Complement Flashcards
complement important in defense against which kind of organisms?
- pyogenic
roles of complement
- promotes inflammatory response
- eliminates pathogens
- enhances immune response
complement and immune complex diseases
- component in both prevention and pathogenesis of immune complex diseases
functions of complement
- opsonization
- inflammation
- lysis
opsonization
- attaches immune cells or antibodies to invading organism
- helps with phagocytosis by PMN/macrophages
inflammation
- induces acute inflammation to dilate blood vessels
- activates mast cells/basophils
- recruits inflammatory phagocytic cells to eat invading organisms
lysis
- generates a group of proteins to form membrane attack complex
- penetrate invading cell’s wall to induce lysis
complement timing in immune response
- one of the earliest immune responses
alternate complement pathway
- C3 -> C3b
- C3b -> C3bBb (C3 convertase) converts for C3 to C3b
- C3bBb3b (C5 convertase) converts C5 to C5b
- C5b interacts with C6-C9 to form membrane attack complex
lectin pathway
- C1-like complex converts C4 to C4b
- C4b interacts with C2b from classical pathway to form C4b2b (C3 convertase)
- Converts C3 to C3b
- forms C4b2b3b (C5 convertase) converts C5 to C5b
- C5b interacts with C6-C9 to form membrane attack complex
classical pathway
- C1 present
- converts C2 to C2b
- C2b interacts with C4b from lectin pathway to form C4b2b (C3 convertase)
- Converts C3 to C3b
- forms C4b2b3b (C5 convertase) converts C5 to C5b
- C5b interacts with C6-C9 to form membrane attack complex
starting points of alternative pathway
what branch of immune system
- C3
- factor B, D
- properdin
- innate immune system
starting points of lectin pathway
what branch of immune system
- plasma-derived mannose-binding lectin
- MBL
- innate immune system
starting points of classical pathway
what branch of immune system
- C1qrs
- C2
- C4
- adaptive immune system
trigger start of alternative pathway
- complement components bind on microbial surfaces and cannot be turned off
- SPONTANEOUS
trigger start of lectin pathway
- MBP normally exists in circulation
- MBP binds to mannose on bacterial surface
- produces enzyme to cleave C4 into C4b and C2 into C2b
trigger start of classical pathway
- interaction of Fc portion of antibody
- IgM
- IgG1, IgG2, IgG3
- c reactive protein with C1q
GM makes CLASSIC Cars
why can complement components not be turned off by microbes?
- their regulatory proteins only exist on host cells, not microbial surfaces
common goal of all three pathways
- make C3b
- deposit C3b on clusters on the target
which acts as an opsonin?
How does it act as an opsonin?
- C3b
- C3b recognized by complement receptor type 1 on phagocyte
- microbes phagocytosed
which are the anaphylaxotoxins
- C3a, C4a, C5a
think A causes Anaphylaxis
which are the chemoattractants?
- C3a, C5a
what do the anaphylatoxins do?
- increases vascular permeability to enhance movement of leukocytes and plasma proteins into tissues
do you chemoattractants do?
- attract neutrophils and monocytes for destruction of pathogen
how does the membrane attack complex kill cells?
- creates perforations in cellular membranes
- induces osmotic lysis of cells
what is the membrane attack complex effective against?
- microbes with thin cell walls (gram negatives)
- Neisseria species
decay accelerating factor (DAF) function
- down regulates C3 convertase
- displaces Bb from C3b
DAF deficiency
- also known as CD55 deficiency
- uncontrolled complement activation that leads to RBC lysis
- leads to paroxysmal nocturnal hemoglobinuria
C1 inhibitor
- protease inhibitor
- down regulates C1r and C1s activation in classical pathway
- prevents complement activation on self cells
C1 esterase inhibitor deficiency
- uncontrolled C1 activation
- leads to excessive vasoactive peptides being generated
- leads to hereditary angioedma
why C1 inhibitor deficiency can lead to hereditary angioedema
- unrelated activation of kallikrein to bradykinin
role of bradykinin
- vasodilation and increases vascular permeability
- ergo edema
what characterizes C1 esterase inhibitor deficiency
- low C4 levels
- high bradykinin
C3 deficiency
- risk of encapsulated bacterial infection
- recurrent pyogenic infections
C5b-C9 deficiencies
- increased susceptibility to Neisseria infections
- severe pyogenesis and sepsis in infants
C1, C2, C4 deficiency
- associated with immune complex disorders
- especially SLE
