Immunology_Class_Notes.pdf

NURS 7053 Advanced Pathophysiology I for DNP Students Immunology - Class Notes Basic Concepts in Immune Function Role of the Immune System in Health and Disease...

NURS 7053 Advanced Pathophysiology I for DNP Students Immunology - Class Notes Basic Concepts in Immune Function Role of the Immune System in Health and Disease The primary function of the immune system is to prevent or eradicate infections Also involved in surveillance and destruction of cancer cells The immune response can cause cell injury and stimulate pathologic inflammation The immune system recognizes and responds to tissue grafts Comparison of Inflammatory and Immune Responses Inflammatory Response (a.k.a. Innate Immunity) Rapid Nonspecific No memory Involves many cells (neutrophils, monocytes/macrophages eosinophils, endothelial cells, platelets, etc.) and plasma systems Immune Response (a.k.a. Adaptive Immunity) Slower Specific Memory Involves lymphocytes and antibodies Can be induced by vaccination 1  NURS 7053 Advanced Pathophysiology I for DNP Students Immunology - Class Notes Antigen A molecule that is recognized by lymphocytes and reacts with antibodies Foreign (non-human) antigen Viruses Bacteria Pollens and other environmental allergens Food or drugs Self-antigen Human Leukocyte Antigen (HLA) Cell surface proteins distinguishing self from non-self Present on all cell membrane except red blood cells Major Histocompatibility Complex (MHC): genomic region consisting of four loci on chromosome 6 that directs synthesis of HLA antigen. RBC antigen (A, B and Rh Antigen) 2  NURS 7053 Advanced Pathophysiology I for DNP Students Immunology - Class Notes Overview of the Immune Response Two Phases: Generation of Clonal Diversity and Clonal Selection (see p. 4) Generation of Clonal Diversity The production of a population of lymphocytes that can as a group, can recognize all foreign antigens The bone marrow produces lymphoid stem cells that migrate to the primary (central) lymphoid organs (thymus or bone marrow). Lymphocytes differentiate into immunocompetent (but still immature) T cells or B cells. The entire population of immunocompentent B and T cells has the ability to recognize all antigen, however each group of B or T cells (i.e., clones) has receptor specificity for one specific antigen. Lymphocytes are released from these organs into the circulation where they migrate to secondary lymphoid tissues (e.g., spleen, lymph nodes, mucosal and cutaneous lymphoid tissues) and take up residence. Clonal Selection The selection and proliferation of mature B and T cells in response to exposure to a specific antigen. Involves antigen processing and presentation by antigen presenting cells (APCs) to the immature lymphocytes Immunocompetent B and T cells with receptor specificity are selected, and stimulated to mature and proliferate (this process is called ‘clonal expansion’) B cells differentiate into antibody-producing plasma cells T cells differentiate into cytotoxic and other T cells These antigen-selected cells mount a defensive response against the foreign antigen Production of B and T memory cells 3 NURS 7053 Advanced Pathophysiology I for DNP Students Immunology - Class Notes 4  NURS 7053 Advanced Pathophysiology I for DNP Students Immunology - Class Notes Induction of the Immune Response Formation of B and T cells, and antibodies in response to antigen (see p. 6) Steps in Antigen Processing and Presentation Macrophage and other antigen presenting cell (e.g., dendritic cells, B cells) phagocytosis of foreign organism or tissue Expression of foreign antigen on surface receptors (MHC Class II) of macrophage Macrophage produces interleukin-I (IL-1) Antigen presentation to helper T (Th or CD4) cells: processed antigen on MHC Class II receptor binds to T cell receptor (TCR) on Th (CD4) cell Th secretes interleukin-2 (IL-2) which stimulates Th to mature into functional Th1 and Th2 cells IL-2 secreted by Th1 and Th2 cells also stimulates proliferation and differentiation of lymphocytes B lymphocytes (stimulated by Th2 cells) B cells proliferate and differentiate into plasma cells Plasma cells produce antibodies T lymphocytes (stimulated by Th1 cells) Cytotoxic T (Tc or CD8 T cells) cells proliferate and are responsible for cell-mediated destruction Memory Cells B and T memory cells are also formed 5 NURS 7053 Advanced Pathophysiology I for DNP Students Immunology - Class Notes 6  NURS 7053 Advanced Pathophysiology I for DNP Students Immunology - Class Notes B Lymphocyte Response Also called the ‘humoral response’ Bursal bound (immunocompetent) B cells are activated by T helper cells Postbursal B cells (plasma cells) produce immunoglobulins (antibodies) Note: Immunoglobulins are glycoproteins produced by plasma cells Immunoglobulin: term used to denote all types Antibody: Immunoglobulins that have specificity for a particular antigen