1. Innate (Non-Specific) Immunity
Divisions of the Immune System
Mechanical, Chemical, and Physical Barriers
Cells and Chemicals in Non-Specific Immunity
Inflammatory Response
Release of Mobilizing Chemicals
Attraction of Phagocytes
Antimicrobial Chemicals
Interferon as an Antiviral
Complement Proteins as Lytic Agents and Opsonizers
The role of fever

2. Body Defenses
(Innate
Immunity)
(Acquired
Immunity)

3. Innate (Non-Specific) Immunity
Divisions of the Immune System
Mechanical, Chemical, and Physical Barriers
Cells and Chemicals in Non-Specific Immunity
Inflammatory Response
Release of Mobilizing Chemicals
Attraction of Phagocytes
Antimicrobial Chemicals
Interferon as an Antiviral
Complement Proteins as Lytic Agents and Opsonizers
The role of fever

4. Nonspecific (Innate) Body Defenses
Mechanical, Chemical, and Competitive Barriers
Skin produces acidic sebum to limit bacterial growth.
Saliva and tears destroy bacteria because they contain lysozyme.

5. Innate (Non-Specific) Immunity
Divisions of the Immune System
Mechanical, Chemical, and Physical Barriers
Cells and Chemicals in Non-Specific Immunity
Inflammatory Response
Release of Mobilizing Chemicals
Attraction of Phagocytes
Antimicrobial Chemicals
Interferon as an Antiviral
Complement Proteins as Lytic Agents and Opsonizers
The role of fever

6. Internal Defenses: Cells and Chemicals
Necessary if microorganisms invade deeper tissues
Phagocytes
Natural killer (NK) cells
Inflammatory response (macrophages, mast cells, WBCs, and inflammatory chemicals)
Antimicrobial proteins (interferons and complement proteins)
Fever

7. Defensive Cells in Non-Specific Defense
Phagocytes (neutrophils and macrophages)
Engulf foreign material into a vacuole
Enzymes from lysosomes digest the material
Free macrophages wander through tissues; fixed macrophages are permanent (e.g liver Kupfer cells, brain microglia

8. Events of Phagocytosis
Phagocyte
adheres to
pathogens or debris. 1
Phagocyte forms
pseudopods that
eventually engulf the
particles forming a
phagosome. 2
Phagosome
(phagocytic
vesicle)
Lysosome
Lysosome fuses
with the phagocytic
vesicle, forming a
phagolysosome. 3
Acid
hydrolase
enzymes
Lysosomal
enzymes digest the
particles, leaving a
residual body. 4
Exocytosis of the
vesicle removes
indigestible and
residual material. 5
(b) Events of phagocytosis.
Figure 21.2b

9. Mechanism of Phagocytosis
Destruction of pathogens
Acidification and digestion by lysosomal enzymes
Respiratory burst
Release of cell-killing free radicals
Activation of additional enzymes
Oxidizing chemicals (e.g. H2O2)
Defensins (in neutrophils)

10. Natural Killer (NK) Cells
Large granular lymphocytes
Target cells that lack “self” cell-surface receptors (MHC proteins).
Induce apoptosis in cancer cells and virus-infected cells
Secrete potent chemicals that enhance the inflammatory response
(Cytotoxic T cells target cells that have “self” antigens (MHC I proteins)

11. Innate (Non-Specific) Immunity
Divisions of the Immune System
Mechanical, Chemical, and Physical Barriers
Cells and Chemicals in Non-Specific Immunity
Inflammatory Response
Release of Mobilizing Chemicals
Attraction of Phagocytes
Antimicrobial Chemicals
Interferon as an Antiviral
Complement Proteins as Lytic Agents and Opsonizers
The role of fever

12. Inflammatory Response
Triggered whenever body tissues are injured or infected
Prevents the spread of damaging agents
Disposes of cell debris and pathogens
Sets the stage for repair

13. Inflammatory Response
Cardinal signs of acute inflammation:
Redness
Heat
Swelling
Pain
(And sometimes 5. Impairment of function)

