1. Innate Immunity Chapter 15

2. An Overview of the Body's Defenses Resistance to most plant and animal pathogens Species resistance Due to physiological processes of humans that are incompatible with those of the pathogen Correct chemical receptors not present on human cells Conditions may be incompatible with those needed for pathogen's survival Humans don't have innate resistance to a number of pathogens

3. Immune system definitions White blood cells (WBCs)(leukocytes) – innate capacity to recognize and differentiate any foreign material Nonself – foreign material Self – normal cells of the body Pathogen-associated molecular patterns (PAMPs) – molecules shared by microorganisms Pathogen recognition receptors (PRRs) – receptors on WBCs for PAMPs

4. Defense mechanisms of the host To protect the body against pathogens, the immune system relies on a multilevel network of physical barriers, immunologically active cells, and a variety of chemicals First line of defense – any barrier that blocks invasion at the portal of entry – nonspecific Second line of defense – protective cells and fluids; inflammation and phagocytosis – nonspecific Third line of defense – acquired with exposure to foreign substance; produces protective antibodies and creates memory cells – specific

5. Innate Acquired (Adaptive) Third line of defense Overview of the major host defenses Second line of defense First line of defense Details in chapter 16 Innate, natural defenses: present at birth, provide nonspecific resistance to infection Adaptive immunities: specific, must be acquired

6. Innate Second line of defense First line of defense Physical barriers Chemical barriers Genetic barriers Inflammatory response Interferons Phagocytosis Complement Overview of the major host defenses

7. The Body's First Line of Defense Structures, chemicals, and processes that work to prevent pathogens entering the body Skin and mucous membranes of the respiratory, digestive, urinary, and reproductive systems

8. The Role of Skin in Innate Immunity Skin composed of two major layers Epidermis Multiple layers of tightly packed cells Few pathogens can penetrate these layers Shedding of dead skin cells removes microorganisms Epidermal dendritic cells phagocytize pathogens Dermis Collagen fibers help skin resist abrasions that could introduce microorganisms

9. Skin has chemicals that defend against pathogens 1) Perspiration secreted by sweat glands 2) Salt inhibits growth of pathogens 3) Antimicrobial peptides act against microorganisms 4) Lysozyme destroys cell wall of bacteria 5) Sebum secreted by sebaceous (oil) glands helps keep skin pliable and less likely to break or tear while lowering skin pH to a level inhibitory to many bacteria The Role of Skin in Innate Immunity

10. Mucous membranes line all body cavities open to environment Epithelium: Thin, outer covering of the mucous membranes Epithelial cells: Tightly packed to prevent entry of many pathogens Continual shedding of cells carries away microorganisms Dendritic cells below epithelium phagocytize pathogens Goblet and ciliated columnar cells help remove invaders Deeper connective layer that supports the epithelium Produce chemicals that defend against pathogens The Role of Mucous Membranes in Innate Immunity

12. The Role of the Lacrimal Apparatus in Innate Immunity Produces and drains tears Blinking spreads tears and washes surface of the eye Lysozyme in tears destroys bacteria

13. Hydrochloric acid in stomach Digestive juices and bile of intestines Semen contains an antimicrobial chemical Vagina has acidic pH Chemical barriers: First Line of Defense

14. The Role of Normal Microbiota in Innate Immunity Microbial antagonism:Normal microbiota compete with potential pathogens Activities of normal microbiota make it hard for pathogens to compete Consumption of nutrients Create an environment unfavorable to other microorganisms Help stimulate the body's second line of defense Promote overall health by providing vitamins to host

15. Other First-Line Defenses Antimicrobial peptides: Present in skin, mucous membranes, neutrophils Act against a variety of microbes Many organs secrete chemicals with antimicrobial properties Take a look at table 15.2

