Sunday, October 27, 2019

Antigen Presenting Cell (APC): Structure and Function

Antigen Presenting Cell (APC): Structure and Function There are many complex mechanisms employed by the immune system to destroy invading organisms, abnormal cells and contain infections in order to maintain health and life. Antigen presenting cells (APC) are some of the cells that form part of these mechanisms. This essay will look at what APCs are, the different types with examples and their specific roles in the immune response. APCs are cells that take up antigens and present them to lymphocytes during an immune response (Sherwood et al, 2009). The components of APCs that actually do the presenting are Major Histocompatibility complexes (MHCs): Class I and Class II MHC molecules (Sompayrac, 2003). These two complexes provide two different pathways of antigen presentation that stimulates different population of T cells to eliminate the invading pathogen concerned. All nucleated cells of the body express MHC class I molecules and are therefore referred to as non-professional APCs (Kropshofer et al, 2005). MHC class I molecules are like billboards that display on the surface of the cell, peptides of processed endogenous proteins (Sompayrac, 2003).The endogenous proteins could be those encoded by viruses or parasites that have infected the cell. The main focus of MHC class I APCs is on events within the cell. Typically in a viral infection, the virus enters the cell and uses the cells own biosynthetic machinery to produce proteins encoded by viral genes (Wagner et al, 2004). Viral proteins are broken down into peptides by enzymes within the cell (proteasomes) (DeFranco et al, 2007). Following this, the peptides are carried into the endoplasmic reticulum by a TAP transporter (Sompayrac, 2003). After which MHC class I molecules within the cell are loaded with these peptides along with a sample of other normal proteins being made by the cell. This M HC-peptide complex is then transported to the cell surface for presentation. The protein fragments are displayed on MHC class I molecules to cytotoxic T cells (Tc) (Schindler, 1991). Having this mechanism in place allows all body cells to be monitored by CD8+ve Tc cells which inspect the cells. Tc cells detect foreign peptides bound to an MHC so if a cell has been invaded by a virus or parasite, the Tc cells are alerted and respond by destroying the abnormal cell thus preventing the spread of viruses throughout the body (DeFranco et al, 2007). MHC class II molecules are designed to present peptides to helper T cells (Th). Unlike the MHC class I molecules, MHC class II molecules are restricted to certain cell types termed professional APCs. Their focus is on events unfolding in the outside environment so can present samples of antigens derived from exogenous antigens in various parts of the body. Professional APCs display class I and class II MHCs as well as co-stimulatory signals (Sompayrac, 2003). In order to function, T cells, both Tc and Th cells, require activation. For this to happen, T cells need to recognise its cognate antibody in an MHC complex and they also need a co-stimulatory signal which can only be provided by professional APCs (Wellness.com, 2010). Co-stimulation is provided by a protein (B7) on APCs which interlocks with another protein (CD28) on the surface of T cells. Examples of professional APCs are activated macrophages, activated dendritic cells (DC) and activated B cells. DCs are the most important of the APCs as it capable of initiating an immune response by activating naà ¯ve T cells (Sompayrac, 2003). These cells are strategically located in areas of the body such as the skin, mucosal lining of lung and digestive tract where microbes are likely to enter (Sherwood et al, 2009). In normal tissues DCs are immature, expressing few B7 protein and MHC molecules on their surfaces so are poor antigen presenters. However, when a microbe(s) invade the tissue which DCs reside, they mature. DC are specialised as they have pattern recognition receptors on their surface which recognises common features of invading microbes such as LPS on the surface of gram negative bacteria. DCs takes up pathogens through receptor mediated endocytosis and degrade it in a lysosome (DeFranco et al, 2007). During a invasion, cytokines (TNF ÃŽ ±) released by activated mac rophages are recognised by the DC which informs it that innate immune system is under attack. Cytokines bind to receptors on the DC causing it to cease phagocytosis, leave the tissues (site of infection) and migrate through the lymphatic system. Whilst travelling, the DC equips the class II MHC reserves with the antigen and also produces B7 co-stimulatory protein. During this time also, DC upregulates the expression of class I MHC molecules as a precautionary measure that if the DC was infected by a virus or parasite at the site of infection, the antigen could be processed into protein fragments for presentation if necessary (Male, 2004). By the time the DC reaches the lymph node, it has its co-stimulatory molecules and the MHC class II- peptide complex(es) primed and ready to activate naà ¯ve T cells. Lymph nodes have compartments that have bountiful supplies of B and T cells (Schindler, 1991). Whilst at the lymph node, DCs trigger the adaptive immune response by presenting antigens to CD4+ve Th cells with matching receptors (Sherwood, 2009). After which, the APC secrete interleukin, a chemical which activate Th cells. Activated Th cells then secretes cytokines which stimulates the Th into rapid proliferation and differentiation into effector Th cells and memory Th cells (DeFranco et al, 2007). Memory Th cells are useful in future infections by the same pathogen whilst effector Th cells activate B cells to secrete antibodies enhancing other immune activities (Sherwood, 2009). Additionally effector Th cells and antibody molecules depart from the lymph node and enter the circulation which they then leave at the infection site. Antibodies opsonise the bacteria enhancing their uptakes by phagocytes, stimulate Natural killer cells (NK) to directly lyse the bacteria and also activate th e lethal compliment system (Sherwood, 2009). CD4 +ve T-cell on the other hand activate macrophages to become more cytotoxic. It is important that the magnitude of the immune response be in proportion to the seriousness of the attack (Sompayrac, 2003). As previously mentioned DCs migrate to lymph nodes only when activated by battle cytokines. In a serious infection, many cytokines are released and thus more