Defence mechanisms during intestinal infection

A BURET. Defence mechanisms during intestinal infection. Can J Gastroenterol 1991;5(1):34-42. This review examines and compares host defence mechanisms during intestinal infection with th.rec types of organisms: a virus, a bacterium and a ncmato<le parasite (ic, transmissible gastroenteritis virus [TGEV], Helicobaccer jejtmi and Trichinella spiralis). Diarrhea is commonly associated with all of these infections. It appears that T spiralis initiates the most elaborate defence system of the three organisms, involving full range humoral and cellular immunity, as well as mucus hypersecretion, epithelial alterations, altered gut motility and parasite impairment (morphological and physiological). In contrast, intestinal defence against H jejuni and TGEV involves fewer components. The latter seems to initiate the most rudimentary host response. Despite such diff,.rences, these mechanisms exhibit many similarities, thus further illustrating the relalively limited repertoire of defence systems that the intest ine can mount. The mediators translating the insult of any intestinal pathogen into a common response deserve further investigation.

W II EN INFECTED WITll VIRAL, bacterial, protozo;;1l or helmm• th ic orga n isms, a host is confronted with a wide spectrum of morphological, bioch e mi cal an<l antigenic fealures.Despite the tremendous diversity of antigenic stimuli, the re arc nevertheless striking simila rities in host response mechanisms.This is in part due to the relatively limited repertoire of defence syste ms tha t the hosr can mount, despite its enormous complexity.By far, the most common parasitic diseases are those affecting the gastro intestinal syste m ( l ).This review descrihesand compares, when information is available, host d efe nce mechanisms agaimt gastrointestinal infections caused by viral, bacter ia l and ne malode organ isms, ie, transmissible gascroenteritis virus (TGEV) , Helicohacrer jejuni (formerly Campylobacter) an<l Trichinella s/>iralis, al l three common pathoge ns in sw ine (2).Viral gastroenteritis was recently identified as an intestinal disorder of major sig• n ificance in human s (3), hut the pathogenesis of such disturbances is not well understood.In contrast, more information b available on TGEV m swine ( 4).H jejuni is recogn ized as one of the most common causes of human diarrhea worldwide (5,6).This bacterium is also prese nt in wild birds, c hickens, swine, sh eep, cattle and other a nim a ls (2) a nJ , in view of the numerous reports of human infection acquired from both dogs and cats, there is little doubt regarding the zoonotic potential of this infection (7).Ir has been Jemonstrate<l rhat this invasive enreroparhogenic bacterium produces a cholera-li ke tox in whi c h activates aden ylate cyc lase ( 8), but rece nt evidence suggests thc1t enterotoxin does not play a major role in the pathogenesis of H jeju.ni infections in the United States (9).Finally, gastrointestinal n e matodiasis in domestic animals and humans is an infection of worldwide distribution and major econom ic significance.One of the most popular models for the study of this type of infection has been the gastro intestinal phase ofT s/Jiralis ( 10).
Diarrhea is commonly associated with all of the infections mentioned above.Obviously, the cleansing c1ction resulting fr o m this gastrointestina l flushing is an important host defence mechanism in these diseases, but to review the pathophysiology of diarrhea 1 s beyo nd the scope of the present review.
By focusing on t hree types of gastrointestinal infection ( ie, vira l, bac terial and parasitic), the aims of this review are: co describe immunological an d nonimmu nological mucosa!responses co acute intestinal infection; and to identify the similarities and differe nces in host defences during a variety of intestinal insults.
There is no doubt that the host immune system is involved in the protective respo nse against TGEV, H jeju.ni and T s/Jiralis.lt will be demonstrated further that the degree of this involvement varies from o ne type of infectio n co the other.For the sake of clarity, an<l although antibody-med iated and cellular immunity are inextricably linked, they will be addressed separately in this review.
