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The immune system provides an important mechanism by which the body is able to defend itself against potential pathogens. The immune system is composed of two integrated systems, the innate immune system which provides rapid recognition and elimination of potential pathogens and the adaptive immune system, which has developed and evolved in order to protect the body against a broader range of infectious agents (Bonilla and Oettgen 2010). There has been a vast amount of literature produced into how the immune system brings about an immune response and it is now thought of as being divided into innate and adaptive immunity. The following essay will give a summary of how the innate and adaptive immune systems work but also as to why they are thought of as two distinct branches of immunity and also to question whether they are actually as different as it is suggested?
The innate immune system is an evolutionary defence mechanism which serves as protection against a diverse threat of pathogens and microbes (Shanker 2010). It includes the anatomical and physiological barriers such as lactic and fatty acids present on the surface of the skin providing a low pH, however this essay will concentrate on the mechanisms in place for a penetrating pathogen (Turvey and Broide 2010). The two main phagocytic cells involved are polymorphonuclear neutrophills and mononuclear macrophages (Beutler 2004). An activated macrophage has three ways in which it may respond to a pathogen: it may engulf a pathogen and then use lysosomal enzymes to destroy it, it may remove a pathogen from interstitial fluid by binding to it and finally it may destroy the pathogen by releasing toxic necrosis factors such as nitric oxide or hydrogen peroxide (Martini and Nath 2009). Neutrophills function as patrolling cells present in the blood stream looking for any foreign material to initiate an immune response, they contain granules which contain peroxidise, alkaline and acid phosphatases which are used digest and phagocytose invading microbes (Lydyard, Whelan and Fanger 2004). Eosinphils and basophils are less abundant than neutrophils and are able to target proteins which have been coated with antibodies (Martini et al Nath 2009).The third main cell type of the innate system is the natural killer (NK) cell used for immunological surveillance and the destruction of abnormal virus infected cells (Martini and Nath 2009); they recognise the MHC class I which is usually down regulated in virus infected cells and hence activates killer activation receptors to initiate natural cell killing of the infected cell; on the other hand if the NK cell binds to an uninfected cell the killer inhibitory receptors recognise the leader peptides presented by the MHC class I and this provides a negative signal to the NK cell preventing it from killing the healthy self cell (Lydyard, Whelan and Fanger 2004). Macrophages and neutrophils are involved in the first mechanism of innate immunity which is phagocytosis, receptors on the plasma membrane of the phagocyte bind to the surface of the pathogen, a vesicle is then formed which contains the bound target and is then digested via the fusion of the vesicle with lysosomes or peroximsomes (Martini and Nath 2009). The second mechanism that the innate immune system adopts in order to ensure efficient elimination of invading microbes is opsonisation which is the process of making a microbe easier to phagocytose using the complement system (Lydyard, Whelan and Fanger 2004). The complement system is made up of 20 soluble glycoproteinââ‚¬â„¢s which react sequentially with each other to form a cascade of molecular events resulting in the active fragment C3 (Lydyard, Whelan and Fanger 2004). These complement proteins binding to the surface of pathogens attract neutophils and macrophages to the area, macrophage membranes contain receptors which recognise and bind to the complement proteins and also to any bound antibodies, these antibodies involved are called opsonins and so this results in opsonisation and the pathogens are more easily engulfed (Berg et.al 2007). Activated complement proteins also promote the release of histamine from by basophils and mast cells which stimulates inflammation, which is the process by which the body deals with the invasion of a microbe or physical insult (Martini and Nath 2009).
