chapter 14

Chapter 14 Innate Immunity:

1. Characteristics:

·       First line of Defense against infections

·       Non-specific (doesn’t target a specific pathogen)

·       Defense against viruses, bacteria, fungi

·       Immediate response to pathogen

·       Built in and has no “memory”

2. Three lines of Defense:

·       Physical/Mechanical Defenses

·       Chemical Defenses

·       Cellular Defenses

3.  Physical Defenses: Cell Junctions keep pathogens from entering tissues:

a.     Tight junctions

b.     Gap junctions

c.      Desmosomes

4. Physical Defenses: Skin

·       The dead cells of epidermis are covered with keratin. These form tight, dense layer of protein on the surface of the skin.

·       The keratin makes the skin tough and resists breakdown by bacterial enzymes.

·       Fats on the skin create a dry, salty, and acidic environment that inhibits the growth of microbes.

5. Physical Defenses: Mucous membranes (nose, mouth, lungs, urinary and digestive tracts)

·       Mucous membranes consist of a layer of epithelial cells held by tight junctions.

·       The cells secrete mucus, which covers and protects the cell layers and trap debris and microbes.

·       Mucus secretions also contain antimicrobial peptides.

·       In human trachea, cilia push mucus away from the lungs, with trapped debris or microorganisms, up to the esophagus and away from lungs.

6. Mechanical Defenses:

·       Shedding of skin cells

·       Expulsion of mucus via the mucociliary escalator

·       Excretion of feces

·       Secretion of urine and tears. Urine washes out transient microorganisms

·       The eyelashes and eyelids prevent dust and airborne microorganism from getting into the eye. Blinking washes away debris

·       The microbiota in gut/skin compete for nutrients preventing pathogen attachment and infection

7. Chemical Defenses:

·       Sebaceous glands in the dermis secrete oily sebum

·       The sebum blocks bacteria from invading tissue

·       The bacterium Propionibacterium acnes secrete lipase enzymes, degrade sebum, and use it as a food source.

·       This creates an acidic environment on the skin surface that is inhospitable to many pathogens

·       Saliva has lactoperoxidase enzymes

·       The mucus in the esophagus contains antibacterial enzyme lysozyme

·       In the stomach, acidic gastric fluid kills most microbes

·       The intestines have pancreatic and intestinal enzymes, antibacterial peptides, bile produced in the liver, and cells that produce lysozyme

8. Chemical Defenses:

·       The complement system is a group of 30 plasma proteins (C1 through C9) that circulate in blood.

·       These proteins are activated by the presence of microorganisms.

·       Complement proteins are part of innate immunity because they are always found in the blood and tissue fluids, and can be activated quickly

·       When activated, these molecules form the membrane attack complex (MAC), a ring structure which perforates the cell membrane of pathogens, causing them to burst

         Complement activation pathway (function of complement):

·       Opsonization (coat the pathogen)

·       Inflammation

·       Chemotaxis (chemoattractant for neutrophils and white blood cells)

·       Cytolysis (MAC, membrane attack complex; works only on Gram -)

9. Chemical Defenses

·       Antimicrobial peptides (AMPs) secreted by cells have antimicrobial properties.

·       AMPs damage the microorganism membrane, or interfere with cell-wall synthesis

·       A family of AMPs called defensins are produced by epithelial cells throughout the body and by macrophages and neutrophils.

·       Bacteriocins are secreted by microbiota in the gastrointestinal tract

·       Acute-Phase Proteins produced in the liver and secreted into the blood in response to inflammatory molecules (activate complement, remove iron, coat bacteria)

10. Chemical Defenses: Cytokines

·       proteins that act as communication signals between cells

·       stimulate production of chemical mediators

·       stimulate cell functions: cell proliferation, cell differentiation, inhibition of cell division, apoptosis, and chemotaxis

·       Three important classes of cytokines are the

                                               i.     Interleukins (stimulate leukocytes)

                                              ii.     Chemokines (recruit leukocytes)

                                             iii.     Interferons (defense against viruses)

11. Cellular Defenses:

       White Blood Cells (Leukocytes):

·       Agranulocytes

·       Granulocytes

                                                      I.         Neutrophils

                                                     II.         Basophils

                                                    III.         Eosinophils

12. Cellular Defenses: Neutrophils:

·       Destroy bacteria.

·       Migrate through blood vessels to areas of infection, where they kill bacteria.

·       Release defensins and hydrolytic enzymes by phagocytosis.

·       Degranulation: release toxic molecules in affected tissue that kill bacteria.

·       As neutrophils fight an infection, leukocytes, cellular debris, and bacteria build up creating drainage.

13. Cellular Defenses: Eosinophils

·       granulocytes that protect against protozoa and helminths;

·       they also play a role in allergic reactions.

·       Their granules release histamine

14. Natural Killer Cells:

·       Cancer cells and virus-infected cells do not have MHCI on their surface.

·       NK cell recognizes cells lacking MHCI and kill the abnormal cell

15. Cellular Defenses: Phagocytes

·       Phagocytes contain pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs).

·       When Phagocytes recognize a pathogen through a PAMP, it activates genes involved in phagocytosis, cellular proliferation, production, and secretion of antiviral interferons and proinflammatory cytokines, and enhanced intracellular killing.

·       Bacterial PAMPs:

a.     Peptidoglycan

b.     Flagella

c.      LPS