Innate Immunity PDF

Innate Immunity Innate Host Defenses Against Infection Anatomical barriers – Mechanical factors – Chemical factors – Biological factors Humoral components – Complement – Coagulation system – Cytokines Cellular components – Neutro...

Innate Immunity Innate Host Defenses Against Infection Anatomical barriers – Mechanical factors – Chemical factors – Biological factors Humoral components – Complement – Coagulation system – Cytokines Cellular components – Neutrophils – Monocytes and macrophages – NK cells – Eosinophils  Anatomical Barriers - Mechanical Factors System or Organ Cell type Mechanism Skin Squamous epithelium Physical barrier Desquamation Mucous Membranes Non-ciliated epithelium (e.g. GI Peristalsis tract) Ciliated epithelium (e.g. Mucociliary elevator respiratory tract) Epithelium (e.g. nasopharynx) Flushing action of tears, saliva, mucus, urine  Anatomical Barriers - Chemical Factors System or Organ Component Mechanism Skin Sweat Anti-microbial fatty acids Mucous Membranes HCl (parietal cells) Low pH Tears and saliva Lysozyme and phospholipase A Defensins (respiratory & GI Antimicrobial tract) Sufactants (lung) Opsonin  Anatomical Barriers - Biological Factors System or Organ Component Mechanism Skin and mucous Normal flora Antimicrobial membranes substances Competition for nutrients and colonization  Humoral Components Component Mechanism Complement Lysis of bacteria and some viruses Opsonin Increase in vascular permeability Recruitment and activation of phagocytic cells Coagulation system Increase vascular permeability Recruitment of phagocytic cells Β-lysin from platelets – a cationic detergent Lactoferrin and Compete with bacteria for iron transferrin Lysozyme Breaks down bacterial cell walls Cytokines Various effects  Cellular Components Cell Functions Neutrophils Phagocytosis and intracellular killing Inflammation and tissue damage Macrophages Phagocytosis and intracellular killing Extracellular killing of infected or altered self targets Tissue repair Antigen presentation for specific immune response NK and LAK cells Killing of virus-infected and altered self targets Eosinophils Killing of certain parasites  Phagocytosis and Intracellular Killing  Phagocytosis provides a first line of cellular defense against invading microorganisms. Phagocytosis The engulfment of particulate material by a cell, by surrounding the particles with the plasma membrane and internalizing them in a membrane-bounded vacuole (a phagosome). The engulfing and ingestion of bacteria or other foreign bodies by phagocytes. By engulfing and killing microorganisms, phagocytic cells are the principal means by which the immune system destroys invading pathogens. The two kinds of phagocyte that serve this purpose — the neutrophil and the macrophage — have distinct and complementary properties.  A. Phagocytes - Neutrophils (PMNs) PMNs are motile phagocytic cells that have Characteristic nucleus (lobed nuclei), cytoplasm Granules CD 66 membrane marker (an antigen present on the cell surface)  Characteristics of Neutrophil Granules primary granules secondary granules azurophilic; characteristic of young specific for mature neutrophils neutrophils contain contain cationic proteins and lysozyme, NADPH oxidase defensins that can kill components, which are bacteria involved in the generation of proteolytic enzymes like toxic oxygen products elastase, and cathepsin G to lactoferrin, an iron chelating breakdown proteins protein and B12-binding lysozyme to break down protein bacterial cell walls, and myeloperoxidase, which is involved in the generation of bacteriocidal compounds.  Phagocytes - Macrophages Macrophages are phagocytic cells that have a characteristic kidney-shaped nucleus. can be identified morphologically or by the presence of the CD14 cell surface marker. no granules numerous lysosomes  B. Phagocyte Response to Infection The SOS Signals – N-formyl methionine-containing peptides – Clotting system peptides – Complement products – Cytokines released by tissue macrophages Phagocyte response – Vascular adherence – Diapedesis – Chemotaxis – Activation – Phagocytosis and killing  C. Initiation of Phagocytosis Phagocytic cells have a variety of receptors on their cell membranes through which infectious agents bind to the cells. These include: Fc receptors Complement receptors Scavenger receptors Toll-like receptors  D. Phagocytosis Phagocytosis begins following attachment. Steps: a. Attachment a b b. Pseudopod extension: After attachment of a bacterium the phagocyte begins to extend pseudopods around the bacterium. c. Phagosome formation: The pseudopods eventually surround the c bacterium and engulf it, and the e bacterium is enclosed in a phagosome. d d. Granule fusion: the granules or lysosomes of the phagocyte fuse with the phagosome and empty their contents e. Phagolysosome formation: bacterium engulfed in a phagolysosome which have the contents of the granules or lysosomes.  E. Respiratory Burst 1. Oxygen-dependent myeloperoxidase-independent intracellular killing Toxic compounds – Superoxide anion (O2– ), Hydrogen peroxide (H2O2), Singlet oxygen (1O2) and Hydroxyl radical (OH*) 2. Oxygen-dependent myeloperoxidase-dependent intracellular killing Toxic compounds – Hypochlorous acid (OCl– ), and Singlet oxygen (1O2) 3. Detoxification reactions  4. Oxygen-Independent Killing in the Phagolysosome Effector Molecule Function Cationic proteins (cathepsin) Damage to microbial membranes Lysozyme Hydrolyses mucopeptides in the cell wall Lactoferrin Deprives pathogens of iron Hydrolytic enzymes (proteases) Digests killed organisms Summary of Intracellular Killing Pathways Intracellular Killing Oxygen Oxygen Dependent Independent Myleoperoxidase Myleoperoxidase Dependent Independent Nitric Oxide Dependent Killing TNF TNF Nitric Oxide Nitric Oxide  Non-specific Killer Cells NK and LAK cells ADCC (K) cell They all kill foreign and altered self targets Activated macrophages Eosinophils  Natural Killer (NK) cells  also known as large granular lymphocytes (LGL)  kill virus-infected or malignant cells  identified by the presence of CD56 & CD16 and absence of CD3  activated by IL2 and IFN-γ to become LAK cells Lymphokine Activated Killer (LAK) cell kills transformed and malignant cells Regulation of NK Cell Function  K Cells  morphologically undefined  mediate ADCC  have Fc receptor  recognize antibody coated targets  could be NK cells (IgG), macrophages (IgG), eosinophils (IgE) or other cells (IgG)