TGEV Humoral immunity: In transmissible gastroente ritis, passive immunity can be transferred to piglets via ingestion of immune colostrum and milk containing high neutrali zing a ntibody ti tres (11,1 2).A ctive producti on of antibod ies to TGEV has a lso heen J ocumented (13) .Sows inoculateJ with TGEV have been shown to develop neutral izing ::mtihodies for t he virus in Defence mechanisms during intestinal Infection serum (lgM, lgG and lgA) , colostrum (primari ly lgG) and milk ( primarily lgA) (14,1 5).H o wever, the mechanisms of active immunity in transmissible gast roe nteritis re ma in poorly understood .A lthough young pigs that have recovered from transm iss ible gastroenteritis usually resist reinfection (16) , it is wel l documented that circu lat ing an tibo<lies provid e little protectio n aga inst subseq ue nt c ha llenge by the v irus (12,15,17).Thus, serum a ntibodies produced in th is infection do n ot appear to correlate with immunity to this disease.Furthermo re, while secre tory lgA in intestinal secretions may protect the mucosa from infection, anri-TGEV antibodies a re not always derectahle in gut contents from infected a nima ls (16).Interestingly, coron avirus e nteritis in dogs appears to initiate an immune response similar to that just described for T GEV in sw ine, and there is a n antigenic relationship be tween both viral agents (18).In a<ldition, the two orga nisms are serologically cross-reactive (14).Experiments involving inoculation of TGEV into dogs have failed to protect these dogs from canine coronavirus, and similarly, pigs could not be protected from TGEV with canine corornwirus (14,18).Cellular immunity: As me ntio n ed above, productio n of local and c irc ulating antibodies in pigs infected with TGEV do not satisfactorily expla in active immunity against this disease.In contrast, local cell-mediated immunity in the sma ll intestine appears to p lay a major ro le in active immunity to transmiss ible gastroenteritis.The presence of antigen-reactive cells in Peycr's patches during a ll stages of the infec tion demonstrated that Peyer's parches parti c ip ate di rectly in the immune response against this virus, rather than serving only as a site of differentiation for immunoblasts ( 19).The same study clearly showed the occurrence of cellmediated immunity in transmissihle gastroenteritis, and demonstrated that cytotoxic T cells we re involved mo re than B cells both in recovery from a primary infectio n and in protectio n of immune pigs ( 19).T he partic ipation of interferon as yet another line of local defence has also been questioned.It was demonstrated tha t t ra n smi ssi ble gastroenteritis leads tosign ific,mt interfero n productio n in the lumen and mucosa, but that it has no discern ible protective effect of its own (20).High inte rferon ac ti vi ti es ha ve been measured in lymphocyte and macrophage cultures where controlle<l o r inhibited vira l replication was observed (2 1 ).The: type of interferon was n ot Jefined in rhe~e reports.These findings suggest that while interfero n activity on its o wn docs no t protect the host from t ra nsmissible gastroente ritis, it may me<lia te a ntivi ra l cyrot ox ic iry.A similar defence mechanism has been recently descriheJ in bacterial infections ( 22) a nd toxoplasmosis (23 ).
During transmissible gastroenteritis, the lamina propria is infiltrated with mo no nuc lea r cells, neutrophi ls a nd eosinophils (24 ).However, the inflammation is discrete (24 ), and no striking cellular infiltrate other than the lymphocyte proli fera ti ve response has yet been associated with the infection ( 16).In vitro st u<lies ~h owed that macrophages have the ability to control the intrace llula r replication of TGEV without killing it (21 ).O ther authors re po rted that the virus co uld be recove red from the lu ngs of oronasall y infected pigs I 04 days post inoculation , and that t he v irus wa s capable of rep I icating in a lveolar macrop ha ges (2 5 ), thus suggesting that th is organism may be mainta ined ali ve in the lymphatic system for a n extended period.Epithelial alterations: Villous atrophy and fusion and/o r epitheli al sloughing are commo nly associated with transmissible gastroenteritis ( 15,26) as well as with H jeju.ni (27), T s/Jiralis (28,29) and other intestinal in fec ti ons.A decrease in surface area exposed to the pathogen results from these a ltera tions, and thus this mechanism can be conside re d a host Jefence mech a nism aga inst gastrointestinal Jisease.Pathogen impairment: A ny biochemical, morphological or other damage inc urred ro a virulent TGEV from its exposure to t he intestinal en vironment has ye t to he desc ribed.It was demonstrated, however, that lumi na l proteases a nd peptid.:ises g reat ly reduced infect ivity o f atte nu ated TGEV virus, whereas they diJ not inactivate a vi rul e nt virus (30).This rciterateJ the impo rtan t role of pancreatic and mucosa!secretions in imestinal protection.It a lso substantiated the notio n of differential susceptibility to small intestinal secretions as a correlate of virulence.

