Anatomy & Physiology Tony Serino, Ph.D. Immunity Anatomy & Physiology Tony Serino, Ph.D.

Immunity: Topic Objectives Be able to describe the multilevel defenses of the body. Be able to describe the symptoms and triggers for inflammation. Be able to define adaptive immunity, antibodies, antigens and haptens. Be able to explain how haptens can be immunoreactive but not immunogenic. Be able to explain how T and B cells become immunocompetent and activated. Be able to identify the different cell types produced in monoclonal expansion of lymphocyte cell lines and their functions. Be able to identify and explain antibody structure, characteristics of different antibody types and their actions. Be able to explain how APCs activate lymphocytes. Be able to explain how vaccines work and how they are made. Understand the difference between naturally and artificially acquired active and passive immunity

Immune System Provide defense of the body against infectious agents, toxins, foreign bodies, and cancers Two types of defenses: General (Non-specific or Innate) Defense Barriers Normal Flora and Fauna Fever Surveillance Inflammation Non-specific Phagocytic WBCs and NK cells Protective Chemicals Specific (Adaptive) Defense --Lymphocytes

Barriers Prevent infectious agents from penetrating internal environment Epithelium ( thickness, tight junctions, keratin) -especially the skin Cilia and mucus Watery secretions (tears, saliva) Acidity (stomach, urine, vaginal secretions) Normal Flora and Fauna –resident bacteria prevent infectious agents from growing on body surfaces

Surveillance Number of cells and organs to detect invading agents Langerhans cells of skin, Mast cells, Dendritic cells, and organs like: Tonsils, GALT cells Gather antigens and present them to lymphocytes

Fever Rise in Body Temperature Inhibits invading cell growth; increase body metabolism to increase defense/repair cell activity Produced by release of pyrogens from leukocytes Low grade fever is beneficial in fighting infection, high sustained fever may be life threatening

Inflammation Allows more blood defenses into damaged areas Triggered by release of paracrines from damaged tissues (PG), attacking WBCs (cytokines), mast cells (heparin and histamine), and activation of blood protective chemicals (complement and bradykinins) Increases: blood flow through vasodilation (hyperemia) capillary permeability Both lead to local edema If prolonged or systemic, can become life threatening

Inflammatory Response

Phagocytic WBC and NK cells WBCs can distinguish the sugars in mammalian cells and those found on bacteria or other parasites PMNs, macrophage, and mast cells can injure or destroy cells that do not display normal sugars NK cells –related to T-cells but attack any cell not displaying MHC I proteins Kill by secreting perforins and other chemicals

Phagocytosis

Protective Chemicals Chemicals that aid in destroying or retarding infectious agents Interferon –cytokine released when cell attacked by virus; warns other cells in area Lysozyme –antibacterial enzyme present in tears and saliva Complement –blood proteins which can detect and destroy bacteria

Interferon

Complement MAC –membrane attack complex (C3-C9)

Specific (Adaptive) Immunity Individual targets are selected for attack by the lymphocytes that can bind that target (antigen) Antigens (Ag) – any large substance not normally found in the body; these illicit an immune response (immunogenic and immuno-reactive) Haptens are small molecules that can trigger an immune response only if bound to larger molecules (like: pollen, some cosmetics, detergent fragrances, poison ivy animal dander and drugs); they are immuno-reactive but not immunogenic by themselves

Antigenic Determinants Large macromolecules illicit immune response because they have many sites to which immune molecules will attach; proteins have the most of any molecule

Identifying “Self” from “Non-self” T-cells migrate to thymus, B-cells remain in bone marrow (the primary lymphoid tissues) Become immunocompetent -selected for their ability to produce a surface receptor against an antigen and to tolerate self antigens Those that bind weakly to self-antigens are selected, the others are eliminated The strongest self-antigens are the MHC proteins Once competent, the cells are released to move through the blood and aggregate in the secondary lymphoid tissues

Thymic Selection

Movement of Lymphocytes

Cells Involved in Specific Immunity Lymphocytes (B and T cells) -attack antigen bearing agents either chemically (humoral immunity –the B-cells) or physically (cellular immunity –the T-cells) T and B-cell activation to an antigen works best when they are presented with the antigen by another cell APCs (Antigen Presenting Cells) (macrophage, surveillance cells, B-cells, infected cells) display foreign antigenic determinants on their MHC II cell surface proteins to activate the lymphocytes

Memory T cell

B-cell Clonal Expansion

Antibody Structure

Antibody Actions Opsonization –Ag-Ab complex makes ID for phagocytosis easier

Humoral Response

Control of Lymphocyte Response B-cells can be activated by the antigen alone, but it is more effective if they are presented the antigen by APCs or stimulated by T-helper cells Activation of T-helper cells stimulates complete lymphocyte response

MHC I –found on all body’s cells except RBCs Surface proteins usually bound to pieces of intracellular proteins, but when infected they present fragments of the infectious agent

MHC II –found on APCs -bound to phagocytized outer coat molecules of immuno-agent

T-cell Types

Helper T-cells

Clonal Selection of T-cell

Cytotoxic T-cell Attack

Primary Immune Response

Vaccine Production

Types of Acquired Immunity

Immediate Allergic Reaction

Hypersensitivity -like in TB test - Some drug allergies where the drug is precipitated and Ag-Ab is being destroyed 4. Cytotoxic hypersensitivity –mediated by antibodies that lead to damage or destruction of cells –like in ABO test and hemolytic fetal diseases

Pathologies: AIDS AIDS –HIV invades T-helper cells, diminishing effectiveness of immune response; may have as long as 8 year incubation time, 100% fatal

Pathologies Autoimmune Diseases –Immune system targets naturally occurring compounds of the body (usually sequestered proteins) MS, rheumatoid arthritis, Diabetes mellitus (I), etc. Cancer –cancers cells spontaneously form during life, but the immune system keeps them in check; failure results in tumors and metastasis