Structure of Immunoglobulins Antigen-binding fragment (Fab) Contains recognition sites (receptors) for antigenic determinants Confers specificity Crystalline fragment (Fc) Provides biologic function by activation of complement system and inflammatory cells Informs inflammatory mediators that the antigen has invaded the body 7  NURS 7053 Advanced Pathophysiology I for DNP Students Immunology - Class Notes Antibody Classes Have antigenic, structural, and functional differences IgM - general antibody, highest titers present during primary immune responses IgG - general antibody, highest titers present during secondary immune responses IgA – preformed antibody found in sweat, saliva, tears, and breast milk IgE – antibody produced during allergic responses (type I hypersensitivity reactions) Function of Antibodies Begins with antigen binding to form antigen-antibody complexes Neutralize bacteria and viruses Promotes phagocytosis of bacteria and viruses (opsonization) Activate the complement cascade 8  NURS 7053 Advanced Pathophysiology I for DNP Students Immunology - Class Notes Primary and Secondary Immune Responses Confer active acquired immunity Primary: antigenic challenge with production of measurable immunoglobins (antibodies), primarily IgM, after a latent period of about 5 days. Secondary: a second antigen challenge with more rapid and larger production of immunoglobins, primarily IgG. PRIMARY RESPONSE SECONDARY RESPONSE IgG Log of antibody titer IgM IgG IgM Time First Exposure Subsequent To Antigen Exposure to Same Antigen 9  NURS 7053 Advanced Pathophysiology I for DNP Students Immunology - Class Notes T Lymphocyte Response Also called the ‘cellular response’ Cytotoxic T cells (Tc): Attack antigen directly and kill cells bearing foreign antigen Memory T cells (Tm): Induce secondary immune response Other Types of T Lymphocytes Lymphokine-producing T cell (Td): Likely a Th1 cell that is responsible for delayed hypersensitivity reactions Regulatory T cell (Treg): Develop in the thymus or peripheral tissues and suppress B cell and T cell activation Natural Killer Cells Arise from the lymphoid stem cell lineage Account for ~ 10% of the lymphocyte population Recognize virally infected or stressed cells and once activated release interferon-gamma which helps macrophages kill the infected cell Can also engage in direct cell killing of virally infected and cancer cells 10  NURS 7053 Advanced Pathophysiology I for DNP Students Immunology - Class Notes Vaccination A process of stimulating a protective immune response against microbes through exposure to nonpathogenic forms or components of the microbes Types of Traditional Vaccines Most traditional vaccines mainly stimulate the B lymphocyte (i.e., antibody) response Inactivated Virulent microbes are killed to abolish their infectivity and pathogenicity, yet still retain their immunogenicity. Large, multiple doses are often required. Booster vaccinations are required. Live attenuated Microbes are treated to reduce their infectivity and pathogenicity, yet still retain their immunogenicity. May not be safe for immunocompromised individuals. Boosters are required less often. Toxoid Vaccine is made from inactivated bacterial toxin. Subunit vaccines The vaccine is comprised of microbial proteins and/or polysaccharides that stimulate the immune system. Conjugated vaccines Microbial polysaccharides are chemically coupled with proteins so that they can stimulate Th cells. Synthetic vaccines Antigens are formed from recombinant proteins and other molecules in a laboratory environment. 11  NURS 7053 Advanced Pathophysiology I for DNP Students Immunology - Class Notes Type of Vaccine Examples Form of protection Inactivated or killed virus Injected polio, hepatitis A Antibody response Inactivated or killed bacteria Cholera, bubonic plague, Antibody response pertussis Live attenuated virus Measles, mumps, rubella, Antibody response and T cell varicella, flu, oral polio, rabies response Live attenuated bacteria BCG vaccine for TB Antibody response and T cell response Toxoid Tetanus toxoid, diphtheria Antibody response toxoid, rattlesnake venom Subunit (antigen) vaccines HPV Antibody response Conjugate vaccines H. influenza type B Th response Synthetic vaccines Hepatitis B, H1N1 Antibody response Viral vectors Clinical trials of HIV antigen in Antibody response and T cell canary pox vector response DNA vaccines Clinical trials ongoing for several Antibody response and T cell infections response From: Abbas, Lichtman, & Pillai (2016). Basic Immunology. Development of Immunity The immune system cells recognize the antigen associated with the vaccine, destroys the vaccine and then develops ‘memory’ for the antigen. When the actual microorganism is encountered, the immune system mounts the rapid and potent secondary immune response with high levels of antibodies (IgG mainly) and a Tc cell response 12