Acquired Immunity: Humoral & Cell-Med.

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 TH 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 TH 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) Antibody Function movie Agglutination Precipitation (soluble antigens) Transmembrane channel formation and lysis

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 • Conferred naturally from a mother to her fetus • Conferred 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

Cellular (Cell-Mediated) Immune Response 1. Antigens must be presented by macrophages, dendritic cells, or B cells to a T helper (TH) 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 (Tc) cells - CD8+ • Specialize in killing infected cells • Insert a toxic chemical (perforin) • Helper T (TH) cells - CD4+ Recruit other cells to fight the invaders • Interact directly with B cells • A few members of each clone are memory cells Cytotoxic t cells animation Helper t cells animation

Recognition Proteins Found on T cells CD8: special membrane glycoprotein found on cytotoxic T (TC) cells only • CD8 glycoprotein, therefore T cells designated as CD8+ • Function • Bind 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 TH, monocytes, macrophages, dendritic cells • CD4 glycoprotein, therefore Tcells designated as CD4+ • Function • Bind 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

Organ Transplants and Rejection Major types of grafts Autografts – tissue transplanted from one site to another on the same person • Isografts – tissue grafts from an identical person (identical twin) • Allografts – tissue taken from an unrelated person (sometimes successful) Hey buddy, my patch of skin is damaged! Can I have your autograft? • 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 • B cells exposed to foreign antigen and IgE antibodies are made • Reaction triggered by release of histamine from IgE binding to mast cells • Reactions begin within seconds of contact with allergen • Anaphylactic shock – dangerous, systemic response • Delayed hypersensitivity • Triggered by the release of lymphokines from activated helper T cells • Symptoms usually appear 1–3 days after contact with antigen • E.g. reaction to poison ivy, contact dermatitis • Type II - complement lyses antibody-tagged cells • Immediate reactions, life threatening • E.g. Transfusions, hemolytic disease of newborns

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 TH cells and blood viruses Diseases of AIDS Life Cycle of Human Immunodeficiency Virus

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

Acquired Immunity: Humoral & Cell-Med.