Immunity To African Trypanosome

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For many years, sleeping sickness has been a major problem in the African continent generally in West Africa and more specifically in the sub-Saharan areas. The disease is caused by African trypanosome parasites which are usually in tsetse flies. The specie that is responsible for this disease is the Trypasonoma brucei. This species can be categorized into three sub-species; T. b. gambiense, T. brucei, and T. b. rhodesiense. Usually, the parasite has two hosts, that is, a mammalian as the host and an insect, specifically the tsetse fly as the vector. The parasite has to undergo a number of complex changes during its life cycle due to the large differences that exists between the vector and the host; so as to enhance its survival. It has been noted that the parasite has developed various methods that enables it to survive the chemicals that are released by the immune system of the host. Due to this fact, there is need for the development of drugs that can be used to deal with this parasite as the current medicines have proved to be ineffective.

The population in thirty six sub-Saharan countries where are tsetse fly, are at a risk of suffering from African Trypanosomiasis. Although there is a decline in the epidemic in African trypanosomiasis, World Health Organization (WHO) approximates that sixty million people are at risk of the epidemic and half a million are suffering from the infection currently (WHO, para 5-6). African trypanosomiasis also known as sleeping sickness, African lethargy or Congo trypanosomiasis is a parasitic disease that relies on tsetse fly as the vector to reach human and animals. African trypanosomiasis is caused by Trypanosoma brucei rhodensiense in Eastern Africa and Trypanosoma brucei gambiense in Western Africa, this particular type is responsible for ninety five percent of all the reported cases.

Tsetse fly, the disease vector is only found on sub-Saharan Africa. Nonetheless, only a certain type is responsible for the disease and paradoxically some areas are heavily infested by tsetse fly but the population does not suffer from the disease. Those individuals residing in the rural areas who get their livelihood from agriculture, fishing, and animal rearing are at an increased risk of developing the disease. The intensity of the disease varies from region to region and from individual to individual. The disease only exists in Africa. Given the size of the population under the risk of being infected by African Trypanosomiasis, this essay will explore various immunities to the infection.

Immunity to African trypanosome

In the thirty six sub-Saharan countries where the infection is rampant it is generally observed that there is disparity in the infection. Some animals and human being perfectly survive in tsetse fly infested area and they do not suffer the infection of African trypanosome. On the onset of this century, British, French and German scientists made a spirited start to study the immunological reactions to the African trypanosome, although they relaxed their quest in the study, recent years have inspired awareness to the immunity for African trypanosome. Customarily, chemotherapeutic armamentarium has efficiently been used to fight trypanosomiasis than ever before.

Nonetheless, its ability to eliminate or widespread curtail the spread of the diseases has been hampered by the appearance of drug resistant types and the administrative hurdle of continually giving the drug to human being and cattle especially to the pastoralist communities that are always on the move. Consequently, any immunization to curtail the disease is mostly desirable, given that using this method other infection to both man and animal are successfully been controlled.

Non-Specific Constitutional Resistance

It is a scenario where the whole group of a particular species is genetically gifted to resist the infection from a certain parasite (Soltys, para 4). The species might exhibit non- vulnerability where all the members of a particular species are absolutely insusceptible to the diseases caused by the agent. However, in some instances the resistance is comparative where some members of a particular species are less vulnerable than others, here race and individual dissimilarities plays a significant role. For instance, N'Dama cattle of western Africa are known to be trypanotolerant. A relative resistance based on race is clearly exhibited by these cattle.

A study conducted on the cattle by Murray in 1952 where a group of previously infected cattle and another that was not previously exposed were bared to the parasitic infection using a number of strains of both Trypanosoma vivax and T. congolense of diverse geographical origin (Murray, Morrison and Murray, para 3). When lysis protection test was used to study the blood, it was found out that exact antibodies were not detailed bar as a rejoinder to the disease and they depended on certain specific species. On the background of his findings, Murray and company concluded that the ability to withstand trypanosome disease by the N'Dama cattle is an inborn quality peculiar to them but when exposed to the diseases their tolerance is improved.

