mucus and cilia are physical barriers
Low pH in stomach and anti-microbial peptides on skin are chemical barriers
Phagocytes
Neutrophils phagocytose then die
Macrophages and Dendritic cells phagocytose and present antigens (Lymph nodes)
Phagocytosis
Attachment Ingestion and formation of phagosome Phagosome lysosome fusion Digestion Antigen presentation (macrophages and dendritic cells)
PRRs
Pattern recognition receptors
Detect PAMPs
Toll-like receptors (TLRs)
C-type lectin receptors (CLRs)
Intracellular nucleic acid receptors
NLRs
Most cells have intracellular PRRs
Macrophages, DCs and NKs have PRRs on surface
Toll-like receptors
External leucine rich repeat domain which recognises ligands
Ligand binding causes oligomerisation of TLRs and clustering of TIR domains (intracellular)
Signalling cascade activates TFs NF-kB, IRF3 and IRF7
Intracellular RNA receptors
MDA5 detects long dsRNA
RIG-I detects short dsRNA and RNA with triphosphate at 5’ end
PRR signalling
Activates transcription factors Secretion of cytokines to regulate immune response (TNF-a) Interferons to warn cells of viruses Chemokines to recruit immune cells Antimicrobial peptides Enzymes
Inflammation
Tissue damage and bacteria cause resident sentinel cells to release chemoattractants and vasoactive factors
Permeable capillaries allow influx of fluid (complement and proteins) and cells
Phagocytes migrate to site (chemotaxis) and destroy bacteria
IL-6, TNF-a and IL-1
Vasodilation, increased vascular permeability and activation of macrophages, B and T cells (local effects)
Haematopoiesis of neutrophils, fever and acute phase response in liver (systemic effects)
IL-8
Recruits neutrophils and Dendritic cells
IL-10
Inhibits macrophages and Dendritic cells and resolves inflammation
Natural Killer cells
Inhibitory receptors detect self molecules (MHCI). If downregulated by viruses, NK cell detects ‘missing self’
Activating receptors (NKG2D) detect MIC-A and MIC-B expressed on epithelial cells that have detected a virus (altered self)
Active NK cells release perforins and granzymes
Complement system
Serum proteins in the blood
Initiators bind pathogens or antibodies Enzymes (convertases) Opsonins promote phagocytosis Anaphylatoxins cause inflammation Membrane attack proteins lyse pathogens Complement receptors on phagocytes Regulatory proteins limit complement activation
Classical pathway of complement activation
Initiated by binding of antibodies (IgG and IgM) to the surface of a pathogen
Conformational change in the antibody and the constant Fc region is exposed
C1 complex can bind. A C1r subunit converts to a protease and cleaves the other C1r and C1s subunits, starting the cascade
