1. Chapter 15 The Innate Immune Response

2. A Glimpse of History Once it was determined that microorganisms caused disease, scientists began working on showing how the body defended itself from them. In 1882, Elie Metchnikoff (Russian) proposed that phagocytes (“cells that eat cells”) were primarily responsible for the body’s ability to destroy entering microbes.

3. The tissues and fluids of the human body are ideal growth media for entering microbes; however, the interior of the body is generally sterile. To maintain this sterility, humans have developed many lines of defense ranging from barriers to sensors. Protection provided from these defenses is termed innate immunity.

4. First line defenses Barriers that separate and shield the interior of the body from the surrounding environment. Anatomical barriers include skin and mucous membranes; which separate the interior from the exterior, but also secrete antimicrobial substances. Sensor systems recognize when first line barriers have been breached.

5. Two important sensor groups Toll-like receptors and NOD (nucleotide- binding oligomerization domain proteins) are found on or within different cell types. They recognize compounds unique to microbes and then alert host defenses.

6. Other defenses Phagocytes engulf and digest microbes and cellular debris as well as alert for signs of invasion. Cytokines are proteins that function as chemical messengers. ◦ When a cytokine binds to a receptor, it signals a change in cell activities and give them certain powers or prompt them to move to a specific location Inflammation is a coordinated response that allows antibodies and other proteins to leak into tissues.

7. 15.2 First-Line Defenses Skin is the most visible barrier. Epidermis consists of tightly packed cells with – Keratin, a protective protein

8. Mucous membranes (mucosa) are bathed in mucus and other secretions that wash microbes away. Mucus: Traps microbes The respiratory tract is lined with cilia to propel microbes away from the lungs and to the throat for swallowing.

9. Antimicrobial Substances Lysozyme – an enzyme that degrades peptidoglycan is found in tears, saliva, and mucus. – It is most effective against gram positive bacteria, where the peptidoglycan of the wall is more exposed. Peroxidase enzymes are found in saliva and milk, as well as within phagocytes. Lactoferrin is an iron-binding protein found in saliva, mucus, and milk. – Iron is an important component for growth. Lactoferrin prevents the microbes from getting the iron they need.

10. Normal flora 1.Compete with pathogens or alter the environment 2.Members often produce compounds that are toxic to other microbes, thereby preventing their growth. In hair follicles, normal flora break down lipids of body secretions releasing fatty acids that inhibit pathogen growth. 3.Commensal microbiota: One organism (microbe) benefits and the other (host) is unharmed May be opportunistic pathogens

11. 15.3 The Cells of the Immune System These cells can move from one part of the body to another while traveling through the circulatory system. Always found in normal blood, but numbers will increase during an infection

12. 15.4 Cell Communication In order to respond to a threat, cells must be able to communicate in a cooperative fashion. Cells receive signals from the external environment and send the signals to the appropriate places.

13. Surface receptors Membrane proteins to which certain signal molecules bind. Each surface receptor is specific with which molecule it will bind, and the molecule that can bind is termed a ligand.

14. Cytokines Proteins that bind to certain receptors to induce a change in the cell. – They are short lived, but very powerful. – They can act locally, regionally, or systemically.

15. Cytokine Types Chemokines – chemotaxis (directed movement in response to a chemical). – Defense cells have receptors for these, and therefore, they can migrate to appropriate regions. Colony-stimulating factors (CSFs) – stimulate growth and differentiation of different types of leukocytes Interferons (IFs) – Antiviral uses. – Induce fever, contribute to inflammation, and help regulate adaptive immune response.

16. Interleukins (ILs) – Various uses in both innate and adaptive immunity. – Induce adhesion, induce fever, activate natural killer cells, promote antibody responses, etc… Tumor necrosis factors (TNFs) – Cytotoxicity for some tumors, kill target cells, initiate inflammatory responses.

17. 15.5 Sensor Systems Toll-like receptors are pattern recognition receptors that allow cells to signify the presence of microbes outside of the cell NOD proteins do the same, only for inside the cytoplasm of the cell.

18. When a microbe engages a TLR, a signal is transmitted to the nucleus to begin the expression of certain genes. This response can trigger chemokines, or pro-inflammatory cytokines.

19. The Complement System Serum proteins activated in a cascade Activated by – Antigen-antibody reaction – Proteins C3, B, D, P and a pathogen

20. The Complement System C3b causes opsonization (enhanced phagocytosis, usually by coating the particle for ingestion with antibody or complement components) C3a + C5a cause inflammation C5b + C6 + C7 + C8 + C9 cause cell lysis

21. Effects of Complement Activation Opsonization or immune adherence: Enhanced phagocytosis Membrane attack complex: Cytolysis Attract phagocytes

22. Some Bacteria Evade Complement Capsules prevent C activation Surface lipid-carbohydrates prevent membrane attack complex (MAC) formation Enzymatic digestion of C5a

23. 15.6 Phagocytosis Phago: From Greek, meaning eat Cyte: From Greek, meaning cell Ingestion of microbes or particles by a cell, performed by phagocytes

24. 15.7 Inflammation Acute-phase proteins activated (complement, cytokine, and kinins) Vasodilation (histamine, kinins, prostaglandins, and leukotrienes) Redness Swelling (edema) Pain Heat

25. 15.9 Fever Abnormally high body temperature Hypothalamus normally set at 37°C Gram-negative endotoxin cause phagocytes to release interleukin–1 (IL–1) Hypothalamus releases prostaglandins that reset the hypothalamus to a high temperature Body increases rate of metabolism and shivering which raise temperature Vasodilation and sweating: Body temperature falls (crisis)

26. Advantages – Increases transferrins – Increases IL–1 activity – Produces Interferon Disadvantages – Tachycardia – Acidosis – Dehydration – 44–46°C fatal

27. Works Cited Nester, Anderson, Roberts and Nester. Microbiology: A Human Perspective. Tortora, Funke, and Case. Microbiology: An Introduction.