Mechanism of Immunity to Tick infestation in Livestock

Immunological interaction at the tick host interface involves both innate and acquired host defenses against infestation and Immunomodulatory countermeasures by thetick. Acquired resistance to tick infestation involves humoral and cellular immlmoregulatory effector pathways. Tick-borne disease-causing agentspr exploit tick suppression of host defenses during transmission and initiation of infection. Because of the public health importance of ticks and tick-borne diseases, it is crucial that we understand these interactions and exploit them in novel immunological control.


Introduction Perspectives and Overview
The tick-host-pathogen interface is characterized * Disease-causing agents transmitted by bloodby complex immunological interactions. Immuno-feeding arthropods are significant public health logical interaction at the tick host interface involve concerns. In addition to the emergence of new both innate and acquired host defenses against diseases, many well-recognised vector-borne diseases infestation and Immunomodulatory countermeasures are occurring more frequently and are increasing the by the tick. The cellular and molecular immunological range over which they occur. Many factors contribute bases of these host-parasite relationships are being to the emergence and re-emergence of arthropoddefined. Acquired resistance to tick infestation borne diseases: insecticide/acaricide resistance; drug involves humoral and cellular immlmoregulatory resistance; economic and social factors; environeffector pathways. It impairs tick engorgement, ova mental change; and genetic changes in the vectorproduction, and viability Ticks responds by borne pathogens. suppressing antibody production, complement and * On a global basis, ticks are second only to cytokine elaboration by both antigen-presenting cells mosquitoes as vectors of disease-causing agents to and specific T cell subset . Tick countermeasures to humans, and they are the most important arthropod host defenses reduce T-lymphocyte proliferation, transmitting pathogens to other animal species.The elaboration of the Th1 cytokines interleukin-2 and public health importance of ticks is not diminishing. interferon-y, production of macrophage cytokines Furthermore, new tick-borne disease causing agents interleukin-1 and tumor necrosis factor, and antibody are being discovered. Lyme borreliosis, caused by responses. Tick-borne disease-causing agentspr Borrelia burgdorferi, occurs in regions with temperate exploit tick suppression of host defenses during climates, and it is the most frequently reported vectortransmission and initiation of infection. Because of the borne disease in the United States. In the United public health importance of ticks and tick-borne States, the vectors of B. burgdorferi are Ixodes diseases, it is crucial that we understand these scapularis in the east and midwest and Ixodes interactions and exploit them in novel immunological pacificus in the west. In addition to B. burgdorferi, I. control.The dynamic balance between acquired scapularis is a vector of the human pathogens: resistance and tick modulation of host immunity Babesia microti; the causative agent of human affects engorgement and pathogen transmission. So a granulocytic ehrlichiosis and a recently described thorough understanding of mechanism of host encephalitis-like virus, In addition, Ehrlichia immunity to ticks is essential for rational devlopement chaffeensis, transmitted by Amblyomma americanum, of antitick vaccine.
causes human monocytic ehrlichiosis, which was described as a new species in 1991.Furthermore, E. The genetic background of an experimental host chaffeensis infections have been reported from must be considered in any study of acquired Europe and Africa. Throughout the world, it would be immunological resistance. For example, bovine surprising if new emerging and re-emerging tick-breeds differ in their resistance to ticks, a factor borne diseases are not encountered in the coming recognized and extensively used by cattle breeders . years.
The alternative pathway of complement * The tick is clearly not just a crawling activation contributes to expression of acquired hypodermic needle and syringe with regard to the resistance. Levels of complement component C3 transmission of tick-borne pathogens. Tick-increase during tick infestations. In addition, development of tick-specific IgG has been reported for transmitted infectious agents undergo developmental many ixodid host associations. cycles within the vector. The microorganisms can Continuous introduction of saliva during express molecules during the vector phase that are not feeding would allow complexes of circulating evident during infection of the mammalian host.
antibody and antigen to form and be deposited at Additional factors of great importance in tick feeding feeding sites. Subsequent fixation of complement and pathogen transmission are the number and could enhance lesion formation and potentially have diversity of pharmacologically active molecules in an impact on the engorging tick. tick saliva. Those activities include anti-coagulants; Complement activated by either the alternative inhibitors of platelet aggregation; vasodilators; and or classical pathways could contribute to feedingsuppressants of host immune defenses. Ticks, as well lesion formation through anaphylatoxin generation as blood-feeding arthropods in general, are indeed and chemotactic activities. C3a and C5a cause 'smart pharmacologists. This report focusses on the degranulation of mast cells and basophils and a ability of ticks to modulate host immune responses and concomitant release of eosinophil chemotactic factors the potential consequences of that immuno-(histamine, eosinophil chemotactic factor of suppression for pathogen transmission. Furthermore, anaphylaxis) and vasoactive substances. Digestive the inhibition of the action of tick-derived host tracts of ticks that obtained blood meals from resistant immunosuppressants might provide a powerful, hosts contained intact basophils, intact eosinophils, novel, strategy for the control of tick-transmitted and granules of both cell types. Basophil and pathogens. Rather than targeting each individual tickeosinophil granules were observed within tick gut borne pathogen for vaccine development, develop a cells that displayed membrane damage and other signs vector-blocking vaccine to those tick factors essential of injury. Bioreactive molecules released by for successful transmission and establishment of basophils, eosinophils, and mast cells may influence disease-causing agents.