16. Plasma Red blood cells Buffy coat Serum Clot Unclotted Whole Blood Clotted Whole Blood The Body's Second Line of Defense Operates when pathogens penetrate the skin or mucous membranes Composed of cells, antimicrobial chemicals, and processes Many of these components are contained or originate in the blood Processes include phagocytosis, interferon, complement, inflammation Whole blood = Cells + Plasma Serum = liquid portion of blood – clotting factors

17. Defense Components of Blood Plasma Mostly water containing electrolytes, dissolved gases, nutrients, and proteins Complement proteins and antibodies are also found in plasma Serum The fluid remaining when clotting factors are removed Contains iron-binding compounds Iron needed for metabolism Some microbes produce proteins that bind iron

18. Cells and cell fragments in plasma called formed elements Three types of formed elements 1) Erythrocytes: Carry oxygen and carbon dioxide in the blood 2) Platelets: Involved in blood clotting 3) Leukocytes (White blood cells): Involved in defending the body against invaders Divided into granulocytes and agranulocytes Defense Components of Blood- cells

19. Leukocytes Adaptive immunity Gas transportation Innate immunity, second line of defense PhagocytosisInflammation Clotting, inflammation Myeloid stem cell Lymphoid stem cell Erythroid stem cell Blood stem cell in bone marrow Erythrocyte Platelets Basophil Neutrophil Eosinophil MonocyteLymphocyte A schematic representation of hematopoiesis. Figure 15.4

20. Granulocytes Contain large granules that stain different colors Lobed nucleus Three types 1)Basophils – stain blue with basic dye methylene blue 2) Eosinophils – stain red/orange with acidic dye eosin 3) Neutrophils – stain lilac with mix of acidic and basic dyes Neutrophils and eosinophils: Phagocytize pathogens & capable of diapedesis

21. Agranulocytes Cytoplasm appears uniform under a light microscope No lobes, rounded nucleus Two types 1) Lymphocytes Involved in adaptive immunity Natural killer lymphocytes 2) Monocytes Leave the blood and mature into macrophages in tissues Phagocytic cells that devour foreign objects Lymphocyte 20–25% Monocyte 3–8%

22. Lab analysis of leukocytes Differential white blood cell count can signal disease Increased eosinophils indicate allergies or parasitic worm infection Increased leukocytes and neutrophils indicate bacterial diseases Increased lymphocytes indicate viral infections

23. CELLSFUNCTIONS Red blood cellsCarry O 2 and CO 2 PlateletsInvolved in blood clotting and inflammation NeutrophilsPhagocytes; actively engulfs and killers of bacteria Basophilsinflammatory events and allergies EosinophilsActive in worm and fungal infections, allergy, and inflammation MonocytesBlood phagocytes that rapidly leave the circulation Mast cellsTissue cells similar to basophills, trigger local inflammatory reactions and allergic symptoms Dendritic cellsMacrophages relatives; reside throughout the tissues and RES; involved in early immune reactions with foreign matter Natural Killer (NK) cells Related to T cells but displaying no specificity; active against cancerous and virally infected cells LymphocytesPrimary cells involved in specific immune reactions to foreign matter B cellsDifferentiate into plasma cells and form antibodies (humoral immunity) T cellsPerform a number of specific immune responses such as assisting B cells and cell- mediated immunity

24. Unique characteristics of Leukocytes Diapedesis – migration of cells out of blood vessels into the tissues. Also called extravasation Chemotaxis – migration in response to specific chemicals at the site of injury or infection

25. Phagocytosis Cells capable of phagocytosis are called phagocytes How the Immune System Works- Sompayrac, 4 th edition Phagolysosome

26. Nonspecific Chemical Defenses Against Pathogens (TLRs) Toll-like receptors (TLRs) Integral membrane proteins produced by phagocytic cells Bind pathogen-associated molecular patterns (PAMPs). Hence are examples of PRRs (pathogen recognition receptors) Initiate defensive responses Apoptosis Secretion of inflammatory mediators Stimulate adaptive immune response

