Dynamic Tuning of Lymphocytes: Physiological Basis, Mechanisms, and Function

Grossman, Zvi; Paul, William E.

doi:10.1146/annurev-immunol-032712-100027

Cited by 86 publications

(111 citation statements)

References 127 publications

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“…higher parasitaemia) to cause the activation of immune cells. This proposition agrees with the notion of an adaptive cellular interaction, where the activation thresholds of immune cells are being reset to higher levels following each antigen encounter 131, 132. Thus, we propose that every parasite encounter would, presumably, require a higher parasitaemia (antigen load) to stimulate and activate immune cells.…”

Section: Mechanisms Of Reduced Inflammation At High Exposure Levelssupporting

confidence: 88%

Evaluating antidisease immunity to malaria and implications for vaccine design

Ademolue

Awandare

2017

Immunology

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SummaryImmunity to malaria could be categorized broadly as antiparasite or antidisease immunity. While most vaccine research efforts have focused on antiparasite immunity, the evidence from endemic populations suggest that antidisease immunity is an important component of natural immunity to malaria. The processes that mediate antidisease immunity have, however, attracted little to no attention, and most interests have been directed towards the antibody responses. This review evaluates the evidence for antidisease immunity in endemic areas and discusses the possible mechanisms responsible for it. Given the key role that inflammation plays in the pathogenesis of malaria, regulation of the inflammatory response appears to be a major mechanism for antidisease immunity in naturally exposed individuals.

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Section: Mechanisms Of Reduced Inflammation At High Exposure Levelssupporting

confidence: 88%

Evaluating antidisease immunity to malaria and implications for vaccine design

Ademolue

Awandare

2017

Immunology

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“…We consider the no-flux boundary conditions for both variables. In the case without delay (µ = 0) system (14), (15) is similar to the well known system of competition of species in population dynamics. We will consider it also on the whole axis in order to study travelling wave solutions.…”

Section: Constant ϕ Linear ψmentioning

confidence: 95%

“…Depending on the viral load and growth kinetics, the efficacy of the CTL response in determined by a balance of proliferation, anergy induction and activation-induced cell death by apoptosis. The later two take into account the tuning of lymphocytes [14], a key feature of the immune system. …”

Section: Modelmentioning

confidence: 99%

“…Then there exist travelling wave solutions of system (14), (15), that is the solution v(x, t) = V (x − st), c(x, t) = C(x − st), where s is the speed of propagation and the functions V , C satisfy the system of equations…”

Section: Constant ϕ Linear ψmentioning

confidence: 99%

“…Virus-specific cytotoxic T lymphocytes (CTL) play a key role in the dynamics and outcome of virus infections [10,11] . Importantly, that CTL temporal dynamics and viral growth dynamics can under many circumstances be successfully captured using simple conceptual views of the regulation based on predator-prey systems [13], there are other phenomena, such as CTL exhaustion, which do not fit in this simple predator-prey interpretation and demand more complex conceptual models (e.g., the balance of growth and differentiation models) to capture reality [14]. Since long ago, it was observed that virus infections have a strong impact on the immune system [15].…”

Section: Introductionmentioning

confidence: 99%

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Modelling the dynamics of virus infection and immune response in space and time

Bocharov

Meyerhans

Bessonov

et al. 2017

International Journal of Parallel, Emergent and Distributed Sys

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International audienceSpreading of viral infection in the tissues such as lymph nodes or spleendepends on virus multiplication in the host cells, their transport andon the immune response. Reaction–diffusion systems of equations withdelays in proliferation and death terms of the immune cells represent anappropriate model to study this process. The properties of the immuneresponse and the initial viral load determine the regimes of infectionspreading. In the proposed model, the proliferation rate of the immunecells is represented by a bell-shaped function of the virus concentrationwhich increases for small concentrations and decreases if the concentrationis sufficiently high. Here we use such a model system to show that aninfection can be completely eliminated or it can remain present togetherwith a decreased concentration of immune cells. Finally, immune cellscan be completely exhausted leading to a high virus concentration in thetissue. In addition, we predicted two novel regimes of infection dynamicsnot observed before. Infection propagation in the tissue can occur asa superposition of two travelling waves: first wave propagates as a lowlevel infection front followed by a high level infection front with a smallerspeed of propagation. Both of the travelling waves can have a positive or anegative speed corresponding to infection advancement or retreat. Theseregimes can be accompanied by instabilities and the emergence of complexspatiotemporal patterns

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MHC I tetramer staining tends to overestimate the number of functionally relevant self‐reactive CD8 T cells in the preimmune repertoire

2023

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Previous studies that used peptide‐MHC (pMHC) tetramers (tet) to identify self‐specific T cells have questioned the effectiveness of thymic‐negative selection. Here, we used pMHCI tet to enumerate CD8 T cells specific for the immunodominant gp33 epitope of lymphocytic choriomeningitis virus glycoprotein (GP) in mice transgenically engineered to express high levels of GP as a self‐antigen in the thymus. In GP‐transgenic mice (GP+), monoclonal P14 TCR+ CD8 T cells that express a GP‐specific TCR could not be detected by gp33/Db‐tet staining, indicative of their complete intrathymic deletion. By contrast, in the same GP+ mice, substantial numbers of polyclonal CD8 T cells identifiable by gp33/Db‐tet were present. The gp33‐tet staining profiles of polyclonal T cells from GP+ and GP‐negative (GP−) mice were overlapping, but mean fluorescence intensities were ∼15% lower in cells from GP+ mice. Remarkably, the gp33‐tet+ T cells in GP+ mice failed to clonally expand after lymphocytic choriomeningitis virus infection, whereas those of GP− mice did so. In Nur77GFP‐reporter mice, dose‐dependent responses to gp33 peptide‐induced TCR stimulation revealed that gp33‐tet+ T cells with high ligand sensitivity are lacking in GP+ mice. Hence, pMHCI tet staining identifies self‐specific CD8 T cells but tends to overestimate the number of truly self‐reactive cells.

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Dynamic Tuning of Lymphocytes: Physiological Basis, Mechanisms, and Function

Cited by 86 publications

References 127 publications

Evaluating antidisease immunity to malaria and implications for vaccine design

Evaluating antidisease immunity to malaria and implications for vaccine design

Modelling the dynamics of virus infection and immune response in space and time

MHC I tetramer staining tends to overestimate the number of functionally relevant self‐reactive CD8 T cells in the preimmune repertoire

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