Innate Immunity: Nonspecific Defenses of the Host Slos

Innate Immunity: Nonspecific Defenses of the Host SLOs

Differentiate between innate and adaptive immunity. Define toll-like receptors. Differentiate physical from chemical factors, and list examples of each. Describe the role of normal microbiota in innate resistance. Classify phagocytic cells, and describe the roles of granulocytes and monocytes. Define and explain phagocyte and phagocytosis. Explain the different stages of inflammation. Describe the cause and effects of fever. Describe two of the three pathways of activating complement and describe the 3 outcomes. Compare and contrast the actions of -IFN and -IFN with -IFN. Describe the role of transferrins and antimicrobial peptides in innate Copyrightimmunity. © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Cytokines! TLRs on Ms, dendritic cells, epithelial cells PAMPs recognition Horseshoe structure of TLR3, showing attached sugars (spheres) and internal structures

Fig. 16.7 The Concept of Immunity

. Susceptibility: Lack of resistance to a disease. . Immunity: Ability to ward off disease. . Innate immunity: Defenses against any pathogen. . Adaptive immunity: Immunity, resistance to a specific pathogen.

Physical Factors . Epidermis: consists of tightly packed cells with keratin, a protective protein . Two other protective physical factors of skin? . Mucus of mucous membranes Fig 16.3 . Lacrimal apparatus . Saliva . Nose hairs . (Muco)-ciliary escalator

. Fungistatic fatty acids in sebum . Low pH (3-5) of skin . Lysozyme in ______. Low pH (?) of gastric juice . Transferrins in blood

Also important: Antagonism and competitive exclusion of normal microbiota

ANIMATION Host Defenses: The Big Picture Second Line of Defense: Formed Elements in Blood Compare to Table 16.1

60-70% 2-4%

0.5-1%%

3-8%

Phagocytes engulf and kill microorganisms Steps of phagocytosis: • Chemotaxis • Recognition and attachment • Engulfment and creation of phagosome • Fusion of phagosome with lysosome • Destruction and digestion • Residual body  Exocytosis

Foundation Fig 16.7 Microbial Evasion of Phagocytosis

Inhibit adherence: M Streptococcus pyogenes, S. protein, capsules pneumoniae Kill phagocytes: Staphylococcus aureus Leukocidins Lyse phagocytes: Membrane attack Listeriamonocytogenes complex Escape phagosome Shigella Prevent phagosome- HIV lysosome fusion Survive in Coxiella burnetti phagolysosome Phagocytosis and Evasion of Phagocytosis

ANIMATION Phagocytosis: Overview

ANIMATION Phagocytosis: Mechanism

ANIMATION Virulence Factors: Hiding From Host Defenses

ANIMATION Virulence Factors: Inactivating Host Defenses

ANIMATION Phagocytosis: Microbes That Evade It

Tissue damage leads to inflammatory response Purpose: . Destroy pathogen . limit spread of infection . pave way for tissue repair 4 cardinal signs:? Acute-phase proteins (Chemical mediators) activated: . Complement proteins . Cytokines . Specialized proteins such as fibrinogen and bradykinin Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings The Three Stages of Inflammation

1. Vasodilation and increased vessel permeability due to histamine (and other cytokine) release  edema 2. Phagocyte migration and phagocytosis  Margination and diapedesis (emigration)  Chemotaxis(due to various cytokines and components of complement system)  Pus formation  Factors challenging effectiveness of phagocytosis 3. Tissue repair and regeneration depends on type Copyrightof © 2006 tissue Pearson Education, Inc., publishing as Benjamin Cummings Inflammatory Process

Margination

Diapedesis

Compare to Fig 16.8 Treatment of abscess? Fever: Abnormally High Body Temperature

. Hypothalamus acts as body’s thermostat . Endotoxin causes phagocytes to release interleukin–1 (IL–1). IL-1 is an endogenous pyrogen . Hypothalamus releases prostaglandins that reset the thermostat . Body reacts to raise the temperature. How? . When no more IL–1, body

Copyrighttemperature © 2006 Pearson Education, Inc., publishing falls as Benjamin (crisis). Cummings Beneficial effects of moderate fever: Inhibited pathogen growth Increased cellular metabolism  e.g.: . Increased transferrin production . Increased IL–1 activity  T cell production  . Faster repair mechanisms

Problematic effects of high fever: > 40.7C (105F) can be dangerous (Tachycardia, acidosis, dehydration) Death at temp. > 44 - 46C Antimicrobial Substances

1. The complement system 2. Interferons 3. Transferrins: bind serum iron 4. Antimicrobial peptides: cause bacterial cell lysis. Produced by mucous membrane cells and phagocytes.

Series of  30 plasma (serum) proteins, activated in a cascade Three effects of complement system: 1. Enhances inflammatory response, e.g.: attracts phagocytes 2. Increases phagocytosis through opsonization or immune adherence 3. Creates Membrane Attack Complexes (MACs)  Cytolysis

Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Opsonins (complement proteins or antibodies) coat bacteria and promote attachment of micro-organism to phagocyte  Opsonization Classical Pathway

Fig 16.12 Alternative Pathway

Does not require a specific antibody to get started

Fig 16.13

. Capsules prevent Complement activation. . Surface lipid-carbohydrates of some Gram- negatives prevent MAC formation. . Enzymatic digestion of C5a by Gram- positives.

ANIMATION Complement System: Overview

ANIMATION Complement System: Activation

. Family of glycoproteins . Host-cell-specific but not virus-specific . -IFN and -IFN: Produced by virus infected cells. Mode of action is to induce uninfected cells to produce antiviral proteins (AVPs) that inhibit viral replication. . -IFN: Produced by lymphocytes. Causes neutrophils and macrophages to phagocytize bacteria. Also involved in tumor immunology. . Recombinant interferons have been produced. However short-acting and many side-effects. No effect on already infected cells.

Fig 16.15

Applications of Microbiology: Serum Collection Unnumbered Figure 16.1b