HJEJUNI
Humoral immunity: In contrast with transmissi ble gastroenteritis, infeCL ion with H jejuni results in <levclopmcnr of specific scrum lgG, lgM and lgA, which confer immunity to suhscqucnt challenge (31-33).People who have haJ multiple exposures to this bacterium exhibit persistently elevated anti-H jejuni lgG titres associated with little o r no illness (34 ).High titres of anti-H jejuni intestinal lgA reported in rabbits orogastrically inocula ted with the o rganism suggestcJ that mucosa I lgA a lso plays a n important role in a ntihelicobacter immunity (31).In another study, an age-related increase in antihelicobactcr scrum lgA titres was noted a mong childre n living in endemic areas, and this appeared to be the best indicato1 of anti -h c li co bac t e r immunity (35,36).In addition, individu a ls with do c umented l gA immunodeficiencies have frequ ently be e n rep o rt e d to have diffi c ulty recovering fro m H jejuni enteritis (37 ).All of these findings strongly suggest that scrum lgG and lgA, and intestinal lgA are the m ajor antibody co mponents of defence against this m icroorganism.Cellular immunity: Huma n studies (38), as we ll as a nimal mod e ls (2 7 ,32,39), have demonstrated that tissue inflammation in H jejuni infections is characterized by infiltrat ion of the mucosa with ncutrophils.The inflammatory infiltrate a lso revea led increased numbers of mononuclear cells, eosinophils, plasma cells anJ undefined lymphocy tes (32 ,38,39).Diffuse infiltration of the lamina propria with mature plasma cells and undefined lymphocytes has been de monstrated in H jejuni infec tions (32).Another study showed that the major antibody-secreting cell detected in patients suffering from acute H jejuni diarrhea were IgA-producing cells, thus further impl ying that a strong B cell response was associa ted with this infection (40).In other bacterial infectio ns, T cells ha ve been shown to be potent down-or upregulators ofantigen -stimulate<l B cells, thus controlling the amount of antihody production (41 ).However, the exact nature of the interac tio n between T anJ B cells <luring H jejuni infectio ns has not yet been defineJ.Results from a study where H jejani enhanced natural killer cell activ ity in a thymic nude mice, but suppressed natural killer cell activity in heterozygous mice, suggest that natural killer cell acti vity has little importance in defending a n immunocom peten t host ( 42).
