Physiology Unit 3 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 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) 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

LiKle known regarding func4on IgD Immunoglobulin D

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

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 IgM Immunoglobulin M

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