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Immune System. Defense system. Nonspecific Immunity Specific Immunity. First line of defense: Surface membrane barriers. Skin and mucous membrane Layered epidermis and shedding of epithelial cells Sebum inhibits growth of bacteria and fungi Mucous traps microbes, dust and pollutants.
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Defense system Nonspecific Immunity Specific Immunity
First line of defense: Surface membrane barriers • Skin and mucous membrane • Layered epidermis and shedding of epithelial cells • Sebum inhibits growth of bacteria and fungi • Mucous traps microbes, dust and pollutants. • Lacrimal apparatus • Saliva • Vaginal secretions • Flow of urine • Defecation and vomiting • Gastric juices destroy bacteria and their toxins
Second line of defense: chemical and cellular defenses • Antimicrobial proteins • Interferon • Complement • Transferrins • Natural killer cells • Phagocytes • Neutrophils • Dendritic cells • Macrophages • Wandering • Fixed • Eosinophils
Interferons • Produced by lymphocytes, macrophages and fibroblasts. • Interfere with translation of viral proteins • Degrade viral RNA • Activate macrophages and NK cells • Interferon Animation
Complement Complement Cascade Animation
Fever • Regulated my hypothalamus • Due to pyrogens secreted my leukocytes & macrophages • Causes liver and spleen to sequester zinc and iron • Increases metabolic rate (repair)
Inflammatory response Stages Inflammation Animation • Release of Chemical Alarms • Vasodilatation & Permeability of BV • Emigration of phagocytes: Dispose cellular debris & pathogens • Sets the stage for repair • Prevent spread of damaging chemicals & pathogens Signs of inflammation • Redness • Heat • Swelling • Pain • Impairment of function
Adaptive Resistance • Specificity—recognition of particular antigens • Memory—remembers previously encountered antigens • Systemic—immunity is not restricted to the initial infection site • Immune responses • Antibody-mediated or humoral immune responses (late 1800s) • Cell-mediated immune responses (mid 1900s)
T Lymphocytes • CD4 T cell - also known as a T Helper (Th) cell • CD8 T cell - also known as a Cytotoxic T (Tc) cell
Antigens and antigen receptors • Antigens can be entire microbes, parts of microbes or chemical components of pollen, egg white, blood cells,…….
Self antigens: MHC proteins • Antigens on our own cells are self-antigens • MHC proteins are glycoproteins that mark the cell as self. • Class I MHC proteins are on all body cells. Receptors on TC • Class II MHC proteins are only on certain cells that act in the immune response. Receptors on TH • Antigen Processing
Immunocompetence • T and B cells that have not been exposed to an antigen are naïve. • Binding with an antigen completes differentiation into functional B and T cells. • B cells mature in the bone marrow. • T cells mature in the thymus.
Antigen receptors • Genes determine what foreign substance will be recognized. • An antigen determines which T or B cells will be activated. • Lymphocytes make over a billion different receptors. • Gene segments of a few hundred bits are reshuffled and combined--somatic recombination. • The newly assembled gene is expressed as a receptor on the cell surface.
Humoral immune response • Antigen challenge—the meeting between a naïve immunocompetent lymphocyte and an invading antigen. • Occurs in lymphoid tissue such as spleen or lymph node. • If antigen challenge is presented to a B cell then the humoral immune response is provoked.
Immunoglobulin classes • IgD is attached to B-cell plasma membrane • IgM is released during primary response. Indicates current infection. • IgG is the most aboundant. Can cross placenta & blood vessel walls. • IgA found in body secretions prevents attachment to body surfaces. • IgE causes release of histamine (allergies) by attaching to mast cells & basophils.
Immunological memory • Primary immune response • Secondary immune response
Antibody defense: PLANe • Precipitation • Lysis: Complement fixation and activation • Agglutination • Neutralization • Enhancing phagocytosis
Cell-mediated immunity • Antibodies can only inactivate an antigen and NOT destroy it. • Antibodies prepare an organism for destruction by innate defenses. • T cells can only recognize and respond to processed fragments of protein. • T cells are suited for cell to cell interaction and target body cells infected by virus, bacteria and abnormal or cancerous body cells or cells that are transplanted or infused.
