2. Innate Defenses: Inflammation
Chapter 5

3. “human body is continually exposed to conditions that result in damage”
Sunlight, pollutants, trauma
Infectious agents – viruses, bacteria, fungi, parasites
Cancer – damage from within

4. Immunity “multilevel system of interactive defense”
First line of defense – innate resistance – barriers
Second line of defense – inflammation (innate)
Third line of defense – adaptive (acquired) immunity
memory

5. Immunity Levels “interactive”
1st Barriers-physical
-biochemical
2nd Inflammatory Response
-rapid (biochemical & cellular)
-nonspecific
3rd Adaptive
-specific
-memory

6. First Line of Defense Physical and mechanical barriers Skin
Linings of GI, GU & Respiratory tracts
Sloughing of cells
Coughing and sneezing
Flushing
Vomiting
Mucus and cilia

7. First Line of Defense Biochemical barriers
Synthesized and secreted – saliva, tears, ear wax, sweat and mucus
Antimicrobial peptides (skin,urethra)
Normal bacterial flora

9. Second Line of Defense Inflammatory response
“any injury to vascularized tissue”
Classic symptoms – local effect
Redness
Heat Celsus (53 B.C.-7A.D.)
Swelling
Pain
Loss of function

13. Inflammation Goals 1.Limit and control the inflammation process
2.Prevent and limit infection and further damage
3.Initiate adaptive immune response
4.Initiate healing

14. Inflammation Mast cells Plasma proteins Cellular components
Cellular products

15. Mast Cells “cellular bags of granules”
Location:loose CT close to blood vessels
Tissue basophils (blood)
Skin, digestive lining, and respiratory tract

16. Mast Cell

17. Mast Cells Physical injury, chemical agents, immunologic processes
Activation
Physical injury, chemical agents, immunologic processes
Chemical release in two ways
Degranulation and synthesis of lipid-derived chemical mediators

20. Histamine
Vasoactive amine → rapid constriction of large blood vessel – DILATION of post- capillary venules
Retraction of endothelial cells – capillaries
Receptors H1 H2

21. Histamine H1 Pro-inflammatory (smooth muscle bronchi) H2
Receptors H1
Pro-inflammatory (smooth muscle bronchi) H2
Anti-inflammatory (parietal cells – stomach)

22. Mast Cell Degranulation
Chemotactic factors
Neutrophil chemotactic factor –
Kill bacteria – early stages
Eosinophil chemotactic factor – regulate inflammatory response

23. Mast Cell – Mediator Synthesis
Leukotrienes
Product of arachidonic acid – cell membrane
Similar effects – histamine in late stages
Prostaglandins
Similar effects – leukotrienes and PAIN
Platelet-activating factor
Similar effects – leukotrienes and platelet activation

24. Plasma Protein Systems: LIVER
“circulate in the blood as multiple proteins”
Inactive enzymes (proenzymes) – several
– sequential activation
#1 → → → others – “cascade”

25. Plasma Protein Systems: 3
Complement system
Coagulation system
Kinin system

27. Cellular Components of Inflammation
“participate in the inflammatory response”
Granulocytes “cytoplasm granules*”
Neutrophils
Eosinophils
Basophils
Platelets
Monocytes – precursors to tissue macrophages
Lymphocytes (NK cells – tissue and plasma)
*bags of enzymes

29. Neutrophils Pus :” war zone” “polymorphonuclear neutrophils” PMN
Phagocyte – 1° – early inflammation (6-12 hours)
Mediators – attract and activate bacterial proteins, C3a and C5a, mast cell
NCF
Pus :” war zone”

30. Neutrophils

31. Monocyte & Macrophages
“mature tissue cells”-histiocytes
Kupffer's cells – liver
Alveolar macrophages – lung
Microglia – brain
Langerhans cells- skin
24° - replace neutrophils
Macrophage chemotactic factor – from neutrophils → attracts
Resistant bacteria – tuberculosis, leprosy, typhoid fever, brucellosis, listeriosis

33. Macrophage: destroying bacteria

34. Eosinophils “mildly phagocytic” Primary defense against parasites
Regulate vascular mediators from mast cells (Figure 5-3)
Histaminase

35. Natural Killer (NK) Cells
“lymphocyte”
Viruses
Abnormal host cells i.e., cancer

36. Platelets “activation” Degranulation-Synthesis(eosinophils)
Coagulation cascade to stop bleeding
Biochemical mediators – serotonin, similar vascular effects as histamine

37. Phagocytosis
Process by which a cell ingests and disposes of foreign material
Cells migrate out of the blood – basement membrane
Pavementing
Diapedesis

38. Chemotactic Attraction:
“Attracts phagocytes”
Bacterial products
Neutrophil chemotactic factor (mast cells)
Complement – C3a, C5a
Products of clotting and Kinin system

39. Phagocytosis Adherence Engulfment Phagosome formation Lysosome fusion
Destruction of the target

41. Cellular Products
“cellular cooperation – many different types of cells - protein”
Cytokines
Interleukins – IL-1 – macrophage – pyrogen
Interferons – viral infections
Tumor necrosis factor – alpha – macrophage
Chemokines
Induce leukocyte chemotoxis

42. Cytokines

43. Cytokines attracting Macrophages

44. Cytokines:Interferons

45. Local Manifestation of Inflammation
“vascular changes with leakage”
Heat
Redness
Swelling-”fluid leakage from plasma”
Pain

46. Exudative Fluids-local effect
“varies 2° to stage of inflammation and injury”
Serous – watery, early
Fibrous – thick, clotted – more advanced
Purulent – bacterial infection
Hemorrhagic – blood

47. Fever Systemic Manifestations of Inflammation-body Leukocytosis
Endogenous (IL-1), exogenous (pathogen produced)
Act on hypothalamus
Leukocytosis
↑ number – inflammatory products

48. Systemic Manifestations of Inflammation
↑ plasma proteins (liver)
Acute phase reactants – 10 to 40 hours

49. Launching Inflammation

50. Chronic Inflammation Lasting longer than 2 weeks
Often – unsuccessful acute inflammatory response

51. Chronic Inflammation

52. Chronic Inflammation Characteristics
Dense infiltration of lymphocytes and macrophages
Granuloma formation – walling off
Epithelioid cell formation – macrophage differentiation – debris
Giant cell formation – macrophage large phagocytosis