M embrano us epithe lial ce lls (M cells) lining the J ome of Peyer's patches arc involved in antigenic transport fro m the lumen towa rds the underlying lymphoid cells and thus play an important role in mucosa!immunity (43).M cells have been sho wn to transport microorganisms such as viruses ( 44 ), bacteria (45) and some protozoa (46).No informatio n is yet ava ilable o n the possible interaction ofTG EV and Tspiralis antigens with M cells.In contrast, there is ev ide n cc to sugges t that the h ost response to Hjejuni involves M cells, to which these bacteria adhere selective ly (47).Although this mechanism resu lts in phagocyt.osis of some of the o rganisms, it may also provide a route for systemic spreaJ .The net effect on the bacteria and/or o n the host of H jejuni translocation by M cells remains unclear.Mucus: Reports on H jejuni infections are in direct contrast with the commo n observation of goblet cell hyperplasia Juring other intestina l infections.Although it was suggested that H jejuni c he motax is toward mucus may be an important factor in the affi nity of the organism for the intestinal tract (48), this bacterial infection does not appear to induce goblet cell proliferation.O n the contra ry, there is evidence to suggest that goblet cell numbers are decreased in Hjejuni infections (32).As a result, it seems that the protective role of mucus is inhibited by the bacterium.The mechanism by which this o rganism manages to evade and/or interfere with the host's prod uctio n of protective mucus has nor yet been elucidatec.l.Epithelial alterations: As memiont.'t! above, vill ous atrophy is a common finding during H jejuni infections (27).Moreove r, the epithe lial cell sloughing often observed in these infectiom al, lows e liminat io n of infected enterocytes into the lumen.Altered intestinal motility: Altered gut motility ha~ heen observed during H jejuni infections.Increases in repetitive bursts of action potentials have been Jemonstratcd in segments of isolatL'll rabbit ileum exposed to the cell-free supernatant of a culture of H 1e1uni (49).The effect of these disturhances on intestinal peristalsis anJ transit and then potential for eliminating the pathogen remain unknown.Pathogen impairment: There is cvi, dence to suggest that protection against enteric colonization by H jejuni may be mediated by in vivo proJuction of antibodies to the bacteria's flagella (50).
The polar fla ge llum carrieJ hy H Jeiuni seems to be an impo rtant vi rulence foe, cor invo lv ed in epilhclial ac.lheswn (51 ).Aflagellatc bacteria are unable to colonize the intestinal tract (52), an1l flagellin-specific antibodies appear to provide some protection against inte!ltina l colonizatio n (53) .Hence, in vivo production of an antibody against the flagellum of H jejuni may impair hac, terial motility and adhesion, and thus protect the host from infection.

T SPIRALIS
Humoral immunity: 1 mmunc exclusio n is parti c ul a rl y striking 111 trichinosis and is clearl y demonstrated by the mechanism of rapi<l expulsion tn immune animals (54).Rapi<l expulsion requires specific syste mic immurnLyand a local e nteric response in order to reach its full expression ( 5 5).It has been suggested that immune exclusion is the main component of rapid expul, sion of T spiralis parasites (54).It has also been sho wn that rats infecteJ with T spiralis larvae develop a strong 1mm unity to la rva l reinfect ion even though they are not resistant to infec, tion with adult worms (55 ).Another antibody isotype, lgE, appears to be tn• volveJ in host Jefence aga inst CAN J GASTROENTEROL VOL 5 No I JANUARY/FEBRUARY 1991 trichinosis (56,57 ).lgE is che antibody 1sotype most commonly associated with anaphylactic-likc reactions.O ne (unction of anaphylaccic antibodies, described for tissue migrating parasites, is the promotion of ant ibody-dependent killing of nematodes by macrophages and gran ulocytes ( 58). S uch mechanisms have been described in vitro and may be effective against the larval migratory phase ofT spiralis (56), but there is no evidence chat chey operate against the adult worms in the gut.Anaphylactic antibodies are most likely to be involved in the reactions which expe l worms from immune animals, since mast cell numbers are greatly increased in nematode infections, as will be seen further.lnc idenrally, this mechanism, characteristic of trichinosis but nor of TGEV and H jejuni infections, is the basis for the lgEmediated anaphylactic pathology of the infected intestine in trichinosis (57).Cellular immunity: There is evidence to suggest that part of the host protective response against T spiralis in volves an active reduction of fecund icy of the parasite (54 ).It was demonstrated that the transfer of immune mesenteric lymph node ce lls from an infected donor mouse to irradiated infected mice could reduce the fecundity of the worms, thus suggesting that this mechanism may be immune-mediated (59).However, these findings were in contradic ti o n with a previous study in which similar experimental conditions in rats failed to demonstrate a reduction in worm fecundity (60).Whether such a discrepancy reflects a species-dependent factor or another experimental component remains unanswered.Still other studies have demonstrated that injection of thoracic duct lymphocytes obtained from immune rats could protect normal rats against T spiralis ch,illenge (61 ).These immune ce lls increased the rate of expulsion of adult worms from the small intestine.S uccessful transfer of resistance against trichinosis has also been accomplished tn mice via mjection of lymph node cells obtained from immune hosts (62).Prolonged infection reported in athymic mice further indicated the important mediating potential of T cells tn the adaptive immune response against this nematode (62).In yet another study, inj ection of B ce ll -enriched thoracic duct lymphocytes provided strong resistance against trichinosis in rats, and the protection was totally inhibited if these cells were treated with a mitotic inhibitor prior to inoculation ( 63).From these observations, it appeared that acquired resistance to T spiralis is mediated by both of the major classes of lymphocytes, ie, T aml B cells.The above fine.lingsimply that immune T ce lls have a helper function in promoting the formation of protective B cells during T spiralis infection.

