1. Chapter 14 Innate Immunity (Host Defense I: Non-Specific Host Defenses)

2. 3 parts to Immunity I. Nonspecific surface defenses
Structural, Mechanical, Biochemical
II. Innate Immunity (Nonspecific)
Complement, Phagocytosis, Inflammation, Fever, and Viral specific defenses
III. Adaptive Immunity (Specific)
Humoral immunity, Cellular immunity

3. Summary of the major components of the host defenses.
Fig Flowchart summarizing the major components
of the host defenses.

4. Firstline of defense
Barriers
Anatomical
Chemical
Genetic

5. Representation of the primary anatomical and chemical defense barriers.
Fig The primary physical and chemical defense barriers.

6. Anatomical barriers Skin Mucous membrane Outermost layer
Hair follicles
Skin glands
Mucous membrane
Digestive
Urinary
Respiratory
Eye

7. I. Nonspecific surface defenses
A. Structural
1. Epithelial surfaces, tight fit of cells is useful,
first barrier against attack
a. Keratinized skin- thick, strong, waterproof
b. Mucous membranes – thinner, weaker but has
mucous
c. Sloughing of skin sheds microbes and
nutrients quickly

8. Figure 15.1 Surface of human skin (SEM)

9. The Role of Mucous Membranes in Innate Immunity
Mucous membranes line all body cavities open to environment
Two distinct layers
Epithelium
Thin outer covering of the mucous membranes
Epithelial cells are living
Tightly packed to prevent entry of pathogens
Continual shedding of cells carries away microorganisms
Deeper connective layer that supports the epithelium
© 2012 Pearson Education Inc.

10. B. Mechanical (actual physical removal)
1. Peristalsis keeps bacteria from settling, moves it along GI tract.
2. Mucociliary system –
Mucus is produced to
trap organisms and
ciliary movement
sweeps it up and out.
3. Body fluids mechanically removing microbes from
surfaces, urine, tears etc.

11. C. Biochemical (inhospitable environment)
1.Sebum/Fatty acids on skin
2. Sweat makes skin salty
3.Stomach secretions, HCl acid
4. Bile disrupts cell envelope
5. Lysozyme in all skin secretions breaks down peptidoglycan (gram +, or gram - ?)

12. Chemical barriers Sebaceous secretions Eyelid glands – meibomian gland
Tears and saliva – lysozyme
Acidic pH
Sweat
Stomach
Skin
Semen
Vagina

13. Genetic barriers
Different level of sensitivity and resistance to infectious agents
Malaria
Tuberculosis
Leprosy
Fungal infections

14. If the pathogen gets past all of that, then the second layer of defenses, Innate Immunity, comes into play

15. Immunology
Study of the development of resistance to infectious agents by the body
Surveillance of the body
Recognition of foreign material
Destruction of foreign material or agent
Involve nonspecific and specific immune defense systems
White blood cells (wbc) or leukocytes are involved

16. WBC do not destroy self cells, while nonself cells are recognized and destroyed.
Fig Search, recognize,and destroy is the mandate
of the immune system.

17. Systems All systems are integrated Recticuloendothelial system (RES)
Extracellular fluids system (ECF)
Blood or circulatory
Lymphatic

18. The integration of the systems enable the recognition and destruction of foreign particles in the human body.
Fig Connection between the body compartments.

19. Reticuloendothelial (RES)
Network of connective tissue fibers (Reticulum)
Interconnects cells
Allows immune cells to bind and move outside the blood and lymphatic system

20. Extracellular fluid (ECF)
The spaces surrounding tissue cells and RES
Enable immune cells to move

21. Components of blood White blood cells (WBC) or leukocytes
Red blood cells (RBC)
Platelets

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

23. The different stages of hemopoiesis in humans.
Fig Stages in hemopoiesis

24. The three types of stem cells differentiate into blood, platelets, granulocytes, and agranulocytes.
Fig The development of blood cells and platelets.

25. Before We Can Talk About Innate Immunity
Blood as a component of immune response
Plasma leaks out of capillaries, taken up into lymphatic vessels and through the lymph nodes to be filtered.
Erythrocytes – red blood cells
Leukocytes – white blood cells
Thrombocytes – platelets

27. 1. Leukocytes a. Granulocytes i. Neutrophils, 55-90% of all WBC’s
PMN’s, Polymorphonuclear leukocytes, (polies)
- Phagocytic cells, and voracious eaters!
- Mostly stay in tissues
- Short lived 3-8 days

28. A form of innate response preventing bacteria from spreading and have bactericidal properties
NET =
Neutrophil Extracellular Trap

29. ii. Eosinophils, 1-3% of all WBC’s
-More numerous in bone marrow and spleen than in circulation.
-Effective in fighting off eukaryotes like fungi or worms. Contain digestive
enzymes and toxic granules.
When worms invade,
Eosinophils gather around
them and release enzymes
to kill the worm.

