Immune responses coagulation

The first aspect of biocompatibility is a natural immune response. When a foreign object enters the blood stream, it can be attacked by the body s defense system. The first step is protein adsorption on an object surface. It is believed that the amount and type of protein adsorption is one of the most important steps determining whether the object is tolerated or rejected by the body. The next step is cell adhesion, which may cause aggregation and activation of platelets and triggering of the blood coagulation system with resulting thrombus formation. It may not only lead to sensor failure via surface blocking but directly threatens the patient s health. 

Proteolytic enzymes (proteases) are involved in a wide variety of physiological processes including digestion, fertilization, coagulation, and the immune response. Outside of their normal environment, proteases can be extremely destructive and natural human plasma inhibitors inhibit most proteases that escape. Imbalance in protease-protease inhibitor systems can lead to a number of diseases of which pulmonary emphysema is one well-characterized example. This disease results when the protease elastase attacks elas-tin, the major elastic protein in the lung. Considerable effort has been devoted to the synthesis of inhibitors of proteolytic enzymes such as elastase for possible therapeutic use. In the future, specific and selective synthetic protease inhibitors should be useful for treating specific diseases that range from the common cold to chronic disorders such as emphysema. 

A series of proteins collectively called the complement participate in the immune response to the entry of foreign cellular or viral material into the organism. This group of proteins consists of about 20 entities, some of which are enzymes. Complement was first associated with the lysis of foreign red blood cells in the nineteenth century it also participates in the lysis of bacterial cells. The complement activation cascade, very similar to the blood coagulation cascade, involves the stepwise activation, via proteolysis, of various components of the complement system until a final protein complex, the membrane attack unit (also called the C5b-9 complex), is generated. It then punches holes in the membrane to which it is bound. 

Figure 31.1 Potential immune-responses following administration of a viral vector. DIC disseminated intravascular coagulation SIRS systemic inflammatory response syndrome. Image courtesy of Sarah Taplin.

Several vital processes rely on clan PA peptidases. Chief among them are blood coagulation and the immune response, which involve cascades of sequential zymogen activation. In both systems, the chymotrypsin-fold peptidase domain is combined with one more associated protein domains, including apple, CUB, EGF, fibronectin, kringle, sushi, and von Willebrand factor domains. These protein domains are on the N-terminus as an extension of the propeptide segment of the peptidase. Such a trend of N-terminal-associated domains in the SIA peptidase family is common across all forms of life. The domain architecture pairs well with the zymogen activation mechanism, which liberates the proper N-terminus to enable catalytic activity. Often, the associated protein domains remain attached to... 

Proteins also serve as chemical signals in the body. At the level of organ systems, proteins regulate immune responses, cell growth cycles, hormone responses, and many other functions. Blood proteins are involved in coagulation and dissolution of blood clots. Several hormones are short proteins, or polypeptides. Many polypep-... 

Blood-contacting materials have to fulfill particular requirements, as they are immediately exposed to all host defense mechanisms of the body. Thus, the contact of blood with foreign surfaces induces several cascade reactions and activation phenomena. These complex and highly interconnected reactions potentially create clinically significant side effects in the application of medical devices (e.g., cardiovascular implants, extracorporeal circulation, catheters) and interfere with the success of the medical treatments [64]. In certain cases, even the formation of thromboemboli or systemic inflammatory reactions were reported to occur as a consequence of the activation of coagulation enzymes and thrombocytes and/or the activation of the complement system and leukocytes (immune response) at the biointerfaces of the applied materials [65]. 

Opal SM, Esmon CT. Bench-to-bedside review Functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsis. Crit Care 2003 7 23-38. 

In the thrombosis study, the test article is implanted into the vasculature of an animal. After a given period of time the implanted vessel is removed and the test article is observed for clot formations. The other four tests are carried out in test- tubes, with evaluations of specific actions to assess whether or not the test article has an effect on the blood s ability to clot or coagulate, can regulate an immune response, or can damage the cellular components of the blood. 

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