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The Major Pathways of Complement Activation

The complement system is a set of serum proteins that cooperates with the innate and adaptive immune systems to eliminate pathogens from the blood and tissues. It has three main pathways of activation - classical, lectin, and alternative. The pathways converge at the formation of the C5 convertase, which initiates the membrane attack complex. The complement system functions to opsonize pathogens for phagocytosis, elicit inflammatory responses, signal other immune components, clear immune complexes, and directly kill via membrane attack complexes. Dysregulation or deficiencies in complement proteins can have pathological consequences, and pathogens have evolved strategies to evade the complement system.

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Asish Geiorge
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104 views

The Major Pathways of Complement Activation

The complement system is a set of serum proteins that cooperates with the innate and adaptive immune systems to eliminate pathogens from the blood and tissues. It has three main pathways of activation - classical, lectin, and alternative. The pathways converge at the formation of the C5 convertase, which initiates the membrane attack complex. The complement system functions to opsonize pathogens for phagocytosis, elicit inflammatory responses, signal other immune components, clear immune complexes, and directly kill via membrane attack complexes. Dysregulation or deficiencies in complement proteins can have pathological consequences, and pathogens have evolved strategies to evade the complement system.

Uploaded by

Asish Geiorge
Copyright
© © All Rights Reserved
Available Formats
Download as ODT, PDF, TXT or read online on Scribd
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COMPLEMENT SYSTEM

The Major Pathways of Complement Activation

• The classical pathway is initiated by antibody binding


• The lectin pathway is initiated when soluble proteins recognize
microbial antigens
• The alternative pathway is initiated in three distinct ways
• The three complement pathways converge at the formation of the C5
convertase
• C5 initiates the generation of the MAC

Introduction to CS

-A set of serum proteins


-cooperates with both the IIS and the AIS to eliminate blood/tissue
pathogens
-components (proteins) interact with one other through cascades, just like
the blood-clotting system

functions
-opsonize/receptor-mediated phagocytosis
-elicit inflammatory responses
-signal/interface with AIS components
-clear immune complexes
-eliminate apoptotic cells
-directly kill via forming MACs

biological importance of the system


-pathological consequences of mutations in the genes encoding
complement proteins
-broad range of strategies that pathogens have developed to evade CS
-development of CS early in development and evolution

research and history


-activity of the serum, that completes/complements the action of the
antibody

Components of CS
-the activity of CS is the result of complex interactions between >30
glycoproteins
-Synthesized by liver/monocytes(blood)/macrophages, fibroblasts
(tissue)/epithelial cells (of GIT, Genitourinary tracts)
-15% of globulin protein fraction
-3mg/dl
-distributed among blood and cell membranes
-CS components can be categorized into 7 functional categories:
1. Initiator proteins-when activated, initiates the various complement
cascades. Activated through conformational change, which occurs
when they bind to certain membrane ligands.
Example: C1q complex, MBL, ficolins
2. Enzymatic mediators-proteases, which activate other members of
the catalyic cascade through cleavage. They themselves are
activated by other proteases or through binding-induced
conformational change-induced activation.
Example: C3 convertase, C5 convertase, C1r, C1s, MASP2, factor B
3. Opsonins- bind to microbial surface and enhance phagocytosis, serve
as binding tags for phagocytic cells bearing receptors for the opsonins
Example: C3b, C4b (often the larger component from enzymatic
cleavage, except C2a)
4. Complement receptors – are found on immune cells, like
neutrophils. They bind complement proteins/fragments, and signal a
specific cell function like phagocytosis or degranulation etc..
Example: CR1(receptor) binds C3b on pathogen surface and signals
phagocytosis of the C3b-bound pathogen, C5aR(receptor on
neutrophil) binds C5a causing its degranulation.
5. Membrane attack proteins – they
6. Inflammatory mediators
7. Regulatory proteins

Activation pathways of CS
Functions of CS
Regulation of complement activity
Deficiencies of CS
Microbial complement evasion strategies
Evolutionary origins of CS

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