UST Teg parasites to ey cece ourselves re Sete vn and regi exploit this remarkable ability by using controlled doses of living worms to treat autoimmune and allergic disorders. Dar eaten eg ean Ege TT Myst hhe guts of around 1400 million people — about a quarter of the world’s popula infected with at least one species of worm, Although infections with gut-< clling worms Th diarchoea and tiredness, and children infected with worms are stunted in their growth and tend 0 do less well at school than uninfected children, Tob survive in their host long enough to reproduce. They are extraordinarily good at this and have developed sophisticated lifestyles that enable them to survive for years. They thrive in the potentially hostile er ronment of the gut. Gut worms have developed remarkable ability to modify our immune response, Which prevents it from damaging them, ‘worldwide are trying to understand how parasites alter the immune response. We are now beginning to exploit this ability by trolled infectio and inflammatory bowel immune response is out of control successful as parasites, gut worms ne tists sto fight human diseases such as asthma ec, where 1 Kathryn Else and Marcus Svensson Coloured scanning elect hookworm, Infestations of in humans are common Noch Aiea ad India. Human it trating the skin, usually by burrowing ito the fet ofa person, and entering the Bloodstream. The larvae then migrate throughout the body, particularly tothe smal intestine. 280 Infection of the host ‘The first thing its host. People become infected with number of a parasitic worm has to do is to infect fays. A common infection route through the stomach and hatch in the worms moult and grow to their adult stages, Adult ms can be from several centimen centimetres long, depending on the species, Other gi ms have free-living larval stages, which are able to burrow through the skin, They then migrate through the body before arriving in the gut. BIOLOGICAL SCIENCES REWENcognition by the host of the worm ction inthe gut, worms feed and grow. They secrete enctee substances that are ‘foreign’ to the host — pe are called antigens. The host is able to recognise se antigens through cells that form part of the te immune system, which in tum alerts the host Phe fact that Ie is infected (see Biovocical SCIENCES nsw, Vol. 18, No. 1 pp. 2-6). One of the key cell inthe early recognition of a gut worm infection fhe dendritic cell, which is able to capture antigens ough specialised receptors on its cell surface that ognise foreign molecular patterns. Sceniss have 0 recently shown that dendritic cells can send exten- fons betwen the epithelial cells ining the gut to check infections in the gut himen, evelopment of an ‘appropriate’ immune sponse endritic cells that have captured parasite antigens fre now activate. They move in lymph vessels from five gut to the lymph nodes, which are local 10 the ste fo infection. Dendritic eel als break up the parasite antigen into small rogments and within the lymph ode show these antigens ina form that other cells of Lumen Den cell 9g Intestinal mytosa ‘ oe » 6h Blood circulation Figure 1 Gonaation of an adaptive immune response towards ut worms. Dendritic cells phagocytoe (1) worm antigens and lranspoct 2 them to the acal hmph nodes, Her, the antigen is aresented (3) ta Tells that become activated (8). Activated T Calls migrate via the blood (5) tothe gut tissue (6), where they can promate anti-parasit immune respnses (7) NovemaER 2008 the adaptive immune system recognise (see B10106: Teal Scrences Review, Vol. 19, No. 4, pp. 14-17, 34-37) Another important cell type of the adaptive immune system responds to the antigen carried by the dendritic cell. This is a specialised lymphocyte called a CD4+ T helper cell. The CD4+ T helper cell i like the conductor of an orchestra in that it is able to control ‘or ‘help’ other cell types to respond to the infection. It does this by making small, soluble proteins called cytokines, which act as messengers between cells. This message helps both other cells of the adaptive immune system such as CD8+ T cells and B cells, and cell types of the innate immune system. One of the most important recent scientific discov: cries in immunology was made in the 1980s when scientists realised that CD4+ T helper cells can develop into different types of CD4+ T cell. They can become 4+ T helper I cells (Th1), CD4+ T helper 2 cells (Tha), or CD4+ T regulatory cells (Treg). Whether C4+ T cells develop into Thi, Th2 or Treg cells is determined by the conditions around them in the Iymph node when the dendritic cell presents antigen to the CD4+ T cell, Thl cells control she sorts of cells that are good at fighting intracellular single-celled parasites and viruses, Th2 cells contro] the armies of cells that are good at lighting extracellular parasites such as the big multi-cellular worms. Treg cells regulate both Th and Th2 responses, This regulation Is important to keep them under control so that they don't over-respond and in doing so cause damage to the host. In order to eliminate gut worms the host needs to make @ Th2 response, This is the ‘appropriate’ type of helper T cell response to eliminate an extracellular parasite, Activated Th2 cells leave the lymph node and migrate via the blood circulation back to the gut. It is there that they Tocally control innate cells types that are able to eliminate the parasite (see Figure 1) by creating {an environment in the gut that is hostile to survival. Worms versus host immune response ‘This is not a one-sided battle and the gut worms need. to survive, They have developed ways of living in harmony with their hosts. One of these is to make parasite molecules that stimulate the development of the host’s own Treg cells by, as yet. an unknown ‘mechanism This