L4 Complement Flashcards
Complement is a biochemical pathway that is a key part of the innate/adaptive immune system and assists with the innate/adaptive immune system
innate; adaptive
complement enhances/eliminates the inflammatory response, enhances/eliminates pathogens and enhances/eliminates the immune response
enhances, eliminates, enhances
three steps of complement
- opsonization
- inflammation
- lysis
opsonization
acts like a glue to attach substances or antibodies to pathogens to phagocytosis by macrophages (poly-mononuclear neutrophils)
inflammation
induces acute inflammation to dilate blood vessels by activating mast cells/basophils and to recruit inflammatory phagocytic cells to eat the invading organism
lysis
generates a group of proteins able to penetrate the invading organisms cell wall and induce lysis
the order of activation for complement pathways
- alternating
- lectin
- classical
alternating pathway
uses C3, activated spontaneously or via microbial surfaces
c3 –> c3a + c3b (c3b binds to pathogen and can help in opsonization or be converted to C3 convertase), or form C5 convertase whiich can help form membrane attack complex
C3 is present in the circulation system and is produced by the
liver
lectin pathway
activated via microbial surfaces
ex. mannose
mannose binding protein binds to mannose present on bacteria surface, C2 –> C2a + C2B and C4 –> C4a + C4b, C4b and C2b combine to form C3 convertase whcih helps convert C3 to C3b and C3a, C3b will eventually help form C5 convertase which can lead to MAC
classical pathway
activated via antibody attachment and Fc portion, C1
C2 –> C2a + C2B and C4 –> C4a + C4b, C4b and C2b combine to form C3 convertase which helps convert C3 to C3b and C3a, C3b will eventually help form C5 convertase which can lead to MAC
lectins activate the _____ pathway
lectin
the common goal of the three pathways is to deposit clusters of _________ on a target
C3b
anaphylatoxins
increase vascular permeability
C3a, C4a, and C5a
chemoattractants
attract neutrophils and monocytes
C3a C5a
membrane attack complex (MAC)
final phase of complement- C5b-9
lysis
creates perforations in cellular membranes
C3b functions as an
opsonin
microbes coated in C3b are ________ by virtue of C3b being recognized by complement receptor type I (CR1)
phagocytosed
____________ helps to down-regulate the C3 convertase
decay accelerating factor (DAF)
people with lack of DAF
- uncontrolled complement
- leads to RBC lysis
RBC lysis
paroxysmal nocturnal hemoglobinuria (PNH)
C1 inhibitor
protease inhibitor that down regulated C1 activation in the classical pathway of complement
people who lack C1 inhibitor
uncontrolled C1 activation
excessive vasoactive peptides
can lead to angiodema
how does C1 inhibitors regulate angiodema?
C1 inhibits bradykinin pathway
assay for alternative pathway
AH50
assay for lectin pathway
MBL
assay for classical pathway
CH50
C3 deficiency
profound risk of encapsulated bacteria infection
C1, C2, C4 DEFICIENCY
associated with increased risk of immune complex disease example would be systemic lupus erythematosus (SLE)
C1 inhibitor deficiency
excess of vasoactive peptides (bradykinin)
C5b, C6, C7. C8, C9 deficiency
increased susceptibility to Neisseria and meningitidis infections due to not being able to form MAC
MAC can induce lysis only on cells that have thin cell walls such as
neisseria species
The Classical pathway of Complement is activated following antibody:antigen interaction with what component? C1q (and C1r-C1s) C3 convertase C5a C5b, C6, C7, C8, C9
C1q (and C1r-C1s)
T/F Complement activation typically occurs in the order of Alternative, Lectin, and Classical pathways, respectively.
T
t/f Complement components C6, C7, C8, and C9 comprise the anaphylatoxins.
false
T/F Complement component C5a is an opsonin because it coats/labels bacteria.
false
Invasive meningococcal (Neisseria meningitidis) disease and disseminated gonococcal (Neisseria gonorrheae) infections are the only conditions (i.e. no autoimmune diseases) known to be associated with complement deficiencies in: C3 C1q C8 C4 C1 inhibitor
C8
The highest rates of meningococcal disease are seen in infants, who have little natural antibody against Neisseria. Older teens and young adults have much higher rates of colonization (on mucous membranes), higher levels of antibody, but lower levels of disease. Which pathway of complement activation could involve this specific antibody?
classical
You are called to see a patient with severe disease due to meningococcemia in the ICU. He has purpura fulminans and sequelae of sepsis including multisystem organ disease including liver and kidney failure. The resident ordered a CH50 and the result is low. You are trying to decide if this is more likely an acquired or inherited terminal complement deficiency. Which of the following is FALSE:
- Testing for decreased levels of multiple complement components may help distinguish acquired from the inherited defect
- Testing total complement after recovery of this illness may help distinguish acquired from inherited defect
- Liver failure is a cause of low CH50
- Vasculitis is a cause of low CH50
- Obtaining an AH50 to test function of the alternate pathway may help to distinguish acquired from the inherited defect
- Obtaining an AH50 to test function of the alternate pathway may help to distinguish acquired from the inherited defect
The three main anatomic locations involved in attacks of hereditary angioedema are:
Lower extremities, genitalia, abdomen
Eyelids, upper extremity, upper airway
Upper extremity, neck, gastrointestinal tract
Lower extremities, gastrointestinal tract, skin
Skin, upper airway, gastrointestinal tract
Skin, upper airway, gastrointestinal tract
Pathogenesis of angioedema in hereditary angioedema is predominantly mediated by excess: Histamine C1 Inhibitor C3 Bradykinin Membrane Attack Complex
Bradykinin
In Hereditary C1 Inhibitor Deficiency, on would expect the following complement levels: Low C4, Low C1 Inh Low C4, High C1 Inh Normal C4, Low C1 Inh Normal C4, High C1 Inh High C4, High C1 Inh
Low C4, Low C1 Inh
hereditary angioedema
disease due to defect in C1 inhibitor
decreadsed levels of C4 and C2
autosomal dominant
plasma derived C1 inhibitor
neisseria meningitidis
gram negative cocci
produces polysaccharide capsule - major virulence factor
complement deficiencies in C8