30. iii. Basophils, .5-1% of all WBC’s
- These cells are motile and filled with histamine and other chemical mediators. These chemicals result in inflammation and cell communication.
- Mast cells are like
basophils, but are
non motile and found
throughout connective
tissue.

31. b. Agranulocytes
i. Monocytes (3-8%) can be fixed, or wandering.
- Develop into macrophages in the tissues (Differentiate into macrophages (circulation and lymphatics) and dendritic cells (tissue associated)
phagocytic cell (clean up)
- Antigen presenting cell
- releases chemical mediators
- Largest of all WBC’s
- Long Lived
ii. Lymphocytes (20-35%)
- T- lymphocytes train in the thymus (chest area)
Cellular immunity.
- B – lymphocytes are trained in the bone marrow Humoral immunity.
iii. Dendritic cells
- part of monocyte line
- primary job is antigen presentation

34. Lymphatic system Network of vessels that extend to most body areas
Connected to the blood system
Provides an auxiliary route for the return of extracellular fluid to the circulatory system
“Drain off” system for inflammatory response
Contains lymphocytes, phagocytes and antibodies

35. Representation of the lymphatic system.
Fig General components of the lymphatic system.

36. Lymphatic system
Fluids
Vessels
Nodes
Spleen
Thymus
Miscellaneous

37. Fluids Plasma-like fluid (lymph) Formed from blood components Water
Dissolved salts
Proteins (antibodies, albumin)
White blood cells
No red blood cells
Formed from blood components
Diffuse into the lymphatic capillaries

38. Vessels Parallels the blood system Returns lymph to the blood system
Movement of lymph depends on muscle contractions
Permeate all parts of the body except the central nervous system, bone, placenta, and thymus.

39. Lymph nodes Exist in clusters Located Filter for the lymph
along the lymphatic channels and blood vessels
in the thoracic and abdominal cavity regions, armpit, groin and neck
Filter for the lymph
Provide environment for immune reactions

40. Spleen Located in the upper left portion of the abdominal cavity
Filter for blood
traps pathogens and phagocytizes pathogens
Adults can survive without spleen
Asplenic children are severely immunocompromised

41. Thymus Embryo Adult two lobes in the pharyngeal region
High activity (releases mature T cells) until puberty
Adult
Gradually shrinks
Lymph node and spleen supply mature T cells

42. Innate Immunity or Non-specific Immunity
Inflammation
Phagocytosis
Interferon
Complement

43. Inflammation Five major symptoms Redness Warmth Swelling Pain
Loss of function

44. The typical symptoms that occur after injury.
Fig The response to injury

45. Inflammation
Inflammation- a condition brought on by infection, tissue injury, or immune reaction.
1. Inflammation serves to:
a. mobilize & attract immune cells to the site
b. mobilize repair, and clean up of site
c. destroy microbes & block further infection

46. Function Mobilize and attract immune components to the site of injury
Aid in the repair of tissue damage
Localized and remove harmful substances
Destroy microbes and block their invasion

47. Causes Trauma Tissue injury due to physical or chemical agents
Specific immune reactions

48. The major events in inflammation are injury, vascular reactions, edema, and resolution.
Fig The major events in inflammation

49. Stages
Vascular changes
Edema
Fever

50. Vascular changes
Blood cells, tissue cells, and platelets release chemical mediators and cytokines
Chemical mediators
Vasoactive
Affect endothelial cells, smooth muscles of blood vessels
Chemotactic (chemokines)
Affect WBC

51. a. Increased vessel dilation
Altering capillaries
a. Increased vessel dilation
i. Blood supply to tissue increases
ii. Able to carry more leukocytes and serum proteins
iii. Also causes erythema, (redness) and warmth.
b. Increased vessel permeability
i. Allows the leukocytes to move into tissue, though
also allows fluids to leak as well.
ii. Margination
iii. Diapedesis
iiii. Pain

52. Chemical mediators
Cause fever, stimulate lymphocytes, prevent virus spread, cause allergic reactions
Vasoactive mediators
Affect endothelial cells, smooth muscles of blood vessels
Chemotactic (chemokines) mediators
Affect WBC

53. Representation of the effects of chemical mediators during inflammation.
Fig Chemical mediators of the inflammatory
response and their effects.

54. Edema Leakage of vascular fluid (exudate) into tissue
Exudate - plasma proteins, blood cells (wbc), debris, and pus
Migration of wbc is called diapedesis or transmigration
Chemotaxis

55. The transmigration of WBCs is followed by chemotaxis.
Fig Diapedesis and chemotaxis of leukocytes.

56. Inflammatory repair and acute inflammation
a. Inflammation can be painful, debilitating but effective in fighting infection and cleaning up.
i. The area fills with dead leukocytes, bacteria and
tissue cells, this mix is called pus.
ii. Macrophages will begin clean up by consuming the
dead and dying cells.
b. But, the same inflammation can damage normal healthy tissue surrounding the site if it goes on too long. Autoimmune disorders.

