Mechanisms Clearing Incompatible Red Cells - Coursework Example

Mechanisms clearing Incompatible Red Cells Introduction Blood is an integral component of the human body that is responsible for the circulation of oxygen and food particles through the body. However, blood is composed of red blood cells, white blood cells, plasma, and platelets. The immune system of human body plays a significant role in patrolling the circulation while taking note of any different red cells. If the immune system does not work well, human beings would be at a risk of contracting an infectious disease. Blood transfusion may let in incompatible red cells which would then be cleared from blood circulation to avoid further danger. I will start with an insight and origin of blood transfusion while giving a basis of clearance of incompatible Red Blood Cells. The essay focuses on the mechanisms by which the body clears incompatible red cells from the circulation. Red Blood Cells Clearance mechanism and History of Blood Transfusion Attempts of blood transfusion transitioned from 1492 when Pope Innocent VIII developed a comma. Three boys tried to give him blood orally. Unfortunately, none of them got out of it alive. In 1795, the first successful blood transfusion was documented. However, the essence of compatibility in the blood that an individual was given was vital because of the reactions thereof that would lead to haemorrhage, which at the end would result in death. Jean Henry came up with criteria in which matching the donor’s blood with recipient would avoid bleeding. However, the most successful blood transfusion in history took place in August 1825 carried out by James Blundell. The blood transfusion aimed at treating postpartum haemorrhage in a woman. It was surprising to note that James used blood drawn from the husband. Such a case further explained the importance of compatibility in blood transfusion. Emily Ponfick and Landois Leonard also investigated the issue of incompatibility between species’ blood cells. Such a research gave a criterion in which doctors would use during the civil war to avoid a case whereby blood cells of the donor and recipient are incompatible. In 1901, a scientist discovered ABO hence coming up with a conclusion that human blood cells are not the same. Initially, doctors could not differentiate between compatible blood cells and incompatible ones hence making blood transfusion process difficult. After such a discovery, physicians from all over the whole worked hard to discover other antigens that exist in the Red Blood Cells. For instance, a total of 200 blood group antigens were in existence. For a human body to get rid of the incompatible red cells after a transfusion, the immune system should be at its best. However, it is important to understand such a mechanism so as to give an in-depth rationale for a medical doctor when taking up particular role such as blood transfusion. There are two mechanisms for clearance of incompatible red blood cells that would be the basis for discussion. The two include; antibody-dependent RBC and age-dependent mechanism. Antibody-dependent Red Blood Cells clearance mechanism Initially, it had been noted that incompatible transfusion and autoimmune disease among other causes led to incompatibility in red blood cell, which would result in death. However, in the first category of antibody mechanism of clearance, there are two sub-categories which include extravascular haemolysis and complement cascade (intravascular haemolysis). In Complement system, there is involvement of proteolytic events, which lead to the formation of MAC (membrane attack complex). Such an event would then result in compromise of the osmotic homeostasis and the membrane belonging to the target. Three ways exist that may lead to triggering of complement mechanism. These include lectin pathway, classical pathway, and the alternative pathway. IgG3 and IgM can initiate the activation of the classical pathway. Such can be done to the lesser extent of IgG1 and IgG2. When antibodies bind on various blood groups, it will lead to activation of complement. Moreover, such cases include anti-Kell, anti-B or ant-A (usually), and finally anti-Kidd (which takes 50-70% of the available time). Classical pathway usually commences from the work of antibodies IgM and IgGs, which activate C1. Also, complement proteins play a significant role in binding of complement receptors (CR). After the binding process, the CR would then be ready to trigger various actions which include transport of erythrocyte, phagocytosis, and most importantly, antibody production. When C3 has activated, it would then bind to RBC’s surface, which is its major targets to eliminate from the circulation. C3 is usually very reactive hence preferable for the elimination of red cells. Nowadays, doctors have come up with other alternative methods that can be applied in complement removal such as the use of specific antibodies alongside complement components. Another mechanism in this category is the use of Fc receptors (extravascular haemolysis). In this mechanism, phagocytosis is the prime result hence the name extravascular. Fc receptors are present in both humans and mice. In both species, the CD 64 receptors are found in the microphages. CD 64 work hand in hand with microphages to eliminate unwanted RBC from the circulatory system. In human beings, microphages as a key player in RBC clearance is part and parcel of RES (reticuloendothelial system) RES is situated in the reticular connective tissue which is usually in the liver, spleen, lungs, or the bone marrow. RES is also known by its accurate nomenclature as MPS (mononuclear phagocytic system). However, spleen and liver have a hand in getting rid of red cells which are incompatible. Such red cells would have got its way through inappropriate and unchecked blood transfusion. Unwanted blood cells accumulate in the spleen as they awaited elimination from the circulation. The spleen is attributed to the elimination of aged antibodies from the circulation apart from RBCs, which are complement sensitized. The spleen also carries out blood filtration while avoiding the contact of RBC with the microphages. On the other hand, the liver plays a significant role in blood filtration and taking care anomalies in RBC. Kupffer cells are located in the liver, which is the largest grouping of microphages ever known to exist in the human body at one organ. Kupffer cells help a lot in RBC clearance hence making liver a suitable