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Nonspecific Defenses of the Host Chapter 16 I. Introduction: Overview of host defenses • A. Resistance – Ability to ward off disease through body defenses – 1. Nonspecific – All body defenses that protect one from any kind of pathogen. Includes the first and second lines of defense. – 2. Specific – Defenses against specific microorganisms mediated by lymphocytes (white blood cells) and special proteins called antibodies. • B. Susceptibility – Lack of resistance that creates host vulnerability. Figure 16.1 - Overview (1 of 3) II. Skin and Mucous Membranes • A. Mechanical Factors – Include intact skin, keratin, lacrimal apparatus of eye, saliva, mucous with ciliary escalator, and urine. II. Skin and Mucous Membranes • A. Mechanical Factors – Include intact skin, keratin, lacrimal apparatus of eye, saliva, mucous with ciliary escalator, and urine. II. Skin and Mucous Membranes • B. Chemical Factors – Include sebaceous (oil) glands secretion (sebum), perspiration, lysozyme (against GPC), high acidity (pH skin = 3-5, gastric juice = 1-2). • C. Normal flora compete with pathogens, establish conditions unsuitable for pathogens, produce substances harmful to pathogens. Staph on skin III. Phagocytosis • Phagocytosis – Ingestion of a microorganism or particulate matter by phagocytic cells. • A. Formed Elements of the Blood – differential count of WBCs. III. Phagocytosis • B. Specific Kinds of Leukocytes: – Granulocytes (3 types in the blood) • • • • Neutrophils Basophils Eosinophils Dendritic cells (found in lymph nodes, skin, etc. but not in the blood) – Agranulocytes (two types in the blood) • Monocytes • Lymphocytes- three population that appear similar • Natural Killer (NK) cells • B cells • T cells III. Phagocytosis • B. Specific Kinds of Leukocytes: – Granny can’t • • • • • Basophils Eosinophils Neutrophils Dendritic cells She got – Agranulocytes • • • • Monocytes Natural Killer (NK)ey Bi Te III. Phagocytosis • C. Action of Phagocytic Cells – 1. Granulocytes migrate from blood to area of infection and are phagocytic or dump granular contents on pathogens. Eosinophils are often prominent in parasitic infections. – 2. Monocytes enter tissue and become fixed macrophages and then have specific names depending on area. • Examples: dendritic cells-lymph nodes; Kupffer cellsliver; Langerhans-skin – 3. Granulocytes (especially neutrophils) increase the most first and then monocytes increase. III. Phagocytosis • C. Action of Phagocytic Cells Macrophage engulfing rod shaped bacteria III. Phagocytosis • D. Mechanism of Phagocytosis – Chemotaxis, adherence, ingestion, and digestion III. Phagocytosis • E. Inflammation – Bodily response to cell damage characterized by redness, pain, heat, and swelling. – 1. Three stages: • tissue damage, • vasodilation, • phagocytosis. – 2. Goal: • destroy pathogen or limit infection, • then repair damage. Fig 16.8 Process of inflammation III. Phagocytosis • F. Fever – One of the systemic responses to infection – 1. Caused (primarily) by endotoxins released by gram-negative cell walls or viruses. – 2. Endotoxins cause phagocytes to produce IL-1, which acts on the hypothalamus (body’s thermostat). – 3. Hypothalamus releases prostaglandins that reset the temperature of the body to a higher temperature, thus causing fever via vessel constriction and shivering. As fever breaks, vasodilation and sweating occurs, so skin becomes warm. III. Phagocytosis • G. Antimicrobial Substances – 1. Complement System: • A set of cascading serum proteins (30 or so) that participate in lysis of foreign cells, inflammation, and phagocytosis. • Outcomes: inflammation, cytolysis, opsonization (immune adherence) • See overview next slide fig 16.9, 16.10 Outcomes of complement activation Figure 16.9 - Overview (1 of 5) Cytolysis caused by complement Figure 16.10 - Overview (1 of 3) III. Phagocytosis • G. Antimicrobial Substances – 1. Complement System • a. Classic Pathway • Can assist specific immunity (complement). initiated by antigenantibody reaction III. Phagocytosis • G. Antimicrobial Substances – 1.Complement System • b. Nonspecific activation by contact with certain complement proteins and pathogen. • No antibody involved • Called alternate pathway Fig 16.3 Alternate pathway of complement activation III. Phagocytosis • G. Antimicrobial Substances – 1. Complement System • c. When macrophages digest microbes, they release a chemical to stimulate liver to make proteins (lectins) that binds to pathogen and triggers activation of complement. • Called ‘lectin pathway’ III. Phagocytosis • G. Antimicrobial Substances – 2. Interferons (INF) – Antiviral proteins produced in response to viral infection. Host specific but not virus specific. • a. Three types: α, β, and γ interferon • b. Interferon (α and β) works by inducing uninfected cells to produce antiviral proteins (AVPs) that prevent viral replication in surrounding uninfected cells. • c. γ interferon produced by lymphocytes causes neutrophils to kill bacteria • d. They are host-cell-specific, but not virus-specific. – Now human recombinant INFs produced by genetic engineering in bacteria. Used to treat viral infections (α for herpes, hepatitis A and B), β to slow MS Antiviral action of alpha- and beta- interferons Figure 16.15 - Overview