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 to a specific pathogen

3. Host Defenses
Figure 16.1

4. Mechanical Factors Skin
Epidermis consists of tightly packed cells with Langerhans cells.
Keratin, a protective protein

5. Mechanical Factors Mucous membranes
Ciliary escalator: Microbes trapped in mucus are transported away from the lungs
Lacrimal apparatus: Washes eye
Saliva: Washes microbes off
Urine: Flows out
Vaginal secretions: Flow out

6. Chemical Factors fatty acid in sebum Low pH (3-5) of skin
Lysozyme in tears, saliva, and tissue fluids
Low pH ( ) of gastric juice
Transferrins in blood find iron

7. Normal Microbiota
Microbial antagonism/competitive exclusion: Normal microbiota compete with pathogens.

8. Formed Elements In Blood
Table 16.1

9. Differential White 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%

10. White Blood Cells Neutrophils: Phagocytic Basophils: Produce histamine
Eosinophils: Toxic to parasites, some phagocytosis
Monocytes: Phagocytic as mature macrophages
Fixed macrophages in lungs(alveolar), liver (kupffer), bronchi
Wandering macrophages roam tissues
Lymphocytes: Involved in specific immunity

11. Phagocytosis Phago: eat Cyte: cell
Ingestion of microbes or particles by a cell, performed by phagocytes

12. Phagocytosis
Figure 16.8a

13. Microbial Evasion of Phagocytosis
• Inhibit adherence: M protein, capsules
Streptococcus pyogenes, S. pneumoniae
• Kill phagocytes: Leukocidins
Staphylococcus aureus
• Lyse phagocytes: Membrane attack complex
Listeria monocytogenes
• Escape phagosome
Shigella
• Prevent phagosome-lysosome fusion
HIV
• Survive in phagolysosome
Coxiella burnetti

14. Inflammation Redness Pain Heat Swelling (edema)
Acute-phase proteins activated (complement, cytokine, kinins, fibrinogen)
Vasodilation (histamine, kinins, prostaglandins, leukotrienes)
Margination and emigration of WBCs
Tissue repair

15. Chemicals Released by Damaged Cells
• Histamine
Vasodilation, increased permeability of blood vessels
• Kinins
• Prostaglandins
Intensity histamine and kinin effect
• Leukotrienes
Increased permeability of blood vessels, phagocytic attachment

16. Inflammation
Figure 16.9a, b

17. Inflammation
Figure 16.9c, d

18. 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)

19. The Complement System Serum proteins activated in a cascade.
Figure 16.10

20. Effects of Complement Activation
Opsonization or immune adherence: enhanced phagocytosis
Membrane attack complex: cytolysis
Attract phagocytes
Figure 16.11

21. Effects of Complement Activation
Figure 16.12

22. Classical Pathway
Figure 16.13

23. CYTOLYSIS Antibody recognize and attached antigen,
The complement C1 bind to two or more
adjacent antibodies and activated.
C1 activated C2 and C4 by split C2 to C2a and C2b and C4 to C4a and C4b.
C2a and C4b bind to form another enzyme that activate C3 by splitting into two fragment C3a and C3b.
C3b initiates a sequence of reactions involve C5-C9 that called membrane attack complex.
the activated proteins make transmembrane channels in the invading cell lead to loss of ions and cytolysis.
This process called complement fixation.

25. INFLAMMATION C3a and C5a contribute in acute inflammation.
C3a and C5a bind to mast cells, basophiles, and blood platelets to trigger the release histamine which a powerful chemotactic attract phagocytes to site of complement fixation.

26. OPSONIZATION When bound to the surface of a microorganisms .
C3 can interact with special receptors on phagocytes to promote phagocytosis.

27. Alternative Pathway
Figure 16.14

28. Lectin Pathway
The lectin pathway is mediated by circulating proteins called mannan-binding lectin (MBL) - also known as mannan-binding protein (MBP).
MBL binds to mannose-rich glycans .
Activation of the lectin pathway begins when mannan-binding lectin (MBL) binds to the mannose groups of microbial carbohydrates.

29. Lectin Pathway
Two more lectin pathway proteins called MASP1 and MASP2 (equivalent to C1r and C1s of the classical pathway) now bind to the MBL .
This forms an enzyme similar to C1 of the classical complement pathway that is able to cleave C4 and C2 to form C4bC2a, enzymatically splitting molecules of C3 into C3a and C3b.

30. Lectin Pathway
Figure 16.15

31. Interferons (IFNs) Small protein with MW 15000-30000.
Alpha IFN & Beta IFN: Cause cells to produce antiviral proteins that inhibit viral replication
Gamma IFN: Causes neutrophils and macrophages to phagocytize bacteria

32. Interferons (IFNs) 2
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