1. Resistance and the Immune System: Innate Immunity
Chapter 20
Resistance and the Immune System: Innate Immunity

2. Figure 20.01: relationship between host resistance and disease.
20.1 The Immune System is a Network of Cells and Molecules to Defend Against Foreign Substances
Blood cells form an important defense for innate and acquired immunity.
Serum is the fluid part of blood, containing:
water
minerals
salts
proteins, etc.
Plasma is serum that contains clotting agents.
Figure 20.01: relationship between host resistance and disease.

3. Figure 20.02: Major Leukocytes.
Leukocytes (white blood cells) are produced in the bone marrow.
Granulocytes have a granular cytoplasm that contains digestive enzymes and other antimicrobial chemicals.
Neutrophils (polymorphonuclear leukocytes [PMNs]) are phagocytes.
Eosinophils contain toxic compounds to defend against multicellular parasites.
Basophils are similar to mast cells, acting in allergic reactions.
Figure 20.02: Major Leukocytes.

4. Figure 20.02: Major Leukocytes.
Agranulocytes don’t have visible granules in the cytoplasm.
Monocytes are phagocytes that mature into macrophages in tissue.
Lymphocytes move to the lymph nodes after maturation.
Natural killer (NK) cells destroy virus-infected and abnormal cells.
B lymphocytes and T lymphocytes are involved in acquired immunity.
Dendritic cells are found in the skin and other points of pathogen origin.
They are involved in innate and activation of acquired immunity.
Figure 20.02: Major Leukocytes.

5. Figure 20.03A: Human Lymphatic System.
The lymphatic system is composed of cells and tissues essential to immune function.
Lymph is the clear fluid surrounding tissue cells and filling intercellular spaces.
The lymphatic system maintains and distributes lymphocytes.
Figure 20.03A: Human Lymphatic System.

6. Figure 20.03B: Human Lymphatic System.
The primary lymphoid tissues are the thymus and bone marrow.
The secondary lymphoid tissues are the spleen and lymph nodes.
The spleen contains cells that monitor and fight infectious microbes.
The lymph nodes contain phagocytes and lymphocytes.
Figure 20.03B: Human Lymphatic System.

7. Recognition phase (self vs. non-selt) Activation phase (mobilization)
Innate and adaptive immunity are essential components of a fully functional human immune system.
Recognition phase (self vs. non-selt)
Activation phase (mobilization)
Effector phase (attempt to eliminate invader)
Figure 20.04: Example of the Diverse Cytokine Secretion by Immune Cells.

8. Innate Immunity is first nonspecific defense
Adaptive Immunity adapts to invading pathogen
Cytokines are chemical messengers that facilitate both types of immunity
Figure MI 20: Visualizing the Bridge Between Innate and Adaptive Immunity.

9. 20.2 Surface Barriers are Part of Innate Immunity
Host defensive barriers limit pathogen entry
Physical barriers:
The skin is a physical barrier.
Breaches of the skin may allow microbes to enter the blood.
if a pathogen is detected by Langerhans cells, they phagocytize it and induce an adaptive immune response.
Figure 20.05: Outer Surface of the Human.
© Steve Gschmeissner/Photo Researchers, Inc.

10. Figure MF20.01: Who Turned on the Spigot?
Mucous membrane cells produce mucus to trap microbes.
They are then swallowed or coughed out.
Figure MF20.01: Who Turned on the Spigot?
© Dr. Gopal Murti/Photo Researchers, Inc.

11. Chemical Barriers:
Lactobacillus in the human vagina decrease the pH, which resists infection.
The low pH in the stomach destroys most pathogens.
Defensins are antimicrobial peptides found in various bodily secretions.
Lysozyme, found in tears, sweat, and saliva, lyses gram-positive bacterial cells.
Cellular barriers:
The normal microbiota of the body outcompete pathogens for nutrients and attachment sites.

12. Figure 20.06: Pattern Recognition Receptors and Innate Response.
20.3 Coordinated Cellular Defenses Respond to Pathogen Invasion
Innate immunity depends on receptor-recognition of common pathogen-associated molecules.
Pathogen-associated molecular patterns (PAMPs) help the innate immune system recognize pathogens.
Toll-like receptors (TLRs) are signaling receptors on:
macrophages
dendritic cells
endothelial cells
Figure 20.06: Pattern Recognition Receptors and Innate Response.

