1. Foundations in Microbiology Seventh Edition
Lecture PowerPoint to accompany
Foundations in Microbiology Seventh Edition
Talaro
Chapter 14
Host Defenses I
Overview and Nonspecific Defenses
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2. 14.1 Defense Mechanisms of the Host
Host Defenses
Innate, natural defenses: present at birth, provide nonspecific resistance to infection
Adaptive immunities: specific, must be acquired

3. 14.1 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. Figure 14.1

6. Physical or Anatomical Barriers: First Line of Defense
Skin and mucous membranes of respiratory, urogenital, eyes, and digestive tracts
Outermost layer of skin is composed of epithelial cells compacted, cemented together, and impregnated with keratin; few pathogens can penetrate if intact
Flushing effect of sweat glands
Damaged cells are rapidly replaced
Mucous coat impedes attachment and entry of bacteria
Blinking and tear production
Stomach acid
Nasal hair traps larger particles

7. Figure 14.2

8. Nonspecific Chemical Defenses
Sebaceous secretions
Lysozyme, an enzyme that hydrolyzes the cell wall of bacteria, in tears
High lactic acid and electrolyte concentration in sweat
Skin’s acidic pH
Hydrochloric acid in stomach
Digestive juices and bile of intestines
Semen contains an antimicrobial chemical
Vagina has acidic pH

9. Genetic Defenses
Some hosts are genetically immune to the diseases of other hosts
Some pathogens have great specificity
Some genetic differences exist in susceptibility

10. 14.2 Structure and Function of the Organs of Defense and Immunity
The study of the body’s second and third lines of defense is called immunology
Functions of a healthy functioning immune system:
Surveillance of the body
Recognition of foreign material
Destruction of entities deemed to be foreign

11. Figure 14.3

12. Immune System
Large, complex, and diffuse network of cells and fluids that penetrate into every organ and tissue
Four major subdivisions of immune system are:
Reticuloendothelial system (RES)
Extracellular fluid (ECF)
Bloodstream
Lymphatic system

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

14. Body Compartments that Participate in the Immune System
The reticuloendothelial system
The spaces surrounding tissue cells that contain extracellular fluid
The bloodstream
The lymphatic system

15. Figure 14.4

16. Reticuloendothelial System (RES)
Network of connective tissue fibers that interconnects other cells and meshes with the connective tissue network surrounding organs
Inhabited by phagocytic cells – mononuclear phagocyte system – macrophages ready to attack and ingest microbes that passed the first line of defense

17. Figure 14.5

18. Origin, Composition, and Functions of the Blood
Whole blood consists of plasma and formed elements (blood cells)
Serum is the liquid portion of the blood after a clot has formed – minus clotting factors
Plasma – 92% water, metabolic proteins, globulins, clotting factors, hormones, and all other chemicals and gases to support normal physiological functions

19. Figure 14.6

20. A Survey of Blood Cells Hemopoiesis – production of blood cells
Stem cells – undifferentiated cells, precursor of new blood cells
Leukocytes – White blood cells
Granulocytes: lobed nucleus
Agranulocytes: unlobed, rounded nucleus

21. Figure 14.7

22. Granulocytes
Neutrophils – 55-90% - lobed nuclei with lavender granules; phagocytes
Eosinophils – 1-3% - orange granules and bilobed nucleus; destroy eukaryotic pathogens
Basophils – 0.5% - constricted nuclei, dark blue granules; release potent chemical mediators
Mast cells: nonmotile elements bound to connective tissue

23. Agranulocytes Lymphocytes – 20-35%, specific immune response
B (humoral immunity)
Activated B cells produce antibodies
T cells (cell-mediated immunity)
Activated T cells modulate immune functions and kill foreign cells
Monocytes, macrophages – 3-7% - largest of WBCs, kidney-shaped nucleus; phagocytic
Macrophages: final differentiation of monocytes
Dendritic cells: trap pathogens and participate in immune reactions

24. Erythrocytes and Platelet Lines
Erythrocytes: develop from bone marrow stem cells, lose nucleus, simple biconcave sacs of hemoglobin
Platelets: formed elements in circulating blood that are not whole cells

26. Lymphatic System
Provides an auxiliary route for return of extracellular fluid to the circulatory system
Acts as a drain-off system for the inflammatory response
Renders surveillance, recognition, and protection against foreign material

27. Figure 14.8

28. Lymphatic Fluid
Lymph is a plasma-like liquid carried by lymphatic circulation
Formed when blood components move out of blood vessels into extracellular spaces
Made up of water, dissolved salts, 2-5% proteins
Transports white blood cells, fats, cellular debris, and infectious agents

