Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Immunology Chapter 14 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 Immunity is a state of responsiveness to foreign substances such as microorganisms and tumor proteins. It serves three functions: Defense: The body protects against invasion by microorganisms and prevents the development of infection by attacking foreign antigens and pathogens. Homeostasis: Damaged cellular substances are digested and removed. Through this mechanism, the body’s different cell types remain uniform and unchanged. Surveillance: Mutations continually arise in the body but are normally recognized as foreign cells and destroyed. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

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 Innate immunity involves a nonspecific response, and neutrophils and monocytes are the primary white blood cells (WBCs) involved. Innate immunity is not antigen-specific so it can respond within minutes to an invading microorganism without prior exposure to that organism. Active acquired immunity results from the invasion of the body by foreign substances such as microorganisms and subsequent development of antibodies and sensitized lymphocytes. With each reinvasion of the microorganisms, the body responds more rapidly and vigorously to fight off the invader. Active acquired immunity may result naturally from a disease or artificially through immunization with a less virulent antigen. Because antibodies are synthesized, immunity takes time to develop but is long-lasting. Passive acquired immunity implies that the host receives antibodies to an antigen rather than synthesizing them. This may take place naturally through the transfer of immunoglobulins across the placental membrane from mother to fetus. Artificial passive acquired immunity occurs through injection with gamma globulin (serum antibodies). The benefit of this immunity is its immediate effect. Unfortunately, passive immunity is short-lived, because the person did not synthesize the antibodies and consequently does not retain memory cells for the antigen. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

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

Vaccines Under-served children may not receive vaccines. Why? Active immunity occurs either naturally or through vaccine administration. Live or attenuated Killed or inactivated toxins Human immune globulin Animal serum or antitoxins Under-served children may not receive vaccines. Why? Elsevier items and derived items © 2013, 2009, 2005 by Saunders, 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 Most antigens are composed of protein. However, other substances such as large-size polysaccharides, lipoproteins, and nucleic acids can act as antigens. All of the body’s cells have antigens on their surface that are unique to that person and enable the body to recognize self. The immune system normally becomes “tolerant” to the body’s own molecules and therefore is nonresponsive to self-antigens. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Organs of Immunity A, A virus invades the body through a break in the skin or another portal of entry. The virus must make its way inside a cell to replicate itself. B, A macrophage recognizes the antigens on the surface of the virus. The macrophage digests the virus and displays pieces of the virus (antigens) on its surface. C, A T helper cell recognizes the antigen displayed and binds to the macrophage. This binding stimulates the production of cytokines (interleukin-1 [IL-1] and tumor necrosis factor [TNF]) by the macrophage and interleukin-2 (IL-2) and γ-interferon (γ -IFN) by the T cell. These cytokines are intracellular messengers that provide communication among the cells. D, IL-2 instructs other T helper cells and T cytotoxic cells to proliferate (multiply). T helper cells release cytokines, causing B cells to multiply and produce antibodies. E, T cytotoxic cells and natural killer cells destroy infected body cells. F, The antibodies bind to the virus and mark it for macrophage destruction. G, Memory B and T cells remain behind to respond quickly if the same virus attacks again. 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 Lymphocytes are produced in the bone marrow and eventually migrate to the peripheral organs. The thymus is involved in the differentiation and maturation of T lymphocytes and is therefore essential for a cell-mediated immune response. During childhood, the thymus is large. It shrinks with age, and in the older person, the thymus is a collection of reticular fibers, lymphocytes, and connective tissue. 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 When antigens are introduced into the body, they may be carried by the bloodstream or lymph channels to regional lymph nodes. The antigens interact with B and T lymphocytes and macrophages in the lymph nodes. The two important functions of lymph nodes are (1) filtration of foreign material brought to the site and (2) circulation of lymphocytes. The tonsils are an example of lymphoid tissue. The spleen, a peripheral lymph organ, is important as the primary site for filtering foreign antigens from the blood. It consists of two kinds of tissue: white pulp containing B and T lymphocytes and red pulp containing erythrocytes. Macrophages line the pulp and sinuses of the spleen. Lymphoid tissue is found in the submucosa of the gastrointestinal (gut-associated), genitourinary (genital-associated), and respiratory (bronchial-associated) tracts. This tissue protects the body surface from external microorganisms. The skin-associated lymph tissue primarily consists of lymphocytes and Langerhans’ cells (a type of dendritic cell) found in the epidermis of skin. When Langerhans’ cells are depleted, the skin can neither initiate an immune response nor support a skin-localized delayed hypersensitivity response. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