According to Desowitz, acquired immunity is believed to be the racial resistance of the N'Dama cattle to trypanosomes (Desowitz, pp.59). He observed that a N'Dama cattle that was born and bred in tsetse fly infested zone underwent meagre brief parasitaemia in a self cure after the challenge with T. vivax. Conversely, if the same breed was born and reared in an area that was free of tsetse fly, it suffered a chronic kind of diseases that is heralded by intense parasitaemia attacks characteristic of a Zebu born and reared in tsetse fly infested area. These inferences confirmed that a N'Dama cattle bred in an area full of tsetse fly produce an immune response unlike a Zebu cattle that is bred in the same condition that do not produce any immune response.

Variant antigen-specific antibody response

It is induced protective immunity in cattle that is undertaken by generating antibodies that variant antigen type (VAT) react with the surface epitopes on the variable surface glycoprotein (VSG) attached to the parasite (Black and Seed, pp 99). The VAT exact antibodies harmonize the clotting of blood, lysis, and raise macrophage uptake of the trypanosome which immobilizes them. Although there is no difference in response between trypanotolerant and susceptible cattle in their production of trypanodestructive VAT specific antibody, the N'Dama cattle exhibit a superior lgGI response to hidden VSG epitopes. Although not yet clearly documented, it is generally observed that antibody similarity and avidity influences the resistance and distinguishes vulnerability from trypanotolerance.

There is a noticeable dissimilarity in the capacity of various host and specific characters within the species to exhibit unequal resistance to trypanosomiasis. The capability of the Ab response of the host to tolerate trypanosome is only partial. But VSG-exact Ab is responsible for the disastrous removal of the variant antigen type from the blood of the host. Nonetheless, the capacity of VSG-specific Ab to remove the antigen has no functional or genetically correlation to the overall resistance of the host to trypanosomiasis. For the host to be effectively tolerant to trypanosomiasis, it must also contain Th cell of IFN-y that activates macrophage control mechanism. Those animals that produce weak B cell or T cells reaction to the trypanosome antigen ends up being relatively vulnerable to trypanosomiasis while those that produce prominent B or T cell reactions augmented by the necessary macrophage activation stages exhibit a higher degree of tolerance to the trypanosomiasis (Maudlin, Holmes and Miles, pp 348).

High Density Lipoprotein (HDL)

Trypanosome brucei gambiense and T.b rhodensiense are the only strains of African trypanosome that infect human beings. All the strains affect non-primates mammals and cattle becoming a very important veterinary disease. T.b brucei and T.b rhodensiense infects human beings because they are able circumvent the immune system by mutating the gene encoding the protein receptor. Nonetheless, the inborn immunity in human being is able to mediate the effects of trypanosomiasis. A sub class of high density lipoprotein (HDL), what is known by many as the good cholesterol, is responsible for this mediation. The sub class, trypanosome lytic factor-1 or TLF-1 contains two proteins; apolipoprotein L-1 and haptoglobin-related protein that produce an exact and highly toxic against trypanosome effectively curtailing the infection of trypanosomiasis to human. Despite the effectively of the toxin to the African trypanosome, it is completely ineffective and nontoxic to the parasite that cause human sleeping sickness (Sleeping Sickness Commission, pp. 28).