DCs are activated. Before their migration to lymph nodes, activated DCs release chemokines, a chemical which triggers precursor cells (monocytes) to leave the blood stream and become their replacement as DCs in (Sompayrac, 2003). These new DCs are then able to be activated and make their way to the lymph node which amplifies the response to the invasion. The new recruits of DCs are like photojournalists, the antigenic peptide which they carry to the lymph node being a snapshot of the infection site (Sompayrac, 2003). This is useful so if there are changes in the area, the appropriate T cell can be activated and thus elicit the immune response most suitable. If the infection is mild, there will be fewer c ytokines produced, less DCs activated, fewer chemokines released, fewer replacements of DCs therefore the number of DCs that make their way to the lymph node will also be significantly less. Consequently the number of B and T cells that becomes activated in the lymph nodes relies greatly on the number of DCs present. As detailed above DCs play a role in the activation of macrophages. Macrophages are one of the early defences against invaders that initiate the cell mediated immune response (Schindler, 1991). Macrophages are very weak at presenting antigens as they only possess enough MHC molecules and co-stimulatory proteins when activated by battle cytokines e.g. IFN ÃŽ ³ (DeFranco et al, 2007). Macrophages function in the re-stimulation of experienced T cells so they continue to partake in the fight against the pathogen (Male, 2004). They engulf pathogens that have invaded the tissues, process it using internal enzymes and present the peptides on MHC class II molecules. This continual display of antigens is recognised by Th cells which continue to complete their function. Next the activated macrophage releases cytokines are previously mention that act on the DC i.e. TNF ÃŽ ±. Other cytokines released includes IL-1 and IL-8. IL-1 aids in the activation of B and T cells (Schindler, 1991). B cells are the third professional APC. At the start of an infection B cells are naà ¯ve so do not play a definitive role. However throughout the course of the infection B cells become activated. Some B-cells are specific to T-independent antigen so only require binding of its receptor (BCR) to a cognate antigen for activation (Sherwood 2009). Other B-cells are specific to T-dependent antigen so after processing the antigen and displaying it on MHC class II molecules, binding of a Th cell is required for their activation. The MHC class II complex interacts with the TCR on the CD4+ Th cell which recognise the specific antigen on the B cell. Next the helpers release a chemical known as interleukin triggering the activation of the B cell. Activated B cells go through rapid proliferation and differentiation into memory cells and antibody producing plasma cells (Sherwood, 2009). B cells have the advantage of presenting the antigen very quickly so makes the immune response more efficient. The development of two different pathways of antigen presentation i.e. via MHC class I and II molecules can be rationalised in that each ultimately helps to elicit the most appropriate immune response through stimulation of the T cell the population most effective in eliminating the pathogen in question. MHC class I APCs allows for the monitoring of all body cells through Tc cells whilst MHC class II APCs seek the help of Th cells and B cells which directs the immune response in a way that corresponds to the seriousness an infection. Through these functions, APCs ultimately helps to maintain health and life. Should Teens Be Allowed Internet Access? Should Teens Be Allowed Internet Access? The internet is a large market with practically everything available in it. It is a massive network of computers worldwide connected by cables and satellites. Most of the time, it is just referred to as The Net or the World Wide Web (www). The internet today is used for multiple tasks such as receiving email, communicating with people from all around the world, receive text, images, video and sound. It is a very helpful tool for getting any information needed. This is because it has people from all around the globe posting information onto the internet for the use of everybody who access the internet which is a public accessible feather for millions of people nationwide. (Young Media Australia 2008, What is the internet?) However, the internet nowadays is too widely used by tweens and is becoming an issue among our society. This is caused by different factors that may be dangerous to them. This study is to investigate whether it is advisable for tweens to be allowed internet access. We may wonder who exactly are tweens? To be exact, they are individuals who are no longer children anymore yet not a teenager. This means they would fall in the age group of between 11 13 years old. People are doubtful about giving them internet access because they may not be mature enough to differentiate what is good or bad and this may cause them to be susceptible to internet danger. Internet danger is generally caused by people who are not taught with moral ethics and try to inflict damage onto tweens. Advantages of the internet for tweens Offers a wide spectrum of information The internet is a virtual treasure chest full of valuable information. It has a huge amount of publications added everyday and is slowly evolving as one of the greatest source of information. Any form of information from A to Z can nowadays be so easily obtained just by a few clicks on the computer and tons of information show on the screen. Also, with the help of search engines on the internet, the work of hunting for information or data is minimized. Since the internet provides so much of information, it is a great source of reference for students who does research work or even just to look for information which cannot be obtained in school. Through the internet, forums can be accessed and through forums, people are able to trade information and share opinions with each other. (The Advantages Disadvantages Of The Internet n.d.) Communication with the world There are plenty of chat rooms that can be used on the internet such as Live Messenger, Yahoo Messenger, Skype and so on. These chat rooms allow worldwide communication to be possible. As long as computers are connected to the internet, anybody from any part of the world can communicate online. It is very convenient for family members who are apart to communicate with each other instantaneously without the need