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 Cells involved in immune response include: Mononuclear phagocytes Lymphocytes Dendritic cells. Mononuclear phagocytes have a critical role in the immune system. After capture, the macrophage-bound antigen, which is highly immunogenic, is presented to circulating T or B lymphocytes and thus triggers an immune response. 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 In the early research on B lymphocytes (bursa-equivalent lymphocytes) in birds, it was discovered that they mature under the influence of the bursa of Fabricius, hence the name B cells. However, this lymphoid organ does not exist in humans. The bursa-equivalent tissue in humans is the bone marrow. B cells differentiate into plasma cells when activated. Plasma cells produce antibodies (immunoglobulins) (Table 14-2). Cells that migrate from the bone marrow to the thymus differentiate into T lymphocytes (thymus-dependent cells). The thymus secretes hormones, including thymosin, that stimulate the maturation and differentiation of T lymphocytes. T cells compose 70% to 80% of the circulating lymphocytes and are primarily responsible for immunity to intracellular viruses, tumor cells, and fungi. T cells live from a few months to the life span of an individual and account for long-term immunity. T lymphocytes can be categorized into T cytotoxic and T helper cells. Antigenic characteristics of WBCs have now been classified using monoclonal antibodies. These antigens are classified as clusters of differentiation or CD antigens. Many types of WBCs, especially lymphocytes, are referred to by their CD designations. All mature T cells have the CD3 antigen. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Types of Lymphocytes T cells 70%–80% B cells 10%–20% Natural killer (NK) cells <10% T cytotoxic (CD8) cells are involved in attacking antigens on the cell membrane of foreign pathogens and releasing cytolytic substances that destroy the pathogen. These cells have antigen specificity and are sensitized by exposure to the antigen. Similar to B lymphocytes, some sensitized T cells do not attack the antigen but remain as memory T cells. As in the humoral immune response, a second exposure to the antigen will result in a more intense and rapid cell-mediated immune response. T helper (CD4) cells are involved in the regulation of cell-mediated immunity and the humoral antibody response. T helper cells differentiate into subsets of cells that produce distinct types of cytokines (discussed in a later section). These subsets are called TH1 cells and TH2 cells. TH1 cells stimulate phagocyte-mediated ingestion and killing of microbes, the key component of cell-mediated immunity. TH2 cells stimulate eosinophil-mediated immunity, which is effective against parasites and is involved in allergic responses. Natural killer (NK) cells are also involved in cell-mediated immunity. These cells are not T or B cells but are large lymphocytes with numerous granules in the cytoplasm. NK cells do not require prior sensitization for their generation. These cells are involved in recognition and killing of virus-infected cells, tumor cells, and transplanted grafts. The mechanism of recognition is not fully understood. NK cells have a significant role in immune surveillance for malignant cell changes. 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 Clinical uses for Soluble TNF receptor (Enbrel) Rheumatoid arthritis Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Normal Immune Response Comparison of Humoral and Cell-Mediated Immunity Humoral Cellular Cells involved B lymphocytes T lymphocytes Macrophages Products Antibodies Sensitized T cells Cytokines Memory cells Present Humoral immunity consists of antibody-mediated immunity. In contrast, immune responses that are initiated through specific antigen recognition by T cells are termed cell-mediated immunity. Humans need both humoral and cell-mediated immunity to remain healthy. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 14

Normal Immune Response Comparison of Humoral and Cell-Mediated Immunity Humoral Cellular Protection Bacteria Viruses (extracellular) Respiratory pathogens Gastrointestinal pathogens Fungus Viruses (intracellular) Chronic infectious agents Tumor cells Each type of immunity has unique properties and different methods of action; each reacts against particular antigens. Copyright © 2014 by Mosby, an imprint of Elsevier Inc. 15

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. The term humoral comes from the Greek word humor, which means body fluid. Production of antibodies is an essential component in a humoral immune response. 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 Each of the five classes of immune globulins—IgG, IgA, IgM, IgD, and IgE—has specific characteristics. IgG Largest component of total immune globulins; found in plasma and interstitial fluid; only Ig to cross placenta and provide newborn with passive acquired immunity IgA Found in body secretions: saliva, tears, breast milk, colostrum Lines mucous membranes IgM Largest of immune globulins is found in plasma; responsible for primary immune response; forms antibodies to ABO blood antigens IgD Found in plasma; present on lymphocyte surface; assists in differentiation of B lymphocytes IgE Found in plasma and interstitial fluids; causes symptoms of allergic reaction 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 The introduction of antigen induces a response dominated by two classes of immune globulins—IgM and IgG. IgM predominates in the primary response, with some IgG appearing later. After the host’s immune system is primed, another challenge with the same antigen induces the secondary response, in which some IgM and large amounts of IgG are produced. 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.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Infections Localized – limited to a small area Disseminated- spreads beyond site of infection Systemic- spread throughout the body (sepsis) Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Infections Bacterial E Coli, normal in intestine only Virus Influenza Fungal Similar to plants , think mushrooms Candida Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Infections Emerging infections- infectious diseases that have recently increased or threatens to increase in near future. Ebola Lyme Herpes types 6 & 8 Hanta Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Infections Reemerging infections- infections once thought gone but now reemerging Diptheria Pertussis (whooping cough) TB Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Antibiotic Resistant Organisms Methicillin Resistant Staphylococcus Aureus (MRSA) Vancomycin Resistant Enterococcus (VRE, more virulent than MRSA) Streptococcus Pneumonia Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Antibiotic Resistant Organisms HCP have contributed to this Antbx for viral infections Prescribing pts antbx for unnecessary reasons Inadequate drug regimens ( 7 vs 10-14 days) Using broad spectrum antbx instead of 1st line antbx Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Antibiotic Resistant Organisms Pts contribute to this by: Skipping doses Not taking antbx for full duration of therapy Saving unused antbx for “later, just in case” Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Infection Prevention OSHA – Occupational Safety & Health Administration is a federal agency that protects workers from injury or illness in places of employment Employee MUST be provided with appropriate PPE and safety equipment Ebola - THR - 2014 Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Infection Prevention HAI- Healthcare Associated Infections (Nosocomial infections) Risks to pts- Actions to reduce these risks- PPE and HANDWASHING, foam, sanitizer Most susceptible are hospitalized pts and immunosupressed Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

Copyright © 2014 by Mosby, an imprint of Elsevier Inc. Precautions Standard or universal – for all pts Isolation: Airborne- infection suspended in air Droplet- through air or respiratory system Contact- through direct and indirect contact Boxes, carts and signs on door for how to dress before entering pt room Copyright © 2014 by Mosby, an imprint of Elsevier Inc.