Specific adaptive immunity during infection and after recovery

As early as in 19th century it was observed that serum from infected dogs and rabbits with trypanosome equiperdum performed a desirable action on mice infected with the same strain. Although the serum performed no positive action in heterologous trypanosome, T equinum, it produced positive protective actions in mice infected with homogenous species. Moreover, the study was undertaken using cattle crossing a tsetse fly infested region in Cameroon, where each animal received serum from a donkey heavily vaccinate with infested blood. Only a meagre percentage of the cattle were infected during the travel (Soltys, para 7). Equally, when sera from 24 infected with T. gambiense people were used to exhibit the protective antibodies, the results found no traces of the antibody in the sera of five uninfected persons. It was found out that the protective antibodies function by making the trypanosome vulnerable to phagocytosis or lysis or both. This finding formed the background for the production of active immunisation against infections caused by African trypanosome. The immunisation is undertaken using three methods, infection by alive but assuaged trypanosome, although this did not make the animals obvious to the infections, it made them live longer than those animals that were not treated. Secondly, infection by virulent organism followed by drug treatment, the animals are able to resist the infection for a longer period of time than those that are not treated. The adaptability could result due to the combined efforts of residue drugs and antibodies still in the blood system. Lastly, immunization with dead trypanosome, they trigger the production of antibodies which last for a period of more than nine months in the blood system. Consequently, the harsh effects of African trypanosome are moderated.

Innate and adaptive immune system in African trypanosome

Innate immune system is the first line host defence mechanism that serves to limit infection in the early hour after the exposure to the infection causing microorganisms. On top of its role in the early phase of the infection where it offers defence, innate immunity especially in mammals play a role of motivating the consequent clonal response of adaptive immunity. Customarily, adaptive response has been given much emphasizing up until recently when it was discovered that innate defence mechanism is an evolutionary defence mechanism. It plays a central role in producing and directing an immune response to infectious microbes. Pathogen-associated molecular are the recognition receptors pattern molecules involved in the recognition of conserved microbial molecules. The toll-like receptors (TLRs) identify a range of pathogen-associated molecular patterns such as lipopolysaccharide, CpG DNA and flagellin. The importance of innate response is evidenced during infection when the microbial molecule is recognized early helping to shape the subsequent adaptive immune response.

MyD88 and Toll-like receptors 9 (TLR9) helps to generate an innate immune system that is depended on for the development of a type 1 cytokinase which forms the basis of the relative resistance to African trypanosomiasis. The question that arises is, would protection against African trypanosome be enhanced if the immune response is bolstered by artificial stimulation with CpG oligodeoxynucleotide (ODN) which is a TLR9 agonist. In an experiment, a vulnerable BALB/c mice relative resistance to infection was greatly improved by CpG ODN treatment that was known for decreased parasite load, increased production of cytokine and superior B and T cell responses that are parasite specific. Although survival was not improved in comparatively resistant C57BL/6 mice, the early parasite levels were reduced to 100-fold and the majority of the parasites Short Stumpy (SS) and not dividing. Theses observations indicate that innate resistance to trypanosome can be improved. Nonetheless, the effect of CpG ODN treatment was not as pronounced in gamma interferon (IFN-y). this withstanding, the inference for the experiment are that CpG ODN in used can interfere with the developmental life cycle of the parasites and a TLR9 treatment in induced to a vulnerable manner in a dependent manner it can improve the animals resistance to African trypanosomiasis.

TLR9 agonist CpG ODN can be used as a treatment to boost the innate immune response of an infected animal. The experiment showed that CpG ODN noticeably improves resistance to trypanosoma brucei gambiense in vulnerable mouse species. The animal is able to resist the infection due to the decrease in the parasite level, the rise of SS forms of parasite that do not divide, the production of TH1 cytokine rises, the increase in exact parasite-antibody levels and an increased production of T-cell cytokine in response to the antigen (Harris, Mansfield and Paulnock, para 4). When there is no IFN-y, the level of resistance between the SCID mice and the wild type ones is not he same in terms of the effects on resistance parasitemia levels and parasite differentiation.

Role of Th1 and Th2 cells

The resistance or vulnerability of the host to African trypanosome is connected to the predominance of Th1 or Th2 cell cytokine response to microbial Ags. In an experiment undertaken under the Leishmania spp. Model, it was found out that the mouse that possess a superior Th1 cell augmented by IFN-y activation of macrophage were in a position to destroy the parasite and limit the infection while those that only produced IL-4, which is a Th2 cytokine expressed aggravated and dispersed infection. Moreover, when the same experiment was undertaken under the Leishmania model it was demonstrated that even the resistant mice were incapable to control the infection in the absence of the IFN-y an that the neutralization of the IL-4 cytokine permitted the vulnerable mice to resolve the infection. These findings are supported by others from experimental infections such as in mycobacterium tuberculosis, M. leprae as well as Listeria monocytogenes. Consequently, it is generally inferred that the nature of emerging or predominant Th cell response may have the capability of affecting the outcome of the disease.

