Overview of Human Immune System

1. Overview of Human Immune System First Line of Defense (Barriers to infection) 2nd Line of Defense (Once barrier has been crossed-invader is inside) Adaptive or Cell-Mediated Immunity (Specific response to invader)

2. 3 basic functions • To maintain homeostasis • Defend against foreign invaders or cells that have gone awry (abnormal cells-may be precursors to cancer). • What are some foreign invaders? • Bacteria (streptococcus, staphylococcus, others? • Fungi (molds, others?) • Parasites (schistosome or blood flukes, others?) • Viruses: (herpes, papova, HIV, others? • To distinguish between self and non-self • Self should have same chemical markers on cell surface • Non self: • antigen: anything that can trigger an immune response (carry marker molecules) • Pathogens (from previous slide) • Tissues or cells from another person • What if can’t distinguish? Autoimmune disorders:

3. IMMUNE DEFENSES INCLUDE • Non specific defenses • Do not distinguish one type of pathogen from another • External • Internal • Specific defenses (adaptive immunity) • Collectively called “immune system” • Includes production of antibodies • Involves lymphocytes

4. NONSPECIFIC RESPONSES:First Line of Defense • Skin • Physical barrier • Pathogens usually enter through a small cut/scrape • Chemical barrier • Sweat and oil secretions maintain skin pH of 3-5; kills most foreign invaders • Normal flora/fauna outcompete pathogenic varieties • Secretions of glands and mucous membranes • washing action of tears, saliva and mucous inhibit microbes • Contain anti-microbial proteins • Lysozyme-digests cell walls of many bacteria • Ciliated epithelial cells sweep out mucous with trapped particles • Flushing effects of urination and diarrhea • If swallowed, microbe encounters acidic environment of stomach • Kills most microbes • Exceptions: • Hepatitis A virus • Helicobacter pylori • Others? Polio? Rabies (salivary gland infection)

7. NONSPECIFIC DEFENSE MECHANISMS: Second Line of Defense • Internal • act after 1st line of defense has been penetrated • Function early to help limit spread of microbes prior to specific response • Responses associated are • Phagocytes (cell that are amoeba like that engulf and digest pathogen) • May be in fixed locations (lymph nodes) or may roam freely in blood, lymph or interstitial fluid) • Examples: • Neutrophils: -60-70% of leukocytes (wbcs); attracted to infected cells by chemical signals given off by those cells (chemotaxis); can leave blood and enter tissues by ameboid movement; Self destruct as they destroy; Life span only a few days, • Monocytes that become macrophages: Only 5% of wbcs; More effective (than neutrophils); Circulate in blood but once mature will enter infected tissue and develop into macrophages • And if an allergen: basophils; • If a large parasite: eosinophils) • Killer cells and Natural killer cells • Attack body’s own infected cells or attack precancerous cells • Not phagocytic • Attack cell’s outer membrane; cause membrane to lyse (cell bursts open) or cause cell to enter apoptosis (programmed cell death) • Antimicrobial proteins (complement system) • Inflammatory response

9. Macrophage Specifics • Macrophages • Some migrate in lymph, blood and interstitial fluid • Some are fixed in certain tissues • Lung • Liver • Kidney • Brain • Connective tissues • ESPECIALLY IN lymph nodes and spleen • Largest phagocytic cells • Effective, long lived • Extend long pseudopodia attach to/grab invader; pull invader into macrophage; Destroy by • Digestive enzymes (lysosomal-lysozyme) • Reactive oxygen (toxic forms of oxygen)* main antimicrobial property of macrophages • Superoxide anion • Nitric oxide • Some bacteria evade with outer capsules; resistant ones can reproduce inside a macrophage • Antigen presenting cells: calls forth the action of helper T cells in specific immune response.

10. Anti-microbial Protein Specifics • Anti-microbial proteins • 20 kinds of plasma proteins circulating in blood • Role in specific immunities also • When activated by antibody molecules bound to pathogens • Collectively called “complement system” • In non-specific response • Take part in cascades of reactions that defend the body against many bacteria, some parasitic protistans, and enveloped viruses • Activation of some plasma proteins initiates inflammation • Another class called interferons • Secreted by virus-infected cells and diffuses to other cells to inhibit viral reproduction; nonspecific • Activates phagocytes

12. Second Line of Defense: The Inflammatory Response • Redness: arteriole vasodilation increases blood flow to the affected area • Warmth: arteriole vasodilation delivers more blood carrying more metabolic heat, to the tissue • Swelling: Chemical signals increase capillary permeability; plasma proteins escape and disrupt fluid balance across capillary walls; localized edema results. • Pain: Nociceptors (pain receptors) are stimulated by increased fluid pressure, local chemical signals

13. Second Line of Defense Also Includes The Inflammatory Response • Triggered by • Entry of microorganisms (infection) • Damage to tissue (puncture, cut, burn) or killing of cells • Initiated by various chemical signals • From invading organism • Released from cells of body • e.g. histamine released by circulating leukocytes called basophils and by mast cells • triggers dilation • increased permeability so plasma proteins escape (swelling due to shift in fluid balance) • Prostaglandins released which triggers arrival of clotting factors

14. In response to damage and coordinated with inflammatory response: • Neutrophils quickly go to work • Monocytes arrive and mature into macrophages (begin sustained engulfing process); Macrophages also take part in the cleanup and repair operations • Macrophages secrete signaling molecules that act as chemical mediators • Called chemotaxins • Called chemokines

15. 3rd Line of Defense: Adaptive Immunity (Cell Mediated and Specific)

16. Key Concepts to Specific Immunity: 3rd Line of Defense • Requires recognition of antigen (usually recognize surface features of antigen) • Specific lymphocytes have receptor proteins on their surfaces that recognize an antigen and mount a direct immune response against that antigen • B cells provide humoral immunity • Meaning that they respond to antigen by producing and secreting proteins called antibodies into blood and other body fluids • Cell and/or antibodies then bind to intact antigen • T cells produce cell-mediated immunity; Use receptors to directly attach to antigen presented

19. Active Immunity vs. Passive Immunity • Discuss and give examples • Acquired immunity (protection one develops against certain types of microbes or foreign invaders) can be natural or artificial • Natural acquired immunity may be active or passive • Antigens enter body and you catch disease; body produces antibodies, memory cells and specific lymphocytes to “remember” (active) • Antibodies pass from the mother to the fetus (passive) • Artificial acquired immunity may be active or passive • Antigens (weakened, dead or fragments of) are introduced in a vaccine; body produces antibodies, memory cells and specific lymphocytes to “remember” (active) • Preformed antibodies in an immune serum are introduced into the body by injection (e.g. antivenom to treat a snake bite); Body does not produce antibodies (passive)