Eosinophils and mast cel ls arc without question the most prominent componen ts of the cellular reaction to
T spiralis infection (54,64).Eosinophils arc typically observed in the lamina propria as well as within the tissue gnm ulomas surrounding the nematodes (64).In vitro experiments demonstrated that eosi n ophilic granu le proteins efficiently killed T spiralis larvae (65).In contrast with TGEV and H jejuni infections, colonization of the gastrointestinal tract by T spiralis and other nematodes is associated with mucosa[ mastocytosis, which is a thymus-dependent mechanism in parasitized rats (66,67).Although these cells possess the necessary 'tools' to inflict damage, they <lo not appear to be involved in direct killing of the nematodes (67,68).In the rat, mucosa!masc cells secrete a distinct protease, rat mucosa!mast cell protease II (RMCP II), which can be detected in the circulation (69).In rats infected with T spiralis, systemic secretion of RMCP II coincides with expulsion of the ad ult worms (66).Such fine.lingsclearly demonstrate that mucosa I mast eel ls are functionally active during the immune elimination of primary T s/)iralis infections.It was demonstrated that mast cells would adhere to larvae prior to eosinophil adherence in the process of eos inophil -dependent killing of T s/Jiralis (67).Mast cells and eosinophils have been Jescribcd as active partners in parasite killing (70).The sa me authors a lso demonstrated that rhis mechanism was lgE-dependent (70).These associations clearly suggest that CAN J GASTROENTEROL VOL 5 No I JANUARY/FEBRUARY 1991 mast cells influence eosinophils in the killing of parasites during secondary T sJ>iralis infections.The possible mediators involved in this cooperation remain unknown.Yet another possible host defence mechanism involving mast cells occurs via the mediators that they release.Serotonin and histamine have been identified as mediators in t he release of mucus from epithelia l tissue (71,72).Thus, the porenrial for host defence becomes ohv1ous if mast cellreleased histamme and serotonin actively initiates mucus secreuon in vivo during parasitic infection, which remains co be demonstrated.Mast cells can also release vasoacti ve intestinal polypeptide (V IP) (73).VIP isa potent inducer of cyclic AMP-mediated water and e lectrolyte secretion in the intestine (74 ).Since mast cells are activated in T spiralis infection, one can postulate that VIP may be released during lgEmediated reactions in the immune host.This in turn would result in intestinal secretion and thus possibly help the host to eliminate the parasite.Clearly, the fascinating involvement of mast cells duri1:g intestinal infcctiom deserves further investigation.Mucus: When parasites and other orga n isms enter the gastrointestina l lumen, they inevitably Cl)me in contact with the superfic ial mucus layer, a complex mixture of mucin glycoproteins covering the epithelium .That mucus could be involved in protection against parasites is inferred from numerous histological observations of goblet cell hyperplasia associated with infection.The excretion of mucus provides the host with a nonspecific defence mechanism, both as a physical barrier and by its con unu ous cleansing action, which helps to sweep microorganisms towards the villus tip and downstream in the lumen (75).Obviously, the limited Vl)lume offlow along a vi llus (2 µ L/day) is not sufficient to prevent all microorganisms from colonizing this t1rea (75), but mucus has more powerful means of protecting the hmt from parasites.