tick physiological responses, thus causing cellular Acquired Resistance injury and behavioral changes. Histamine, leukotrienes, prostaglandins, eosinophil major basic Tick feeding induces host immune regulatory protein, enzymes, and other mediators of inflammaand effector pathways involving antibodies, tory and immune responses likely contribute to complement, cytokines, antigen-presenting cells, and formation of the lesion at the bite site and affect the T lymphocytes. Immunologically acquired host engorging tick. Ultrastructural analysis of tickresistance to tickfeeding can result in reduced bloodattachment sites on resistant mice revealed the meal volume, decreased engorgement weight, prolonged duration of feeding, diminished production accumulation of large numbers of basophils. of ova, reduced viability of ova, inhibition of molting, Cutaneous immune responses at tick-bite sites and death of engorging ticks. Acquired resistance has during acquisition and expression of acquired resistance require the participation of antigen-been most often observed after infestation by female presenting cells, antigen-specific T and B lymphocytes, ticks. However, feeding male ixodids also induce Langerhans cells and cytokines. acquired resistance, but to a lesser degree than that Bovine resistance to tick infestation consists of caused by females alone or together with males.
innate and acquired components. Bos indicus cattle Host grooming is an important factor in exhibit the strongest innate resistance. Natural and reducing tick burden .Immunological mediators acquired resistance of Hereford calves to B. microplus induced by tick antigens introduced into host skin seem unrelated, and individual animals differ in contribute to the itch sensation, which stimulates natural susceptibility to infestation .Innate resistance, grooming.
which partly reflects the ability to mount a more contributes to successful establishment of infection by intense immune response to infestation, appears to be tick-borne pathogens. Tick salivary glands contain linked to breed differences in immune response apyrase, which inhibits platelet aggregation by capabilities .As for acquired resistance, upon exposure hydrolyzing adenosine triphosphate (ATP) and to tick salivary-gland immunogens, B. indicus had adenosine diphosphate (ADP) to adenosine heightened immune responsiveness compared with monophosphate (AMP) and orthophosphate. Bos taurus, as measured by macrophage elaboration of Prostaglandin E2 (PGE2), which is produced by tick interleukin-l (IL-1) and in vitro proliferation of B and salivary glands, inhibits platelet aggregation and T lymphocytes to mitogens. The tropics and causes vasodilation .Salivary apyrase may prevent subtropics have placed strong selection pressures on aggregation of neutrophils and mast cell degranulation. B. indicus cattle to enable them to withstand harsh A. americanum saliva contains very high concenenvironmental factors in addition to parasites and trations of PGE2 and I. dammini saliva contains other disease-causing agents .Selection of animals prostacyclin, which blocks platelet aggregation, with the ability to limit tick infestation by heightened inhibits mast cell degranulation, and induces immune responsiveness results in a survival advantage.
vasodilation. Intrinsic and extrinsic pathways of By the third or fourth infestation, B. taurus cows coagulation are inhibited by elements of D. andersoni and calves repeatedly infested with D. andersoni saliva that act upon factors V and VI1 .Salivary-gland adults developed peripheral blood lymphocytes extracts of R. appendiculatus contain a 65-kDa anticoagulant that inhibits the activity of factor Xa or reactive in vitro with salivary-gland extracts of the other components of the prothrombinase complex. same ixodid species. Purebred B. indicus calves infested with A. americanum developed in vitro Tick Modulation of Host Immune Function lymphocyte responsiveness to this tick's salivary-Vector-mediated immunosuppression of the gland extract after the first, second, and third host helps in both blood-meal acquisition as well as in infestations, whereas the reactivity of cells from effective transmission of pathogens. In addition, the crossbred animals was considerably less . responses to both arthropods and pathogens involve Changes in tick salivary-gland proteins during common elements of the immune system. the course of feeding point to an array of tick Tick feeding also suppressed the generation of a immunogens and responses to host factors. In addition primary IgM response to a thymic-dependent to other components in saliva, immunogens unique to immunogen. Immunosuppression was attributed to attachment cement could contribute to host reactivity. lymphocytotoxic factors in tick salivary glands. Attachment cement likely serves to expose saliva Reduced lymphocyte proliferative responses and immunogens to host skin and allow them to be cytokine elaboration resulting from salivary-gland adsorbed during feeding and, possibly, be a site of extracts of other tick species were not caused by continued exposure after detachment. Similar cytotoxicity. Tick salivary gland-derived molecules antigenic determinants were detected in attachment reduce host T-lymphocyte function, which could cement and salivary glands of several ixodid species .