organ for clearance of incompatible red cells from the blood circulation system. After administering splenectomy, doctors found out that a lot of RBC accumulated in the spleen while the lesser amount was noted in the liver. Transfused Cr51-RBC was the primary target for the clearance mechanisms the two organs. Such RBC is incompatible hence need to eliminate from the blood circulation arises. Age-dependent Red Blood Cells clearance Mechanism In human beings, the life span of RBC is 115 to 120 days. In mouse, the lifespan is 50 to 60 days. However, when the RBC are aged and can no longer perform the desired activities of metabolism and circulation of oxygen, they are eliminated from the circulation. Red Blood Cells which are older may be connected to binding surface antibodies as compared to younger ones. The fact that RBC has no mitochondria explains the reason when they leave the bone marrow; there would be no grand synthesis of protein at all. RBC can quickly degrade because of the proteins that it harbours which are highly degradable. The resulting degradation would then lead to exposure of neoantigens, which would make it easier for antibodies in circulation to recognize and act on them. There are some of the notable elements which regulate the lifespan of RBC and homeostasis. They include aggregation, oxidation and Phosphorylation of proteins. The aging determinants of the Red Blood Cells include the clustering of Band 3 and protein 4.1. Furthermore, oxidative stress aids in clearing incompatible red cells from blood circulatory system. On the other hand, Vitamin E is important in preventing the oxidative damage of RBC. People with a lower count of Vitamin E would have high chances of damaging of Red Blood Cells and their elimination from the circulation. Also, animals showed the same instance of damaged RBC due to the deficiency of the first vitamin. Moreover, doctors have found out that animals lacking the vitamin showed an increase in the breakdown of Band 3 in the products they derived from the animals. Based on oxidative stress, it was evident that the more the amount of RBC damaged due to oxidation harboured lack of vitamin E as compared to the older population with the vitamin. Another important differentiating aspect of the Red Blood cells was that more aged RBC had a higher density as compared to younger RBCs. Contents of Hb which was derived from the body play a significant role in comprehending age-dependent clearance mechanism of RBCs. The process would then lead to smaller and more compatible Red Blood Cells in the body hence avoiding complications such as haemorrhage. Moreover, the entire process ensures that older stock of RBC containing Hb diminishes through loss of their membrane. Consequently, the Red Blood Cells lead to rigidity and more density. When there is the lesser rate of deformation of the RBC, then it indicates that the RBC are getting more mature. However, the resulting red blood cells have to devise a way of getting into the circulation after the above process. The process that involves the RBC squeezing their way back to the circulation is known as the splenic architecture. However, failure to reconnect back to the blood circulation, the aged red blood cells would then remain intact in the spleen. In most cases, the spleen acts as a store for the damaged RBCs while the liver plays that role though in lesser instances. The liver does that through the aid of the Kupffer cells, as seen earlier. The aging of RBC is significant mechanism which ensures that the incompatible and unwanted Red Blood Cells are no longer part of the blood circulation system, while giving way for new ones. Such a process is called membrane alterations of the Red Blood Cells, which would then lead to phosphatidylserine (PS) exposure. However, any cell that harbours high levels of phosphatidylserine would aid the phagocytic cells to recognize them hence making their elimination from the blood circulation comfortable. Also, the presence of receptors in microphages is an explanation of how RBCs are eliminated from the circulation. The receptors include Stabilin 2 and 1. However, Stored Red Blood Cells are prone to exhibit such characteristics hence a focus on them would give a better view of the elimination of incompatible Red Blood Cells from the body’s blood circulation. Moreover, eryptosis is another notable mechanism that aids in clearing of RBCs which have been singled out to be of less function from blood circulation system. The process involves the shrinkage of cells, membrane blebbing, exposure of phosphatidylserine and the activation of proteases. The process also takes into consideration the significant role of the microphages which finally eliminate the targeted damaged Red Blood Cells from the circulation. Conclusion Red Blood cells clearance it crucial to the functioning of the body. However, there are two mechanisms which include antibody-dependent RBC clearance mechanism and age-dependent mechanism. In the antibody-dependent mechanism, there are two subcategories, which include extravascular and intravascular haemolysis. In the second mechanism, oxidative stress plays a significant role in clearing RBC. Also, membrane alteration would lead to exposure of phosphotidylserine (PS) hence making it easier for phagocytic cells to recognize the incompatible cells. Consequently, the phagocytic cells would carry out the clearance of the unwanted cells. Having such understanding would be crucial in dealing with complications relating to incompatibility between donors and recipients in blood transfusion. In the past, it was difficult for doctors to carry out successful blood transfusion because of the difficulty of haemorrhage. More scholars in future should take up the roles of carrying out extensive researches to further understand the roles of microphages in Red Blood Cells’ clearance in human beings as well as in mice. Bibliography Connor J, Pak CC, Schroit AJ. Exposure of phosphatidylserine in the outer leaflet of human red blood cells. Relationship to cell density, cell age, and clearance by mononuclear cells. Journal of Biological Chemistry. 1994 Jan 28;269(4):2399-404. Khandelwal S, Van Rooijen N, Saxena RK. Reduced expression of CD47 during murine red blood cell (RBC) senescence and its role in RBC clearance from the circulation. Transfusion. 2007 Sep 1;47(9):1725-32. Lee SH, Looareesuwan S, Wattanagoon Y, Ho M, Wuthiekanun V, Vilaiwanna N, Weatherall DJ, White NJ. 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