Figure 1:this image taken by an electron micrograph shows pores in a membrane which has been attached by a Tc cell, taken and adapted from Berg et al (2007)
Here you can see how the membrane has been interrupted
Figure 2: showing how antigens have many antigen determination sites taken and adapted from Martini and Nath 2007
Complementary bindingIn contrast to the innate immune system the cells of the adaptive immune system involve T and B lymphocytes (Bonilla and Oettgen 2010 ). Each T cell produced goes through a selection process, T cells which recognise and bind strongly to self antigens and MHC are killed off by phagocytic macrophages in order to prevent a self immune reaction (Lydyard, Whelan and Fanger 2004). Once the selection process is complete the T cells complete maturation into either T helper (Th) cells or T cytotoxic (Tc) cells in the lymphoid tissue (Lydyard, Whelan and Fanger 2004). Tc cells attack antigens directly both chemically and physically by releasing perforin which destroys the plasma membrane, shown by figure one, secreting toxic lymphotoxin which kills the target cell and finally Tc cells have the ability to activate genes in the target cells nucleus which signal for the target cell to die (Martini and Nath 2009). B cells are activated by Th helper cells so they are able to proliferate and develop into plasma cells which secrete and produce large quantities of antibodies specific to a complementary antigen (Bonilla and Oettgen 2010). The antibody does not bind to the entire surface of the antigen it binds to specific regions which are termed antigenic determinant sites, shown by figure two, once this binding is complete this results in an antigen-antibody complex which leads to several pathogen destruction and elimination mechanisms: Firstly the attraction of eosinophils, neutrophils and macrophages which are able to phagocytose the pathogen, on binding of the antibody to the antigen the antibody molecule changes shape which opens up areas for complement protein binding, shown by figure three, which leads to opsonisation, stimulation of basophils and mast cells which promotes inflammation and finally antibodies may bind to specific sites on viruses and bacterial toxins which were the sites used to attach to the host and so this results in neutralisation (Martini and Nath 2009). http://www.ncbi.nlm.nih.gov/bookshelf/picrender.fcgi?book=stryer&part=A4729&blobname=ch33f31.jpg
Becomes available once the antigen is bound.
Figure 3: shows the light and heavy chain of the antibody structure also shows the antigen and complementary protein binding sites taken and adapted from Martini and Nath 2009.
It has become apparent that the innate and adaptive immune responses are thought of as two distinct processes primarily because as seen previously the two systems use very different cells and mechanisms to eliminate potential pathogens, Figure four gives an overview into the differences between the two systems. Despite this the main comparison that you have to start with when looking at why innate and adaptive are thought of as two separate components of immunity is the fact that we are born with innate immunity it is a evolutionary ancient defence mechanism that exists from birth (Berg et al 2007). Adaptive immunity on the other hand is acquired and adapted through exposure to specific antigens, it has evolved as a consequence of the broad variability of antigenic receptors and the many types of mutations that pathogens can undergo in order to avoid detection from the host (Bonilla and Oettgen 2010).
Figure 4: an overview into the differences between adaptive and innate immunology taken and adapted from Turvey and Broide 2010The two systems also have very different recognition and activation mechanisms. The innate immune system relies on a limited number of receptors known as pathogen associated molecular patterns (PAMPS) which are expressed on the surface of a large variety of microbes such as LPS found in gram negative bacteria ( Berg et al 2007). These PAMPs are recognised by pathogen recognition receptors such as toll like receptors (TLRs). TLRââ‚¬â„¢s are dimeric proteins, they all share the same cytoplasmic signalling domain however they differ in their extracellular regions with each region binding to a specific pathogenic component for example TLR5 binds to the bacterial flagellum component and TLR4 binds bacterial lipolysccaride (Mellman 2010). The TLR binds to the PAMP signalling which activates pathways in the nucleus such as the NFkB complex which initiates phagocytosis (Mellman 2010).
Figure 5: shows how APC cells such as dendrites engulf pathogen proteins and fragment them so that they can be presented on the cell surface, taken from Martini and Nath 2009.In comparison the T cells of the adaptive immune system recognise and bind to pathogens via the major histocompatability complex. Tc cells express a CD8 protein on their surface which recognises the class I MHC peptide complex and the Th cells express a CD4 protein on their surface which recognises the MHC class II as peptide antigens from particular pathogens are presented in the MHC class (Berg et.al 2007). The B cells, on the other hand recognise pathogens by specific complementary antigen-antibody binding (Underwood and Cross 2009).