suppress regulatory and effector pathways involved in Pharmacological Properties of Tick Saliva acquired resistance. Boophilus microplus infestation of purebred B. taurus caused a marginal decrease in Salivary gland-derived molecules have antihenumbers of T lymphocytes, beginning with the second mostatic, vasodilatory, antiinflammatory, and immunosuppressive properties. Several tick salivary-gland infestation and lasting until the end of a fourth factors appear to have more than one biological exposure . activity. For example, molecules inhibiting coagula-Tick modulation of host immunity inhibits tion and enhancing vasodilation contribute to regulatory and effector pathways involved in formation of the feeding site. Antiinflammatory and acquisition and expression of acquired resistance. immunosuppressive molecules reduce host defenses Inhibition of the alternative pathway of complement that impair tick engorgement. Tick-mediated host activation, antianaphylatoxin activity, and reduction immunosuppression appears to achieve a balance of natural killer cell function suppresses the innate between reduction of immune defenses that limit response pathways of the host immune system. engorgement and maintenance of sufficient Reduced antibody responses facilitate feeding by immunocompetence for host survival. In addition, reducing host immunoglobulins reactive with tick tick-induced host immunosuppression likely salivary-gland molecules. Analysis of host cytokine networks reveals that macrophage and THl-Repeated, or continuous, exposure brings lymphocyte function are suppressed by tick salivary-feeding ticks into contact with the immune effector gland extracts. Tick countermeasures appear to target elements induced by primary infestation. Primary the major pathways involved in acquired host introduction of tick saliva stimulates generation of immunuity. memory T and B lymphocytes, which assure a more Tick modulation of host immunity appears to be vigorous immune response upon reinfestation. mediated by salivary gland-derived proteins and Eosinophils act as feedback regulators of possibly by PGE2. PGE, inhibits TH1, but not TH2, basophil and mast cell-derived bioactive molecules. production of cytokines. Efforts to identify, isolate, Basophil and mast cell-derived histamine, leukotriene and characterize tick salivary gland-derived B4, and the eosinophil chemotactic factor of molecules that suppress host immune responses are anaphylaxis attract eosinophils to the bite site. under way. A vaccine would allow more complete Macrophages observed in feeding lesions are probably development and expression of host immunity to the involved in the elimination of antigen, as well as in vector and any introduced pathogens.
antigen processing and presentation to any influx of immunocompetent cells.

Resistance
Very little is known about the specific mechanisms that disrupt tick feeding, impair egg The following model accounts for recognized production, and reduce viability. Histamine, host defenses and tick countermeasures to these eosinophil basic protein, prostaglandins, leukotrienes, responses. Obviously, the responses of different tick enzymes, and other biologically active molecules and host species will vary. released might all be contributing factors. Although The introduction of tick saliva into the skin of an antibodies, lymphocytes, complement, and other unsensitized host causes degranulation of mast cells, elements of the immune and inflammatory responses possibly via enzymatic breakdown of plasma participate in acquired resistance, their specific roles membranes. Chemoattractants and vasoactive factors must still be established. For example, how do tick-released in this manner could contribute to formation reactive immunoglobulins affect the feeding ixodid? of the modest leukocytic influx observed at tick-What is the importance, if any, of prostaglandins, attachment sites during primary exposure. Generation leukotrienes, eosinophil basic protein, and other of C5a by activation of the alternative complement constituents of cells attracted to bite sites on resistant pathway would contribute to cellular influx at the bite hosts? Do cytokines and acute-phase proteins have a site. Ticks can modulate both innate and primary direct role in expression of acquired resistance? immune responses of hosts. Tick saliva contains Cytotoxic T lymphocytes and natural killer cells have inhibitors of the alternative pathway of complement not been implicated in antitick resistance. However, activation, anaphylatoxins, and natural killer cells, which are all innate defenses. Tick saliva also reduces this topic remains to be fully investigated. The macrophage cytokine elaboration, which impairs the immunogens involved in acquisition and expression earliest steps in development of antitick immunity by of acquired resistance must be identified and altering signals to T and B lymphocytes. T-characterized. Certainly, a considerable body of lymphocyte proliferative capacity is impaired, as interesting work awaits us. shown by Con A responses. Furthermore, THl-Anti-Tick Vaccine lymphocyte production of IL-2 and IFN-y is reduced, Acaricide resistance is a significant threat to while TH2-lymphocyte cytokine elaboration of IL-4 is effective control of ticks and tick-borne diseases. The normal. Reduced TH1 lymphocyte function would development of antitick vaccines represents one of the diminish delayed type hypersensitivity to tick most promising alternatives to chemical control and immunogens, which contributes to the cellular influx has the advantages of target-species specificity, at attachment sites on resistant hosts. Reduced IFN-y environmental safety, lack of human health risk, ease would impair macrophage activation.
of administration, and cost. Numerous investigators In resistant animals, basophils appear to be have used whole-tick extracts and salivaryattracted to attachment sites by soluble mediators and glandhomogenates as vaccine immunogens, which T lymphocytes. Tick salivary antigens introduced over induced variable levels of protection. Particular the course of engorgement could result in an equally attention has focused on concealed or novel long-term release of bioactive molecules from mast immunogens not normally introduced into the host cells already present as well as from infiltrating mast cells.