1. 16
Innate Immunity: Nonspecific Defenses of the Host

2. Student Learning Outcomes
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. The Concept of Immunity
Immunity: Ability to ______________________.
Susceptibility: Lack of ________________to a disease.
Innate immunity: ________________Specific or not?
Adaptive immunity: __________________________
Fig 16.1

4. The Body’s Defensive Cells
Can you name them?
Host Toll-like receptors (TLRs) attach to
Pathogen-associated molecular patterns (PAMPs)
Binding to TLRs induces release of cytokines that regulate the intensity and duration of immune responses

5. TLRs = ? 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]

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

7. First Line of Defense: Skin & Mucous Membranes
Physical Factors
Epidermis
Mucus of mucous membranes
(Muco)-ciliary escalator
Nose hairs
Lacrimal apparatus
Saliva
Fig 16.3

8. Fungistatic fatty acids in sebum Skin pH and osmolarity
Chemical Factors
Fungistatic fatty acids in sebum
Skin pH and osmolarity
Lysozyme in _______________________
pH of gastric juice
Transferrins in blood
Also important: Antagonism and competitive exclusion of normal microbiota
Lysozyme in perspiration, tears, saliva, and tissue fluids.

9. 1st Line Defense in Human
Mastering: Host Defenses – The Big Picture

10. Formed Elements in Blood
Compare to Table 16.1
Red Blood Cells
Transport O2 and CO2
White Blood Cells:
Phagocytosis
Histamine
Kill parasites. Involved in allergies

11. Formed Elements in Blood
White Blood Cells cont:
Phagocytosis
Natural killer cells
Destroy target cells
Cell-mediated immunity
Produce antibodies
Blood clotting

12. Second Line of Defense: Formed Elements in Blood
60-70%
2-4%
0.5-1%%
3-8%
20-25%

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

14. Phases of Phagocytosis
Foundation Fig 16.7

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

16. Phagocytosis and Evasion of Phagocytosis
Phagocytosis: Overview
Phagocytosis: Mechanism
Review the Following MasteringAnimations
Virulence Factors: Hiding From Host Defenses
Virulence Factors: Inactivating Host Defenses
Phagocytosis: Microbes That Evade It

17. Inflammation Tissue damage leads to inflammatory response Purpose:
Destroy pathogen
limit spread of infection
pave way for tissue repair
Acute-phase proteins activated (such as TNF-, kinins, and other cytokines)  quickly leads to 1st stage of inflammation (?)
4 (5) cardinal signs:?

18. The 3 Stages of Inflammation
Vasodilation and increased vessel permeability due to histamine, kinins, prostaglandins, and other cytokines
Phagocyte migration and phagocytosis
Margination and diapedesis (emigration)
Chemotaxis(due to various cytokines and components of complement system)
Pus formation
Tissue repair and regeneration depends on type of tissue

19. Inflammatory Process
Margination
Diapedesis
Fig 16.8

20. Inflammation review
Treatment of abscess?

21. Fever: Abnormally High Body Temperature
Hypothalamus acts as body’s thermostat. Normally set at?
Endotoxin causes phagocytes to release interleukin–1 (IL–1). IL-1= 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).

22. 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

23. Antimicrobial Substances
Complement system
Interferons
Transferrins: _________________
Antimicrobial peptides: cause bacterial cell lysis. Produced by mucous membrane cells and phagocytes.

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

25. The Complement System Foundation Fig 16.9 MAC
Complement System Overview
MAC

26. Opsonins (complement proteins or antibodies) coat bacteria and promote attachment of micro-organism to phagocyte  Process is called ______________

27. Classical Pathway
Fig 16.12

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

29. 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
Mastering Animations: Complement System
Overview
Activation
Results

30. Interferons (IFNs) Family of small glycoproteins 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.

31. Interferons (IFNs)
Fig 16.15

32. the end Review Questions: 1 – 4 and 9
Multiple Choice Questions: 1 – 3, 5, 6, and 8 – 9
Critical Thinking Questions: 1 and 2
Clinical Application Questions: 2 and 3
the end