Figure 4: shows how the cell beaks down pathogen proteins into small peptide fragments which are expressed=d on the surface of the cell by the MHC, taken from Martini, Nath 2007.When thinking about innate and adaptive as two distinct systems of immunology it is very evident that one of the main differences between the two is specificity. The innate immune system is not specific to one particular pathogen it has pattern recognition receptors for a vast number of similar pathogens. The adaptive immune system however is extremely specific due to the fact that the host produces specific antibodies complementary to a specific antigen. Antibodies are specific due to variability in the tips of the light and heavy chains, slight differences in the amino acid sequence here alters the shape of the antibody binding site and hence giving it its specificity ( Martini and Nath 2007). This suggests that the adaptive immune system acts as a compensation for inabilities of the innate system.
Figure 5: shows how a second immune response is much more powerful and quicker, taken from Underwood, Cross (2009)One of the main prominent features of adaptive immunity is the fact that it has ability to become more efficient on subsequent exposure to a particular pathogen via adaptive memory, whereas innate immunity does not share this same ability (Kurtz. J 2004) . An activated B cell divides several times to produce daughter cells which leads to the formation of memory B cells, these cells remain in the blood for a period of time after the first exposure to a pathogen so that if a second exposure is encountered they have the ability to rapidly divide and differentiate to secrete large quantities of antibodies to give a quicker a more efficient second immune response (Martini and Nath 2009), shown by figure five . Despite this however new research from Shanker. A 2010 reported that new experiments completed in mice has shown that NK cells that bear the virus specific Ly49H receptors stay around in the lymphoid and non lymphoid tissue for several months following infection from cytomegalovirus and so it could be said that maybe adaptive and innate immunity are not as different as it is thought with regards to memory. http://www.studentconsult.com/common/showimage.cfm?mediaISBN=9780443068881&FigFile=F9780443068881-009-f014.jpg&size=fullsize
It is clear to see why the innate and adaptive immune systems are often considered separately but it is important to remember that they both make up one defence mechanism, they both make up our immune system and therefore they must overlap and interact in order to produce an efficient immune response. In particular dendritic cells play a vital role in linking the two systems together they are able to recognise microbial antigens using innate receptors which then leads to initiation of the adaptive immune response caused by the dendritic cells presenting peptide antigens on the MHC, shown by figure six, to the T helper cells with CD4 protein on their surface, this enables the T cell to recognise the antigen and initiate an immune response (Lydyard, Whelan and Fanger 2004). Chemokines of the innate immune system are also responsible for initiating an adaptive immune response; when a TLR becomes activated via the recognition of a PAMP many inflammatory mediators and chemokines are released from resident tissue macrophages and dendritic cells which activates T and B cells to initiate the adaptive immune response (Luster. A 2010). Moreover in the majority of the MHC class II antigens are found on macrophages and so it concludes that the phagocyte responsible for the innate immune system is necessary to present antigens to initiate a T cell adaptive immune response (Beutler 2004). Shanker. A 2010 concluded that CD8 T cells secrete a large amount of humoral factors which promotes the activation and recruitment of macrophages in adipose
Figure 6: shows how APC cell beaks down pathogen proteins into small peptide fragments which are then expressed on the surface of the cell by the MHC, taken from Martini, Nath 2007.tissue from an obesity model of chronic inflammation, this suggests that adaptive immunity is also required to initiate an innate immune response, showing that they are both dependant on each other.
It is clear to see the reasons as to why immunity has been divided into innate and adaptive as they both have individual purposes; the innate system is the natural evolutionary immunity which serves as a general defense mechanism to a vast variety of microbes whereas adaptive immunity has evolved through receptor gene alterations in order to specifically recognize and protect against the ever expanding pool of pathogens. Despite this both systems rely heavily on each other for the compensation, activation and regulation of immunity which hence relies on an intricate balance between the two (Shanker 2010). It is also interesting and must be noted that new research from Shanker. A 2010 suggests that the innate and adaptive immune systems may not be as different in many aspects such as immunological memory as it is presently thought and I predict that time and research will delve deeper into this theory.