Download THE SPECIFIC IMMUNE RESPONSE

Physiology Unit 3 THE SPECIFIC IMMUNE RESPONSE The Adap4ve Arm of the Immune System •  Specific Immune Response •  Internal defense against a specific pathogen •  Acquired as you are exposed to diseases –  The immune system “learns” –  Memory cells remain for every pathogen your are exposed to •  My adap4ve immunity is not the same as yours! The Adap4ve Arm of the Immune System •  Controlled by the lympha4c system •  A coordinated mechanism involving a link between APC’s and lymphocytes –  APC’s are non-­‐specific –  Lymphocytes are specific •  Iden4fies specific foreign an4gens Lymphocytes •  Lymphocytes must recognize the specific pathogen to be aKacked •  Any molecule or cell that the host does not recognize as self –  Lymphocytes recognize an2gens • 
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Proteins or large carbohydrates Protein coats of virions Specific an4gens on foreign cells Cancer cells Transplanted cells •  Lymphocyte trafficking increases the likelihood that they will contact their specific an4gen •  Lymphocytes are circula4ng through lymph, lymph organs and the blood all the 4me Lymphocytes •  B Lymphocytes (mature in Bone marrow) –  APC to helper T-­‐cells –  Produce plasma cells which secrete an4bodies •  T Lymphocytes (migrate and mature in the Thymus) –  Helper T cells •  Necessary for amplifica4on of the immune response •  Ac4vate B-­‐cells and Killer T-­‐cells –  Killer (Cytotoxic) T cells •  AKack and kill your own cells that have become cancerous or infected with virus Roles of Lymphocytes Stages of Specific Immune Response Encounter and Recogni2on 1.  Encounter and recogni4on of a foreign an4gen by lymphocytes –  Each lymphocyte is specific for just one type of an4gen –  ≈ 100 million dis4nct an4gen receptors –  Progeny of lymphocytes are called clones Stages of Specific Immune Response Lymphocyte Ac2va2on 2.  Lymphocyte ac4va4on (B and/or T lymphocytes) –  Binding of an4gen to receptor –  Causes the lymphocyte to undergo mul4ple rounds of mitosis to produce clones – clonal expansion –  Some lymphocytes will be effector cells and be part of the aKack response –  Some lymphocytes will be set aside as memory cells for quicker subsequent responses in the future Stages of Specific Immune Response The A>ack 3.  The aKack launched against specific an4gens by the ac4vated lymphocytes u  Ac4vated B cells differen4ate into plasma cells and secrete an4bodies into the blood (but themselves remain in lymph nodes) – 
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An4bodies recruit and guide other cells to perform the aKack An4bodies inac4vate an4gens in plasma An4bodies bind to bacteria for compliment ac4va4on u  Ac4vated Killer T cells directly aKack and kill cells –  Plasma cells, helper T cells, killer T cells that par4cipated in the aKack die by apoptosis •  Prevents the immune response from becoming excessive and poten4ally destroying its own 4ssues The 5 classes of An4bodies Immunoglobulins •  5 classes based on the amino acid sequence of constant ends •  Classes –  IgA –  IgD –  IgE –  IgG –  IgM IgA Immunoglobulin A •  Mucosal immunity –  Secreted by mucus membranes lining diges4ve, respiratory, UG tract and prostate –  Found in body secre4ons •  Breast milk •  Sweat •  Tears –  Provides protec4on against microbes that mul4ply in mucus secre4ons IgD Immunoglobulin D •  LiKle known regarding func4on IgE Immunoglobulin E •  Defense against mul4cellular parasites •  Ac4vates mast cells and/or basophils to secrete histamine •  Implicated in allergic responses •  Found in lungs, skin, mucus membranes IgG Immunoglobulin G •  Most abundant an4body in blood and ECF –  Binds to many kinds of pathogens (bacteria, virions, fungi) –  Causes agglu4na4on –  Neutralizes toxins –  Ac4vates the compliment pathway –  Opsoniza4on for phagocytosis –  Directs marked virions to the proteosomes •  Crosses the placenta for fetal immunity IgM Immunoglobulin M •  Produced primarily by the spleen •  Found in serum and lymph •  Too large to move into ECF •  Most abundant upon first exposure to an infec4on •  Natural an4body •  Causes agglu4na4on •  Ac4vates the compliment pathway Func4on of Helper T Cells •  Helper T Cells –  Express CD4 proteins in their plasma membranes –  Amplify the response of B-­‐cells and other helper T-­‐cells –  Ac4vated by binding to an4gen •  Once ac4vated, secretes IL-­‐2 a cytokine that that acts on B cells and other helper T cells •  B cells cannot func4on adequately unless they are s4mulated by cytokines from helper T cells Func4on of Killer T Cells •  Cytotoxic T cells –  Express CD8 proteins in their plasma membranes –  Must travel through the blood to seek out their targets –  AKack and directly kill cells by secre4ng chemicals –  AKack host cells (your own cells): •  Cancer cells •  Viral infected cells CD Classifica4on of T Cells •  CD proteins are in the plasma membrane of T cells •  CD4: –  Helper T cells –  Macrophages •  CD8: –  Cytotoxic T cells •  CD4 popula4ons decimated by HIV B Cell Receptors •  The receptor on B cells for