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The Immune Response:

The Immune Response:. Introduction to Immunity Part I: Innate Immunity: Major Cells Part II: Innate Immunity: The Inflammatory Response Part III: Treatment of Inflammation Part IV: Adaptive Immunity. Introduction to Immunity. Functions of the Immune Response. The Immune Response.

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The Immune Response:

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  1. The Immune Response: • Introduction to Immunity • Part I: Innate Immunity: Major Cells • Part II: Innate Immunity: The Inflammatory Response • Part III: Treatment of Inflammation • Part IV: Adaptive Immunity

  2. Introduction to Immunity

  3. Functions of the Immune Response

  4. The Immune Response The Immune Response:A collective and coordinated response of cells of the immune system 1. Protects host from invasion of anything foreign • Ex. foreign pathogens, bacteria, parasites, viruses, the environment in general 2. Distinguishes “self” from non-self • Ex. cancer, autoimmune reactions • The immune system has a surveillance mechanism to identify itself • When it recognizes something that is nonself, the immune system has mechanisms to kill the cell • When the surveillance system breaks down or is over-challenged, disease occurs 3. Mediates healing • Modulate inflammatory process and wound repair • Immunity and inflammation are wrapped up together to make healing more efficient

  5. Results of Immune Dysfunction or Deficiency

  6. Results of Immune Dysfunction or Deficiency • Immunodeficiency • Do not have the requisite amount of immunological ability • Cannot keep up with what is going on • Allergies/Hypersensitivities • The response to something is exaggerated • Transplantation pathology • Autoimmunity

  7. Innate Immunity

  8. Innate Immunity • Natural resistance that a person is born with • Do not need anything else special • Comprises physical, chemical, and cellular barriers that keep the self and the nonself apart • First line of defense • Ex. skin, mucosa • When radiator heat comes on, it dries out the mucosal membranes and makes you more susceptible to microorganisms • A person in the healthcare system needs to take care of the skin because dry skin makes a person more susceptible to invasion

  9. Adaptive Immunity

  10. Adaptive Immunity • Acquired • When you are born and come into contact with antigens in the environment, your body mounts a response • Are able to recognize the pathogen in the future • Specific • Amplified response with memory • Has a recognition system • There is a molecular memory in the body about what happened • Able to respond more quickly to the pathogen when interact with it in the future

  11. Components of the Adaptive Immune Response

  12. Components of the Adaptive Immune Response • Divided into two major components: • Cell-mediated adaptive immunity - T cells • Antibody-mediated (humoral immunity) • Circulating antibodies • B cells produce the antibodies for humoral immunity • Antibody-mediated immunity is triggered by encounters with Antigens (Ags) b. Antibodies are also known as Immunoglobulins (Igs)

  13. Part I: Innate Immunity

  14. Primary Immune Cells of Innate Immunity

  15. Primary Immune Cells of Innate Immunity • Monocytes, macrophages, dendritic cells • Neutrophils • Eosinophils • Basophils • Mast cells • Natural killer cells

  16. Monocytes, Macrophages, and Dendritic cells

  17. Monocytes, Macrophages, and Dendritic cells • Phagocytic cells that are located in different areas of the body • While macrophages are important cells of the innate immunity, they also play key role in adaptive immunity • Monocytes in blood  Macrophages in tissues: • Dendritic cells are phagocytic cells in the nervous system • Include Kupffer, Langerhans, alveolar, peritoneal oligodendrocytes etc • Phagocytize antigen  present antigen (APC-antigen presenting cell) • Internalize and consume pathogens with lysosomes and peroxisomes • Process the antigen out of the substance that is foreign • Takes the antigen, sticks it outside of itself, and presents it • When activated, secrete cytokines (tumor necrosis factor, interleukin-1, and others), oxygen radicals, proteolytic enzymes, arachidonic acid metabolites, prostaglandins • Release molecules that are very important in inflammation • Macrophages are phagocytes

  18. Neutrophils

  19. Neutrophils • AKA Polymorphonuclear leukocytes (PMN) • Antigen binding and non-specific phagocytosis • Inflammatory response: First-line defender against bacterial invasion, colonization, and infection • Important in innate immunity • Responsible for antigen binding and phagocytosis

  20. Eosinophils

  21. Eosinophils • Inflammatory response • Fight parasites (worms especially) • May release chemicals in respiratory tract during allergic asthma • Release chemical mediators

  22. Basophils

  23. Basophils • Release potent mediators during allergic responses (e.g. histamine) • Have binding sites for IgE antibodies (Type 1 Hypersensitivity) • The antibody will bind to antigen, and the basophil will release the inflammatory substances • Reside in blood

  24. Mast Cells

  25. Mast Cells • Also from bone marrow and share characteristics with basophils • Located in tissues; not blood • Releases histamine which is the hallmark of tissue inflammatory response.

