The Complement System Flashcards
What are the three pathways of complement activation?
Classical, alternative, lectin
What are the 3 functions of major complement components?
Release of inflammatory and chemotactic mediators
Opsonization of microbes
Direct killing of microbes
Classical pathway name?
Antigen-antibody complex
Alternative pathway name?
Bacterial endotoxin
Lectin pathway name?
Mannose-binding lectin
When does the complement system occur?
Early on
What cells are leukocytes?
Macrophages, granulocytes, NK cells, dendritic cells
Locations of proteins in CS?
circulate in serum, cell surfaces (as receptors), neutrophil granules
What type of role does the complement system play in the adaptive system?
regulatory role
Functions of complement system in innate defense system (3)?
Protection against infections
Regulation of inflammation
Removal of damaged cells
What cells produce the proteins of the complement system?
Hepatocytes, monocytes, macrophages, epithelial cells in GI tract
Describe how the biochemical cascade principle works.
Proteins are synthesized as inactive precursors in health
They are ACTIVATED by cleavage by another complement protein immediately upstream to it
Results in active B protein that can continue to activate other proteins via subsequent cleavage
Nomenclature of inactive complement. Example?
simple number
C1
Cleavage product nomenclature? Example?
lower case letter suffix
C3b
Biochemical cascade is an extremely efficient process of __________.
amplification
letters of the alphabet alone in CS are?
Factors
How is the complement system activated? (2 ways)
pathogen itself or antibody bound to pathogen
Final goal of complement system? 3 methods?
Removal of the pathogen
Phagocytosis by macrophages and neutrophils
Direct killing
Facilitates inflammatory responses that help to fight the pathogen
Describe 3 steps of CS activation?
- Classical, alternative, lectin pathways
- Generation of C3 convertase
- Generation of terminal membrane attack complex and other complement fragments which all facilitate removal of the pathogen
What is the classical pathway activated by?
antibody bound to the pathogen
REQUIRES ADAPTIVE
What is the alternative pathway activated by?
directly to pathogen surface
What is the lectin pathway activated by?
lectin binds to mannose on pathogen cell wall
Sequence of the classical pathway?
C1 C4 C2 C3 C5-C9
Write out the sequence of the classical pathway?
Slide 22
Most common CS pathway?
Alternative
Alternative pathway components nomenclature?
Capital letters are called factors
Draw out alternative pathway.
Slide 25
What does mannan-binding lectin recognize?
carbohydrates on the surface of pathogens
Write out the lectin binding pathway?
Slide 27
All three pathways generate ONE key effector protein called?
C3 convertase
Review slide 33. Draw out mechanism.
What is the first consequence of CS?
Chemotaxis of leukocytes via C3a and C5a
Function of C3a?
a potent anaphyatoxin: causes contraction of smooth muscles. increases vascular permeability, causes degranulation of mast cells and basophils
Function of C5a?
Stimulates neutrophil chemotaxis, adhesion, activation, and degranulation
Causes release of prostaglandins and leukotrienes
Consequence 2 of CS?
Opsonization and phagocytosis via C3b
What is consequence 3 of CS?
lysis of pathogens via C5-C9
Draw out pathway of consequence 2?
Slides 37 and 38
CD55 function?
accelerates degradation of complement factors on red blood cells, leukocytes, platelets, and endothelial cells to protect them from complement attack
Draw out pathway of consequence 3.
Slide 41
What does the CS need to be regulated?
potent system
C1 inactivator function?
inhibits activated C1 components in the classical pathway
Factor H function?
similar function than CD55 in alternative pathway
CD59 function?
inhibits assembly of the MAC
Complement receptors function?
ensure removal of antigen antibody complement complexes
Describe the impact of C3 deficiency in Brittany Spaniels.
Renders the WHOLE complement system dysfunctional
SO
-reduced killing of bacteria by MAC
-reduced phagocytosis of bacteria
-deficiencies in acute inflammatory reactions with lower recruitment of leukocytes
-reduced ability to make antibodies
Brittany Spaniels have an increased susceptibility to ___________.
bacterial infections
Dogs less than 2 years developed serious _____________. Treatment?
Bacterial infections; antibiotics
Brittany Spaniels with C3 deficiency at 4-7 years?
renal disease and ultimately renal failure
Inflammation of glomerulus (glomerulonephritis)
Factor H deficiency observed in what species?
Yorkshire pigs
Recall function of Factor H?
regulates the alternative pathway
Deficiency of factor H results in?
Uncontrolled, overactive complement activation on healthy cells
Constant inflammatory state and autoimmune diseases
Renal failure (overabundance of C3 in kidney)
Three pathways are activated by? (List)
Results in formation of?
Alternative- pathogen
Classical- antibody bound to pathogen
Lectin- mannose on pathogen surface
ALL C3 convertase
Consequences (3) are triggered by and final outcome?
Recruitment of inflammatory cells
C3a, C5a
Destruction of pathogen by inflammatory cells
Opsonization of pathogen
C3b
Phagocytosis of pathogen
Formation of membrane attack complex on pathogen surface
C5-C9
Lysis of the pathogen
