Chapter 14 Defense Mechanisms Topics • Innate - Non specific – First line of defense - Defense Mechanisms – Second line of defense - Non-specific immunity • Acquired - Specific – Third line of defense Summary of the major components of the host defenses. First line of defense • Barriers – Anatomical – Chemical Anatomical barriers The trachea contain cilia that entrap and propel particles out of the respiratory tract • Skin – Outermost layer Ciliary Escalator – Hair follicles – Skin glands – Dequamation • Mucous membrane – Digestive F – Urinary – Respiratory – Eye 1 Chemical barriers Immunology • Sebaceous secretions • Study of the development of resistance to • Tears and saliva – lysozyme infectious agents by the body • Acidic pH – Surveillance of the body – Sweat – Recognition of foreign material – Stomach – Destruction of foreign material or agent – Skin • Involve nonspecific ( Second line ) and – Semen specific ( Third line ) immune defense – Vagina - mediated by presence of systems Lactobacillus • White blood cells (WBC) or leukocytes are involved Search, recognize, and destroy is the mandate WBC of the immune system • WBC recognize "self" markers on the host cell – Do not attack or do not respond to host cell • WBC recognize non-self markers on the invading microbe –Attack or respond to microbe Blood Hemopoiesis • Stem cells precursors • Production of blood • Hemopoiesis – Starts at the embryonic stage • Components • Yolk sac and liver – Continues during adult stage – Hematopoietic stem cells in bone marrow 2 Lymphoid The macroscopic composition of whole blood Myeloid White blood cells Neutrophils • Present in high numbers in blood and • Leukocytes tissue – Granulocytes (large cytoplasmic • Phagocytizes bacteria – granules granules) contain digestive enzymes • Neutrophils • Basophils • First to arrive during an immune • Eosinophils response (inflammation) – Agranulocytes • T cells • B cells • Monocytes Eosinophils Basophils • Contain granules with hydrolytic enzymes • Present in low in number in the body • Attach and destroy large eucaryotic • Function is similar to eosinophils. pathogens ( worms ) Involved in allergic reactions due to cytoplasmic granules • Associated with inflammation and allergies • Localized basophils are called mast cells 3 Lymphocytes Monocytes • Specific immunity • Agranulocyte – T cells cellular immunity • Differentiate into macrophages – B cells humoral/antibody immunity (circulation and lymphatics ) and • Third line of defense dendritic cells (tissue associated) • Present throughout the body • Phagocytosis Lymphatic system Lymphatic system • Network of vessels, cells, and tissues that • Fluids extend to most body areas • Vessels • Connected to the blood system • Provides an auxiliary route for the return of • Nodes extracellular fluid to the circulatory system • Spleen • “Drain off” system for inflammatory response • Thymus • Contains lymphocytes, phagocytes and • Miscellaneous (GALT antibodies Representation of the lymphatic system. Gut-associated lymphoid tissue (GALT) • Recognized incoming microbes from food • Supply lymphocytes for antibody response • Ex. Appendix, lacteals, Peyer’s patches 4 Non-specific Immunity Inflammation Second Line of Defense • Four major symptoms • Inflammation – Redness • Phagocytosis – Warmth • Interferon – Swelling • Complement – Pain That result in Cellular Damage Inflammation - 1 Causes • Trauma • Tissue injury due to physical or chemical agents • Reaction to foreign pathogens or bodies (ie medical implants) Inflammation - 2 Function • Mobilize and attract immune components to the site of injury • Localized and remove harmful substances • Destroy microbes and block their invasion • Aid in the repair of tissue damage 5 Chemical mediators during inflammation. 1. Vascular changes • Blood cells, tissue cells, and platelets release chemical mediators and cytokines • Chemical mediators – Vasoactive • Affect endothelial cells, smooth muscles of blood vessels – Chemotactic (chemokines) • Affect WBC The transmigration of WBCs is followed by chemotaxis. 2. Edema • Leakage of vascular fluid ( exudate ) into tissue • Exudate - plasma proteins, blood cells (WBC), debris, and pus • Migration of WBC is called diapedesis or transmigration – Chemotaxis 3. Fever Phagocytosis • Caused by pyrogens – reset the hypothalamic thermostat Neutrophils and (increase temperature) monocytes/ macrophages (and • Pyrogens – Microbes and their products (ex. LPS) dendritic cells) are called – Leukocyte products (ex. lnterleukins) professional phagocytes – IL-1 resets the thermostat • Inhibits microbe and viral multiplication, reduces nutrient availability, increases Eosinophils immune reactions 6 Phagocytosis Macrophages Neutrophils - First to arrive during an • Monocytes/macrophages motile immune response (inflammation) • Specialized/Residents: • Neutrophils are primary components – Alveolar lungs of pus – Langerhan cells skin Monocytes/Macrophages - – Kupffer cells liver Differentiate into macrophages • 1) Responsible for phagocytosis (circulation and lymphatics) and • 2) Interact with B and T cells dendritic cells (tissue associated) Mechanism of Phagocytosis 1. Chemotaxis & binding • Chemotaxis • Directed by • Ingestion – Pathogen-associated molecular patterns (PAMPs ) • Phagolysosome • Peptidoglycan • Destruction • LPS – Foreign debris 2. Ingestion • Pseudopods enclose the pathogen or foreign material • Form a phagosome or phagocytic vacuole 7 3. Phagolysosome • Lysosomes fuse with the phagosome • Other antimicrobials chemicals are released into the phagolysosome 4. Destruction • Within the phagolysosome – A) Oxygen-dependent mechanisms – Similar to byproducts of respiration – B) Oxygen-independent mechanisms – due to numerous hydrolytic enzymes • Undigestible debris are released Interferon • Produced due to viral infections, microbe infections, RNA, immune products, and antigens 8 Classes Activity • Ex. Virus - binds to host cell • Interferon alpha • A signal is sent to the nucleus to – Product of lymphocytes and macrophages synthesized (transcription and translation) • Interferon beta interferon – Product of fibroblasts and epithelial cells • Interferon is secreted • Interferon gamma • Binds to other host cells – Product of T cells • Host cells produce antiviral proteins – inhibit viral multiplication or translation • Not virus-specific Interferon is produced, released, and taken-up by a near-by cell, where by original cell is not protected but the recipient cell is protected. Other Roles of Interferon • Activates and instructs T and B cell development • Inhibits cancer cells • Activates macrophages Fig. 14.20 The antiviral activity of interferon. Pathways Complement • Classical • Consist of ~26 blood proteins – Activated by the presence of antibody bound to microbes • Produced by liver hepatocytes, • Lectin lymphocytes, and monocytes – Activated when a host serum protein binds a • Pathways sugar (mannan) in the wall of fungi and other • Cascade reaction microbes • Alternative • Stages – Activated when complement proteins bind to cell wall or surface components of microbes 9 The three complement pathways, their activators, and the complement proteins involved. Stages • Initiation • Amplification and cascade • Polymerization • Membrane attack Table 14.1 Complement pathways Fig. 14.21a Fig. 14.21b Fig. 14.21d 10 Complement does 3 things • Inflammation C3a, C4a, C5a • Opsonization C3b • MAC killing C5-C9 11.