The complement system is a component of normal plasma. It aids the process of opsonisation which is the targeting of bacteria by phagocytes in essence ‘complementing’ antibodies. [Charles A Janeway, 2001]. While primarily seen as being immune-privileged, it has recently been proven that the CNS plays a role in the system due to sustained brain inflammation becoming a factor in many neurodegenerative diseases. While it is known the complement system has a beneficial effect by eliminating aggravated and toxic proteins, insufficient or excess activation of the system may have a detrimental effect due to the activation of microglia, secretion and production of harmful products. [Marco Bonifati, Uday Kishore, 2006]
There are 3 main pathways by…show more content… They occur in 3 forms, ramified, amoeboid and activated. Ramified microglia are the most inactive, they are large structures which have little movement, cannot act as antigen presenters and also cannot engulf pathogens. They are present so that when an infection occurs it can be dealt with quickly. [Aloisi,2001]. Amoeboid microglia are smaller molecules which travel through the CNS looking for pathogens and damaged neurons, they are also able to phagocytose certain molecules. The final type of microglia are active, these cause neuroinflammation by releasing pro-inflammatory factors. Microglia are always searching for toxic agents and damaged tissues in the brain and spinal cord, which make up the CNS. Most infectious agents are not a threat to the CNS due to the blood brain barrier. However, if pathogens are introduced directly to the CNS or manage to travel through the lack of antibodies in the CNS could be disastrous. For this reason active microglia must be able to recognise and swallow pathogens. They also need to act as antigen-presenting cells to activate T cells. Due to the urgency when toxins enter the CNS, microglia are extremely sensitive and react to small pathological changes aggressively. This is achieved by the use of sensitive potassium channels detecting small changes in extracellular potassium. [Dissing-Olesen L,…show more content… AD can cause neuronal loss, extracellular deposition of amyloid plaques and neuronal tangles. The main cause of AD is thought to be excess deposits of amyloid plaques. [Marco Bonifati, Uday Kishore, 2006]. The amyloid plaques are constituted by extracellular deposition of aggregated amyloid peptide Aβ, a cleavage product of neuronal amyloid precursor protein (APP), [Zhang Z et al, 2000] cleavage produces Aβ1-40 and Aβ1-42 the latter being the more aggregated and neurotoxic. Deposits of Aβ may be the most obvious cause of AD as they are clearly seen in scans and post-mortem examinations however it is evident that sustained brain inflammation is a characteristic of an AD brain. This strengthens the link between brain pathogens which cause an inflammatory response when released and amyloid plaques which are present in an AD brain. Subjects presenting a higher number of NFTs and amyloid plaque deposits but still displaying no signs of AD have been seen to have less neuroinflammation suggesting that it is necessary for the symptoms of AD to progress leading to degradation of neurons and eventually dementia. [Lue et al,1996] Processes such as complement activation [Emmerling et al., 2000], glial cell activation [Meda et al., 2001], acute phase protein synthesis [Abraham, 2001], chemokine expression [Xia et al., 1998] and major histocompatibility complex (MHC) antigen
