The Role Of Coagulation In Immune System

With the advent of multicellular life came an increased necessity to guard against pathogen invasion, resulting in the fast evolution of the said immune system.

Blood serine proteases diverged from complement-like proteases to form the coagulation system, which evolved from such an early innate immune system. Bleeding is the most serious threat to survival following a wound, followed by the possibility of infection. Thus, activating inflammation in hemostasis is likely beneficial.

Horseshoe crabs, for example, use a combination clotting and immune system in which coagulation plugs wounds and entraps germs. Although there are linkages between clotting and immunity in animals, they are indirect and take longer to manifest.

Coagulation occurs instantly, with the intrinsic or extrinsic route starting a protease cascade that leads to fast thrombin activity, fibrin deposition, and platelet activation, ultimately leading to hemostasis. Innate immunity is slower and often necessitates the detection of pathogen-associated molecules to activate apical cytokines such as interleukin-1 (IL-1) to guide inflammation and eventually acquired immunity.

Inflammation causes tissue factors to be released, which promotes coagulation, whereas thrombin causes inflammation by cleaving proteolytic enzyme receptors (PARs). These slower kinetics may allow bacteria to grow within a wound, for example. As a result, a more direct and faster relationship between hemostasis and immunity in animals would boost host fitness.

Coagulation Activation

Higher creatures’ blood coagulation and immune systems are assumed to share a common ancestor. All through infections, the blood coagulation process is triggered, and hemostatic system components are directly involved in immune reaction and immune system modulation. The current consensus is that activating coagulation is advantageous for bacterial and viral infections. It inhibits infection spread and promotes pathogen death and tissue restoration. 

Overactivation, on the other hand, can result in thrombosis, depletion of hemostatic substances, and secondary bleeding. This review will outline current information on blood clotting and pathogen infection, with an emphasis on the most recent research on the involvement of various components of a blood-clotting system for select bacteria infections.

Inherited immunity

The host immune system to injured human hosts and invading pathogens, like the coagulation system, is quick and local, minimising harm and facilitating recovery.

This is performed by rapidly identifying potentially harmful substances and simultaneously mobilising cell, structural, and chemical processes for efficient inactivation, breakdown, and/or removal.

Inflammation and hemostasis

If triggered during an infection, hemostasis and inflammation can control each other in a concerted action. The effectiveness of eradicating the invading virus is hugely reliant on the amplitude of the host’s coagulative and inflammatory reactions. Under non-infectious situations, both systems are generally down-regulated. However, as soon as they detect an invading pathogen, they could become activated and begin immune responses and wound healing processes. 

The amplitude of these reactions must be in a physiologically appropriate range to ensure successful pathogen clearance. Under some situations, host regulatory systems might fail, resulting in systemic activation of coagulation and inflammatory cascades that can progress to severe proportions. These problems, which are associated with substantial morbidity and death, are nearly hard to cure.

Coagulation’s effects on complement activation and regulation

• The function of the complement cascade in coagulation, immunity, and ‘immune thrombosis’ is becoming more recognised, with a growing body of research investigating the relationships between coagulation and complement activation.
• Thrombin, plasmin, damaged endothelium, DNA, and neutrophil elastase are just a few of the thrombosis-related putative complement activators that have been examined. 
• Peter Ward, who discovered in 1967 that the plasmin-split component of C3 showed strong chemotactic potential on polymorphonuclear (PMN) cells, hinted at the link between plasmin and complement.

Conclusion

In higher species, evolution resulted in the segregation of these processes.

Furthermore, as a result of this divergence, thrombocytes and plasmatic coagulation subsystems emerged. These findings explain why, even in evolved creatures like vertebrates, there is some crossover between immunity and hemostasis. Several clinical occurrences relating to coagulation and resistance can be addressed by this overlap and are compatible with the notion of coagulation and the immune system coevolution.