14. Inflammatory Response
Macrophages and epithelial cells of boundary tissues bear Toll-like receptors (TLRs)
TLRs recognize specific classes of infecting microbes
Activated TLRs trigger the release of cytokines that promote inflammation

15. Inflammatory Response
Inflammatory mediators (“Alert” chemicals)
Histamine (from mast cells)
Blood proteins
Kinins, prostaglandins (PGs), leukotrienes, and complement
Released by injured tissue, phagocytes, lymphocytes, basophils, and mast cells
Action of inflammatory chemicals
Dilation of arterioles, resulting in hyperemia
Increased permeability of local capillaries and edema (leakage of exudate)
Exudate moves foreign material into lymphatic vessels, delivers clotting proteins to form a scaffold for repair and to isolate the area

16. Inflammatory Response - Second Line of Defense
Release of histamines, complement, prostaglandins, and kinins from injured cells
Vasodilation and increased permeability of local capillaries, increasing edema and swelling
3. Activation of pain receptors by swollen tissue pressure
Attraction of phagocytes and other lymphocytes to the area through chemotaxis: leukocytosis, margination, diapedesis

17. Steps of Attraction of Leukocytes
Innate defenses
Internal defenses
Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents.
Capillary wall
Basement membrane
Endothelium 1
Leukocytosis. Neutrophils enter blood from bone marrow.
Figure 21.4, step 1

18. Steps of Attraction of Leukocytes
Innate defenses
Internal defenses
Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents.
Capillary wall
Basement membrane
Endothelium 1
Leukocytosis. Neutrophils enter blood from bone marrow. 2
Margination. Neutrophils cling to capillary wall.
Figure 21.4, step 2

19. Steps of Attraction of Leukocytes
Innate defenses
Internal defenses
Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents.
Capillary wall
Basement membrane
Endothelium 1
Leukocytosis. Neutrophils enter blood from bone marrow. 2
Margination. Neutrophils cling to capillary wall.
Diapedesis. Neutrophils flatten and squeeze out of capillaries. 3
Figure 21.4, step 3

20. Steps of Attraction of Leukocytes
Innate defenses
Internal defenses
Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents.
Chemotaxis. Neutrophils follow chemical trail. 4
Capillary wall
Basement membrane
Endothelium
Leukocytosis. Neutrophils enter blood from bone marrow. 1
Margination. Neutrophils cling to capillary wall. 2
Diapedesis. Neutrophils flatten and squeeze out of capillaries. 3
Figure 21.4

21. Innate (Non-Specific) Immunity
Divisions of the Immune System
Mechanical, Chemical, and Physical Barriers
Cells and Chemicals in Non-Specific Immunity
Inflammatory Response
Release of Mobilizing Chemicals
Attraction of Phagocytes
Antimicrobial Chemicals
Interferon as an Antiviral
Complement Proteins as Lytic Agents and Opsonizers
The role of fever

22. Inflammatory Response - Second Line of Defense
Release of histamines, complement, prostaglandins, and kinins from injured cells
Vasodilation and increased permeability of local capillaries, increasing edema and swelling
3. Activation of pain receptors by swollen tissue pressure
Attraction of phagocytes and other lymphocytes to the area through chemotaxis: leukocytosis, margination, diapedesis
Clotting proteins leaking into the area wall off damaged sections; interferon & complement may also be released

23. Antimicrobial Proteins: Inteferon
Produced by most leukocytes and lymphocytes
Function
Reduce inflammation, active macrophages, activate macrophages and mobilize NK cells
Hinder microorganisms’ ability to reproduce
Viral-infected cells secrete IFNs
IFNs enter neighboring cells
Neighboring cells produce antiviral proteins that block viral reproduction
Genetically engineered IFNs for hepatitis, herpes, MS

24. How Interferon Activates the Production of Antivirals
Innate defenses
Internal defenses
Virus 1
Virus enters cell.
New viruses
Viral nucleic acid
Antiviral proteins block viral reproduction. 5 2
Interferon genes switch on.
DNA
Nucleus
mRNA 4
Interferon binding stimulates cell to turn on genes for antiviral proteins.
Cell produces interferon molecules. 3
Interferon
Host cell 2 Binds interferon from cell 1; interferon induces synthesis of protective proteins
Host cell 1 Infected by virus; makes interferon; is killed by virus
Figure 21.5, step 5

