The intracellular protozoan Toxoplasma gondii is a widespread opportunistic parasite of humans and animals. Normally, T. gondii establishes itself within brain and skeletal muscle tissues, persisting for the life of the host. Initiating and sustaining strong T-cell-mediated immunity is crucial in preventing the emergence of T. gondii as a serious pathogen. The parasite induces high levels of gamma interferon (IFN-γ) during initial infection as a result of early T-cell as well as natural killer (NK) cell activation. Induction of interleukin-12 by macrophages is a major mechanism driving early IFN-γ synthesis. The latter cytokine, in addition to promoting the differentiation of Th1 effectors, is important in macrophage activation and acquisition of microbicidal functions, such as nitric oxide release. During chronic infection, parasite-specific T lymphocytes release high levels of IFN-γ, which is required to prevent cyst reactivation. T-cell-mediated cytolytic activity against infected cells, while easily demonstrable, plays a secondary role to inflammatory cytokine production. While part of the clinical manifestations of toxoplasmosis results from direct tissue destruction by the parasite, inflammatory cytokine-mediated immunopathologic changes may also contribute to disease progression.

https://cmr.asm.org/content/cmr/11/4/569.full.pdf

Regulation and Function of T-Cell-Mediated Immunity during Toxoplasma gondii Infection

Plant biologists have long recognized that host defence against parasites and pathogens can be divided into two conceptually different components: the ability to limit parasite burden (resistance) and the ability to limit the harm caused by a given burden (tolerance). Together these two components determine how well a host is protected against the effects of parasitism. This distinction is useful because it recognizes that hosts that are best at controlling parasite burdens are not necessarily the healthiest. Moreover, resistance and tolerance can be expected to have different effects on the epidemiology of infectious diseases and host–parasite coevolution. However, studies of defence in animals have to date focused on resistance, whereas the possibility of tolerance and its implications have been largely overlooked. The aim of our review is to (i) describe the statistical framework for analysis of tolerance developed in plant science and how this can be applied to animals, (ii) review evidence of genetic and environmental variation for tolerance in animals, and studies indicating which mechanisms could contribute to this variation, and (iii) outline avenues for future research on this topic.

/pdf/decomposing-health-tolerance-and-resistance-to-parasites-in-3g7zkxp648.pdf

Decomposing health: tolerance and resistance to parasites in animals.

Concomitant infections are common in nature and often involve parasites. A number of examples of the interactions between protozoa and viruses, protozoa and bacteria, protozoa and other protozoa, protozoa and helminths, helminths and viruses, helminths and bacteria, and helminths and other helminths are described. In mixed infections the burden of one or both the infectious agents may be increased, one or both may be suppressed or one may be increased and the other suppressed. It is now possible to explain many of these interactions in terms of the effects parasites have on the immune system, particularly parasite-induced immunodepression, and the effects of cytokines controlling polarization to the Th1 or Th2 arms of the immune response. In addition, parasites may be affected, directly or indirectly, by cytokines and other immune effector molecules and parasites may themselves produce factors that affect the cells of the immune system. Parasites are, therefore, affected when they themselves, or other organisms, interact with the immune response and, in particular, the cytokine network. The importance of such interactions is discussed in relation to clinical disease and the development and use of vaccines.

/pdf/concomitant-infections-parasites-and-immune-responses-mtsorqbtes.pdf

Concomitant infections, parasites and immune responses.

The egg the exoskeleton growth and moulting the epidermis musculature the nervous system the pseudocoelom the secretory-excretory system the digestive system the reproductive system nematode pathology.

The Structure of Nematodes

If cytokines are constitutively expressed by and act on neurons in normal adult brain, then we may have to modify our current view that they are predominantly inflammatory mediators. We critically reviewed the literature to determine whether we could find experimental basis for such a modification. We focused on two "proinflammatory" cytokines, interleukin (IL)-1 and tumor necrosis factor-alpha (TNFalpha) because they have been most thoroughly investigated in shaping our current thinking. Evidence, although equivocal, indicates that the genes coding for these cytokines and their accessory proteins are expressed by neurons, in addition to glial cells, in normal brain. Their expression is region- and cell type-specific. Furthermore, bioactive cytokines have been extracted from various regions of normal brain. The cytokines' receptors selectively are present on all neural cell types, rendering them responsive to cytokine signaling. Blocking their action modifies multiple neural "housekeeping" functions. For example, blocking IL-1 or TNFalpha by several independent means alters regulation of sleep. This indicates that these cytokines likely modulate in the brain behavior of a normal organism. In addition, these cytokines are likely involved in synaptic plasticity, neural transmission, and Ca2+ signaling. Thus, the evidence strongly suggests that these cytokines perform neural functions in normal brain. We therefore propose that they should be thought of as neuromodulators in addition to inflammatory mediators.

"Inflammatory" cytokines: neuromodulators in normal brain?

Light microscopic examination of the buffy coat zone of a microhaematocrit capillary tube expressed on to a slide was found to be consistently more reliable than other standard techniques in detecting trypanosomes in the circulation of cattle. This method alaos allowed identification of different trypanosome species. Optimal results were obtained using darkground illumination.

An improved parasitological technique for the diagnosis of African trypanosomiasis.

Genetic resistance to parasitic disease: particularly of resistance in ruminants to gastrointestinal nematodes.

The responses of susceptible Ndama and Zebu cattle to needle challenge with Trypanosoma congolense were followed using parasitological, haematological and radio-isotopic methods and compared with those of corresponding uninfected animals. In both breeds, infection became patent at the same time but peak parasitaemias were significantly lower, were attained later and were of short duration in the Ndama. All infected animals became anaemic, the severity of which correlated with the level and duration of parasitaemia. However, even when parasites could no longer be detected in the blood, packed cell volumes showed little tendency to recover. The anaemia was due to increased intravascular red cell destruction and was more pronounced in the Zebu. Haemodilution was not a feature. Increased red cell syntheisis occurred in infected animals of both breeds but particularly in the Zebu; this accounted for the capacity to maintain packed cell volume levels following the initial drop associated with parasitaemia. However, in most cases red cell synthesis was less than expected from the degree of anaemia, suggesting impairment of bone marrow function. Measurement of red cell iron utilization indicated that this was due to effective from re-utilization from degraded red cells arising from reticulo-endothelial blockade. It is concluded that the anaemia in this disease and its underlying processes are broadly in line with the number of parasites in the blood and that the superior resistance of the Ndama cattle lies in their ability to control parasitaemia rather than their capacity to mount a more efficient erythropoietic response.

Bovine trypanosomiasis: the red cell kinetics of ndama and Zebu cattle infected with Trypanosoma congolense.

Immunogenetic Influences on Tick Resistance in African Cattle With Particular Reference to Trypanotolerant N'Dama (Bos Taurus) and Trypanosusceptible Gobra Zebu (Bos Indicus) Cattle

Max Murray

Papers

An improved parasitological technique for the diagnosis of African trypanosomiasis.

Genetic resistance to parasitic disease: particularly of resistance in ruminants to gastrointestinal nematodes.

Bovine trypanosomiasis: the red cell kinetics of ndama and Zebu cattle infected with Trypanosoma congolense.

Immunogenetic Influences on Tick Resistance in African Cattle With Particular Reference to Trypanotolerant N'Dama (Bos Taurus) and Trypanosusceptible Gobra Zebu (Bos Indicus) Cattle

Bovine ostertagiasis: structure, function and mode of differentiation of the bovine gastric mucosa and kinetics of the worm loss.