Lecture 18 BIO 311D 1st EditionOutline of Last Lecture I. HemoglobinII. Carbon Dioxide TransportIII. Respiratory AdaptationsIV. The Immune SystemVI. Barrier DefensesVII. Inflammatory ResponsesOutline of Current Lecture I. Antimicrobial peptides and proteinsII. Inflammatory ReponsesIII. Evasion of Innate Immunity by pathogensIV. Antigen by recognition T CellsV. Immuniology memoryVI. B and T cell developmentCurrent LectureAntimicrobial 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 inflammationInflammatory 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 responseEvasion 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 yearIn 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 partsof 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 moleculeAntigen 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 regionsdiffer 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 membraneAntigen 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 responseB 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 memoryGeneration 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 formedOrigin 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 nonfunctionalProliferation 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 againImmunological 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 responseThree Innate Defenses share with invertebrates:- Barrier defense- Cellular Innate defense- Peptides and proteinsTwo defenses unique to vertebrates:-