Chapter 15 The Innate Immune Response Innate immune the immunity from microbes that we acquire from birth o Pattern recognition the system by which specific molecules respond to specific antigens o Adaptive immunity immunity that develops throughout the life as we are exposed to pathogens o Antibodies bind to antigens deactivating and marking for destruction Overview of the innate immune response First line defenses the barriers that separate the interior of the body from the environment o Skin and mucous membranes o Various receptors detect when the membrane has been breeched Toll like receptors and NOD proteins which are found on or within various cell types Complement system proteins circulating in the blood which when activated set off a chain of events that leads to removal and destruction of pathogen o Phagocytes cells that specialize in engulfing foreign matter o Cells communicate with each other via cytokines chemical messengers that alert the body to invaders o Inflammation coordinated immune response that recruits many aspects of innate defense Cells that line the blood vessels or near site undergo changes that allow proteins of the complement system to leak into the tissues and allow phagocytes to bind to blood vessel and roam freely in tissues First line Defenses Physical Barriers o Skin Our external barriers along with our normal microbiota aid in the removal and destruction of pathogens Composed of the dermis and the epidermis composed of dead skin cells and keratin which are thick layers of connective tissue Cells continuously fall off expelling attached microbes o Mucous membranes Digestive genitourinary and respiratory tracts Propel microbes where it is easiest to excrete them Peristalsis rhythmic contractions of GI tract Lined with cilia that help move bacteria and foreign particles Mucociliary escalator in resp tract Antimicrobial substances o Lysozyme degrades peptido and exists in the eye and on the skin tissues and phagocytes o Peroxidase enzymes salvia and milk tissues and phagocytes Produce oxidizing effects Ineffective against catalase positive bacteria o Lactoferrin iron binding protein found in salvia mucous and milk Similar to transferring which is found in the blood and tissue fluids By sequestering iron both of these proteins withhold Fe from microbes impeding growth Short antimicrobial peptides produced by neutrophils and epithelial cells Insert into bacterial membranes forming pores and disrupt the integrity of cell o Defensins o Transferrins Normal Microbiota Chemicals that bind to iron and sequester microbes in the blood o Normal flora of the body o Compete against pathogens for nutrients limiting pathogen growth o Produce toxins that limit growth o Prevent the cell from binding by covering binding sites Cells of the immune system Hematopoiesis the formation of blood cells o Originate from a pluripotent cell by CFU stimulating factors cytokines o Differeniate and develop functioning properties Erthocytes RBCs Leukocytes important in host defense Platelets fragments arising from megakarocytes Granulocytes o Granules filled with bioactive chemicals o Neutrophils Called poymorphonuclear named for there multiple lobes of single nucleus Increase during bacterial infections granules pale pink contain antimicrobial chemicals degradative enzymes Phagocytize foreign matter release defensins and damage cells o Eosinphils o Basophils Parasitic infections granules red with acidic eosin dye histaminase antimicrobials Allergic reactions and inflammation Contain histamine and other chemicals Similar to mast cells granules histamine etc increase capillary permeability granules dark purple with basic methylene blue dye Mononuclear Phagocytes o Mononuclear phagocyte system MPS Monocytes circulate in the blood Macrophages in all tissues except liver spleen and lymph o Engulf cells and bring it to immune system APCs Dendritic Cells Lymphocytes o Adaptive immunity o B cells and T cells o NK cells are nonspecific Cell Communication Surface Receptors o Proteins that span the membrane o Each receptor is specific Ligand Cytokines or cell death o Locally or systemically o Chemokines promote chemotaxis of immune cells o CFU multiplication and differentiation of leukocytes o Interfeurons viral infections o Interluekins produced by leukocytes and have diverse functions o Tumor necrosis inflammation response and death of tumor cells o Pro inflammatory cytokines contribute to inflammation Adhesion molecules o Allow cells to adhere to other surfaces o Ex phagocytes at the site of needed blood clot Sensor systems Toll like receptors and NOD proteins o TLRs allow cells to ID the presence of microbes outside of the cell o Bind to cytokine receptors which induce a change in the cell s growth differeniation movement o NOD proteins sense microbes inside the cell o Both of pattern recognition receptor The complement System o Series of proteins in the blood that bath the tissues o Classical pathway specific immune pathway antibody antigen complexes expose binding sites on antibodies to compliment proteins C1 protein can then bind to the antibody at this site setting off an enzyme reaction cascade o Alternative pathway is nonspecific pathway no antibodies required but their 2 different paths to activating compliment one involves C3b protein or plasma proteins bind to the surface of a microbe which sets off the enzyme cascade which activates all the compliment proteins o Lectin pathway mannan binding lectins Whn bindied the MBL interacts with the complement and activates it o Inflammation C3a and C5a induces changes in endothelial cells that line the vessels Contribute to permeability and inflammation C5b is also a chemoattractant Form an attack complex that creates pores in the membrane o Lysis of foreign cells o Opsonization C3b coats with opsonins Mark for destruction Sensors that detect long double stranded DNA o Normal cells do not have long DNA because proteins are made from templates from short mRNA o Long RNA molecules are detected and alpha and beta interfeurons are emitted from the cell o The activated forms of the antiviral proteins will then generate mass cell death apoptosis Phagocytosis Scavenger receptor stimulates the engulfing of foreign material when binds The process of phagocytosis o Series of compelx steps o Chemotaxis Recruited to the site of infection o Recognition and attachment Various receptors to bind directly or indirectly Ex on surface of pathogen or one