29. Lymphatic Vessels
Lymphatic capillaries permeate all parts of the body except the CNS, bone, placenta, and thymus
Thin walls easily permeated by extracellular fluid which is then moved through contraction of skeletal muscles
Functions to return lymph to circulation; flow is one-direction – toward the heart – eventually returning to blood stream

30. Figure 14.9

31. Lymphoid Organs and Tissues
Classified as primary and secondary
Primary lymphoid organs – sites of lymphocytic origin and maturation – thymus and bone marrow
Secondary lymphoid organs and tissues – circulatory-based locations such as spleen and lymph nodes; collections of cells distributed throughout body tissues – skin and mucous membranes – SALT, GALT, MALT

32. Lymphoid Organs
Thymus – high rate of growth and activity until puberty, then begins to shrink; site of T-cell maturation
Lymph nodes – small, encapsulated, bean-shaped organs stationed along lymphatic channels and large blood vessels of the thoracic and abdominal cavities
Spleen – structurally similar to lymph node; filters circulating blood to remove worn out RBCs and pathogens
Miscellaneous – GALT, Peyer’s patch

34. 14.3 Actions of the Second Line of Defense
Recognition
Inflammation
Phagocytosis
Interferon
Complement

35. Recognition
Protein receptors within cell membrane of macrophages, called Toll-like receptors
Detect foreign molecules and signal the macrophage to produce chemicals which:
Stimulate an inflammatory response (nonspecific)
Promote the activity of B and T cells (specific)

36. Figure 14.11

37. Inflammatory Response
Classic signs and symptoms characterized by:
Redness – increased circulation and vasodilation in injured tissues in response to chemical mediators and cytokines
Warmth – heat given off by the increased blood flow
Swelling – increased fluid escaping into the tissue as blood vessels dilate – edema; WBC’s, microbes, debris, and fluid collect to form pus; helping prevent spread of infection
Pain – stimulation of nerve endings
Possible loss of function

38. Figure 14.12

39. Events in inflammation
Figure 14.13
Insert figure 14.13
Events in inflammation

40. Figure 14.14

41. Unique Characteristics of Leukocytes
Diapedesis – migration of cells out of blood vessels into the tissues
Chemotaxis – migration in response to specific chemicals at the site of injury or infection

42. Figure 14.15 Diapedesis and chemotaxis of leukocytes

43. Fever
Initiated by circulating pyrogens which reset the hypothalamus to increase body temperature; signals muscles to increase heat production and vasoconstriction
Exogenous pyrogens – products of infectious agents
Endogenous pyrogens – liberated by monocytes, neutrophils, and macrophages during phagocytosis; interleukin-1 (IL-1) and tumor necrosis factor (TNF)
Benefits of fever:
Inhibits multiplication of temperature-sensitive microorganisms
Impedes nutrition of bacteria by reducing the available iron
Increases metabolism and stimulates immune reactions and protective physiological processes

44. Phagocytosis General activities of phagocytes:
To survey tissue compartments and discover microbes, particulate matter, and dead or injured cells
To ingest and eliminate these materials
To extract immunogenic information from foreign matter

45. Phagocytes and Phagocytosis
Main types of phagocytes:
Neutrophils – general-purpose; react early to bacteria and other foreign materials, and to damaged tissue
Eosinophils – attracted to sites of parasitic infections and antigen-antibody reactions
Macrophages – derived from monocytes; scavenge and process foreign substances to prepare them for reactions with B and T lymphocytes

46. Figure 14.16 Developmental stages of monocytes

47. Figure 14.17 Site-specific macrophages

48. Mechanisms of Phagocytic Recognition, Engulfment, and Killing
Chemotaxis and ingestion: phagocytes migrate and recognize PAMPs
Phagosome
Phagolysosome: lysosome fused with phagosome (death ~30 minutes)
Destruction and elimination
Oxygen-dependent system (respiratory burst)
Liberation of lactic acid, lysozyme, and nitric oxide

49. Figure 14.18

50. Interferon
Small protein produced by certain white blood cells and tissue cells
Interferon alpha – lymphocytes and macrophages
Interferon beta – fibroblasts and epithelial cells
Interferon gamma – T cells
Produced in response to viruses, RNA, immune products, and various antigens
Bind to cell surfaces and induce expression of antiviral proteins
Inhibit expression of cancer genes

51. Figure 14.19

52. Complement
Consists of 26 blood proteins that work in concert to destroy bacteria and viruses
Complement proteins are activated by cleavage (cascade reaction)
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

53. Stages in the Complement Cascade
Initiation
Amplification and cascade
Polymerization
Membrane attack

54. Figure 14.20(a)

55. Figure 14.20(b, c, d)

56. Figure 14.21