Acquired Immunity: Humoral & Cell-Med. Distinction of Humoral versus Cell-Mediated Acquired Immunity Antigens and Antigenic Determinants: Non-self and MHC proteins Cell Types of the Humoral Response and How they Develop B and T cell receptors and immunglobulins (antibodies) Antibody Structure and Classes Activation of B cells and Clonal Selection Immunity and Secondary Response Time, Vaccines Antibody Actions Passive and Active Immunity Monoclonal Antibodies Players in the Cell Mediated (Adaptive) Response Activation of Cytotoxic T and B cells via T H cells Other T cells and their function Tissue grafting Immune disorders: Allergies Immune disorders: Immunodeficiency

Secondary Response (Immunity) Figure 12.13

Types of Vaccines  Live, attenuated vaccines: passed through unnatural host or a related non-virulent virus Benefits: Strong immune response, provide extended response Potential Problems: Underattenuation, mutation back to virulent form  Inactivated/dead “whole” microbial vaccines Benefits: Moderately immune response, less chance of causing disease Potential problems: incomplete inactivation  Subunit vaccines: pieces of outer layer of microbes, often produced through biotechnology Benefits: No chance of causing disease, safer Problems: Weaker immune response

Subunit Vaccines Made of Microbial Parts

Vaccine Production: Coinfecting With Two Strains

Acquired Immunity: Humoral Response Distinction of Humoral versus Cell-Mediated Acquired Immunity Antigens and Antigenic Determinants: Non-self and MHC proteins Cell Types of the Humoral Response and How they Develop B and T cell receptors and immunglobulins (antibodies) Antibody Structure and Classes Activation of B cells and Clonal Selection Immunity and Secondary Response Time Antibody Actions Passive and Active Immunity Monoclonal Antibodies Players in the Cell Mediated Response Activation of Cytotoxic T and B cells via T H cells Other T cells and their function Tissue grafting Immune disorders: Allergies Immune disorders: Immunodeficiency

Results of Antibody Binding to Antigen Agglutination (coralling of the invader) Precipitation (removal of soluble antigens from blood and lymph) Neutralization (blocking antigen's activity and binding) Opsonization (faciliating macrophage phagocytosis) Tagging, complement fixation, and transmembrane channel formation (lysis of pathogen) Agglutination Precipitation (soluble antigens) Transmembrane channel formation and lysis Antibody Function movie

Active vs Passive Immunity  Active Immunity Your B cells encounter antigens and produce antibodies Active immunity can be naturally or artificially acquired (e.g via vaccination)  Passive Immunity Antibodies are obtained from someone else oConferred naturally from a mother to her fetus oConferred artificially from immune serum or gamma globulin - e.g. snake antitoxin Immunological memory does not occur Protection provided by “borrowed antibodies”

Monoclonal Antibodies  Antibodies prepared for clinical testing or diagnostic services  Produced from descendents of a single cell line  Examples of uses for monoclonal antibodies Diagnosis of pregnancy Treatment after exposure to hepatitis and rabies HIV/AIDS detection in ELISA Assays Identifying microbes by using fluorescent-tagged antibodies against known organisms

Monoclonal Antibodies Can Be Used To Deliver Cell Poisons E.g. Rutuxin-mab for non-Hodgkin’s lymphoma tags B cells, causing apoptosis, NK cell, or complement lysis

Acquired Immunity: Humoral Response Distinction of Humoral versus Cell-Mediated Acquired Immunity Antigens and Antigenic Determinants: Non-self and MHC proteins Cell Types of the Humoral Response and How they Develop B and T cell receptors and immunglobulins (antibodies) Antibody Structure and Classes Activation of B cells and Clonal Selection Immunity and Secondary Response Time Antibody Actions Passive and Active Immunity Monoclonal Antibodies Players in the Cell Mediated Response Activation of Cytotoxic T and B cells via T H cells Other T cells and their function Tissue grafting Immune disorders: Allergies Immune disorders: Immunodeficiency

Cellular (Cell-Mediated) Immune Response 1. Antigens must be presented by macrophages, dendritic cells, or B cells to a T helper (T H ) cell (called “antigen presentation”) 2. T cells must recognize non-self antigen and self MHC proteins (double recognition) 3. After antigen binding, clones form as with B cells, but different classes of cells are produced

Cell-Mediated (Adaptive) Response

Types of T Cells  Cytotoxic T (T c ) cells - CD8 + Specialize in killing infected cells Insert a toxic chemical (perforin)  Helper T (T H ) cells - CD4 + Recruit other cells to fight the invaders Interact directly with B cells  A few members of each clone are memory cells Helper t cells animation Cytotoxic t cells animation

Recognition Proteins Found on T cells CD8: special membrane glycoprotein found on cytotoxic T (T C ) cells only CD8 glycoprotein, therefore T cells designated as CD8+ Function oBind to class I MHC molecules on almost every body cell to identify “self” from “non-self” but to kill “bad” self-cells CD4: different membrane glycoprotein found on T H, monocytes, macrophages, dendritic cells CD4 glycoprotein, therefore Tcells designated as CD4+ Function oBind to and recognize class II MHC molecules on dendritic cells, macrophages, or B cells to verify they have a security force name tag”.

