1. Immunity Biology 2122 Chapter 21

2. Introduction Innate or nonspecific defense: – First-line of defense – Second-line of defense The adaptive or specific defense system – lymphocytes, the production of antibodies specific to certain antigens The immune system is a ‘functional’ system

3. Innate Defense System Epidermis and keratin-cells provide a tough barrier to penetrate ▫ Resistant to weak acids, bases, toxins The mucous membranes physical barrier ▫ 3-5 pH ▫ HCl in the stomach (pH 2) ▫ Saliva contains lysozyme ▫ Mucus

4. Internal Defense If the surface defenses are broken, microorganisms will invade deeper tissue areas. Nonspecific cells and chemicals – prevent the ‘invaders’ from penetrating deeper into the body Cells involved- Nonspecific Cells: – 1. Phagocytes- Neutrophils, Eosinophils – 2. Natural Killer Cells – 3. Mast cells When body tissues are damaged – inflammatory response is set into motion which involves a series of chemicals

5. The Role of Phagocytes Monocytes will leave the bloodstream and be converted into the ‘main’ phagocytes called macrophages. They can be free (lungs) or fixed in position (Kupffer cells in the liver) Other WBCs involved: – 1. Neutrophils – 2. Eosinophils – 3. Mast cells Phagocytosis – Phagosome – Phagolysosome – Opsonization – Respiratory Burst – Animation Animation

6. Natural Killer Cells Large granular lymphocytes - non-specific Detect ‘non-self’ cells via the surface receptors. Eliminate cancerous or infected cells. The mode of killing is via the release of cytolytic chemicals called perforins Not Phagocytic

7. What is an ‘inflammatory’ response? When tissues are injured – ‘healing process’ that eliminates debris and pathogens in the affected area. – Identifiable signs of an inflammation are redness, heat, swelling and pain. Macrophages have surface membrane receptors called Toll-like Receptors or TLRs. ▫ If activated, TLR triggers the release of chemicals called cytokines that cause inflammation and attract WBCs to the site of the injury

8. Inflammatory Chemicals Histamines released by basophils and mast cells, microorganism or chemicals released by neutrophils Promotes vasodilation; permeability of capillaries Kinins produced from the cleavage of a plasma protein called kiniogen Induces chemotaxis of leukocytes; same roles as histamine Prostaglandins or PGs – fatty acid molecules – generated by lysosomal enzymes of neutrophils and other cells – Production of free radicals

9. Inflammatory Chemicals - Effects Most of the chemicals: 1.‘Vasodilation’ of blood vessels 2. Increases the permeability of capillaries causing fluid to leak out into the extracellular space exudate fluid and contains clotting factors and antibodies 3. Causes swelling (edema), which causes pressure on nerves, results in pain Dilutes harmful substances; brings oxygen and nutrients; entrance of clotting proteins

10. Inflammatory Response 1.Release of Chemical Mediators 2.Vasodilation, increased permeability of capillaries 3.Attraction of neutrophils, monocytes, leukocytes, “chemotaxis” 4.Vasodilation leads to “hyperemia”, redness swelling 5.Capillary permeability leads to exudate, pain, swelling, clotting Leukocytes migrate -----  Margination ----  Diapedesis --- --  Phagocytosis of dead tissue and cells, etc.

11. Phagocyte Mobilization Neutrophils are first followed by macrophages 1. Leukocytosis – injured cells release leukocytosis inducing factors which promote the fast release of neutrophils from red marrow. 2. Margination – Blood flow slows in the injured region and the neutrophils will attach to CAMs called selectins on the endothelial cells. 3. Diapedesis – Neutrophils are able to squeeze through the walls 4. Chemotaxis – chemotactic agents (inflammatory chemicals) attract neutrophils and other WBCs to the injury site Animation

12. Phagocyte Chemotaxis and the Inflammatory Response Animation Link Leukocyte Migration Animation

13. Other Nonspecific Defense Systems Antimicrobial proteins attack pathogens directly or indirectly – Interferon and complement proteins Complement Protein Animation Interferons (IFNs) are small proteins that are secreted by cells infected by viruses to protect other cells which have not been infected. – Stimulate synthesis of PKR protein that interfers with vial replication in healthy cells – Lymphocytes secrete gamma interferon; leukocytes secrete alpha interferon – Also can activate NK cells and macrophages which have anti-cancer capabilities (attack malignant cells)

14. Interferon Animation

15. Complement Proteins Includes 20 plasma proteins which circulate in their inactive form in the blood. They are nonspecific! When activated they release chemical mediators which: – Amplify the inflammatory process – Kill pathogens via lysis – Complements both innate and adaptive (specific responses) – Activated via the classical pathway or alternative pathway Complement Protein Animation

16. Fever This is a systemic response to invading microorganisms Pyrogens (chemicals) released by leukocytes and macrophages exposed to a pathogen cause the body’s temperature to be reset (hypothalamus) Mild or moderate fevers cause the liver and spleen to hold onto iron and zinc (necessary for bacteria to replicate) Increases the metabolic rate of cells which increases healing. ▫ High temperature ‘denature’ enzymes