its specific an4gen is the an4body it secretes •  Constant ends •  Determine an4body class •  IgA, IgD, IgE, IgG, IgM •  Bind to macrophage •  Variable ends •  Bind an4gens •  A near infinite variety! T Cell Receptors •  T cell receptors for an4gens are integral membrane proteins –  Stay bound to the membrane of T cells •  T cell receptors can not bind an4gen unless the an4gen is first complexed with MHC proteins –  2 classes of “self” plasma membrane proteins •  T cell receptor then combines with the en4re complex of an4gen and MHC protein MHC Proteins •  Different from person to person •  Act as cellular ID tags – markers of biological self •  Binding to MHC proteins –  Class I MHC proteins –  Bind to the CD8 protein on killer T cells –  Class II MHC proteins –  Bind to the CD4 protein on helper T cells • A group of proteins: the major
histocompatibility complex are
called MHC proteins
• Also called human leukocyteassociated antigens or HLA
antigens
An4gen Presen4ng Cells (APC) •  T cells can bind an4gen only when the an4gen appears on the plasma membrane of a host cell complexed with the MHC proteins •  Host cells bearing these complexes are called an2gen presen2ng cells Presenta4on to Helper T cells •  APCs for helper T cells express the class II MHC proteins •  Macrophage •  B cells •  Dendri4c cells 1.  Aher an an4gen has been phagocy4zed by an APC (non-­‐
specific response) it is broken down into smaller pep4des 2.  The digested epitopes (fragments) bind to class II MHC proteins within an endosome of the APC 3.  The epitope-­‐MHC complex is transported to the cells surface and displayed in the plasma membrane An4gen Presenta4on to Helper T Cells Lymphokines •  APC binding to the helper T cell causes the APC to secrete large amounts of lymphokines 1.  IL-­‐1 and tumor necrosis factor (TNF) secreted by APCs 2.  s4mulate helper T cells to secrete IL-­‐2 3.  Ac4vates more helper T-­‐cells and B-­‐
cells Presenta4on to Cytotoxic T cells •  Any host cell can act as an APC to a cytotoxic T cell 1.  Any host cell that is cancerous 2.  Any host cell that has become infected with virions •  APCs for Cytotoxic T cells express the class I MHC proteins •  The cancerous or virion infected cells synthesize the an4gen that complexes with the class I MHC protein Defenses Against Viral Infected Cells and Cancer Cells •  Killer T cells secrete perforin •  Destruc4on results in the release of virions into the ECF where they can be directly neutralized by circula4ng an4bodies An4body-­‐Mediated Response Humoral Response •  Communica4on by an4bodies in the blood •  Humoral responses are the major long-­‐term defenses against –  Bacteria in the extracellular fluid –  Virions in the extracellular fluid –  Other microorganisms in the extracellular fluid –  Toxins in the extracellular fluid •  Once bound to an an<body, cannot infect other body cells –  Becomes immobilized and is tagged for macrophage An4bodies Allow Phagocytes to Bind to Pathogens Ac4ve Immunity •  Resistance that is built up as a result of the body’s contact with foreign an4gens •  B cells secrete the an4bodies against the an4gen •  Provides long las4ng (possibly permanent) immunity •  Occurs when you are exposed to a disease (natural) •  Occurs when you receive a vaccine (ar4ficial) •  Takes 4me to develop Passive Immunity •  The direct transfer of an4bodies from one person or another •  You receive preformed an4bodies •  Provides instant, temporary immunity •  Occurs during –  Breast feeding (IgA) –  Transplacental transfer of an4bodies (IgG) •  Occurs when you receive preformed an4bodies in an injec4on –  An immunoglobulin shot (e.g. against hepa44s or tetanus) Acute Phase Response •  Many systemic responses to infec4on –  Fever –  Decrease in plasma iron and zinc •  bacteria need iron for cell division –  Liver secretes acute phase proteins •  Many effects on the inflammatory response to minimize local 4ssue damage, for 4ssue repair and clearance of cellular debris and microbial toxins –  Increased produc4on and release of neutrophils and monocytes –  Release of amino acids from muscle –  Release of faKy acid from adipocytes Acute Phase Response Disorders of the Immune System Immunodeficiency •  Immunodeficiency •  May be caused by aging, stress, or viral infec4on •  May lead to “opportunis4c” diseases or cancer •  Manifested by a “failure” of the immune system to protect from these diseases Disorders of the Immune System Autoimmune disorder •  Autoimmunity –  an immune response is mounted against “self” an4gens •  Host an4gens that are transformed or previously hidden •  Include –  Diabetes mellitus Type I –  Systemic Lupus –  Rheumatoid Arthri4s Hypersensi4vi4es •  Immune responses to environmental agents cause inflamma4on •  Immediate hypersensi4vi4es (allergies) –  An4body (IgE) produc4on and mast cell secre4on of histamine –  Hay fever, allergies, penicillin, bee s4ng •  Delayed hypersensi4vi4es –  Overs4mula4on of lymphocytes and macrophages –  Take 2-­‐3 days to develop –  Chronic inflamma4on and cytokine release –  Against “tuberculin”, transplant rejec4on