Summary of B Cell Activation  B cells can be activated directly by antigen or from a TH cell activated by an antigen-presenting macrophage

Summary of the Immune Response

Acquired Immunity: Humoral Response Distinction of Humoral versus Cell-Mediated Acquired Immunity Antigens and Antigenic Determinants: Non-self and MHC proteins Cell Types of the Humoral Response and How they Develop B and T cell receptors and immunglobulins (antibodies) Antibody Structure and Classes Activation of B cells and Clonal Selection Immunity and Secondary Response Time Antibody Actions Passive and Active Immunity Monoclonal Antibodies Players in the Cell Mediated Response Activation of Cytotoxic T and B cells via T H cells Other T cells and their function Tissue grafting Immune disorders: Allergies Immune disorders: Immunodeficiency

Organ Transplants and Rejection  Major types of grafts Autografts – tissue transplanted from one site to another on the same person Hey buddy, my patch of skin is damaged! Can I have your autograft? Isografts – tissue grafts from an identical person (identical twin) Allografts – tissue taken from an unrelated person (sometimes successful) Xenografts – tissue taken from a different animal species (rarely successful)

Allergies (Hypersensitivity)  Abnormal, vigorous immune responses  Type I -IgE antibodies bind to mast cells Immediate hypersensitivity oB cells exposed to foreign antigen and IgE antibodies are made oReaction triggered by release of histamine from IgE binding to mast cells oReactions begin within seconds of contact with allergen oAnaphylactic shock – dangerous, systemic response Delayed hypersensitivity oTriggered by the release of lymphokines from activated helper T cells oSymptoms usually appear 1–3 days after contact with antigen oE.g. reaction to poison ivy, contact dermatitis  Type II - complement lyses antibody-tagged cells Immediate reactions, life threatening oE.g. Transfusions, hemolytic disease of newborns

Acquired Immunity: Humoral Response Distinction of Humoral versus Cell-Mediated Acquired Immunity Antigens and Antigenic Determinants: Non-self and MHC proteins Cell Types of the Humoral Response and How they Develop B and T cell receptors and immunglobulins (antibodies) Antibody Structure and Classes Activation of B cells and Clonal Selection Immunity and Secondary Response Time Antibody Actions Passive and Active Immunity Monoclonal Antibodies Players in the Cell Mediated Response Activation of Cytotoxic T and B cells via T H cells Other T cells and their function Tissue grafting Immune disorders: Allergies Immune disorders: Immunodeficiency

Disorders of Immunity: Immunodeficiencies  Autoimmune Diseases (antibodies attack own tissues) Multiple sclerosis – Schwann cells and oligodendrocytes forming myelin sheaths are destroyed, slowing communication, esp. muscles Myasthenia gravis – antibodies blocking acetylcholine receptors on post-synaptic side of neuromuscular junction; muscle weakness Juvenile diabetes – destroys pancreatic beta cells that produce insulin Rheumatoid arthritis – destroys joints by attacking tissues and causing inflammation Systemic lupus erythematosus (SLE) – affects kidney, heart, lung and skin Glomerulonephritis – impairment of renal function Grave’s disease - antibodies bind to TSH receptors on thyroid follicular cells, stimulating overproduction of thyroxine  Inefficient lymphocyte programming (e.g. T cells that escaped "education")  Appearance of self-proteins in the circulation that have not been exposed to the immune system (eggs, sperm, eye lens)  Cross-reaction of antibodies produced against foreign antigens with self-antigens Rheumatic fever - Anti-streptococcal antibodies also attack myocardium and joints; --> arthritis, congestive heart failure  Acquired Immune Deficiency Syndrome (AIDS)

HIV and Acquired Immunodeficiency Syndrome Titers of T H cells and blood viruses Diseases of AIDS Life Cycle of Human Immunodeficiency Virus

Acquired Immunity: Humoral Response Distinction of Humoral versus Cell-Mediated Acquired Immunity Antigens and Antigenic Determinants: Non-self and MHC proteins Cell Types of the Humoral Response and How they Develop B and T cell receptors and immunglobulins (antibodies) Antibody Structure and Classes Activation of B cells and Clonal Selection Immunity and Secondary Response Time Antibody Actions Passive and Active Immunity Monoclonal Antibodies Players in the Cell Mediated Response Activation of Cytotoxic T and B cells via T H cells Other T cells and their function Tissue grafting Immune disorders: Allergies Immune disorders: Immunodeficiency

Activation of T and B Cells Through T H cells MHC "self" identifying protein