57. Fever
1. Systemic body wide physiological response to infection cytokines tell the hypothalamus to increase temperature.
2. Three parts to fever: Chill, fever, crisis.
a. Chill - Physical reactions, goose bumps or
shivering occur, heat is increasing.
b. Fever – prolonged elevated temperature.
c. Crisis – sweating and cooling of body temperature.
3. The increased temp. is actually the optimal temp. for phagocytic cell activity. Inhibits temp sensitive microbes such as cold virus, or mycobacterium.

58. Fever Caused by pyrogens Pyrogens
reset the hypothalamic thermostat (increase temperature)
Vasoconstriction
Pyrogens
Microbes and their products (ex. LPS)
Leukocyte products (ex. lnterleukins)
Inhibits microbe and viral multiplication, reduces nutrient availability, increases immune reactions

59. Figure 15.15 One theoretical explanation for the production of fever in response to infection
Hypothalamus
Hypothalamus secretes prostaglandin, which resets hypothalamic thermostat.
Chemicals secreted by phagocytes travel in blood to hypothalamus.
Nerve impulses
cause shivering, higher metabolic rate, inhibition of sweating, and vasoconstriction.
These processes increase body termperature to the point set by the hypothalamic thermostat.
Wound

60. Phagocytosis
Neutrophils and eosinophils
Macrophages
Mechanism

61. Phagocytosis
Phagocytes recognize, engulf and destroy invading pathogens.
Macrophages and neutrophils
Principle means of eliminating pathogens!
4 steps to phagocytosis:
1. Recognition
2. Engulfment
3. Digestion
4. Expulsion

63. Neutrophils and eosinophils
Early responders to inflammation
Neutrophils are primary components of pus
Eosinophils are primary responders to parasitic infections

64. Macrophages Monocytes transform into macrophages Scavengers
Histiocytes – reside in one location (ex. Alveolar, Kupffer, Langerhans)
Drift throughout the RES
Undergo phagocytosis,
Interact with B and T cells

65. 1. Recognition a. Phagocytes have proteins called cell surface
receptors. These bind to the antigenic determinants
of pathogens.
i. Recognizes cells different from “self”
ii. LPS of gram negatives
iii. Peptidoglycan
b. Complement proteins help to form a bridge between
the macrophage and the pathogen aiding
phagocytosis. (opsonization)

66. 2. Engulfment & 3. Digestion
a. Once attached, the macrophage extends pseudopods around the pathogen and engulfs it, producing a phagosome (a membrane bound vacuole, or pocket)
b. The phagosome merges with a lysosome forming a phagolysosome, and the chemicals within it digest the pathogen. Usually in 30 minutes or less!
(or the next one is free! Ha ha!)

67. Destruction Within the phagolysosome Undigestible debris are released
Oxygen-dependent system
Oxidative burst (oxidizing agents)
Enzymes
Nitric oxide
Undigestible debris are released

68. 4. Expulsion
a. After digestion the phagolysosome fuses with the cell membrane and expels undigested materials.

69. A summary of the mechanism of phagocytosis.
Fig The phases in phagocytosis

70. Interferon
Produced due to viral infections, microbe infections, RNA, immune products, and antigens

71. Virus specific defenses
Interferons – small proteins that impair viral
replication, and are passed from virally infected
cells to neighboring healthy cells.
a. Virus nonspecific, very potent.

72. Complement Consist of 26 blood proteins
Produced by liver hepatocytes, lymphocytes, and monocytes
Pathways
Cascade reaction
Stages

73. Complement (complement cascade)
Complement – a defense system consisting of serum proteins found in blood, lymph, and extra cellular fluids.
1. Consequences of the complement cascade
a. Cytolysis - bursting the invaders cell wall.
b. Initiate inflammation - cascade protein lyses a
mast cell releasing histamine, and enacting
inflammation.
c. Opsonization - “prepare for dinner” cascade
proteins attach to capsule enabling the
macrophage to engulf it more easily.

74. 2. Methods of triggering complement
a. Classical pathway- complement is activated by the presence of an antibody bound to a microorganism.
b. Lectin pathway- when a host protein binds to a sugar present in the walls of fungi and other microbes.
c. Alternative pathway – complement proteins bind to normal cell wall and/or surface components of microbes.

75. The three complement pathways, their activators, and the complement proteins involved.
Table 14.1 Complement pathways

76. Stages Initiation Amplification and cascade Polymerization
Membrane attack

78. Membrane attack complex