Cell-mediated immunity: T-cells • Activation of T cells—T cell receptors bind to antigen presented by the antigen-MHC complex. • CD4 and CD8 proteins interact with antigen and help maintain MHC-antigen coupling. • Types of T-cells • Helper T cells (CD4) • Cytotoxic T cells (CD8) • Memory T-cells
Activated T cell • Activation leads to enlargement, differentiation and proliferation of T cells. • T cells that are reproduced are clones of originally activated T cell. • Activation, differentiation and proliferation occurs in secondary lymph organs and tissue. • Activation leads to release of inflammatory cytokines.
Homeostatic imbalances : Immunodeficiencies • Abnormally behaving immune cells • Severe combined immunodeficiency (SCID) syndromes • Congenital conditions • Acquired immune deficiency syndromes • Hodgkin’s Disease • HIV • AIDS
Homeostatic imbalances : Autoimmune disease • Tend to be more prevalent in women • Type I diabetes—destroys pancreatic beta cells • Multiple sclerosis—destroys myelin sheaths • Myasthenia gravis—impairs communication between nerve and muscle • Lupus erythematosus—systemic disease of skin, kidneys, heart, and lungs • Rheumatoid arthritis—destruction of joints
Organ transplants • Autografts—grafts from the same person to another body site • Isografts—grafts between genetically identical individuals • Allografts—grafts among the same species • Xenografts—grafts taken from another animal species
Hypersensitivities Acute SubacuteSubacute Delayed Immediate cytotoxic Immune complex
Type I Hypersensitivity Type I Hypersensitivity Animation Type II Hypersensitivity
Type III Hypersensitivity Type III Hypersensitivity
Animations • Flash animation of a NK cell interacting with a normal body cell. • Flash animation of a NK cell interacting with a virus-infected cell or tumor cell not expressing MHC-I molecules. • Flash animation of apoptosis by NK cells. • HIV Replication
Resources • Components of the Immune System Animation
Essential knowledge 2.D.4: Plants and animals have a variety of chemical defenses against infections that affect dynamic homeostasis. • a. Plants, invertebrates and vertebrates have multiple, nonspecific immune responses. • Invertebrate immune systems have nonspecific response mechanisms, but they lack pathogen-specific defense responses. • Plant defenses against pathogens include molecular recognition systems with systemic responses; infection triggers chemical responses that destroy infected and adjacent cells, thus localizing the effects. • Vertebrate immune systems have nonspecific and nonheritable defense mechanisms against pathogens. • b. Mammals use specific immune responses triggered by natural or artificial agents that disrupt dynamic homeostasis. • The mammalian immune system includes two types of specific responses: cell mediated and humoral. • In the cell-mediated response, cytotoxic T cells, a type of lymphocytic white blood cell, “target” intracellular pathogens when antigens are displayed on the outside of the cells. • In the humoral response, B cells, a type of lymphocytic white blood cell, produce antibodies against specific antigens. • Antigens are recognized by antibodies to the antigen. • Antibodies are proteins produced by B cells, and each antibody is specific to a particular antigen. • A second exposure to an antigen results in a more rapid and enhanced immune response.
Essential knowledge 3.D.2: Cells communicate with each other through direct contact with other cells or from a distance via chemical signaling. • a. Cells communicate by cell-to-cell contact. • Immune cells interact by cell-cell contact, antigen-presenting cells (APCs), helper T-cells and killer T-cells. [See also 2.D.4] Essential knowledge 3.D.4: Changes in signal transduction pathways can alter cellular response. • a. Conditions where signal transduction is blocked or defective can be deleterious, preventative or prophylactic. • Diabetes, heart disease, neurological disease, autoimmune disease, cancer, cholera