What are the major functions of the Immune System? Regulation and Protection Fight disease Prevent future infections What is a pathogen? Any disease causing agent Ex: bacteria, viruses, parasites, toxins, fungi What is the difference between innate and adaptive immunity? Innate immunity – target any pathogen (nonspecific); found in all organisms Adaptive immunity – targets one specific pathogen (specific) – varies from individual to individual (genetics!) FIRST LINE OF DEFENSE: NONSPECIFIC EXTERNAL DEFENSES Skin – water-proof barrier Sweat Tears Cilia – respiratory tract Mucous membranes Acids in stomach Commensal microbes living on the skin Ex: INTERNAL DEFENSES Macrophages – large phagocytic white blood cells Natural Killer (NK) cells – WBCs that target cancer cells Interferons – proteins produced by viral infected cells to limit spreading of viral infection How Interferons Work: What is the role of a phagocyte (macrophage)? Nonspecific White blood cells Engulf and destroy any material they do not recognize Act as “Antigen Presenting Cells” following phagocytosis for possible specific response SECOND LINE OF DEFENSE: NONSPECIFIC Inflammatory Response SECOND LINE OF DEFENSE: Inflammatory Response FUNCTION: to disinfect and clean injured tissues; prevent spreading of infection Triggered by any damage to tissue Can be localized or widespread Results in Redness, Heat Production, Swelling Why is the inflammatory response considered to be innate immunity? The response is the same regardless of whether the invader has been previously encountered THIRD LINE OF DEFENSE: ADAPTIVE IMMUNITY “custom-tailored” defenses to each specific invader Provides a strong and long lasting defense Lymphocyte activity (B-cells and T-cells) What is an antigen? Any molecule that elicits an adaptive (specific) immune response Ex: parts of microbes, proteins on microbes, toxins, mold, pollen Foreign Molecules! What are the two major divisions of mammalian adaptive immunity? Cell-Mediated – T cells (lymphocytes) Humoral – B cells (lymphocytes) How is the specific immune response triggered? Non-specific phagocytes present antigens from pathogens to lymphocytes (B and T cells) Interconnectedness between nonspecific and specific defenses! Cell-Mediated Response Specific T-cells are developed to target specific antigens These T-cells trigger the destruction of those pathogens and infected cells through cell-cell interactions How do cytotoxic T cells destroy infected cells? Following recognition and binding to the MHC/antigen complex on infected cells, T-cells will “shoot” a perforin complex into the membrane of cells which triggers cell death via lysis or apoptosis Cytotoxic T cell Activity What about T-helper cells? Lymphocytes (T-cells) that support the action of the specific immune response (humoral and cell mediated) Cell-cell communication (autocrine AND juxtacrine) Adaptive Immune Response OVERVIEW Humoral Response Specific B-cells are developed that produce and secrete antibodies that bind to specific antigens. These antibodies bind to the antigens on pathogens and target them for destruction by T-cells, phagocytes, or prevent them from causing further infection How is the “perfect” antibody found and produced? How are the perfect T-cells found? How is the correct B and T cell discovered for a specific antigen? CLONAL SELECTION T-cells and B-cells have specific receptors on their cell membranes that respond to specific antigens Only cells whose receptors react with the specific antigen undergo rapid cell division This results in a MASSIVE and EFFICIENT adaptive immune response What is an antibody? “Y-shaped” protein produced by B-cells Attaches to one specific antigen and helps counter its effects **One gene can synthesize millions of Different antibodies via alternative splicing** Antibodies do not kill pathogens, what do they do? Antibodies bind to antigens and prevent further infection Mark pathogens for destruction by macrophages How does the production of memory cells help promote long lasting immunity? B-lymphocytes (and some T-lymphocytes) produce memory cells which last for a very long time Activated by a second exposure to the antigen Stronger and faster response What is the purpose of a vaccine? How are vaccines produced? To prevent infection from a specific pathogen by introducing the antigens of the pathogen to the immune system Two types of vaccines: Live-attenuated viruses (weakened) Dead viruses What happens in your body when you receive a vaccination? Humoral immune response is triggered Production of antibodies and memory cells **Why is it that vaccines do NOT always provide life- long lasting immunity?** Mutations in the pathogens DNA changes their antigens, making the produced antibodies ineffective What is the difference between active and passive immunity? Passive Immunity: receiving premade antibodies; short lasting Ex: breastmilk, antibody injection; antivenom Active Immunity: the person’s own immune system actively produces antibodies; long lasting Ex: vaccine, natural exposure to a pathogen What about Allergies? Immune response to non-pathogenic foreign molecules (allergens) Inflammatory response activated (often in the respiratory system) due to release of histamine Treatment: antihistamines, epinephrine What is an autoimmune disease? Immune response to populations of body cells Treatments: immunosuppressant drugs; alleviation of specific symptoms Ex: Type 1 diabetes mellitus: cytotoxic T cells attack insulin producing cells Ex: MS: T cells react against myelin sheath Ex: Rheumatoid arthirtis: antibodies target cartilage and bone cells at joints Prokaryotes Immune Systems Restriction Enzymes! Cut up foreign DNA (of a bacteriophage) at specific restriction site sequences Protect their own DNA by adding methyl groups to the same restriction sites (preventing cutting) Bacteriophages have evolved mechanisms to evade this defense Prokaryotic Immunity A: Restriction Enzyme is successful B: Evolved mechanisms in bacteriophages to evade degradation Fungi and Plants Immunity Rely on the production of a wide variety of chemicals that can cause unpleasant effects in would-be pathogens and predators Fungi – Death Cap Mushroom If consumed, can cause irreversible liver failure in humans Fungi – Penicilium genus Produce antibiotics (like penicillin) to protect against bacterial infections Plants – Defenses against Pathogens First line of defense – physical barrier of epidermal cells If that fails, plant cells are damaged by infection… In response, plants… Seal off the infected areas Release microbe-killing chemicals to signal local cells to do the same -> infected and local cells induce cell death Plant hormones also secreted to prevent systemic spreading of the pathogen to other parts of the plant AND to stimulate production of defense chemicals Figure 33.13B_s6 5 3 Enhanced local response 1 Binding of the pathogen’s Avr protein to the plant’s R protein R protein 6 4 Avirulent pathogen Avr protein 2 Signal transduction pathway Hormones Additional defensive chemicals Signal transduction pathway Recognition between R and Avr proteins, Systemic acquired leading to a strong local response resistance Plant defenses against herbivores Herbivores are animals that mainly eat plants. Plants use chemicals to defend themselves against herbivores and pathogens. Plants counter herbivores with physical defenses, such as thorns, and chemical defenses, such as distasteful or toxic compounds. Figure 33.13A_s5 Plant defense against herbivores 5 4 Wasp is attracted The wasp lays eggs 3 Synthesis and release of chemical attractants Plant cell 1 Damage to plant and chemical in caterpillar saliva 2 Signal transduction pathway Animals – Invertebrates - Insects Innate Immunity Only (LACK adaptive immunity) Examples of Physical Barriers: Exoskeleton Low pH Lysozyme enzyme secretion to break down bacterial cell walls Immune cells capable of phagocytosis Production of antimicrobial proteins to help destroy invaders