  26. Natural Killer Cells

  27. Natural Killer Cells Natural Killer Cells: an effector cell important in innate immunity. • Small % of lymphocytes • Part of the lymphocyte population but are a small amount • Can bind with antibody coated target cell  Antibody dependent cell-mediated cytotoxicity (ADCC) • Can recognize the antibody and destroy the cell • Can attack virus-infected cells or cancer cells without help or activation first • Important in immunosurveillance • Can recognize antigen without MHC restrictions • Major histamine compatibility • NO MEMORY • Lives by the minute by doing what it does • Regulated by cytokines, prostaglandins and thromboxane • Release NK perforins, enzymes, and toxic cytokines to destroy target cells

  28. Outline of Immunity

  29. Cytokines and the Immune Response

  30. Cytokines and the Immune Response • Small, low molecular weight proteins (hormone-like) which are produced during all phases of the immune response. • They are released form one area, move, and act on another area • Short half-life • Work in a parocrine system (acts locally) rather than an endocrine system • This is characteristic of many of the immunological cytokines • Primarily made by T cells and macrophages (lymphokines/ monokines) and act primarily on immune cells • Lymphokines – a cytokine released from a lymphocyte (T cell) • Monokines – a cytokine released from a macrophage

  31. Processes that Cytokines are Involves in

  32. Processes that Cytokines are Involves in • Innate immunity • Adaptive immunity • Hematopoiesis

  33. Cytokines and Innate Immunity

  34. Cytokines and Innate Immunity • IL-1, IL-6, TNF (tumor necrosis factor) are important in the early inflammatory response. • Derived mainly from macrophages,endothelial, and dendritic cells, and lymphocytes (T cells) • Processes • Stimulate acute phase protein production by the liver • Stimulate the hypothalamus for a fever response • Increase adhesion molecules on the vascular endothelium

  35. Acute Phase Protein Production by the Liver

  36. Acute Phase Protein Production by the Liver • Overlaps with the ESR • Increases cytokine release in the body-sensed by the liver-liver increases amount of acute-phase proteins (complement, clotting factors) • Increased cytokines due to inflammation causes liver to produce more proteins, which increases ESR

  37. Stimulate Hypothalamus for Fever Response

  38. Stimulate Hypothalamus for Fever Response • Hypothalamus in the base of the brain thermoregulates the body • One of the main reasons that you get a fever is because a cytokine burden increases enough to pass through the vasculature of the hypothalamus and resets the temperature of the body • Reason why anti-inflammatory decrease fever – decrease the burden of the cytokine production, which decreases the reason that the hypothalamus causes fever

  39. Increase in Adhesion Molecules

  40. Increase in Adhesion Molecules • Cytokines trigger the endothelium to put out adhesion molecules so that when a macrophage comes by it sticks to it and squeezes between the endothelium cells out into the tissue to fight infection

  41. Cytokines and Adaptive Immunity

  42. Cytokines and Adaptive Immunity • Activate immune cells to proliferate and differentiate into effector and memory cells.

  43. Cytokines and Hematopoiesis

  44. Cytokines and Hematopoiesis • Cytokines that stimulate bone marrow pluripotent stem cells, progenitor cells and precursor cells to produce large numbers of platelets, erythrocytes, lymphocytes, neutrophils, monocytes, eosinophils, basophils and dendritic cells are termed Colony Stimulation Factors (CSFs)

  45. PART II Innate Immunity: THE INFLAMMATORY RESPONSE

  46. Inflammation

  47. Inflammation Reaction of vascularized tissue to local injury(cellular) manifesting as redness, swelling, heat, pain, loss of function • Non-specific, chain of events similar regardless of injury type and extent • Stereotypic no matter the size of the injury • Includes vascular and cellular changes • Triggered when FIRST LINE OF Defense's integrity has been breached (skin, mucus membranes and damaged the endothelium or gotten to a vessel) • May be from the outside into the body or from the inside of the body out (ex. vacularitis) • Unpleasant and uncomfortable, but essential for survival • May lead to inflammatory diseases

  48. Acute Inflammation

  49. Acute Inflammation • 1. vascular phase • 2. cellular phase

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