Mucus-mediated protection against T spiralis 111volves t he immune system of the host, c learly illustrating the complex intrtcacie~ of the immu1wlogical and non immunological ho~t responses.).An association of goblet cell hyperplasia with the onset of worm expu lsion has been recorded in rats and mice infected with the nematode (77).It was observed that during rapid expulsion, the larvae failed co penetrate the epithelium (78, 79).At the time of this infection, T spiralis appeared to be trapped within the mucus layer (78).

38
This experiment also demonstrated the significant role of parasite-specific immunoglobulins in the physical entrapment of nematodes within the mucus layer.Larvae were sensitized with immune and nonimmune serum or bile and then carefully mixed with mucus from immune and nonimmune rats.Bile failed to promote any mucus trapping as did serum from native rats, whereas significant trapping occurred when the organisms had been exposed to immune serum; no difference between immune and nonimmune mucus was observed in this process ( 78).Rapid expulsion ofT spiralis can be blocked by pretreating immune rats with corticosteroids (80), thus further illustrating the significance of immune involvement in this process.From these results, it was suggested that parasite-specific immunoglobulins, but not IgA, were essential co mponents of the process of T spiralis mucus t rapping.Such findings leave little doubt about the potent barrier effect that mucus can have on the establishment of this nemacode.
Epithelial alterations: In T spiralis infection, villous atrophy and crypt hyperplasia have been shown to coincide with the expulsion of adult worms (81 ).
In thymectomized mice, worm expulsion, villous atrophy and crypt hyperplasia were either reduced or absent (81 ), thus confirming previous studies which demonstrated chat villous atrophy was T cell-mediated (82).This suggests that local ce ll -mediated responses are involved in both the pathogenesis of the lesions and the expulsion of the parasite.Loss of brush border microvillous surface area has been associated with many gastrointestinal d iseases ( 83).Yersiniosis (84) and giardiasis (85) both result in a diffuse reduction of brush border surface area in the host's sm all intestine.It is possible that this common mechanism is yet another component of the complex host defence system against intestinal insult, exposing less mucosa!surface area to a pathogen and its antigen(s).It appears that this morphological a lteration can be coupled with a biochemical ch ange in the brush border.Indeed, intestinal brush border from immune rats previously exposed to T spiralis had a persistent, lower binding capacity for wheat germ agglutinin than normal microvilli from control rats (86).Whether bioch emical alterations to brush borders may disorient microorganisms and prevent their invasion or attachment co enteric epithelial cells remains to be answered.Altered intestinal motility: Altered gut motility has been reported during T spiralis infections.Significantly increased intestinal transit was demonstrated in primary infections (79,87) but not following a secondary challenge (79).It has been suggested that corticosteroids may be responsible for the inhibited respon se observed in immune rats (54), via a mechanism where corticostero ids would inhibit mast cell synthesis of leukocriene, a potent smooch muscle stimulator (88).The effect of a ltered sm a ll bowel propulsion on parasite development and/or expulsion remains co be clarified.
CAN] 0ASTROENTEROL VOL S No l JANUARY/FEBRUARY 1991 Pathogen impairment: R educed fecundity of T spiralis resulting from hostparasite interactions (5 4) and morphological damage to adult worms ( 61) have been reported as potentially importanc host defence components against trichinosis.H owever, damaged worms seem to recover and survive as effectively as undamaged worms (55).Hence, the significance of these injuries remains unclear.

SUMMARY AND CONCLUSIONS
The findings reviewed above clearly illustrate the significant role played by humoral a nd mucosa!antibodymediated host defence in immunity to H jejuni and T spiralis.While it is virtually beyond dispute chat passive immunity to TGEV can be conferred on the young via immune milk, the significance of specific anti-TGEV antibodies in active immunity to chis d isease is still poorly understood.The mechanisms by which lymphocytes promote defence against a pathogen appear co d iffer during the three types of infection discussed here.D uring transmissible gastroenteritis, the major T cell -dependent host defence mechanism seems to follow the cytotoxic route, where a killer T cell recognizes antigen on the surface of a virus-infected cell and responds by killing the target cell.Helper T cells may also be involved in host defence against the virus via macrophage activation.The cytotoxic and phagocycic mechanisms observed in TGEV infection may be interferon-mediated.