The presence of the B cell response to variant surface glycoprotein (VSG) determinants expressed in by the trypanosome variant in the bloodstream of the host is responsible for its partial control of the African trypanosome. Nonetheless, it is well known that other immune elements contribute to the resistance which does not solely depend on the VSG-specific B cell response. A recent experiment has verified that a mouse with a BL/10 or BL/6 genetic background, which has the capability to moderately resist trypanosoma brucei rhodensiense, increase polarized VSG-exact Th1 cell response on the onset of the infection. The response includes IFN-y and IL-2 secretion in response to parasite Ags and a degree of tissue partitioning where peritoneal CD4+ T cells produce the strongest cytokine reaction. The experiment concluded that the production of IFN-y associated with the Th1 cell responses is a key factor that determines the moderate level of host resistance. Moreover, it was observed that capability of the host to IL-4 served no particular purpose to the host, it was neither helpful nor was it dangerous.

T cell

There are changes in the functions of the T cell in trypanosomiasis both in vivo and in vitro. When a histological examination was carried on an infected mouse, it was found out that an extensive B cell enlargement in the nymph nodes and spleen to the extent of replacing the thymus dependant area in T.b brucei infected mouse. Although, the exact trypanosoma antigen-exact T cell was hard to recognize, a transitory proliferative response by the T cell was noted on the onset of the infection followed by the lack of the response. The kinetoplastid protein membrane of several African trypanosomes has the potential of stimulating the proliferation of T lymphocytes. A robust trypanosome specific T cell production happens in cattle after the treatment. In human, the T cells have Tαβ antigen receptors which contain surface markers that permit the discrimination of CD4+ T cell, helper T cells and CD8+ T cells hat are cytotoxic. The production of the two subset of T cell have a noticeable effect on the cytokine response of IFN-y and IL-2, which the host a relative tolerance to African trypanosomiasis (Hertz, Filutowicz and Mansfield, para 10-14).


All the steps of an immune reaction in the inflammatory phase, mononuclear phagocytes play a central task. They act as the antigen presenting cells in an exact immunity in tandem with antibodies and cytokines. They are also involved in immunosuppressive and immunopathological occurrences. In an infected host there is a noticeable increase in macrophages of the liver, spleen and bone marrow. The increased sensitivity of macrophages to environmental changes makes them to respond to stimuli through adopted response. Moreover, their secretions have various tasks and they have the capability to synthesis cytokines and effector mediators. In the existence of a homologous antiserum, macrophages execute an imperative role of protecting the host against trypanosomes. Furthermore, some macrophages have the capacity to produce reactive oxygen intermediaries (ROI) which are among the most toxic species they produce. Thus, the host gains its tolerance of trypanosome from the fact that trypanosomes are highly sensitive to these species especially hydrogen peroxide and hydrochloric acids produced during phagocytosis (Vincendeau and Bouteille, para 13-15).


Of the 54 African countries, animal and human population in 36 risks being infected by African trypanosome. The infection is lethal if not treated in time which has lead to more death in cattle than any other veterinary disease in Africa. Although human beings are naturally immune to African trypanosome apart from Trypanosome brucei gambiense and T.b rhodensiense, their cattle are so lucky for they suffer the brunt of the infection. Those areas that are heavily infested by tsetse fly, the disease vector, experience low development economically and socially because a lot of time and resources are channelled towards the eradication of the insects. Luckily, some immunity from the infections have mediated the effects of the infections which would otherwise be catastrophic, ranging from HDL in human being, variant antigen specific antibody to non specific constitutional response in animals helps the animals and man survive in those tsetse fly infested areas.