Alternative pathway: Sometimes microorganisms or its toxins can
directly activate complement system, which is an innate and non-specific
reaction. Sooner microorganisms are coated by complement molecules leading to
its uptake by phagocytosis.
Once
the pathogen has crossed the physical barrier and enters the body, alternative
pathway interacts with the microorganism’s (non-specific immune response). Now let us
move into the details of these pathways.
Alternative pathway step wise
explanation
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| Alternative Pathway |
In Alternative pathway step wise
explanation, only initial steps( up to step 3) differ from classic pathway.
- Step 1: Activation of C3(H2O) and factorB (C3(H2O)+B complex) by binding of non-specific activators like endotoxins, bacterial cell wall fragments, viral envelopes or any antigenic fragments.
- Step 2: Factor D, a protease cleaves C3(H2O)+B complex to produce C3bBb
- Step 3: C3bBb complex is a C3 convertase,which generates more C3b.
- Step 4: C3b forms complex with C4b2b producing C5 convertase (C4b2b3b).
- Step 5: C5 convertase cleaves C5 to C5a and C5b. C5a is an anaphylatoxin and chemotactic factor (not involved in the down pathways).
- Step 6: C5b binds to C6 and C7 to form a complex initially then interacts with C8 and C9 to produce the “membrane attack complex (MAC)”(C5b6789). This membrane attack complex causes cell lysis.
How
body’s own cells are protected from membrane attack complex?
Human
cells have a glycoprotein situated on the cell surface called as decay
accelerating factor (DAF). DAF prevents the formation of membrane attack
complex by destabilizing C3 and C5 convertase.