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Immune System Chapter 43 Introduction to the Immune System The human body must defend itself against unwelcome intruders. It must also deal with abnormal body cells, which, in some cases, may develop into cancer. Two major kinds of defense have evolved to counter such threats. Innate Defenses Acquired Defenses Overview of the Immune System External Barriers: intact skin epidermis Acid mantle of skin Keratin Intact mucous membranes Mucus Nasal hairs Cilia Gastric juice Acid mantle of vagina Lacrimal secretion Urine Oil (sebum) secretions Internal Cellular Defenses: Phagocytic cells Neutrophils Monocytes Eosinophils Dendritic cells Internal Cellular Defenses Phagocytic Responses Pseudopodia Ingestion Vacuole Fuse with lysosome Digestion Exocytosis Internal Cellular Defenses: Natural Killer Cells Non-specific Perforins Apoptosis Natural Killer (NK) Cells (Cytotoxic lymphocyte) Promote cells lysis by direct cell attack against virus-infected or cancerous body cells Referred to as null third population cells that are spontaneous non antigen recognizing. Lack surface antigen receptors but recognize certain surface sugars on infected or cancerous cells Release cytolytic chemicals (perforins) that attack a targets cell's cell membrane and bore hole. Granzymes are released and cellular enzymes disrupted. Present in spleen, lymph nodes, red bone marrow, and blood Inflammatory Response Inflammatory Response Cardinal signs of inflammation redness, pain, heat and swelling Local versus systemic inflammation Septic shock Interferons - proteins that diffuse to nearby cells, where they stimulate the synthesis of a protein known as PKE, which then interferes with viral replication in those cells by blocking protein synthesis at the ribosomes Gamma interferon - produced by lymphocytes, mobilizes and activates macrophages and NK cells, stimulates synthesis and expression of more class I and II MHC, and enhances activity of B cells and cytotoxic T cells Alpha interferon - produced by most leukocytes, mobilizes and activates macrophages and NK cells Beta interferon - produced by fibroblasts, mobilizes and activates macrophages and acts to reduce inflammation Complement - twenty plasma proteins that amplify the inflammatory response, lyses microorganisms and enhances phagocytosis by opsonization. Two pathways: classic and alternative. Pyrogens - secreted by macrophages and signal the body to increase temperature; high body temperature inhibits microbial multiplication and enhances body repair processes. Antigen (Ags) Antigens are substances that can mobilize immune system and provoke a response Are considered nonself ii. Nonself Antigens Types: Complete antigen - functional properties: immunogenecity - stimulate B and T cell formation and antibody production reactivity - react with B and T cells Small antigens (peptide, nucleotide, hormones) - may bind to body's own biological molecules (proteins); antigen when bound to body's own molecules may cause an immune response, this is called an allergy. Small antigens are called haptens (incomplete antigen) and alone are not immunogenic. Reactivity (immune response) is dependent upon antigen structure; localized regions, antigenic determinants are where antibodies or B and T lymphocytes can bind. iii. Self Antigens Are not foreign or antigenic to us, but are strongly antigenic to other individuals egs. blood transfusions and organ transplants Major Histocompatibility Complex (MHC) antigens Found on all cells except RBCs Involved in tissue recognition (aids in transplantation recognition) Two types of MHC antigens: MHC class I found on all body cells MHC class II found on antigen present cells Antigen Presentation Ingestion of the antigen Digestion of antigen into peptide fragments Fusion of vesicles (peptide fragments with MHC-II molecules) Binding of peptide fragments to MHC-II molecules Insertion of antigen-MHC-II complex into plasma membrane ACQUIRED IMMUNITY All cells have cell surface macromolecules Adaptive immunity is sensitive to specific infections Antigens distinguish self versus non-self ACQUIRED IMMUNITY ACQUIRED IMMUNITY Humoral Immunity Also known as antibody-mediated immunity Utilizes B-lymphocytes Recognizes antigen directly Made in the bone marrow Clonal Selection and Proliferation Antibody Structure Antibody Classes Antibody Classes Antibody Functions Cell-Mediated Immunity Utilizes T-lymphocytes T-cells are made in the bone marrow but mature in the thymus gland. Cannot recognize antigens directly Cell-Mediated Immunity CLASS I MHC PROTEIN CLASS II MHC PROTEIN Helper T-Lymphocyte Stimulation Helper T-cells stimulate B-cells Cytotoxic T-Lymphocyte Stimulation Overview of Adaptive Immunity Adaptive Immunity Problems with the Immune System Blood Transfusion Reaction Tissue Rejection Allergies Autoimmune disease Immunodeficiencies Blood Transfusion Reactions Rhesus Factor Blood Type Presence of Type of Receive? D Antigen? Antibody? Rh Positive Yes None + and - No Anti-D - only Rh Negative Tissue Transplant and Rejection Autograft Isograft Allograft Xenograft Allergies or Hypersensitivities Type I Type II Type III Type IV Autoimmune Diseases Multiple sclerosis Rheumatoid arthritis Systemic lupus Grave's disease Type I diabetes mellitus Immunodeficiency Diseases Primary Immunodeficiency a.k.a. “inborn” SCID Secondary Immunodeficiency a.k.a. “acquired” Drugs Stress and Hodgkin’s AIDS