THE IMMUNE SYSTEM

 A pathogen is an infectious agent that causes disease; most are viruses, bacteria, or protists.  Organisms have tiered levels of defense, starting with general defenses (skin, membranes, enzymes) to more targeted and specific responses. PATHOGENS & LEVELS OF DEFENSE

Innate Immunity:  Found in all animals (and plants)  Occurs immediately upon infection  Does not rely on previous infection  Uses receptor proteins that bind to molecules that are absent from the animal’s own body Acquired immunity (aka adaptive immunity)  Found only in vertebrates  Enhanced by previous exposure  Detects pathogens with greater specificity INNATE IMMUNITY VS ACQUIRED IMMUNITY

 Insects are protected inside and out by chitin. The digestive tract of insects also produce lysozyme (digests microbial cell walls) and have a low pH.  Hemocytes circulate in hemolymph (insect blood) and can carry out phagocytosis; other cells produce and secrete microbe-killing chemicals (such as anti-microbial peptides).  Immune response cells are recognizing unique molecules on outside of fungi (polysaccharides) and bacteria (polymers of sugars and amino acids).  In fruit flies, pieces of fungal cell wall bind to a cell recognition protein. This in turn activates another protein (known as Toll) which starts a signal transduction pathway that stimulates the nucleus to begin the synthesis pathway for antimicrobial proteins. IMMUNE RESPONSE IN INVERTEBRATES

① Barrier Defenses:  skin, mucous membrane lining digestive, respiratory, urinary, and reproductive tracts. Mucus traps microbes and other particles. Ciliated epithelial cells then sweep mucus and other particles upward.  Saliva and tears (both of which contain lysozyme) also help prevent colonization as does the low pH of the stomach. ② Cellular Innate Defenses:  Leukocytes (phagocytic WBC) detect pathogens. TLR (Toll-like receptor) on leukocytes recognize fragments of molecules characteristic of certain pathogens.  TLR3 recognizes double-stranded RNA  TLR4 recognizes lipopolysaccharides (found on bacteria)  Both trigger a series of defenses. IMMUNE RESPONSE OF VERTEBRATES

 WBC recognizes and traps microbe in a vacuole.  Vacuole fuses with lysosome.  Nitric oxide and other gases (produced by lysosome) poison microbe while lysozyme and other enzymes degrade microbial components.  Neutrophils are most abundant phagocytic cells. Signals from infected tissues attract neutrophils which then engulf and destroy microbes.  Macrophages both patrol body and are permanent residents of certain organs (spleen, lymph nodes, and other tissues of lymphatic system). These cells engulf and destroy microbes. IMMUNE RESPONSE OF VERTEBRATES

 Eosinophils provide protection against multicellular invaders. These cells don’t perform phagocytosis, rather they “attach” to parasite and then release destructive enzymes.  Dendritic cells populate tissues that are in contact with the environment; these are mostly involved in acquired immune response. IMMUNE RESPONSE OF VERTEBRATES

 In mammals, pathogen recognition triggers production and release of many peptides and proteins that attack microbes or impede their reproduction.  Interferons are proteins that provide innate defense against viral infection:  Virus-infected body cells secrete interferon  Nearby uninfected cells produce substances that inhibit viral reproduction limiting cell-to-cell spread of viruses.  Some WBC secrete a different interferon that helps activate macrophages.  Interferons are now being produced by pharmaceutical companies. ANTIMICROBIAL PEPTIDES AND PROTEINS

 Complement system is composed of about 30 proteins that work together to fight infection. Proteins circulate in inactive state and are activated by substances on surface of microbes. Activation results in cascade of biochemical reactions which lead to lysis of invading cells. ANTIMICROBIAL PEPTIDES AND PROTEINS

 Histamine (stored in mast cells) is released at site of tissue damage.  Histamine triggers nearby blood vessels to dilate and become more permeable; activated macrophages (and other cells) discharge additional signaling molecules that further promotes blood flow to area—this results in redness and heat in area of wound.  Capillaries leak fluid into neighboring tissues (hence swelling).  Activated complement proteins promote further release of histamine and help attract phagocytes.  Nearby epithelial cells secrete signaling molecules which attract neutrophils and macrophages. These cells leave blood stream and carry out phagocytosis and inactivation of microbes.  Waste accumulates as pus (a fluid of WBC, dead microbes and cell debris). INFLAMMATORY RESPONSE

 Some toxins produced by pathogens as well as pyrogens (released by activated macrophages) can reset the thermostat of an organism to higher temperature. This increase in temperature may enhance phagocytosis. FEVER

 NK Cells recognize and eliminate certain diseased cells in vertebrates.  All cells have Class I MHC molecules on their surface. Cells that have a viral infection or are cancerous often quit producing this molecule. NK cells recognize these cells and kill them.  Some microbes are capable of producing a capsule that hides polysaccharides (ex: Streptococcus pneumoniae). Others are resistant to breakdown by lysosomes. NATURAL KILLER (NK) CELLS

Allergies:  Allergies are exaggerated response to antigens (known as allergens).  Usually involves IgE antibodies.  Ex: Hay Fever  Plasma cells secrete IgE antibodies specific to antigens on pollen grains.  Antibodies attach base to mast cells in connective tissue.  Second arrival of pollen grains attaches to IgE on mast cell  mast cells release histamine (degranulation)  dilation and increased permeability of blood vessels  Ex: Anaphylactic Shock  Due to widespread mast cell degranulation  causes abrupt dilation of peripheral blood cells. DISRUPTIONS TO THE IMMUNE SYSTEM

 In an autoimmune disease, the body turns against certain of its own cells.  Ex: Lupus  Body develops antibodies against histones and DNA AUTOIMMUNE DISEASE

 In an immunodeficiency disease, the ability of the immune system to protect against pathogens is defective or absent.  Can be inborn or acquired.  An inborn immunodeficiency results from a genetic or developmental defect in the immune system.  An acquired immunodeficiency develops later in life due to exposure to chemical or biological agents.  Ex: Hodgkin’s cancer, AIDS IMMUNODEFICIENCY DISEASE