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 the activativation of complement and describe the 3 outcomes.
Compare and contrast the actions of -IFN and -IFN with -IFN.
Describe the role of transferrins in innate immunity.

3. The Concept of Immunity
Immunity: Ability to ______________________.
Susceptibility: Lack of ________________to a disease.
Innate immunity: ________________Specific or not?
Adaptive immunity: __________________________

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

6. Horseshoe structure of TLR3, showing attached sugars (spheres) and internal structures
Fig. 16.8

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
Fig 16.1

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

9. Formed Elements in Blood
Second Line of Defense:
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

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

11. Process/Phases of Phagocytosis
Phagocytes engulf and kill microorganisms
Chemotaxis
Adherence: Recognition and attachment
Ingestion: Engulfment and creation of phagosome
Digestion:
Fusion of phagosome with lysosome
Destruction and digestion
Residual body  Exocytosis

12. Phases of Phagocytosis
Various Mechanisms of Microbial Evasion of Phagocytosis!!
Compare to Foundation Fig 16.8

13. 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:?

14. 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

15. Inflammatory Process
Margination
Diapedesis
Fig 16.9

16. Inflammation review
Treatment of abscess?

17. Fever: Abnormally High Body Temperature
______________acts as body’s thermostat. Normally set at?
Endotoxin causes phagocytes to release interleukin–1 (IL–1). IL-1= endogenous pyrogen
Hypothalamus releases prostaglandins  thermostat reset to ?
Body reacts how?
What happens when no more IL–1?

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

19. Antimicrobial Substances
Complement system
Interferons
Iron-binding proteins: _____________
Antimicrobial peptides: cause bacterial cell lysis. Produced by mucous membrane cells and phagocytes.

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

21. The Complement System Foundation Fig 16.12 MAC
Complement System Overview
MAC

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

23. 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.

24. Interferons (IFNs)
the end
Compare to Fig 16.14