Innate (Non-Specific) Immunity Divisions of the Immune System Mechanical, Chemical, and Physical Barriers Cells and Chemicals in Non-Specific Immunity Inflammatory Response Release of Mobilizing Chemicals Attraction of Phagocytes Antimicrobial Chemicals Interferon as an Antiviral Complement Proteins as Lytic Agents and Opsonizers The role of fever

Body Defenses (Innate Immunity) (Acquired Immunity)

Innate (Non-Specific) Immunity Divisions of the Immune System Mechanical, Chemical, and Physical Barriers Cells and Chemicals in Non-Specific Immunity Inflammatory Response Release of Mobilizing Chemicals Attraction of Phagocytes Antimicrobial Chemicals Interferon as an Antiviral Complement Proteins as Lytic Agents and Opsonizers The role of fever

Nonspecific (Innate) Body Defenses Mechanical, Chemical, and Competitive Barriers Skin produces acidic sebum to limit bacterial growth. Saliva and tears destroy bacteria because they contain lysozyme.

Innate (Non-Specific) Immunity Divisions of the Immune System Mechanical, Chemical, and Physical Barriers Cells and Chemicals in Non-Specific Immunity Inflammatory Response Release of Mobilizing Chemicals Attraction of Phagocytes Antimicrobial Chemicals Interferon as an Antiviral Complement Proteins as Lytic Agents and Opsonizers The role of fever

Internal Defenses: Cells and Chemicals Necessary if microorganisms invade deeper tissues Phagocytes Natural killer (NK) cells Inflammatory response (macrophages, mast cells, WBCs, and inflammatory chemicals) Antimicrobial proteins (interferons and complement proteins) Fever

Defensive Cells in Non-Specific Defense Phagocytes (neutrophils and macrophages) Engulf foreign material into a vacuole Enzymes from lysosomes digest the material Free macrophages wander through tissues; fixed macrophages are permanent (e.g liver Kupfer cells, brain microglia

Events of Phagocytosis Phagocyte adheres to pathogens or debris. 1 Phagocyte forms pseudopods that eventually engulf the particles forming a phagosome. 2 Phagosome (phagocytic vesicle) Lysosome Lysosome fuses with the phagocytic vesicle, forming a phagolysosome. 3 Acid hydrolase enzymes Lysosomal enzymes digest the particles, leaving a residual body. 4 Exocytosis of the vesicle removes indigestible and residual material. 5 (b) Events of phagocytosis. Figure 21.2b

Mechanism of Phagocytosis Destruction of pathogens Acidification and digestion by lysosomal enzymes Respiratory burst Release of cell-killing free radicals Activation of additional enzymes Oxidizing chemicals (e.g. H2O2) Defensins (in neutrophils)

Natural Killer (NK) Cells Large granular lymphocytes Target cells that lack “self” cell-surface receptors (MHC proteins). Induce apoptosis in cancer cells and virus-infected cells Secrete potent chemicals that enhance the inflammatory response (Cytotoxic T cells target cells that have “self” antigens (MHC I proteins)

Innate (Non-Specific) Immunity Divisions of the Immune System Mechanical, Chemical, and Physical Barriers Cells and Chemicals in Non-Specific Immunity Inflammatory Response Release of Mobilizing Chemicals Attraction of Phagocytes Antimicrobial Chemicals Interferon as an Antiviral Complement Proteins as Lytic Agents and Opsonizers The role of fever

Inflammatory Response Triggered whenever body tissues are injured or infected Prevents the spread of damaging agents Disposes of cell debris and pathogens Sets the stage for repair

Inflammatory Response Cardinal signs of acute inflammation: Redness Heat Swelling Pain (And sometimes 5. Impairment of function)

Inflammatory Response Macrophages and epithelial cells of boundary tissues bear Toll-like receptors (TLRs) TLRs recognize specific classes of infecting microbes Activated TLRs trigger the release of cytokines that promote inflammation

Inflammatory Response Inflammatory mediators (“Alert” chemicals) Histamine (from mast cells) Blood proteins Kinins, prostaglandins (PGs), leukotrienes, and complement Released by injured tissue, phagocytes, lymphocytes, basophils, and mast cells Action of inflammatory chemicals Dilation of arterioles, resulting in hyperemia Increased permeability of local capillaries and edema (leakage of exudate) Exudate moves foreign material into lymphatic vessels, delivers clotting proteins to form a scaffold for repair and to isolate the area

Inflammatory Response - Second Line of Defense Release of histamines, complement, prostaglandins, and kinins from injured cells 2. Vasodilation and increased permeability of local capillaries, increasing edema and swelling 3. Activation of pain receptors by swollen tissue pressure 4. Attraction of phagocytes and other lymphocytes to the area through chemotaxis: leukocytosis, margination, diapedesis

Steps of Attraction of Leukocytes Innate defenses Internal defenses Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents. Capillary wall Basement membrane Endothelium 1 Leukocytosis. Neutrophils enter blood from bone marrow. Figure 21.4, step 1

Steps of Attraction of Leukocytes Innate defenses Internal defenses Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents. Capillary wall Basement membrane Endothelium 1 Leukocytosis. Neutrophils enter blood from bone marrow. 2 Margination. Neutrophils cling to capillary wall. Figure 21.4, step 2

Steps of Attraction of Leukocytes Innate defenses Internal defenses Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents. Capillary wall Basement membrane Endothelium 1 Leukocytosis. Neutrophils enter blood from bone marrow. 2 Margination. Neutrophils cling to capillary wall. Diapedesis. Neutrophils flatten and squeeze out of capillaries. 3 Figure 21.4, step 3

