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University of Toronto St. George

Feb 2 Another aspect of the innate immune systemthe complement system Theme of pathogen recognition in absence of antibody also is involved in complement system and how complement system can work together with antibodies to provide for elimination of pathogens Immunize rabbits with cholera bacteria and took serum from immunized rabbitsexpect to contain antibodies Found two things the serum caused the bacteria to form aggregates and these aggregates seemed to form granules Bacteria have been killed in some way Take immune serum and heat itlet it cooladd it to bacteriaobserved clumping but no lysis no granule formationconclude heat sensitive factor involved Then took heated immune serum then added normal rabbit serumclumping and granule formation Normal serum does not contain antibodiesdoes not contain clumpingHeated immune serum alone not enough to cause lysisnormal rabbit serum alone notenough to cause lysisbut TOGETHER were bacteriocidalSecond factor present in normal serumheatsensitive and required to cause lysis Destroyed at 55 degreesnonspecific because did not need to come from immunized rabbitactive only when in association with factor causing aggreutinationComplement not a single factor a CASCADE of proteins that are present in plasma and these proteins when activated trigger cascade that can ultimately lead to lysis of bacteria Three distinct pathways by which complement can be activatedmannose binding lectin pathwaylectin carbohydrate binding protein that can bind to surface of a variety of pathogens trigger complement activation Classical pathway triggeed by antigenantibody complexespathway triggered in Bordets experimentsrequired immune serum or antibodies from immune serum to trigger complement pathway Third pathway alternative pathway that can do few different thingscan directly trigger complement activation Each pathway feeds into sepcific step in complement cascadelead to triggering of variety of effector mechanismsBordet identified kililng of pathogens by inducing lysis Pathways mediated by proteins found in normal serum Lead to C3 convertasestage that brings the pathways togetherC1q r s complex trigger C4 and 2leading to c3 convertase C3 and factors B and D involvedlead to generation of C3 convertase C3 convertase triggers conversation or activatio of another component of complement pathway C3the activation of various complement proteins frequently requires those proteins to be cleaved C3 is cleaved to C3b and C3b has a number of functions included in these functions is activation of terminus set of proteins that caus elysis of bacteria and C3b combined to surface of pathogens and lead to opsonization beause bind to complement receptors on phagocytesleading to removal of inmune complex
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