Revisão integrativa dos fatores que desencadeiam a resposta imunológica ao vírus da dengue com enfoque no desenvolvimento de modelos matemáticos
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Data
2022-06-23
Autores
Ribeiro, Beatriz Pinheiro da Silva
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Estudos experimentais e observacionais indicam que a resposta imune adaptativa ao vírus
da dengue tem aspectos protetores e prejudiciais. A infecção primária oferece imunidade protetora contra a reinfecção com o mesmo sorotipo, e proteção cruzada transitória à infecção
com outros sorotipos do vírus da dengue. A longo prazo, essa resposta imune não específica
(sorotipo heterólogo) aumenta o risco de desenvolvimento de dengue hemorrágica. Propomos
uma revisão dos modelos matemáticos com enfoque na imunologia da dengue para estabelecer
o "estado da arte". A revisão bibliográfica foi realizada através de pesquisas em artigos científicos armazenados em bases de dados tradicionais do conhecimento biomédico e utilizou os
seguintes descritores: modelos matemáticos, dengue, dengue hemorrágica, imunologia. Foram
estabelecidos critérios de pesquisa como o intervalo de publicação de 2000 a 2022, e os idiomas português e inglês. Todos os modelos encontrados conseguem reproduzir qualitativamente
a dinâmica viral, celular e a resposta imune observada em pacientes que foram infectados pelo
DENV. Porém, como esses pacientes procuram o serviço hospitalar quando os sintomas da
dengue já se manifestaram, os dados não trazem informação sobre o inicio da infecção e portanto as séries temporais são curtas e incompletas. Essa é uma das maiores dificuldades no
entendimento da resposta imune ao DENV visto que o homem é o único hospedeiro que desenvolve a doença. Entre os modelos matemáticos que abordam a resposta humoral, três trazem
propostas novas de como modelar a dinâmica entre as populações de anticorpo, vírus e células
alvo num contexto de competição de anticorpos (segunda infecção heteróloga) por epítopos do
vírus. Essa parece ser uma abordagem bastante promissora.
Experimental and observational studies indicate that the adaptive immune response to the virus dengue fever has both protective and harmful aspects. Primary infection provides protective immunity against re-infection with the same serotype, and transient cross-infection protection with other dengue virus serotypes. In the long term, this non-specific immune response (heterologous serotype) increases the risk of developing dengue hemorrhagic fever. we propose a review of mathematical models focusing on dengue immunology to establish the state of the art". The bibliographic review was carried out through searches in scientific articles stored in traditional databases of biomedical knowledge and used the following descriptors: mathematical models, dengue, dengue hemorrhagic fever, immunology. Were established search criteria such as the publication interval from 2000 to 2022, and the Portuguese and English languages. All models found can reproduce qualitatively the viral, cellular dynamics and the immune response observed in patients who were infected by DENV. However, how do these patients look for the hospital service when the symptoms of dengue fever has already manifested itself, the data do not provide information about the onset of infection and therefore the time series are short and incomplete. This is one of the biggest difficulties in understanding of the immune response to DENV since man is the only host that develops the disease. Among the mathematical models that address the humoral response, three bring new proposals for how to model the dynamics between antibody, virus and cell populations target in the context of antibody competition (second heterologous infection) for epitopes of the virus. This appears to be a very promising approach.
Experimental and observational studies indicate that the adaptive immune response to the virus dengue fever has both protective and harmful aspects. Primary infection provides protective immunity against re-infection with the same serotype, and transient cross-infection protection with other dengue virus serotypes. In the long term, this non-specific immune response (heterologous serotype) increases the risk of developing dengue hemorrhagic fever. we propose a review of mathematical models focusing on dengue immunology to establish the state of the art". The bibliographic review was carried out through searches in scientific articles stored in traditional databases of biomedical knowledge and used the following descriptors: mathematical models, dengue, dengue hemorrhagic fever, immunology. Were established search criteria such as the publication interval from 2000 to 2022, and the Portuguese and English languages. All models found can reproduce qualitatively the viral, cellular dynamics and the immune response observed in patients who were infected by DENV. However, how do these patients look for the hospital service when the symptoms of dengue fever has already manifested itself, the data do not provide information about the onset of infection and therefore the time series are short and incomplete. This is one of the biggest difficulties in understanding of the immune response to DENV since man is the only host that develops the disease. Among the mathematical models that address the humoral response, three bring new proposals for how to model the dynamics between antibody, virus and cell populations target in the context of antibody competition (second heterologous infection) for epitopes of the virus. This appears to be a very promising approach.
Descrição
Palavras-chave
DENV, Equações diferenciais ordinárias, Limiares, Resposta imunológica