The lymphocycic response during H jejuni infections is still unclear, but B cells appear to be a major component in host defence against chis disease.It remains to be s hown whether thi s response involves a T h elper route similar to chat seen in trichinosis, where a T cell recognizes nematode a ntigens and responds by secreting lymphokines that stimulate B cells to mature and secrete antibodies.
Whi le the clinical symp toms induced in the intestinal mucosa are similar in all three infections, the underlying inflammatory cellular responses are quite different.H jejuni infections a re characterized by neutro philia, a nd trichin osis by eosinophilia and local mastocytosis.In both infectio ns, lymphocytes, macrophages and plasma cells increase in numbers at the infected site.The cellular response co TGEV is not as we ll defined.Howeve r, while no striking cellular infiltrate seems to be associated with the infectio n, inflammatory cells activated during the disease appear to invo lve primarily lymphocytes and macrophages.Pa neth cells are found within the epithelium, at the bottom of crypts.There is evidence to suggest that microbes that progress deep into crypts ca n be cleared from these areas by Paneth ce lls, which are capable of phagocyrosing and degrading intestinal microorganisms (89,90).The influence of these particular cells in controlling any of the three infections dealt within this review is n ot known at this time.
Ano ther striking difference among the viral, bacte rial and parasitic infec-tio ns reviewed in this paper is the mucous response to each of these pathogens.While little is known about the invo lvement of muc us secretion in defence against TGEV, it appears that H jejuni infection does not elicit muc us hypersecret ion.In contrast, mucus trapping, likely immunoglob ulinmcdiated, plays an impo rta nt role in intest inal defence aga inst T spiralis.
Finally, while TGEV does no t seem to be impaired morphologically o r otherwise by its exposu re to the intestinal en vironment, there is little do ubt that such exposure can impair H jejuni and T spiralis.
This review illustrates the many host factors contributing co t h e defe nce against T GEV, H jejuni and T spiralis.
Table 1 summarizes the similarities and differences between th e mechanisms a host will use for protection against these three pathogens.Ir certainly docs not reflect the complex intricacies of host defence against microorganisms.It ap- Such evidence suggesrs chat a variety of inju rious agents may elicit a similar syndrome in the intestine via common mcdiacors which remain to be ident1, fie<l.While mucosa I mast cells appearro play a centra l role in t he intestinal defence system (Figure l ), t he association between immunoparho logy anJ protection deserves further investigation.

8 Figure 1 )
Figure 1) Overview of the main interactions leading to the five major types of intestinal defence systems discussed in this review.Rather than auempnng to be all encompassing, this chart illustrates the central role mucosa!mast cells may play in intestinal defence against infection.Solid arrows /nreracnon of immune and nonimmune elements; Broken arrows Initiation of enceric response; Wavy arrows Release of cytokines or other products

TABLE 1
Summary of the host defence mechanisms involved in self-protection against three pathogens Despite the unquestionable Intricacies of theirInvolvement In host defence.Immune and nonlmmune responses were /Isled separately.Substantiating references ore listed.TGEV Tronsmlss/ble gastroenteritis virus: + Protective component of host defence: + -Factor Involved In host defence.but too lesser degree: -Factor not Involved In host defence: ?Involvement (or nonlnvolvement) of o factor.postulated from related findings: NO No doto oval/able 9. Prez-Perez GI, Cohn DL, Guerrant RL, Panon CM, Reller LB, Blaser MJ.Transmissible pears, however, that the host response against T spiralis is rhe most elaborate of the three examples studied in this review.As discussed earlier, the symproms associated with t he three pathogens studi ed are very similar, and yet, as shown in Table 1, the cellular response to each o rgan ism may Jiff er.