An Immunological Model of Trypanosoma (Tkypanozoon) Brucei Brucei in the Vervet Monkey (Cercopithecus Aethiops)
Year: 1982
Type: dissertation
Abstract: The vervet monkey was susceptible to two stocks and a \nclone of T. brucei. At a dose of 1 x 10"* inoculated parasites the \nstocks killed the monkeys either in acute or chronic infection. \nAlso, the cloned parasite showed a dose-dependent response. \n0 \nMonkeys died during acute infection when inoculated with 1 x 10 \ncloned trypanosomes. However, those inoculated with 5 x 10 or \n1 x 10 3 parasites gave variable disease pictures and died either \nduring sub-acute or chronic infection particularly when \nstaphylococcal and streptococcal secondary infections supervened. \nTo effectively interpret the results in a T. brucei-infected \nmonkey it was first necessary to establish the normal parameters \nfor conventional cell-mediated responses in a normal uninfected \nmonkey. In the peripheral blood of the vervet monkey, T \n(erythrocyte rosettes) and B (Stnlg) formed 70 and of 10% lymphocytes, \n6 , respectively. Peripheral blood lymphocytes at 2 x 10 per ml, \nresponded optimally to non-specific mitogens, Con A and PHA but not \n14 \nto LPS when cultured for 72 - 120 hours and pulsed with C-TdR for \n16 hours terminally, as also did lymphocytes contained in ten-fold \ndiluted whole blood. \nMeanwhile responder lymphocytes at 3 x 10 per ml were \noptimally stimulated in an MLC type reaction with an equal \nconcentration of xenogeneic CLA^ cells when co-cultured for \n168 hours and pulsed as above. The stimulation by allogeneic or \nsemi-xenogeneic cells from vervet monkeys or humans was poor. \nThe relationship between infection, treatment and self-cure \nr ^ c t tn i"rr.Mne responses vas alco studied. After \nimmunization with tetanus toxoid, and 2, 4-dinitrochlorobenzene \n(DNCB) monkeys were inoculated with 1 x 10^ trypanosomes. \nSubsequently, their lymphocytes were tested in vitro with Con A, \nPHA and xenogeneic CIA^ cells (in MLC); their DTH tested in vivo \nwith DNCB and their sera examined for specific (anti-trypanosome \nand anti-tetanus) and non-specific (heterophile) antibodies. \nInitially total IgM and heterophile antibodies were highly \nelevated while the IgG levels were only slightly raised. Meanwhile \nonly the primary IgM (but not IgG) anti-tetanus antibodies and the \nMLR were enhanced. Subsequently, in vitro Con A, PHA and MLC \nlymphocyte responses, DNCB skin reactivity and both IgM and IgG \nanti-tetanus antibodies were depressed through the course of \ninfections. Similarly, monkeys that survived the infection without \ntreatment also showed depressed cell-mediated immune parameters. \nBerenil treatment restored quickly, within 3 days the \nanti-tetanus antibody responses to normal. However, in vitro \nCon A, PHA and MLC as well as in vivo skin responses reverted \nto normal slowly after more than 30 days in the previously \nT. brucej-infected monkeys. Berenil had no effect on the immune \nresponses of uninfected control monkeys. \nMonkeys inoculated with 1 x 10 trypanosomes died of acute \ninfection within 2 - 3 weeks while showing depressed lymphocyte \nresponses to Con A and PHA. In the monkeys infected with \n1 x 10^ trypanosomes self-cure occurred and cleared the parasitaemia \nin the blood. However, self-cure did not abrogate the \nimmunodepression as evidenced by persistently depressed \nstimulation indices from Con A-and PHA-stimulated lymphocytes \nduring the period of absence of detectable parasitaemia and 155 \ndays after the start of the experiment. This suggested that the \ntrypanosomes were perhaps still present in some occluded sites \ne.g. CNS or tissues, from where they probably exerted their \npersistent immunodepressive effect. \nDuring infection leucocytes and their sub-sets changed \nnumerically and proportionally. In monkeys inoculated with \n8 4 1 x 10 or 1 x 10 trypanosomes leucopenia occurred accompanied \nby lymphocytopenia, neutrocytosis and monocytosis. The \nlymphocytopenia, was associated with low absolute erythrocyte \nrosette (T) and surface membrane immunoglobulin-bearing (B) cells \nand initially reduced but subsequently normal absolute "null" cell \ncounts. \nThe proportions of lymphocytes decreased while those of \nneutrophils and monocytes increased, respectively. Normocytic \nand hypochromic anaemia was the most prominent feature of \nT. brucei infection in the vervets. It persisted in animals that \ndied of the disease but was abrogated by Berenil treatment and \nself-cure both of which restored to normal the total counts and \nsubpopulations of leucocytes in the chronically infected animals.
Author: Arthur Cyrus
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2894180089