1. Nonspecific Defenses of the Host
Chapter 16
Nonspecific Defenses of the Host

2. Nonspecific Defenses of the Host
Susceptibility Lack of resistance to a disease
Resistance Ability to ward off disease
Nonspecific resistance Defenses against any pathogen
Specific resistance Immunity, resistance (antibodies) to a specific pathogen

3. Host Defenses
Overview of the body’s defenses
Figure 16.1

4. Mechanical Factors Skin (works generally if intact)
Describe the role of the skin and mucous membranes in nonspecific resistance.
Skin (works generally if intact)
Epidermis consists of tightly packed cells with
Keratin, a protective protein, waterproof

5. Human skin layers

6. Mechanical Factors Mucous membranes (overcome by large numbers)
Differentiate between mechanical and chemical factors, and list five examples of each.
Mucous membranes (overcome by large numbers)
Ciliary escalator: Microbes trapped in mucus are transported away from the lungs
Lacrimal apparatus: Washes eye, removes microbes
Saliva: Washes microbes off teeth and gums, tongue
Mucus traps microbes, moved up and out by ciliary escalator
Urine: Flows out
Vaginal secretions: Flow out

8. Ciliary escalator
Microbes trapped in mucus produced by goblet cells, then propelled upward by cilia

9. Chemical Factors Fungistatic fatty acid (unsaturated) in sebum
Sweat washes off skin (contains lysozyme)
Low pH (3-5) of skin
Lysozyme in perspiration, tears, saliva, and tissue fluids
Low pH ( ) of gastric juice prevents microbe growth (except Helicobacter pylori)
Transferrins in blood bind iron removing this nutrient
NO (nitrous oxide) inhibits ATP production of microbes

10. Normal Microbiota
Describe the role of normal microbiota in nonspecific resistance.
Microbial antagonism/competitive exclusion: Normal microbiota compete with pathogens, preventing their growth on the host.

13. Phagocytosis Phago: eat Cyte: cell
Ingestion of microbes or particles by a cell, performed by phagocytes (certain white blood cells)
Define phagocytosis and phagocyte.

14. Differential White Cell Count
Define differential blood cell count.
Percentage of each type of white cell in a sample of 100 white blood cells
Neutrophils
60-70%
Basophils
0.5-1%
Eosinophils
2-4%
Monocytes
3-8%
Lymphocytes
20-25%

15. White Blood Cells
Leukocytes (white blood cells) divided into granulocytes (neutrophils, basophils, eosinophils), lymphocytes, and monocytes
Granulocytes: (dominate early in infection)
Neutrophils: Phagocytic (most important)
Basophils: Produce histamine
Eosinophils: Toxic to parasites, some phagocytosis
Lymphocytes: Involved in specific immunity
Monocytes: Phagocytic as mature macrophages
Fixed macrophages in lungs, liver, bronchi
Wandering macrophages (enlarged monocytes) roam tissues

16. Principle kinds of leukocytes

17. Lymphatic system

18. Macrophage engulfing rod-shaped bacteria

19. Phagocytosis
Describe the process of phagocytosis, and include the stages of adherence and ingestion.
Figure 16.8a

20. Microbial Evasion of Phagocytosis
• Inhibit adherence: M protein, capsules
Streptococcus pyogenes, S. pneumoniae
• Kill phagocytes: Leukocidins
Staphylococcus aureus
• Lyse phagocytes: Membrane attack complex
Listeriamonocytogenes
• Escape phagosome
Shigella
• Prevent phagosome-lysosome fusion
HIV
• Survive in phagolysosome
Coxiella burnetti
Classify phagocytic cells, and describe the roles of granulocytes and monocytes.

22. Inflammation – body response to cell damage
Redness
Pain
Heat
Swelling (edema)
Acute-phase proteins activated (complement, cytokine, kinins) – short, intense
Chronic inflammation is a prolonged response
Vasodilation (histamine, kinins, prostaglandins, leukotrienes)
Margination and emigration of WBCs
Tissue repair
List the stages of inflammation.

23. Chemicals Released by Damaged Cells
Describe the roles of vasodilation, kinins, prostaglandins, and leukotrienes in inflammation.
• Histamine
Vasodilation, increased permeability of blood vessels
• Kinins
• Prostaglandins
Intensity histamine and kinin effect
• Leukotrienes
Increased permeability of blood vessels, phagocytic attachment

24. Inflammation
Figure 16.9a, b

25. Inflammation
Describe phagocyte migration.
Figure 16.9c, d

26. Phagocyte migration and Phagocytosis
Phagocytes can stick to lining of blood vessels
They also can squeeze through blood vessels
Pus is the accumulation of damaged tissue, dead microbes, granulocytes, macrophages
Figure 16.9c, d

27. Fever: Abnormally High Body Temperature
Hypothalamus normally set at 37°C
Gram-negative endotoxin cause phagocytes to release interleukin 1
Hypothalamus releases prostaglandins that reset the hypothalamus to a high temperature
Body increases rate of metabolism and shivering to raise temperature
When IL-1 is eliminated, body temperature falls. (Crisis - sweating)

28. Outcomes of Complement Activation System
Serum proteins (liquid in blood) activated in a cascade.
Activate one another in a cascade to destroy invading microorganisms
Figure 16.10

29. Effects of Complement Activation
List the components of the complement system.
Cytolysis caused by complement
Opsonization or immune adherence: enhanced phagocytosis
Membrane attack complex: cytolysis
Attract phagocytes
Figure 16.11

30. Effects of Complement Activation (inflammation)
Figure 16.12

31. Classical Pathway of complement activation
Pathway initiated by antigen-antibody reaction
Results in cytolysis, inflammation, and phagocytosis.
Describe three pathways of activating complement.
Figure 16.13

32. Alternative Pathway of complement activation
Pathway initiated by contact between proteins and pathogen
Figure 16.14

33. Lectin Pathway of complement activation
Mannose-binding lectin binds to mannose, enhancing phagocytosis via classical and alternative pathways
Figure 16.15

34. Some bacteria evade complement
Capsules prevent C activation
Surface lipid-carbohydrates prevent MAC formation
Enzymatic digestion of C5a

35. Interferons (IFNs)
Define interferon.
Compare and contrast the actions of a-IFN, b-IFN, and c-IFN.
Alpha IFN & Beta IFN: Cause cells to produce antiviral proteins that inhibit viral replication
Interferons are host-cell specific, but not virus-specific
Gamma IFN: Causes neutrophils and macrophages to phagocytize bacteria

36. Interferons (IFNs) – antiviral action of alpha and beta interferons2
The infecting virus replicates into new viruses. 5
New viruses released by the virus-infected host cell infect neighboring host cells. 6
AVPs degrade viral m-RNA and inhibit protein synthesis and thus interfere with viral replication. 1
Viral RNA from an infecting virus enters the cell. 3
The infecting virus also induces the host cell to produce interferon on RNA (IFN-mRNA), which is translated into alpha and beta interferons. 4
Interferons released by the virus-infected host cell bind to plasma membrane or nuclear membrane receptors on uninfected neighboring host cells, inducing them to synthesize antiviral proteins (AVPs). These include oligoadenylate synthetase, and protein kinase.
Figure 16.16