Question

Briefly describe the crosstalk of complement with other immune systems. How does this affect your understanding of the body as a whole unit, rather than a collection of separate systems?

Answer 1

Crosstalk with other immune system:-

1. Tool like receptors
2. T cell immunity
3. B cell immunity
4. Regulation of Treg cell
5. Blood clotting system
6. Kinin system

Interaction between TLR (Tool Like Receptor) and complement-

• Shapes Innate responce, antagonistic and synergistic
• Synergistic: TNF, IL- 1B, IL-6 in vitro through C3aR and specialy C5aR signaling.
• In the apparant absence of c5a genetic ablation of C5aR inhibits TLR-2 induced cytokine production in DCs suggesting that C5aR has has a C5a independent effect on TLR signaling.
• C3aR, ....C5aR, mice failed to produce T cell immunity
• Underlying mechanism not clear
• c5aR in TLR modulatory receptor
• Prophomonas gingivalis (TLR-2 ) impares NO2 dependent killing in macrophage (c5aR-TLR-1 Crosstalk)
• CR3 facilitates TLR-2, TLR4 induced signaling

B cell immunity:-

• Complement issential in B cell immunity
• C1q and CR as well as CD21/CD35 essential for elimination of self reactive B cell
• CR2 mediates antigen independent signal- survival of B cell in germinal center
• CR2+CR19+CR81 has strong costimulatory effect on B cell
• B cell can act as source of C5
• Memory B cell can produce C5 suggesting that B cell may serve as a local source of C5 in secondary lymphoid tissue.
• Complemet plays acessory role in induction of immune system
• Formation of memory B cell also complemnt dependent process

T cell immunity-

• CR1, CR2 essential for production of antibody and T cell responce
• Blocking CR1 CR2 - inpaired Ab, intact T cell responce
• CR1 CR2 deficient mice- intact T Cell responce but pathogen specific T cell responce was absent
• CD46 promotes formation of T reg cell
• Complement and T cell responce depend on environment
• In asthama early senstization phase C5aR signaling protect lung
• In inflamatory phase c5ar signaling Th2 responce

Complement and coagulation-

• Complement activates coagulation vice versa
• Coagulation ➡️ factor XII➡️ cleaves C1➡️ activates classical pathway
• C5a induces tissue factor, PA-1 & inhibits fibrinolysis
• MASP2 favours formation of thrombin which cleaves C5
• Certain pathogen counteracts procoagulatory mechanism.
• C3a in pitutarygland
• C3a, C3aR involved in neural crest formation in early embryogenesis
• Remodeling of syneptic connection

The above mentioned description clears that most of body immune system is covered by crosstalk of complement with other immune system,

It is working as a whole unit covering remodeling of bones, coagulation, B and T cell immunity, favours liquid metabolism and TLR induced immunity and signaling.