Chapter 14 Immunology Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Immunity Is the body’s ability to resist disease Serves three functions Defense Homeostasis Surveillance Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Types of Immunity Innate Present at birth First-line defense against pathogens Acquired Developed immunity Active Passive Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Antigens Substances the body recognizes as foreign that elicit an immune response Most are composed of protein. Antibodies Immune globulins produced by lymphocytes in response to antigens Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Organs of Immunity Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Immune Response to Virus Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Lymphoid Organs Central (primary) lymphoid organs Thymus gland Thymus gland shrinks with age. Involved in the differentiation and maturation of T lymphocytes Bone marrow Produces red blood cells, white blood cells, and platelets Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Lymphoid Organs Peripheral lymphoid organs Lymph nodes Tonsils Spleen Lymphoid tissues associated with the gut, genitals, bronchi, and skin Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Macrophages and Lymphocytes in Immune Response Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 10

Normal Immune System Cells of Immune Response Mononuclear phagocytes Include monocytes in the blood and macrophages found throughout the body Capture, process, and present antigens to lymphocytes to initiate an immune response Capture antigens by phagocytosis Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune System Cells of Immune Response Lymphocytes Produced in the bone marrow Eventually migrate to peripheral organs Differentiate into B and T lymphocytes T Cytotoxic cells T Helper cells Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Types of Lymphocytes Copyright © 2014 by Mosby, an imprint of Elsevier Inc. T cells70%–80% B cells10%–20% Natural killer (NK) cells<10%

Normal Immune Response Dendritic Cells Important in activating the immune response Capture antigens at sites of contact with the external environment Transport an antigen until it encounters a T cell with specificity for the antigen Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cytokines Soluble factors secreted by WBCs and a variety of other cells in the body Act as messengers among cell types Instruct cells to alter their proliferation, differentiation, secretion, or activity Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cytokines Currently at least 100 different cytokines Have a beneficial role in hematopoiesis and immune function Can have detrimental effects Chronic inflammation Autoimmune diseases Sepsis Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cytokine types Interleukins Interferons Tumor necrosis factor Colony-stimulating factors Erythropoietin Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cytokines IL-1 Augments immune response Inflammatory mediator Promotes maturation and clonal expansion of B cells Enhances activity of natural killer cells Activates T cells and macrophages Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cytokines IL-2 Induces proliferation and differentiation of T cells Activates T cells, NK cells, and macrophages Stimulates release of other cytokines Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cytokines IL-3 (multicolony-stimulating factor) Hematopoietic growth factor for hematopoietic precursor cells Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cytokines IL-4 B-cell growth factor Stimulates proliferation and differentiation of B cells Induces differentiation into TH2 cells Stimulates growth of mast cells Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cytokines IL-5 B-cell growth and differentiation Promotes growth and differentiation of eosinophils Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cytokines IL-6 T- and B-cell growth factor Enhances inflammatory response Stimulates antibody secretion Promotes differentiation of B cells into plasma cells Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cytokines IL-6 Induces fever Synergistic effects with IL-1 and TNF Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cytokines  -Interferon (  -IFN) and β-interferon (β-INF) Inhibit viral replication Activate NK cells and macrophages Antiproliferative effects on tumor cells Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cytokines γ-Interferon (γ-IFN) Activates macrophages, neutrophils, and NK cells Promotes B-cell differentiation Inhibits viral replication Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Mechanism of Action of Interferon Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cytokines Tumor necrosis factor (TNF) Activates macrophages and granulocytes Promotes the immune and inflammatory responses Kills tumor cells Responsible for extensive weight loss Associated with chronic inflammation and cancer Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cytokines Colony-stimulating factors (CSFs) Granulocyte colony-stimulating factor (G- CSF) Granulocyte-macrophage colony- stimulating factor (GM-CSF) Macrophage colony-stimulating factor (M- CSF) Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Comparison of Humoral and Cell-Mediated Immunity HumoralCellular Cells involved B lymphocytes T lymphocytes T lymphocytes Macrophages Macrophages ProductsAntibodies Sensitized T cells Sensitized T cells Cytokines Cytokines Memory cells Present Present Present 30

Normal Immune Response Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Comparison of Humoral and Cell-Mediated Immunity HumoralCellular Protection BacteriaBacteria Viruses (extracellular)Viruses (extracellular) Respiratory pathogensRespiratory pathogens Gastrointestinal pathogensGastrointestinal pathogens FungusFungus Viruses (intracellular)Viruses (intracellular) Chronic infectious agentsChronic infectious agents Tumor cellsTumor cells 31

Normal Immune Response Humoral Immunity Antibody-mediated immunity Antibodies produced by plasma cells (differentiated B lymphocytes) Primary immune response is evident 4 to 8 days after initial exposure to antigen. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Humoral Immunity Five classes of immune globulins Each has specific characteristics IgG lgA lgM lgD lgE Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Humoral Immunity When an individual is exposed to an antigen for a second time, the response is faster (1 to 3 days) and lasts longer. Main product of secondary response is IgG rather than IgM. Memory cells account for more rapid production of IgG. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Primary and Secondary Immune Response Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cell-Mediated Immunity Immune responses initiated through specific antigen recognition by T cells Several cell types involved in cell- mediated immunity T lymphocytes Macrophages NK cells Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Cell-Mediated Immunity Important roles Immunity against pathogens that survive inside cells (viruses, some bacteria) Fungal infections Rejection of transplanted tissues Contact hypersensitivity reactions Tumor immunity Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Effects of Aging on the Immune System Immunosenescence ↑ Incidences of tumors Greater susceptibility to infection ↑ Autoantibodies ↓ Cell-mediated immunity Thymic involution Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Effects of Aging on the Immune System Immunosenescence ↓ Delayed hypersensitivity reaction ↓ IL-1 and IL-2 synthesis ↓ Expression of IL-2 receptors ↓ Proliferation response of T and B cells ↓ Primary and secondary antibody responses Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Audience Response Question A patient with a sore throat and rhinitis has an elevated level of IgG in the blood. The nurse explains that the patient’s symptoms are most likely caused by a.an allergy. b.exposure to toxic fume. c.an initial viral infection. d.a re-infection by bacteria. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.