Uploaded March 2019 | Updated September 2026, 3 weeks ago

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This video is part 3 of Innate immunity - Complement System (Humoral factors)

Content:
0:00 Introduction
1:50 Classical Pathway
5:42 Alternative Pathway
7:23 Mannose Binding Lectin Pathway
13:07 What Does the a's Do?
14:39 QUIZ

All information in my immunology videos are from:
- Book: Immunology, Eighth Edition by David Male, Jonathan Brostoff, David Roth and Ivan Roitt
- Additional research in PubMed
- University lecture materials

Mechanisms of complement system:
- Membrane Attack Complex
- Chemotaxis
- Opsonization
- Anaphylatoxins

Classical Pathway:
Antibody required (adaptive immune system)

Step 1: C1q binds
Step 2: C1r activates C1s
Step 3: C1s cleaves C4, C2
Step 4: C4b and C2b works as C3 convertase
Step 5: C3 convertase cleaves C3. Binds to surface as opsonin or binds to c3 convertase and works as C5 convertase
Step 6: Membrane attack complex forms on gram negative bacteria.

Alternative Pathway:
Step 1: C3 undergoes spontanous cleavage in bloodstream. C3b bineds to surface of bacteria
Step 2: Factor B binds
Step 3: Protease (Factor D) cleaves Factor B into Bb
Step 4: Properdin (Factor P) stabilizes the binding and form C3 convertase
Step 5: Same steps as before from here

Mannose Binding Lectin Pathway:
Step 1: Active Macrophage release Interleukin 1, interleukin 6 and tumor necrotic factor alpha and work as Endogenic Pyrogens
Step 2: Cytokines go to Hypothalamus and release Prostaglandins E2 (PGE2) which causes fever
Step 3: IL-6 goes to liver and release acute phase proteins (C-reactive protein (CRP) and Mannose Binding Lectin (MBL))

C Reactive Protein (CRP) functions:
Works as Opsonins and activate the classical pathway of the complement system

Mannose Binding Lectin (MBL) pathway:
Starts 1-2 days after infection:

Step 1: MBL will bind to Mannose (monosacharide) on capsules and surface of fungi
Step 2: Mannan binding lectin serine protease 1 (MASP-1) binds MBL and act as and enzyme.
Step 3: same pathways as before
!!!!Note!!! No MAC is formed on Capsules

C4a, C5a and C3a works as:
Anaphylatoxins: Increase permeability of capillaries and activate mast cells
Chemotaxis: directs phagocytes to the area.

Complement system can remove complex from the blood stream