Nature of the Immune System

1. Nature of the Immune System Non-Specific Immunity Terry Kotrla, MS, MT(ASCP)BB

2. Immunity – Very Complex System

3. Cellular versus Humoral Immunity • Cellular - Researchers observed that foreign substances were removed by specialized cells in a process known as phagocytosis. • Humoral - Other researchers postulated that substances in the blood provided protection from microorganisms, humoral immunity.

4. Natural versus Acquired Immunity • Natural immunity – born with the ability to resist infections by normal bodily functions. • Acquired immunity – requires exposure to a pathogen or microbial agent, upon recovery lifelong immunity is acquired.

5. Natural (Nonspecific , Innate) Immunity • Non-specific immunity • First line of defense against infection • Two mechanisms – external and internal

6. External • Composed of structural barriers to keep infectious agents out of the body. • Intact skin • Cilia • Physiological factors.

7. Physical barriers – Intact Skin

8. Intact Skin • Difficult for a pathogen to penetrate, • Sweat creates high salt conditions. • Oil layer, fatty acids and acid pH present makes an inhospitable environment for microorganisms. • Normal flora prevent other microorganisms from establishing an infection – “competitive exclusion”.

9. Natural Immunity - Cilia

10. Natural Immunity • Stomach acid (HCl) kills pathogens and sterilizes food. • Mucus lining of lungs traps pathogens and cilia move particles out to throat and it is swallowed. • Coughing and sneezing. • Tears wash away pathogens and have bacteriocidal enzymes. • Flushing action of urine • Circulating cells and tissue cells • Wax in ears http://tinyurl.com/27lk4og • Normal flora prevents growth of opportunistic pathogens in mouth, large intestine and reproductive system

11. Factors Modify Defense Mechanisms • Age • Hormones • Drugs and chemicals • Malnutrition • Fatigue and stress • Genetic determinants

12. Nonspecific Immunity: Second line of defense • Inflammatory response - four classic signs are redness, swelling, heat and pain. • Dilation of capillaries (hyperemia) to increase blood flow to area • Chemotaxis - chemicals released which cause phagocytic white cells to migrate to the area. • Increased capillary permeability allowing white cells to go to injured area, a process known as “diapedesis” • Formation of exudate - same composition as plasma and it contains antibacterial substances, phagocytic cells, and drugs and antibiotics, if present.

13. Inflammatory Response

14. Inflammatory Response

15. Phagocytosis • The following 3 diagrams illustrate the process of phagocytosis. • Be intimately familiar with the process.

16. Inflammatory Response

17. Second Line of Defense • If bacteria are not successfully killed locally, may further invade the host by way of the lymphatics to the regional lymph nodes. • within lymph nodes the bacteria meet other phagocytic cells • bacteria may overcome these and gain access to the bloodstream where they meet circulating phagocytes (neutrophils and monocytes). • may pass through the bloodstream and reach organs such as the liver and spleen where they come into contact with tissue macrophages. • although a powerful defense system, this final phagocytic barrier may be overcome, with seeding of the microorganism to organs such as bone, brain, and kidney, terminating in fatal septicemia.

18. Phagocytosis -MEMORIZE • Initiation is caused by damage to the tissues, either by trauma or as a result of microbial multiplication. • Chemotaxis, attraction of leukocytes or other cells by chemicals. • Opsonization - Opsonization coating a pathogen by substances so as to enhance phagocytosis. • Adherence - firm contact between phagocyte and microorganism. • Engulfment into cytoplasm and enclosed in a vacuole. • Digestion enzymatic contents in vacuole destroy the microorganism. • Number of killing mechanisms operating in the vacuoles of phagocytic cells. • One of the major mechanisms involves hydrogen peroxide which, acting along with an intracellular enzyme, is rapidly lethal to many bacteria.

19. Phagocytosis

20. Phagocytosis • http://www.cellsalive.com/ouch.htm • http://health.howstuffworks.com/adam-200096.htm • http://tinyurl.com/6oa779

21. Cells of the Non-Specific Immune System • Cells involved in non specific immunity. • Phagocytic cells • Mononuclear phagocytes • Polymorphonuclear phagocytes • Eosinophils • Mediator cells • Basophils and mast cells • Platelets

22. Cells involved in specific immunity • Lymphocytes • Plasma cells

23. Origin of immune cells • Origin of all these cell types are from pluripotentialstem cellsfound in the bone marrow. • These self replicating cells differentiate into two types of "committed" stem cells. • One group differentiates further and matures to become platelets, erythrocytes (red blood cells), monocytes or granulocytes. • Second group produces cells of the lymphoid lineonly. • The lymphoid line will develop into 2 different types, T and B cells, depending upon where they complete their maturation, thymus or bone marrow. • Will be discussed in detail later

24. Phagocytic Cells • Mononuclear phagocytes- include both circulating bloodmonocytes and tissue macrophages found in various tissues of the body. • Arise from bone marrow stem cells • Not end cells, they may divide. • Ingest and destroy material such as bacteria, damaged host cells or tumor cells (non-specific immunity). • Stay in peripheral blood 70 hours - migrate to tissues, double in size, then called tissue macrophages. • Tissue macrophages named according to tissue location- liver=Kupffer cells, brain-microglial cells, etc. • Phagocytosis takes place to a greater degree in tissues.

