1. 16
Innate Immunity: Nonspecific Defenses of the Host

2. SLOs Differentiate between innate and adaptive immunity.
Define toll-like receptors.
Differentiate physical from chemical factors, and list examples of each.
Describe the role of normal microbiota in innate resistance.
Classify phagocytic cells, and describe the roles of granulocytes and monocytes.
Define and explain phagocyte and phagocytosis.
Explain the different stages of inflammation.
Describe the cause and effects of fever.
Describe two of the three pathways of activating complement and describe the 3 outcomes.
Compare and contrast the actions of -IFN and -IFN with -IFN.
Describe the role of transferrins and antimicrobial peptides in innate immunity.

3. TLRs on Ms, dendritic cells, epithelial cells
Cytokines!
TLRs on Ms, dendritic cells, epithelial cells
PAMPs recognition
Toll-like receptors (TLRs) play a crucial role in the recognition of invading pathogens and the activation of subsequent immune responses against them. Individual TLRs recognize distinct pathogen-associated molecular patterns (PAMPs).
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single membrane-spanning non-catalytic receptors that recognize structurally conserved molecules derived from microbes. Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs which activates immune cell responses.
They receive their name from their similarity to the protein coded by the Toll gene identified in Drosophila in 1985 by Christiane Nüsslein-Volhard.[1]

4. Horseshoe structure of TLR3, showing attached sugars (spheres) and internal structures
Fig. 16.7

5. The Concept of Immunity
Susceptibility: Lack of resistance to a disease.
Immunity: Ability to ward off disease.
Innate immunity: Defenses against any pathogen.
Adaptive immunity: Immunity, resistance to a specific pathogen.
Fig 16.1

6. First Line of Defense: Skin and Mucous Membranes
Physical Factors
Epidermis: consists of tightly packed cells with keratin, a protective protein
Two other protective physical factors of skin?
Mucus of mucous membranes
Lacrimal apparatus
Saliva
Nose hairs
(Muco)-ciliary escalator
Fig 16.3

7. Fungistatic fatty acids in sebum Low pH (3-5) of skin
Chemical Factors
Fungistatic fatty acids in sebum
Low pH (3-5) of skin
Lysozyme in _______________________
Low pH (?) of gastric juice
Transferrins in blood
Also important: Antagonism and competitive exclusion of normal microbiota
Lysozyme in perspiration, tears, saliva, and tissue fluids.

8. 1st Line Defense in Human
ANIMATION Host Defenses: The Big Picture

9. Second Line of Defense: Formed Elements in Blood
Compare to Table 16.1
60-70%
2-4%
0.5-1%%
3-8%
20-25%

10. Process of Phagocytosis
Phagocytes engulf and kill microorganisms
Steps of phagocytosis:
Chemotaxis
Recognition and attachment
Engulfment and creation of phagosome
Fusion of phagosome with lysosome
Destruction and digestion
Residual body  Exocytosis
Fig 16.7

11. Phagocytosis
Foundation Fig 16.7

12. 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

13. Phagocytosis and Evasion of Phagocytosis
ANIMATION Phagocytosis: Overview
ANIMATION Phagocytosis: Mechanism
Review the Following Textbook Animations
ANIMATION Virulence Factors: Hiding From Host Defenses
ANIMATION Virulence Factors: Inactivating Host Defenses
ANIMATION Phagocytosis: Microbes That Evade It

14. Inflammation Tissue damage leads to inflammatory response Purpose:
Destroy pathogen
limit spread of infection
pave way for tissue repair
4 cardinal signs:?
Acute-phase proteins (Chemical mediators) activated:
Complement proteins
Cytokines
Specialized proteins such as fibrinogen and bradykinin

15. The Three Stages of Inflammation
Vasodilation and increased vessel permeability due to histamine (and other cytokine) release  edema
Phagocyte migration and phagocytosis
Margination and diapedesis (emigration)
Chemotaxis(due to various cytokines and components of complement system)
Pus formation
Factors challenging effectiveness of phagocytosis
Tissue repair and regeneration depends on type of tissue

16. Inflammatory Process
Margination
Diapedesis
Compare to Fig 16.8

17. Treatment of abscess?

18. Fever: Abnormally High Body Temperature
Hypothalamus acts as body’s thermostat
Endotoxin causes phagocytes to release interleukin–1 (IL–1). IL-1 is an endogenous pyrogen
Hypothalamus releases prostaglandins that reset the thermostat
Body reacts to raise the temperature. How?
When no more IL–1, body temperature falls (crisis).

19. Beneficial effects of moderate fever:
Inhibited pathogen growth
Increased cellular metabolism  e.g.:
Increased transferrin production
Increased IL–1 activity  T cell production 
Faster repair mechanisms
Problematic effects of high fever:
> 40.7C (105F) can be dangerous (Tachycardia, acidosis, dehydration)
Death at temp. > C

20. Antimicrobial Substances
The complement system
Interferons
Transferrins: bind serum iron
Antimicrobial peptides: cause bacterial cell lysis. Produced by mucous membrane cells and phagocytes.

21. The Complement System
Compare to Foundation
Fig 16.9

22. Complement System Summary
Series of  30 plasma (serum) proteins, activated in a cascade
Three effects of complement system:
Enhances inflammatory response, e.g.: attracts phagocytes
Increases phagocytosis through opsonization or immune adherence
Creates Membrane Attack Complexes (MACs)  Cytolysis

23. Opsonins (complement proteins or antibodies) coat bacteria and promote attachment of micro-organism to phagocyte  Opsonization

24. Classical Pathway
Fig 16.12

25. Alternative Pathway
Does not require a specific antibody to get started
Fig 16.13

26. Some Bacteria Evade Complement
Capsules prevent Complement activation.
Surface lipid-carbohydrates of some Gram-negatives prevent MAC formation.
Enzymatic digestion of C5a by Gram-positives.
ANIMATION Complement System: Overview
ANIMATION Complement System: Activation
ANIMATION Complement System: Results

27. Interferons (IFNs) Family of glycoproteins
Host-cell-specific but not virus-specific
-IFN and -IFN: Produced by virus infected cells. Mode of action is to induce uninfected cells to produce antiviral proteins (AVPs) that inhibit viral replication.
-IFN: Produced by lymphocytes. Causes neutrophils and macrophages to phagocytize bacteria. Also involved in tumor immunology.
Recombinant interferons have been produced. However short-acting and many side-effects. No effect on already infected cells.

28. Interferons (IFNs)
Fig 16.15

29. Applications of Microbiology: Serum Collection
Unnumbered Figure 16.1a
Applications of Microbiology:
Serum Collection

30. Unnumbered Figure 16.1b
the end