13. Table 20.01: Recognized Human Toll-Like Receptors.
TLRs mediate a specific response to distinct PAMPs.
They stimulate the secretion of cytokines.
The TLR response must be regulated to prevent infection an immune disorders.
Table 20.01: Recognized Human Toll-Like Receptors.

14. Figure 20.07: Mechanism of Phagocytosis.
Phagocytosis is a nonspecific defense mechanism to clear microbes from infected tissues.
Phagocytosis is the capture and digestion of foreign particles.
Phagocytized microbes are held in a phagosome.
The phagosome is acidified, killing or inactivating the pathogen.
Phagosomes also fuse with lysosomes (phagolysosome).
Respiratory burst, enzymes and other products kill and digest the pathogen
Figure 20.07: Mechanism of Phagocytosis.

15. Formation of Neutrophil Extracellular Traps (NETs)
Some neutrophils transform into extracellular fibers (NETs).
Nuclear envelope and granule membranes disintegrate and mix.
Pathogens get caught in NET fibers.
Antimicrobials degrade and kill pathogens.
Figure 20.08: Formation of NETs.
Adapted from Lee, Warren, L. and Grinstein, S., Science 303 (2004): 1477–1478.

16. Inflammation plays an important role in fighting infection.
Pathogen’s presence and tissue injury trigger inflammation.
Tissue macrophages initiate phagocytosis and secrete cytokines.
Capillary walls dilate, causing edema, heat, redness and pain.
Chemokines attract phagocytes come to site of injury.
Fibrin wall forms around injury preventing the spread of the pathogens.
Figure 20.09: The Process of Inflammation.

17. Figure MF 20.04: Being Skeptical.
Moderate fever benefits host defenses.
Low to moderate fever supports the immune system
inhibits rapid microbial growth.
Encourages rapid tissue repair.
Heightens phagocytosis.
Pyrogens are cytokines produced by:
some leukocytes.
fragments from pathogens.
They affect the hypothalamus, causing elevated body temperature.
If a temperature rises above 105°F in an adult, host metabolic inhibition can occur.
This can cause convulsions and death.
Figure MF 20.04: Being Skeptical.
© Blend Images/Jupiterimages

18. Figure 20.10: Natural killer (NK) cell recognition.
Natural killer cells recognize and kill abnormal cells.
NK cells are formed in the bone marrow, and migrate to:
tonsils
lymph nodes
spleen
When activated, they produce cytokines that trigger response by macrophages and other cells.
Then they move into blood and lymph where they kill:
cancer cells
virus-infected cells
When an NK cell recognizes a cell as “nonself” it releases cytotoxic perforins and granzymes.
Figure 20.10: Natural killer (NK) cell recognition.
Adapted from: Delves and I.M. Roitt, N Engl J Med. 343 (2000):

19. Figure 20.11: Concept Map of complement pathways.
Effector Molecules Damage Invading Pathogens
Complement marks pathogens for destruction.
Complement is a series of proteins that circulate in the bloodstream.
They activate in the presence of microbes.
In the classical pathway, antibody-microbe complexes activate complement proteins that activate C3 convertase.
In the alternative pathway, the complement protein C3 binds to the pathogen cell surface to activate C3 convertase.
Figure 20.11: Concept Map of complement pathways.

20. Figure 20.12AB: Membrane attack complex (MAC).
Complement fragments
trigger an inflammatory response
Bind to the pathogen surface (opsonization)
Enhance phagocytosis
Form a membrane attack complex which causes lysis of pathogen
Reproduced from Carlos Rosado et al, Science 317 (2007): Reprinted with permission from AAAS.
Figure 20.12AB: Membrane attack complex (MAC).

21. Interferon Puts Cells in an Antiviral State
Viral infected cells produce Interferons (IFNs) that are protein cytokines that trigger:
macrophage activation.
production of substances to interfere with RNA viral reproduction.
Figure 20.13: The Production and Activity of Interferon.

22. Figure 20.14: Innate Defense Barriers to Pathogens.