Lecture 18 BIO 311D 1st Edition Outline of Last Lecture I Hemoglobin II Carbon Dioxide Transport III Respiratory Adaptations IV The Immune System VI Barrier Defenses VII Inflammatory Responses Outline of Current Lecture I Antimicrobial peptides and proteins II Inflammatory Reponses III Evasion of Innate Immunity by pathogens IV Antigen by recognition T Cells V Immuniology memory VI B and T cell development Current Lecture Antimicrobial Peptides and Proteins Peptides and proteins function in innate defense by attacking pathogens or impeding their reproduction Interferon proteins provide innate defense interfering with viruses and helping activate macrophages About 30 proteins make up the complement system which causes lysis of invading cells and helps trigger inflammation Inflammatory Responses The inflammatory response such as pain and swelling is brought about by molecules released upon injury of infection Mast cells a type of connective tissue release histamine which triggers blood vessels to dilate and become more permeable Activated macrophages and neutrophils release cytokines signaling molecules that enhance the immune response Pus a fluid rich in white blood cells dead pathogens and cell debris from damaged tissues Inflammation can be either local or systemic throughout the body Fever is a systemic inflammatory response triggered by pyrogens released by macrophages and by toxins from pathogens Septic shock is a life threatening condition caused by an overwhelming inflammatory response Evasion of Innate Immunity by Pathogens Some pathogens avoid destruction by modifying their surface to prevent recognition or by resisting breakdown following phagocytosis Tuberculosis TB is one such disease and kills more than a million people a year In adaptive immunity receptors provide pathogen specific recognition The adaptive response relies on two types of lymphocytes or white blood cells Lymphocytes that mature in the thymus above the heart are called T cells and those that mature in bone marrow are called B cells Antigens are substances that can elicit a response from a B or T cell Exposure to the pathogen activates B and T cells with antigen receptors specific for parts of that pathogen The small accessible part of an antigen that binds to an antigen receptor is called an epitope B cells and T cells have receptor proteins that can bind to foreign molecules Each individual lymphocyte is specialized to recognize a specific type of molecule B cells and T cells have receptor proteins that can bind to foreign molecules Each individual lymphocyte is specialized to recognize a specific type of molecule Antigen Recognition by B Cells and Antibodies Each B cell antigen receptor is a Y shaped molecule with two identical heavy chains and two identical light chains The constant regions of the chains vary little among B cells whereas the variable regions differ greatly The variable regions provide antigen specificity Binding of a B cell antigen receptor to an antigen is an early step in B cell activation This gives rise to cells that secrete a soluble form of the protein called an antibody or immunoglobulin Ig Secreted antibodies are similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane Antigen Recognition by T Cells Each T cell receptor consists of two different polypeptide chains called a and b The tips of the chain form a variable V region the rest is a constant C region T cell and B cell antigen receptors are functionally different T cells bind to antigen fragments displayed or presented on a host cell These antigen fragments are bound to cell surface proteins called MHC molecules MHC major histocompatibility complex molecules are host proteins that display the antigen fragments on the cell surface In infected cells MHC molecules bind and transport antigen fragments to the cell surface a process called antigen presentation A T cell can then bind both the antigen fragment and the MHC molecule This interaction is necessary for the T cell to participate in the adaptive immune response B Cell and T Cell Development The adaptive immune system has four major characteristics Diversity of lymphocytes and receptors Self tolerance lack of reactivity against an animal s own molecules B and T cells proliferate after activation Immunological memory Generation of B and T Cell Diversity By combining variable elements the immune system assembles a diverse variety of antigen receptors The immunoglobulin Ig gene encodes one chain of the B cell receptor Many different chains can be produced from the same gene by rearrangement of the DNA Rearranged DNA is transcribed and translated and the antigen receptor formed Origin of Self Tolerance Antigen receptors are generated by random rearrangement of DNA As lymphocytes mature in bone marrow or the thymus they are tested for self reactivity Some B and T cells with receptors specific for the body s own molecules are destroyed by apoptosis or programmed cell death The remainder are rendered nonfunctional Proliferation of B Cells and T Cells In the body there are few lymphocytes with antigen receptors for any particular epitope In the lymph nodes an antigen is exposed to a steady stream of lymphocytes until a match is made This binding of a mature lymphocyte to an antigen initiates events that activate the lymphocyte Once activated a B or T cell undergoes multiple cell divisions This proliferation of lymphocytes is called clonal selection Two types of clones are produced short lived activated effector cells that act immediately against the antigen and long lived memory cells that can give rise to effector cells if the same antigen is encountered again Immunological Memory Immunological memory is responsible for long term protections against diseases due to either a prior infection or vaccination The first exposure to a specific antigen represents the primary immune response During this time selected B and T cells give rise to their effector forms In the secondary immune response memory cells facilitate a faster more efficient response Three Innate Defenses share with invertebrates Barrier defense Cellular Innate defense Peptides and proteins Two defenses unique to vertebrates Interferon Complement system Barrier Defense Examples Cilia helps propel pathogen out of respiratory system Mucus fluid helps trap any pathogens Skin Low pH which prevents growth of any type of bacteria and forms an external barrier Tears from