Innate Immunity Flashcards
What are the anatomical barriers?
- Antaomical/physical barrier
- Skin
- Mucous membranes
What are the physiological barriers?
- Body tempt
- Low pH
- Chemical mediators
- Phagocytic
- inflammatory
What are the 7 major cell types of the immune system and their key characteristics?
Neutorphil:
- 50-70% of WBC
- Short lived
- Circulate in blood and migrate to tissues
- Multi lobed nucleus
- Primary granules: sites of enzymes that kill phagocytosed pathogen
- Secondary granules: primary involving replenishing primary granules and regulate toxins produced during pathogen lysis
- Granules fuse with vacuole to form phagolysosome
Esoinophil:
- Granular
- Phagocytosis
- Release granules during parasitic
- Help N cell response in GALT via IgA production
Basophil:
- Granular
- May act as APC
Monocyte/macrophage:
- Dispersed through tissue
- Signal infection by releasing cytokines (help recruit other cells and activate subsequent adaptive response)
- Have many receptors for many bacterial constituents
Mast cells: secrete histamines
- Mucosal (respiratory and intestinal epithelia)
- Connective tissue (under skin)
- Kill and phagocytose
- Activated by anaphylatoxins (complement products)
- Vasodilation, inc vascular permeability
- Release histamine and leukotrienes
○ Attract cells and amplify response
Dendritic: APC
NKC:
- Large interferon secreting cytotoxin granulated lymphocytes
- No antigen specific receptor
- 5-10% of peripheral blood
- Have activating and inhibitory receptors - balance determines response
- Important against tumors and viral infection
How do NKC recognize targets?
- Missing cell recognition/Induced self recognition: ligation of activating NK receptors so target cell killing
- Normal cells present MHCI on NK which sends inhibitory signals
- If cells infected MHCI down regulated go missing so no more inhibitory signals
- Cells start expressing molecules only induced by stress, starts upregulating stress molecules
- Stress patterns recognized by NK activating receptors
- Once activated will kill target cell - Self recognition - leave cell
- Ligation of inhibitory NK receptors so no cell killing
What are the steps of chemotaxis?
- Rolling
- Low affinity
- Mediated by selectins
- Integrin activation by chemokines
- Chemokines bind to surface of epithelial cells
- Integrins bind high affinity
- Stable adhesion
- Because tight binding
- Migration through endothelium
- Diapedesis (squeezing through endothelial layer)
What 3 pattern recognition tecqniques are used?
- Detect conserved microbial structures (PAMP)
- Detect metabolic consequences of cell infection/injury (DAMP)
- Detect self
How do NK cells recognise missing self?
- NK use MHC class 1
- Some recptors on cell surface to recognise extracellular paterns, others on inside to detect viral pathogen
Define opsonization?
Coat with opsonin (bind to antigen but also can be bound by phagocytes)
- link pathogen to receptors on phagocyte
What are the two most important opsonins?
- antibody and complement
What are the steps in opsonization?
- Antibody binds to receptor on pathogen
- Complement binds to cell surface of pathogen
- Bound antibody and complement can now bind to neutrophil and activate it
- Neutrophil engulfs bacteria and lyses it
What are the killing mechanisms of neutrophils?
Oxygen dependent
Oxygen independent
Define cytokine?
- Short lives small secreted proteins involved in cell-cell communication
- Powerful biological effect at low concentration
What are the types of cytokines?
- Interleukins - between leukocytes
- Growth factors
- Cytotoxic: tumor necrosis factor
- Chemokines - chemotaxis and movement
- Interferon . Antiviral effects (only immune cell produce atype 2)
How do cytokines act?
- Affects gene expression
What are the important cytokines released by activated macrophages?
- IL-1 alarm cytokine causing fever
- IL-6 acute phase proteins acting over long distances
- IL-8 chemotactic for neutrophils
- IL-12 directs adaptive immunity and activates NK
- TNF A: alarm cytokine
What is a consequence of too much cytokine release?
Bacterial septic shock: massive release of alarm cytokines and activated macrophages
- Bacterial endotoxins cause massive TNFA and IL1 release
- Increased vascular permeability causes severe drop in blood pressure
What is the function of DCs?
- netowrk of cells located at likely sites of infection
- reocgnise and secrete cytokines: phagocytose and reocgnise PAMP
- Migrate to lymph node to activate T lymphocyte
- Direct link between acquired and adaptive
What is complement?
- functionally linked proteins and GPs complements activity of specific antibody
- Forms triggered enzyme cascade system
- When activated become active enzymes (part of protein cleaved off)
- Catalyze cleave of lots of molecules down chain and convert next molecule to active enzyme
What is the function of complement?
- Lysis
- Opsonization
- Activation of inflammatory response
- Cause mast cell degranulation
- Clearance of immune complexes
Where are complements synthesized?
- Mainly synthesized in liver as inactive precursors but also produced by monocytes and macrophages
How is complement activated?
- Classical pathway:
- antibody bound to antigen
- conformational antibody chain activates complement - Alternate pathway: direct activation by surfaces of pathogens themselves
- Direct contact with bacteria - Lectin pathway: antibody independent
What happens to the inactive precursors?
- Components made as inactive precursors have to be cleared
○ Cleared products have proinflammatory properties
What is the half life of complements?
- Complements have very short half life
○ Diluted in body fluids
○ Specific regulatory protein regulate complement activity
How is complement release controlled?
- Lability
- Dilution
- Regulatory proteins
