16 Innate Immunity: Nonspecific Defenses of the Host

Student Learning Outcomes 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 the activativation of complement and describe the 3 outcomes. Compare and contrast the actions of -IFN and -IFN with -IFN. Describe the role of transferrins in innate immunity.

The Concept of Immunity Immunity: Ability to ______________________. Susceptibility: Lack of ________________to a disease. Innate immunity: ________________Specific or not? Adaptive immunity: __________________________

The Body’s Defensive Cells Can you name them? Host Toll-like receptors (TLRs) attach to Pathogen-associated molecular patterns (PAMPs) Binding to TLRs induces release of cytokines that regulate the intensity and duration of immune responses

= ? TLRs PAMPs recognition

Horseshoe structure of TLR3, showing attached sugars (spheres) and internal structures Fig. 16.8

First Line of Defense: Skin & Mucous Membranes Physical Factors Epidermis Mucus of mucous membranes (Muco)-ciliary escalator Nose hairs Lacrimal apparatus Saliva Fig 16.3 Fig 16.1

Fungistatic fatty acids in sebum Skin pH and osmolarity Chemical Factors Fungistatic fatty acids in sebum Skin pH and osmolarity Lysozyme in _______________________ pH of gastric juice Transferrins in blood Also important: Antagonism and competitive exclusion of normal microbiota

Formed Elements in Blood Second Line of Defense: Formed Elements in Blood Compare to Table 16.1 Red Blood Cells Transport O2 and CO2 White Blood Cells: Phagocytosis Histamine Kill parasites. Involved in allergies

Formed Elements in Blood White Blood Cells cont: Phagocytosis Natural killer cells Destroy target cells Cell-mediated immunity Produce antibodies Blood clotting

Process/Phases of Phagocytosis Phagocytes engulf and kill microorganisms Chemotaxis Adherence: Recognition and attachment Ingestion: Engulfment and creation of phagosome Digestion: Fusion of phagosome with lysosome Destruction and digestion Residual body  Exocytosis

Phases of Phagocytosis Various Mechanisms of Microbial Evasion of Phagocytosis!! Compare to Foundation Fig 16.8

Inflammation Tissue damage leads to inflammatory response Purpose: Destroy pathogen limit spread of infection pave way for tissue repair Acute-phase proteins activated (such as TNF-, kinins, and other cytokines)  quickly leads to 1st stage of inflammation (?) 4 (5) cardinal signs:?

The 3 Stages of Inflammation Vasodilation and increased vessel permeability due to histamine, kinins, prostaglandins, and other cytokines Phagocyte migration and phagocytosis Margination and diapedesis (emigration) Chemotaxis(due to various cytokines and components of complement system) Pus formation Tissue repair and regeneration depends on type of tissue

Inflammatory Process Margination Diapedesis Fig 16.9

Inflammation review Treatment of abscess?

Fever: Abnormally High Body Temperature ______________acts as body’s thermostat. Normally set at? Endotoxin causes phagocytes to release interleukin–1 (IL–1). IL-1= endogenous pyrogen Hypothalamus releases prostaglandins  thermostat reset to ? Body reacts how? What happens when no more IL–1?

Beneficial effects of moderate fever: Inhibited pathogen growth Increased cellular metabolism  e.g.: Increased transferrin production Increased T cell production Faster repair mechanisms Problematic effects of high fever: > 40.7C (> 105F) can be dangerous (Tachycardia, acidosis, dehydration) Death when > 44 - 46C

Antimicrobial Substances Complement system Interferons Iron-binding proteins: _____________ Antimicrobial peptides: cause bacterial cell lysis. Produced by mucous membrane cells and phagocytes.

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

The Complement System Foundation Fig 16.12 MAC Complement System Overview MAC

Opsonins (complement proteins or antibodies) coat bacteria and promote attachment of micro-organism to phagocyte  Process is called ______________ Some bacteria evade complement system!!

Interferons (IFNs) Family of small glycoproteins 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.

Interferons (IFNs) the end Compare to Fig 16.14