of using email or snail mail. (The Advantages Disadvantages Of The Internet n.d.) Saves times in completing tasks Before internet existed, there were many tasks that took a lot of time to complete. Now with the help of internet in the modern society, the time used to complete these tasks is reduced by an uncanny amount. One example would be students using the internet to communicate with teachers online. Students who are slacking in studies may have extra classes with teachers through communication programs. This greatly reduces students time needed to revise on their own and yet not fully comprehend the subject. Also, assignments done can be sent to teachers via the computer with the use of email. Educational games programs Games nowadays intrigue tweens and play a big role in their lives. Computer games are constantly being played by tweens from all around the world and the internet has a huge load of these games. Specifically, educational games are the games that have positive effect on tweens. These games can provide practice in problem solving and logic and also provide practice in use of fine motor and spatial skills. Furthermore, some of the educational games require two players or more so this allows parents to occasionally play together with the child and have some family bonding. These games being fun activities help to relieve stress and help keep the mind fresh. (Effects Of Video Game Playing On Children 2009) Risks disadvantages tweens might face However good the internet might appear to be and have many advantages upon tweens, the ugly side of internet should also be reviewed carefully to actually determine whether the internet is more harmful than helpful to tweens. Access to inappropriate content or information The internet being the treasure chest to all information, it also contains negative contents such as pornography and violence. Tweens who accidentally access to pornography may see images that would scar them for life and may potentially cause problems in their future life as these images may surface without warning. It is always internet pornography that is the first exposure to tweens of these sexual images and the images they see causes their brain to play mind tricks on them. This causes human intimacy to be planted into them as something twisted and perverted and this implantation is irreversible. Ultimately, this may lead to sexual deviancy and crime, which in turn affects their future relationships and marriages. (Children as Victims n.d.) Violence also can make a huge impact on tweens. Tweens who are exposed to violence would generally be more hot-tempered and are very likely to have antisocial behavior such as threatening aggression and assault. This is because they are brainwashed into the world of violence and cannot distinguish between fantasy and reality. They may think that violence is the only way to settle problems and that being violent shows charisma and looks macho-like. (Children And Media Violence 2009) Chance to come across internet predators An internet predator is usually an adult who exploits vulnerable children or tweens for sexual or abusive purposes, or also known as paedophiles. These people try to do these out of the norm things to satisfy their personal fetish. They would try to use the internet as a way of getting in contact with tweens and try to coax them to meet up. At this point, these tweens who are not under adult supervision may not be mature enough to think that this is potential danger and would simply just agree to meeting with this anonymous person. This would allow tweens to be vulnerable to these internet predators to carry out their dirty activities. In some reported cases, these paedophiles have raped and killed innocent children. (What are the risks involved with my child using the internet n.d.) Become victims of cyber bullying Cyber bullying is quite common nowadays in the virtual world. What exactly does cyber bullying mean? It basically is any form of harassment that occurs via the internet. Posting fake videos on web sites, leaving mean and evil emails towards somebody are forms of cyber bullying. Tweens who are cyber bullied would feel very depressed and overwhelmed as they do not know who these people are who cyber bully them. These helpless victims would usually suffer quietly and be mentally imbalanced because they usually dont tell an adult about this issue and just keep it to themselves. (What is Cyberbullying? n.d.) Be subjected to invasion of privacy, unsolicited advertising financial risks There are plenty of commercial websites on the internet that may invade privacy by requesting for personal information. Tweens may be encouraged to complete questionnaires and enter competitions that lead to the divulgence of personal information or incur unforeseen costs. Also, some sites have advertisements that encourage tweens to acquire products which are costly and unnecessary for them. (What are the risks involved with my child using the internet n.d.) Addiction to the internet It is very easy for tweens to get addicted to the internet because it is so interactive. With all the contents available on the internet, tweens would opt to sit in front of a computer all day and this would cause them not to have time to finish assignments or work and decrease the time for socializing with people in person. This usually also causes tweens to be less healthy as they would lack the exercise needed for their body. (What are the risks involved with my child using the internet n.d.) Conclusion To look at the whole argument in an unbiased way, a comparison has to be made between the advantages and disadvantages of the internet. It may appear that it is not advisable for tweens to be allowed internet access because of all the negative effects it may cause. However, from a survey carried out, majority of the people agree that tweens should be given internet access and that the advantages outweigh the disadvantages of the internet. These negative effects are avoidable and it basically comes down to the way tweens use the internet and how much they understand about the internet. These problems may be avoided if they are guided along the way by an adult because an adult is able to differentiate whats good and whats not on the internet and teach tweens how to avoid these sites on the internet. Most of the tweens who suffer from internet disadvantages are those who are ignorant and are not taught well on how to utilize internet as a powerful tool. (1615 words)

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