28. Protein molecules released by host cells to nonspecifically inhibit the spread of viral infections Cause many symptoms associated with viral infections Two types Types I (alpha and beta) Type II (gamma) Nonspecific Chemical Defenses Against Pathogens (Interferons)

30. Consists of 26 blood serum proteins that work in concert to destroy bacteria and viruses. Liver is main source of complement proteins. Complement proteins are activated by cleavage (cascade reaction) resulting in lysis of the foreign cell. Complement can indirectly trigger inflammation and fever. Pathways Classical: activated by the presence of antibody bound to microorganism Lectin pathway: nonspecific reaction of a host serum protein that binds mannan Alternative: begins when complement proteins bind to normal cell wall and surface components of microorganisms Nonspecific Chemical Defenses Against Pathogens (Complement)

31. Pathways by which complement is activated.

32. Membrane attack complexes (MAC). Function of MAC is to punch a hole on the foreign cell surface killing it Tegla CA, Cudrici C, Patel S, et al. MEMBRANE ATTACK BY COMPLEMENT: THE ASSEMBLY AND BIOLOGY OF TERMINAL COMPLEMENT COMPLEXES. Immunologic research. 2011;51(1):45-60.

33. Nonspecific response to tissue damage Classic signs and symptoms characterized by: Redness (rubor) – increased circulation and vasodilation in injured tissues in response to chemical mediators Warmth (calor) – heat given off by the increased blood flow Swelling (tumor) – increased fluid escaping into the tissue as blood vessels dilate – edema; WBC’s, microbes, debris, and fluid collect to form pus; prevents spread of infection Pain (dolor) – stimulation of nerve endings Two types of inflammation: acute and chronic Inflammation

34. Acute inflammation Develops quickly and is short lived Is typically beneficial Is important in the second line of defense Dilation and increased permeability of the blood vessels Migration of phagocytes Tissue repair Chronic inflammation Long-lasting Damage to tissues can cause disease Inflammation

35. The dilating effect of inflammatory mediators on small blood vessels and increased vascular permeability.

36. The major events in inflammation Also see Figure 15.14 from textbook

37. Fever A body temperature over 37  C Results when pyrogens trigger the hypothalamus to increase the body's core temperature Various types of pyrogens Bacterial toxins Cytoplasmic contents of bacteria released by lysis Antibody-antigen complexes Pyrogens released by phagocytes that have phagocytized bacteria

38. Continues as long as pyrogens are present Outcomes of fever Enhances effects of interferons Inhibits growth of some microbes May enhance the activities of phagocytes, cells of specific immunity, and the process of tissue repair Fever

40. Each of the following choices is a way that the epidermis acts as a nonspecific defense EXCEPT ________. A.constant presence of T cells B.acts as a physical barrier C.continual cell turnover D.presence of dendritic cells

41. What is the role of ciliated cells in the human airway? A.to sweep microbes trapped in mucus away from the lungs B.to prevent microbes from attaching C.to sweep microbes trapped in mucus down to waiting alveolar macrophages D.to sweep microbes into the bloodstream, where they can be attacked by complement proteins

42. What is the primary function of neutrophils? A.to phagocytize pathogens B.to carry oxygen and carbon dioxide C.to aid in blood clotting D.to clear away dead tissue

43. Phagocytes have Toll-like receptors on their surface that help them recognize pathogenic microbes. These receptors and proteins recognize ________. A.self proteins B.surface proteins C.PAMPs D.70S ribosomes

44. What is the term for the process in which pathogens are coated with antimicrobial proteins to increase the likelihood of phagocytosis? A.opsonization B.chemotaxis C.diapedesis D.endocytosis

45. What is the primary function of eosinophils? A.to coat pathogens with antimicrobial proteins B.to engulf Gram-negative bacteria C.to attach to and attack parasitic worms D.to aid in blood clotting

46. What is the function of the membrane attack complex? A.to phagocytize pathogens B.to opsonize pathogens C.to cause the release of interferon D.to form a circular hole in the membrane of pathogens