Host Defenses I: Overview and Nonspecific Defenses Chapter 14 Copyright © The McGraw-Hill Companies, Inc) Permission required for reproduction or display.

Learning Objectives Define first and second line of host defense Describe the role of skin and mucous membranes in innate immunity. Differentiate physical from chemical protective barriers, give examples of each Describe parts of the immune system and the role they play in the innate non-specific immunity List and describe the stages in inflammation and phagocytosis Describe three complement activation pathways, explain the consequences of complement activation

3 Overview of Host Defenses

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Innate Defenses Constitutive defenses Always on guard, but do not improve with repeated exposures Physical defenses Chemical defenses Phagocytic defenses Inflammatory defenses Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Urination Defecation Mucus Intestinal enzymes Stomach acid Mucus Low pH Wax Sweat Intact skin Cilia Saliva (lysozyme) Mucus Tears (lysozyme) Sebaceous glands

Skin as a Protective Barrier First line of defense Epidermis consists of tightly packed cells with Keratin, a protective protein Surface area of about 2 m 2 Dead cells Secretions Shed Cells

Mucous Membranes Lack keratin Ciliary escalator Mucous production and cell turn-over Sneezing and coughing Normal biota Washing microbes out: Lacrimal apparatus Saliva Urine Vaginal secretions

Chemical Factors Fungistatic fatty acid in sebum. Low pH (3-5) of skin. Lysozyme in perspiration, tears, saliva, and tissue fluids. Low pH ( ) of gastric juice. Iron chelators.

Noxious Molecules Hydrochloric acid (stomach) Bile acids (gall bladder) Fatty acids (sebum) Sodium chloride (sweat)

Enzymes Lysozyme and lysostaphin in tears and secretions DNase and RNase on skin Proteases Typsin, chymotrypsin, etc. in digestive tract

Chelators Limit availability of essential metals like iron. There are three main types in our body Hemoglobin - RBC Lactoferrin - Secretions Transferrin – Serum Starved for iron, many microbes cannot grow

Genetic Defenses Host specificity Genetic mutations

Immune System: Second and Third Line of Defense 1.Surveillance 2.Recognition 3.Destruction

Immune Defense Systems Reticuloendothelial system (RES) Connective tissue network Provides passageway for immune system cells and fluids Extracellular fluid Bloodstream Lymphatic system

Lymphatic System System of vessels, cells and organs, which Render surveillance, recognition and protection against foreign material

Lymphatic System Organs Thymus: site of T-cell maturation Lymph nodes: filter out materials from lymph, provide cells and sites for immune reactions. Spleen: filters out dead RBS, filters out infectious agents, site of phagosytosis GALT: immunity against intestinal pathogens Appendix Peyer’s patches

Hematopoiesis and Differentiation of Blood Cells Yolk sack Liver and lymphatic organs Bone marrow

Blood Cells

Signs of Inflammation Rubor – Redness Tumor – Swelling Dolor – Pain Calor – Heat Functio laesa Loss of Function

Causes of Inflammation Increased blood flow Erythema Increased vascular permeability Influx of phagocytes and serum proteins to the region of infection Exudate

Inflammation Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display Macrophage Lymphocytes Scar Resolution/Scar Formation Newly healed tissue Edema due to collected fluid Rubor (inflammation) Edema and Pus Formation Vascular ReactionsInjury/Immediate Reactions Bacteria in wound Mast cells release chemical mediators Vasoconstriction Clot Vasodilation Seepage of plasma and migration of WBC out of blood vessels Neutrophil Bacteria Scab Neutrophils Pus Fibrous exudate

Stages in Inflammation Immediate reactions Chemical mediators and cytokines (histamines, kinines, prostaglandines) released Vasoconstriction Vascular reactions Contraction of endothelial cells, vasodilation Leakage of blood components into the damaged site. Edema and pus formation Influx of fluid Accumulation of neutrophils, cell debris and bacteria Pyogenic bacteria Resolution Clearance of pus by macrophages

Chemotaxis Diapedesis (transmigration) Chemotaxis

Toll-Like Receptors Surface receptors Bind to molecular patterns TLR4  LPS Signal sent to nucleus Cytokine production is induced Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Foreign molecule Nucleus Toll-like receptor Cytokines Interleukins Inflammatory mediators Macrophage

Types of Phagocytic Cells Professional Phagocytes Neutrophils - 70% of WBC Monocytes Macrophage - tissues Non-Professional Phagocytes Epithelial Cells

1. Chemotaxis by phagocyte Bacterial cells PAMPs 2. Adhesion of bacteria Pattern recognition receptor on host cell 3. Engulfment into phagocytic vacuole Lysosomes 4. Phagosome 5. Phagolysosome formation Nucleus 7. Release of residual debris 6. Killing and destruction of bacterial cells Phagocytosis

Mechanisms of Killing Enzymatic Hydrolysis Lysozyme, Lipases, Proteases, Nucleases Oxidative Burst NADPH oxidase and cytochrome B – produce superoxide anion Superoxide dismutase – hydrogen peroxide Myeloperoxidase – hypochlorite (bleach)

Effects of Complement Activation Opsonization or immune adherence: enhanced phagocytosis. Membrane attack complex: cytolysis. Chemotaxis: attract phagocytes.

Classical Pathway Figure 16.12

Alternative Pathway Figure 16.13

Lectin Pathway Figure 16.14

Fever Advantages Limits iron availability Inhibits bacterial growth Interferes with viral replication Increases effectiveness of some immune molecules Disadvantages Tachycardia Acidosis Dehydration Fever (elevated host body temperature) Caused by interleukin 1 or exogenous pyrogens

Antiviral Defense Molecules Interferons Produced during viral infection Antiviral protein production Blocks virus replication Synthesis of antiviral proteins Nearby cell Signals activation of genes Infected cell IFN gene Virus infection Viral nucleic acid Assembly of viruses Virus release Attachment of IFN to special receptor Degrades virus nucleic acid Synthesis of IFN