Innate Immune System Flashcards
Innate Immunity
This is the first response, its fast, there is no specificity or memory
Physical barriers in innate immunity
Skin and epithelial mucosa: Resp/GI/GU tracts
Cilia – muco-ciliary escalator
Secretions: sweat, tears, saliva, gastric acid, sebaceous glands, mucus, breast milk
Saliva: lysozyme, IgA, IgG, lactoferrin
Normal flora
Commensal bacteria – compete for nutrients, prevent attachment, release fatty acids and antibacterial proteins, prevent invasion
Lactobacilli in vagina – cause acidic pH (4.0-4.5)
Physiological
Temperature (fever), pH, location of immune cells within the bloodstream – can readily attack when and wherever microbes invade
Cells of the innate immunity
phagocytes, eosinophils, basophils, mast cells, Natural Killer cells (NK)
Complement in the innate immune system
acute phase reactants, cytokines, chemokines, matrix metallo-
proteinases, defensins
Pattern-recognition receptors the innate immune system
recognition receptors such as toll-like receptors (TLR) binding to PAMPs
(pathogen associated molecular patterns) or DAMPs (damage associated molecular patterns to stimulate a response by cells of the innate immune system.
Mechanisms of the innate immune system
Inflammation
Recruitment of immune cells
Activation of complement
Opsonisation
Phagocytosis (and endocytosis)
Inflammation
Vasodilation Loosening of endothelial tight junctions Increased cell adhesion molecules Chemotaxis Smooth muscle contraction
Resulting from damage to tissue (prostaglandin and leukotriene release), allergens (mast cell degranulation, histamine release), microbial infection (release of endotoxins, exotoxins, TLR’s, Interleukins, nitric oxide), complement activation (C3a, C5a), autoimmunity (immune complexes, complement, T-cell)
Phagocytosis
- Phagocyte moves towards the microbe
- Phagocyte attaches to microbe via opsonin
- Endocytosis of microbe with phagosome
- Phagosome fuses with lysosome
- Oxygen-dependent species result in microbe death (lyzozymes, lipases, proteases, RNAses and DNAses)
- Release of microbe products
Cells that carry out phagocytosis
Macrophages, neutrophils, eosinophils, dendritic cells
Chemostaxis of phagocytes
Chemically attracted to the site of infection
Opsonization
Coating process with opsonins that facilitates attachment.
Opsonins
Complement
Antibodies
Plasma Proteins
Complement System
Large group of serum proteins that participate in the lysis of foreign cells, inflammation and phagocytosis
Classical Pathway Complement System
Initiated by an immune reaction of antibodies
Alternative Pathway Complement System
Initiated by direct interaction of complement protiens with microbial polysaccharides
Consequences of Complement Activation
Cytolysis due to the formation of a membrane attack complex (C3b-C5-C5b) which produces lesions in microbial membranes
Inflammation due to complement components (C3a and C5a) triggering the release of histamine which increases vascular permeabilty
Opsonisation
B cell activation
Immune complex clearance
Membrane Attack Complex
- Antibody molecules attach to the antigens on the pathogens plasma membranes
- Complements proteins link two antibody molecules
- Activated complement proteins attach to pathogens membrane
- MAC pores in the membrane and causes cell lysis
Life span neutrophils
Few days
Main function neutrophils
Phagocytosis
Degranulation release of bacteriocidal components (peroxidase, defensins, acid and alkaline phosphatases)
Main targets of neutrophils
Bacteria and fungi
Receptors Neutrophils
Toll like receptors Complement IgG Chemokine IL-8 Chemoattractant C5a ICAM + VCAM - adhesion to endothelium
Life span eosinophils
8-12 days
Main function of eosinophils
Extracellular killing via degranulation of peroxidase, major basic protein (induced mast cell and basophil degranulation), IL-8 and cytokines
Main targets of eosinophils
Parasites
IL-5 and IL-3 stimulate
Production and release of eosinophils from basal membrane
Expression of IgE receptors on eosinophils
Main function of basophils
Degranulation release of histamine, prostaglandins and leukotrienes and cytokines (IL-4, IL-13)
Main targets of basophils
Parasites
Receptors of basophils
Surface bound IgE
C3a, C5a anaphylatoxins
Toll-like receptors
Mast cells are present in
Tissues exposed to the external environment
Main function of mast cells
Degranulatin through cross-linkage of IgE receptors Histamine Proteases Reactive oxygen species Cytokines – TNF alpha, IL-4, IL-13 Leukotrienes and prostaglandins
Receptors on Mast cells
Surface bound IgE C3a and C5a Damage associated molecular patterns Toll like receptors Complement Others: that can bind drugs e.g. opioids / antibiotics
Tissue based monocytes
Kupffer (liver), Microglial (brain), Mesangial (kidney)
Life span of macrophages
Months to years
Main function of macrophages
Phagocytosis
Antigen presentation to T cells
Release of TNF-alpha, IL-2, IL-6
Receptors on macrophages
Toll like receptors
Fc for IgG and IgA
C3b
MHC class I and II
Dendritic cells
Present in tissues exposed to the external environment. Once activates migrate to the lymphoid tissues.
Main function of dendritic cells
Phagocytosis
Antigen presentation to CD4+ T cells via MHC II
Shape enhances activation
Secrete TNF alpha, IL-12, IL-23
Follicular Dendritic Cells
Mesenchymal origin
Within follicles of lymphoid tissue
Do not express MHC II but interact with B cells
Natural Killer Cells are activated by
IFN and macrophage derived cytokines
Main functions of natural killer cells
Bind to and kill virus-infected and cancerous cells –reduced MHC I expression
Release of perforin + granzymes from granules
Perforates cell, inserts proteolytic enzymes, induces apotosis
Also induce apotosis by binding to FasL molecules on virus
Release IFN gamma and TNF alpha
Are inhibited by normal ‘self’ signal via MHC I
Receptors present on NKC’s
Killer activation receptors Killer inhibitory receptors – recognise MHC class I Toll-like receptors Fc receptors Adhesion molecules FasL
