1. Ch 12
Host Defenses I:
Nonspecific Defenses

2. SLOs Differentiate between innate and adaptive immunity.
Define and explain PRRs and PAMPs
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.
Explain the antiviral action of interferons
Describe the role of transferrins and antimicrobial peptides in innate immunity.

3. 12.1 Defense Mechanisms of the Host
Immunity: Ability to ______________________.
Susceptibility: Lack of ________________to a disease.
Innate immunity: ________________Specific or not?
Acquired immunity: __________________________
Fig. 12.1

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

5. Ciliary Defense
Fig. 12.3

6. Fungistatic fatty acids in sebum Skin pH and osmolarity
First Line of Defense: Nonspecific 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.

7. Concept Check
For each of the barriers below, state whether it is a physical, chemical, or genetic barrier.
Hydrochloric acid of the stomach
Sloughing of skin
Lysozyme in saliva and tears
Mutation in the gene for complement proteins
Ciliary escalator
Answer: A. Chemical, B. Physical, C. Chemical, D. Genetic, E. Physical

8. 12.2 Second and Third Lines of Defense: An Overview
Kick in if 1st level of defense breached
System of protective cells and fluids
Includes inflammation and phagocytosis
Rapid action at local and systemic levels
Immune system responsible for:
Body surveillance
Recognition of foreign and abnormal material
Destruction of these entities

9. The Body’s Defensive Cells
Can you name them?
Host has PRRs (Pattern Recognition Receptors), e.g.: Toll-like receptors (TLRs). These attach to
Pathogen-associated molecular patterns (PAMPs)
Binding to PRRs induces release of cytokines that regulate the intensity and duration of immune responses

10. PRRs = ? PAMP 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]

11. Formed Elements of Blood
Red Blood Cells
Transport O2 and CO2
White Blood Cells:
Phagocytosis
Histamine
Kill parasites. Involved in allergies

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

13. Fig. 12.7

14. Review Communicating Body Compartments on your own if necessary
MPS
Lymphatic system (Thymus, LNs, Spleen)
Blood
Fig. 12.4

15. 12.3 The Second Line of Defense
Generalized and nonspecific defenses that support and interact with specific immune responses:
Phagocytosis
Inflammation
Fever
Antimicrobial proteins
Three Types of Phagocytes:
Neutrophils
Monocytes
Macrophages

16. Phagocytosis: Cornerstone of Inflammation and Specific Immunity
Neutrophils (part of PMNs):
General purpose phagocytes
Early inflammatory response to bacteria and other foreign materials and to damaged tissue
Primary component of pus
Monocytes and Macrophages
Stationary Macrophages, e.g.:
Fig. 12.8

17. 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

18. Phagocytosis Various Mechanisms of Microbial Evasion of Phagocytosis!!
Compare to Table 12.1

19. Inflammation
Tissue damage leads to inflammatory response
Purpose:
Destroy pathogen
limit spread of infection
pave way for tissue repair
Powerful defense mechanism but has potential to CAUSE disease. CVD due to chronic inflammation? Aging?
Easily identifiable by 4 (5) cardinal signs: Rubor, Calor, Tumor, Dolor, and loss of function
CVD = cardio vascular disease

20. The 3 Stages of Inflammation
Vascular Reaction: Vasodilation and increased vessel permeability due to histamine, chemokines, prostaglandins, and other cytokines
Pus Formation: Phagocyte migration and phagocytosis
Margination and diapedesis (emigration)
Chemotaxis(due to various cytokines and components of complement system)
Resulution: Tissue repair and scar formation. Depends on type of tissue
Table 12.3 not so good

21. Diapedesis
Margination
Fig

22. Inflammation review
Treatment of abscess?

23. Fever: An Adjunct to Inflammation
Abnormally High Body Temperature.
______________acts as body’s thermostat. Normally set at?
Exogenous vs. Endogenous pyrogens
Endotoxin causes phagocytes to release interleukin–1 (IL–1). IL-1 acts on hypothalamus

24. Fever cont. Thermostat set to higher temp. Body reacts how?
What happens when no more IL–1?

25. 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, seizures)
Death when > C

26. Antimicrobial Proteins
Interferons
Complement system
Antimicrobial peptides
Iron-binding proteins: _____________
transferrins

27. 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 T- 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)
Compare to Fig 12.11

29. 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

30. The Complement System Compare to Fig 12.12 MAC
Complement System Overview
MAC

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

32. Antimicrobial Peptides
Produced by MM and phagocytes
15 – 20 amino acids
Cause bacterial cell lysis by inserting themselves into prokaryotic membranes
Research looks for ways to turn them into therapeutic drugs
Fig 12.13
the end