25. Monocyte and Tissue Macrophage

26. Neutrophils • Characterized bya large nucleus, 3 - 5 lobes, and specific granules in the cytoplasm. • Arise from bone marrow stem cells. • They are end cells. • Primary function is ingestion (phagocytosis). • Clear body of debris such as dead cells and thrombi. • Able to move into tissues by diapedesis.

27. Neutrophils with Ingested Material

28. Neutrophil Involved in Phagocytosis

29. Eosinophils • Easily distinguished by the presence of largegranules in their cytoplasm which appear red when stained by routine hematology stains. • Much less phagocytic than macrophages or neutrophils • Function is far from clear, however the numbers increase greatly in certain parasitic diseases and allergic diseases. • Both neutrophils and eosinophilscontain specific granules, the granules contain various enzymes which are released under certain circumstances.

30. Eosinophil

31. Mediator Cells • Influence the immune response by releasing various chemical substances into the circulation. • Have a variety of biological functions • Increase vascular permeability • Contract smooth muscle • Enhance the inflammatory response • Two types • basophils/mast cells • Platelets

32. Basophils • Basophils easily identified due to large numbers of bluish-black granules in the cytoplasm. • The granules are a source of mediators such as histamine (vasoactive amine that contracts smooth muscle) and heparin. • Basophils and platelets are found in the circulation, mast cells are situated in the tissues of skin, lung and GI tract. • Bind IgE, a type of antibody formed during allergic reactions. • Circulating basophils greatly resemble tissue mast cells and it is likely that they are closely related in function. • Basophils exist on a few hours in bloodstream. • Both of these cells play a role in hypersensitivity (allergic) reactions

33. Basophil

34. Mast cells • Resemble basophils. • Fixed in the tissues they are connective tissue cells. • Widely distributed through out the body. • Long life span, 9-18 months. • Plays a role in hypersensitivity reactions by binding IgE.

35. Platelets • Small non-nucleated cells derived from megakaryocytesof the bone marrow. • Important in blood clotting. • Contribute to the immunological tissue injury occurring in certain types of hypersensitivity reactions by releasing histamineand related substances which are contained within specialized granules in their cytoplasm.

36. Megakaryocyte & Platelets

37. Dendritic Cells • Primary function is phagocytosis. • Process antigen material and present it on the surface to other cells of the immune system, function as antigen-presenting cells. • Act as messengers between the innate and adaptive immunity. • Classified according to tissue location. • Found on skin and all major organs.

38. Soluble Factors • Many soluble tissue and serum substances help to suppress the grow of or kill microorganisms. • Interferons - family of proteins which are important non-specific defense mechanisms against viral infections. • Transferrin - Bacteria do not thrive well in serum that contains low levels of iron but high levels of transferrin. • Complement - a group of proteins that are essential for bacterial destruction and plays an important role in both non-specific and specific immune mechanisms.

39. Acute Phase Reactants (Proteins) • Defined-normal serum constituents that increase rapidly because of infection, injury, or trauma to tissues. • Acute-phase proteins are a class of proteins whose plasma concentrations increase or decrease in response to inflammation. • This response is called the acute-phase reaction . • In response to injury local inflammatory cells (neutrophils, granulocytes and macrophages) secrete a number of cytokines into the bloodstream, most notable of which are the interleukins. • The liver responds by producing a large number of acute-phase reactants.

40. C-Reactive Protein • Increases rapidly within 4-6 hours of infection or injury. • Returns to normal rapidly once condition subsides. • Used to monitor healing and has also increased in usefulness in diagnosing Myocardial Infarction.

41. Serum Amyloid A • Major protein secreted during the acute phase of inflammation. • Has several roles, including • Removes cholesterol from cholesterol-filled macrophages at site of injury – clean up. • recruitment of immune cells to inflammatory sites, and • Thought to play a role in cholesterol metabolism

42. Complement • A series of serum proteins involved in mediation of inflammation but also involved in • opsonization, • chemotaxis, and • cell lysis.

43. Alpha-1 Antitrypsin • Increases during acute inflammation. • Protects tissues from enzymes of inflammatory cells, especially elastase. • When the lungs do not have enough alpha-1 antitrypsin, elastase is free to destroy lung tissue. • As a result, the lungs lose some of their ability to expand and contract (elasticity). This leads to emphysema and sometimes makes breathing difficult.

44. Haptoglobin • Binds irreversibly to free hemoglobin to protect kidneys from damage and prevent loss of iron by urinary excretion. • Haptoglobin - hemoglobin complex removed by RES, mainly spleen. • Used to monitor hemolysis

45. Fibrinogen • A coagulation factor integral to clot formation which serves as a barrier to prevent spread of microorganisms further in the body. • Levels increase with tissue inflammation or tissue destruction. • Thought to play a key role in the inflammatory response and development of rheumatoid arthritis.

46. Ceruloplasmin • Principal copper transporting protein in plasma, plays a role in iron metabolism and histamine regulation. • Stimulates the immune system to fight infections, repair injured tissues and promote healing. • Depletion found in Wilson’s disease, causes the body to absorb and retain excessive amounts of copper. • Copper deposits in the liver, brain, kidneys, and the eyes. • The deposits of copper cause tissue damage, necrosis (death of the tissues), and scarring, which causes decreased functioning of the organs affected. • Liver failure and damage to the central nervous system (brain, spinal cord) are the most predominant, and the most dangerous, effects of the disorder.

47. References • http://www.horton.ednet.ns.ca/staff/Selig/isu/Immunity/Innate.htm • http://www.metacafe.com/tags/neutrophil/most_popular/