results in the potentially anti-parasitic ‘Th2 response being weakened by parasite-induced Treg cells, so that the response is no longer strong enough to eliminate the worm infection. In effect the parasite {s ensuring its own survival in its host by manipulating the host’s immune system. This in part is why gut parasites are able to live in the human gut for several Are worms good for us? Scientists are now beginning to exploit the ability of gut worms to promote the development of Teg cel Diseases where our immune system gets out of control and attacks our own body (autoimmune diseases) 35Figure 2 A worm infecting gut issue. Tissue section showing a whipworm embedded in the gut tissue ofits host. This isthe type of worm being used to treat ntlammatry bowel Aisease, The large ed goblet cells the gu tssue are thought be part ofthe mechanism involved in elimingting the worm infection, Scale bar represents 100 ym, 36 and allergic diseases where our immune system over- responds to an obnoxious substance are becoming more and more common in the developed world where gut worm infections are rare. In contrast, autoimmune and allergic diseases remain uncommon in underdeveloped ‘countries where gut worm infections exist. Scientists do not fully understand the correlation between these observations. They think that because parasitic worms TERIVIS expiainea Adaptive immune system The part of the immune system that develops a long-term response to infec tion. Celis of the adaptive imimune system can recog: rise and remember experience of a particular type of infection. Ths isthe part of the immune system used ta create immunity to diseases by vaccination and includes T cells and 8 cells ‘Antigen Substances that are not produced by the body. They are said ta be ‘foreign’ to the bady, Antigens can be presented by specialised antigen- presenting cel io Tand B cells, which then become. activated Host An organism that harbours another organism (for example a parasite) either in it or on it, usually providing both a place to live and food. Inflammation The local response to an injury, charec- {etised by tedness and swelling, It involves dilation of blood vessels and the movernent cf immune cells out of the blood and into the damaged tissue, Innate immune system The partof the immune system that provides en immediate defence against infection This defence is not long-lasting and does net prevent subsequent infections, The innate immune system includes cells such as goblet cells and macrophages, ‘and physical barriers such as the skin and mucus, are uncommon in the developed world we have lost a balanced immune system, due to the absence of worm= induced Treg cells. Using worms to protect ourselves Rather than trying to find ways of eliminating gut parasites from infected people, some scientists are now trying to give gut worms to people that do not have parasite infections but who suffer instead from diseases such as inflammatory bowel disease and asthma, If our bbody’s immune system attacks the lining of our gut, the result is inflammation and bleeding (see Broto The presence of wormsappears to alleviate the symptoms fof autoimmune diseases and asthma by promoting regulated immune responses. Will the presence of worms interfere with the success of vaccination programmes in developing counties? Is eradication of gut worms essential for future successful vaccination programmes against cisceses such as HIV and tuberculosis? Is there any danger associated with giving a worm jnfection to try to regulate inflammatory responses that have got out of hand? What are the desired characteristics of a parasitic ‘worm chosen to treat inflammatory diseases of man? Kathryn Else is 2 Professor in immunology at the Univer sily of Manchester. Her research focuses on understanding anisms of immunity to intestinal parasitic ‘ons. Dr Marcus Svensson is @ postdoctoral rese sociate at the University of Manchester, with an interest in the mechanisms that regulate call migration rom the am into infected tissues, Student Unit Guides will focus your revision, build your confidence and strengthen your exam technique. Each guide: anes the aims of the AS or A2 qualification a strategies to improve revision » provides an examiner the key content and identifying opportunities to | the skils required by the unit 1 presents graded answers to questions typical of with comments on the rengths ani response, giving you an insight into the mind of You can see the ful ist of biology unit guides, sample pages of sele at wwwphilipallan.co.uk. To contact our Cust Services Department. telephone 01235 827720, rovenceR 2009 overview of the unit, summarsi weaknesses of each suides and order online KEY points CD44 T cells exist as several different subsets including T helper 1, T helper 2, and T regulatory cells T helper 2 calls control the sorts of immune responses that are able to eliminate big extra cellular gut worms. T helper 1 cells contral the types of immune responses that are able to eliminate intracellular single-celled parasites, T regulatory cells regulate Th and Th2 responses, sa they do not get out of control Gut worms have developed ways to stop the T helper 2 cells from eliminating them. One of these mechanisms i to promate the davelonment of Treg calls. in he absence of gut warms in the developed world, exaggerated Thl and Th2 responses accur. This is. leacing to an increase in asthma and autoimmune diseases. althaugh the immunological mechanisms behind this increase are complex, one of the likely causes is reduced regulation of immune responses. Scientists are exploring the use of gut parasites as a treatment for asthma and autoimmune diseases by explating their ability to induce Treg cells, nd offers cextibit ‘the unit the examiner ener erg eats Poy