Steps of Attraction of Leukocytes Innate defenses Internal defenses Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents. Chemotaxis. Neutrophils follow chemical trail. 4 Capillary wall Basement membrane Endothelium Leukocytosis. Neutrophils enter blood from bone marrow. 1 Margination. Neutrophils cling to capillary wall. 2 Diapedesis. Neutrophils flatten and squeeze out of capillaries. 3 Figure 21.4

Innate (Non-Specific) Immunity Divisions of the Immune System Mechanical, Chemical, and Physical Barriers Cells and Chemicals in Non-Specific Immunity Inflammatory Response Release of Mobilizing Chemicals Attraction of Phagocytes Antimicrobial Chemicals Interferon as an Antiviral Complement Proteins as Lytic Agents and Opsonizers The role of fever

Inflammatory Response - Second Line of Defense Release of histamines, complement, prostaglandins, and kinins from injured cells 2. Vasodilation and increased permeability of local capillaries, increasing edema and swelling 3. Activation of pain receptors by swollen tissue pressure 4. Attraction of phagocytes and other lymphocytes to the area through chemotaxis: leukocytosis, margination, diapedesis 5. Clotting proteins leaking into the area wall off damaged sections; interferon & complement may also be released

Antimicrobial Proteins: Inteferon Produced by most leukocytes and lymphocytes Function Reduce inflammation, active macrophages, activate macrophages and mobilize NK cells Hinder microorganisms’ ability to reproduce Viral-infected cells secrete IFNs IFNs enter neighboring cells Neighboring cells produce antiviral proteins that block viral reproduction Genetically engineered IFNs for hepatitis, herpes, MS

How Interferon Activates the Production of Antivirals Innate defenses Internal defenses Virus 1 Virus enters cell. New viruses Viral nucleic acid Antiviral proteins block viral reproduction. 5 2 Interferon genes switch on. DNA Nucleus mRNA 4 Interferon binding stimulates cell to turn on genes for antiviral proteins. Cell produces interferon molecules. 3 Interferon Host cell 2 Binds interferon from cell 1; interferon induces synthesis of protective proteins Host cell 1 Infected by virus; makes interferon; is killed by virus Figure 21.5, step 5

Antimicrobial Proteins: Complement What they are About 20 blood proteins that circulate in an inactive form Include C1–C9, factors B, D, and P, and regulatory proteins Function Major mechanism for destroying foreign substances Amplifies all aspects of the inflammatory response Kills bacteria and certain other cell types by cell lysis Enhances both nonspecific and specific defenses

Complement Activation Two pathways Classical pathway Antibodies bind to invading organisms C1 binds to the antigen-antibody complexes (complement fixation) Alternative pathway Triggered when activated C3, B, D, and P interact on the surface of microorganisms

Complement is Activated in Two Ways Classical pathway Alternative pathway Antigen-antibody complex Spontaneous activation + + Stabilizing factors (B, D, and P) + complex No inhibitors on pathogen surface Opsonization: Enhances inflammation: coats pathogen surfaces, which enhances phagocytosis stimulates histamine release, increases blood vessel permeability, attracts phagocytes by chemotaxis, etc. Insertion of MAC and cell lysis (holes in target cell’s membrane) Pore Complement proteins (C5b–C9) Membrane of target cell Transmembrane channel (membrane attack complex) causing lysis Figure 21.6

Inflammatory Response - Second Line of Defense Release of histamines, complement, prostaglandins, and kinins from injured cells 2. Vasodilation and increased permeability of local capillaries, increasing edema and swelling 3. Activation of pain receptors by swollen tissue pressure 4. Attraction of phagocytes and other lymphocytes to the area through chemotaxis: leukocytosis, margination, diapedesis 5. Clotting proteins leaking into the area wall off damaged sections; interferon & complement may also be released Increased local metabolic rate raises the local temperature to increase rate of repair processes 7. Production of a fever (stimuated by pyogenic compounds) . 8. Dead or dying neutrophils, dead cells, and pathogens may form, walling off a sac of pus to form an abscess.

Figure 21.3 Innate defenses Internal defenses Tissue injury Release of chemical mediators (histamine, complement, kinins, prostaglandins, etc.) Release of leukocytosis- inducing factor Leukocytosis (increased numbers of white blood cells in bloodstream) Vasodilation of arterioles Increased capillary permeability Attract neutrophils, monocytes, and lymphocytes to area (chemotaxis) Leukocytes migrate to injured area Local hyperemia (increased blood flow to area) Capillaries leak fluid (exudate formation) Margination (leukocytes cling to capillary walls) Initial stimulus Physiological response Signs of inflammation Diapedesis (leukocytes pass through capillary walls) Leaked protein-rich fluid in tissue spaces Leaked clotting proteins form interstitial clots that wall off area to prevent injury to surrounding tissue Result Phagocytosis of pathogens and dead tissue cells (by neutrophils, short-term; by macrophages, long-term) Heat Redness Pain Swelling Locally increased temperature increases metabolic rate of cells Possible temporary limitation of joint movement Temporary fibrin patch forms scaffolding for repair Pus may form Area cleared of debris Healing Figure 21.3

Fever Abnormally high body temperature Hypothalmus heat regulation can be reset by pyrogens (secreted by white blood cells) High temperatures inhibit the release of iron and zinc from liver and spleen needed by bacteria Fever also increases the speed of tissue repair by increasing metabolic rate

Innate (Non-Specific) Immunity Divisions of the Immune System Mechanical, Chemical, and Physical Barriers Cells and Chemicals in Non-Specific Immunity Inflammatory Response Release of Mobilizing Chemicals Attraction of Phagocytes Antimicrobial Chemicals Interferon as an Antiviral Complement Proteins as Lytic Agents and Opsonizers The role of fever