25. Antimicrobial Proteins: Complement
What they are
About 20 blood proteins that circulate in an inactive form
Include C1–C9, factors B, D, and P, and regulatory proteins
Function
Major mechanism for destroying foreign substances
Amplifies all aspects of the inflammatory response
Kills bacteria and certain other cell types by cell lysis
Enhances both nonspecific and specific defenses

26. Complement Activation
Two pathways
Classical pathway
Antibodies bind to invading organisms
C1 binds to the antigen-antibody complexes (complement fixation)
Alternative pathway
Triggered when activated C3, B, D, and P interact on the surface of microorganisms

27. Complement is Activated in Two Ways
Classical pathway
Alternative pathway
Antigen-antibody complex
Spontaneous activation + +
Stabilizing factors (B, D, and P) +
complex
No inhibitors on pathogen
surface
Opsonization:
Enhances inflammation:
coats pathogen
surfaces, which
enhances phagocytosis
stimulates histamine release,
increases blood vessel
permeability, attracts
phagocytes by chemotaxis,
etc.
Insertion of MAC and cell lysis
(holes in target cell’s membrane)
Pore
Complement
proteins
(C5b–C9)
Membrane
of target cell
Transmembrane channel (membrane attack complex) causing lysis
Figure 21.6

28. Inflammatory Response - Second Line of Defense
Release of histamines, complement, prostaglandins, and kinins from injured cells
Vasodilation and increased permeability of local capillaries, increasing edema and swelling
3. Activation of pain receptors by swollen tissue pressure
Attraction of phagocytes and other lymphocytes to the area through chemotaxis: leukocytosis, margination, diapedesis
Clotting proteins leaking into the area wall off damaged sections; interferon & complement may also be released
Increased local metabolic rate raises the local temperature to increase rate of repair processes
Production of a fever (stimuated by pyogenic compounds) .
Dead or dying neutrophils, dead cells, and pathogens may form, walling off a sac of pus to form an abscess.

29. Figure 21.3 Innate defenses Internal defenses Tissue injury
Release of chemical mediators
(histamine, complement,
kinins, prostaglandins, etc.)
Release of leukocytosis-
inducing factor
Leukocytosis
(increased numbers of white
blood cells in bloodstream)
Vasodilation
of arterioles
Increased capillary
permeability
Attract neutrophils,
monocytes, and
lymphocytes to
area (chemotaxis)
Leukocytes migrate to
injured area
Local hyperemia
(increased blood
flow to area)
Capillaries
leak fluid
(exudate formation)
Margination
(leukocytes cling to
capillary walls)
Initial stimulus
Physiological response
Signs of inflammation
Diapedesis
(leukocytes pass through
capillary walls)
Leaked protein-rich
fluid in tissue spaces
Leaked clotting
proteins form interstitial
clots that wall off area
to prevent injury to
surrounding tissue
Result
Phagocytosis of pathogens
and dead tissue cells
(by neutrophils, short-term;
by macrophages, long-term)
Heat
Redness
Pain
Swelling
Locally increased
temperature increases
metabolic rate of cells
Possible temporary
limitation of
joint movement
Temporary fibrin
patch forms
scaffolding for repair
Pus may form
Area cleared of debris
Healing
Figure 21.3

30. Fever Abnormally high body temperature
Hypothalmus heat regulation can be reset by pyrogens (secreted by white blood cells)
High temperatures inhibit the release of iron and zinc from liver and spleen needed by bacteria
Fever also increases the speed of tissue repair by increasing metabolic rate

31. Innate (Non-Specific) Immunity
Divisions of the Immune System
Mechanical, Chemical, and Physical Barriers
Cells and Chemicals in Non-Specific Immunity
Inflammatory Response
Release of Mobilizing Chemicals
Attraction of Phagocytes
Antimicrobial Chemicals
Interferon as an Antiviral
Complement Proteins as Lytic Agents and Opsonizers
The role of fever