COMPREENDENDO A IMUNOLOGIA NOS TRANSPLANTES DE TECIDOS OFTALMOLÓGICOS

Introdução: O transplante de órgãos, um dos maiores avanços da medicina, se tornou popular, sendo mais comum para córneas, envolvendo a substituição, completo (penetrante) ou parcial (lamelar ou profundo) da córnea doente. A esperada eficácia do transplante é quase sempre alcançada, devendo aos cuidados tanto com doador quanto receptor, relevando da rejeição do tecido até os cuidados após intervenção. Objetivo: Compreender a importância da imunologia para os transplantes de tecidos oftalmológicos. Materiais e Métodos: Pesquisa bibliográfica digital, no google academic, combinando os termos transplantes, imunogenética e córnea. Resultados: A rejeição do transplante é processo imunológico de descompensação da córnea transplantada. A principal razão para o bom efeito está no privilégio da córnea, devido ao viés imunológico que ocorre no segmento anterior, abreviado ACAID (Anterior Chamber Associated Immune Deviation), que perde sua eficiência num processo inflamatório, aumentando o número de células de Langerhans e a expressão de antígenos classe I e II do complexo principal de histocompatibilidade, aumentando citocinas pró-inflamatórias oculares, provocando neovascularização da córnea. A perda do privilégio imunológico é acompanhada de rejeição, e seu mecanismo pode ser dividido em três etapas: (a) Rejeição do braço aferente - reconhecer o sistema imunológico de antígenos heterólogos como principal componente da rejeição do braço aferente. As células de Langerhans são um fator chave nesse processo, pois além de estimular os linfócitos B e T, processam e apresentam antígenos ao sistema imunológico; (b) Estágio central da rejeição - reconhecer um antígeno como heterólogo ativa os linfócitos T imaturos para proliferar e realizar a expansão clonal; (c) Braço eferente da rejeição - reação eferente da rejeição do transplante de córnea, mediada por células e nenhum anticorpo envolvido. As principais células que comandam a destruição do enxerto são os linfócitos T CD4+, que recrutam outras células efetoras: macrófagos, leucócitos polimorfonucleares e linfócitos NK (natural killer), que liberam citocinas, como o fator de necrose tumoral, destruindo células do doador. Conclusão: O endotélio com capacidade de replicação limitada é a razão do insucesso do transplante do doador. A compreensão dos aspectos imunológicos da rejeição, as manifestações clínicas e a classificação da rejeição são fundamentais aos oftalmologistas na personalização do tratamento.

Neutrophils in COVID-19

Strong evidence has been accumulated since the beginning of the COVID-19 pandemic that neutrophils play an important role in the pathophysiology, particularly in those with severe disease courses. While originally considered to be a rather homogeneous cell type, recent attention to neutrophils has uncovered their fascinating transcriptional and functional diversity as well as their developmental trajectories. These new findings are important to better understand the many facets of neutrophil involvement not only in COVID-19 but also many other acute or chronic inflammatory diseases, both communicable and non-communicable. Here, we highlight the observed immune deviation of neutrophils in COVID-19 and summarize several promising therapeutic attempts to precisely target neutrophils and their reactivity in patients with COVID-19.

Mechanisms of sex hormones in autoimmunity: focus on EAE

Sex-related differences in the occurrence of autoimmune diseases is well documented, with females showing a greater propensity to develop these diseases than their male counterparts. Sex hormones, namely dihydrotestosterone and estrogens, have been shown to ameliorate the severity of inflammatory diseases. Immunologically, the beneficial effects of sex hormones have been ascribed to the suppression of effector lymphocyte responses accompanied by immune deviation from pro-inflammatory to anti-inflammatory cytokine production. In this review, we present our view of the mechanisms of sex hormones that contribute to their ability to suppress autoimmune responses with an emphasis on the pathogenesis of experimental autoimmune encephalomyelitis.

Viral Infections and Autoimmune Disease: Roles of LCMV in Delineating Mechanisms of Immune Tolerance

Viral infections are a natural part of our existence. They can affect us in many ways that are the result of the interaction between the viral pathogen and our immune system. Most times the resulting immune response is beneficial for the host. The pathogen gets cleared thus protecting our vital organs with no other consequences. Conversely, the reaction of our immune system against the pathogen can cause organ damage (immunopathology) or lead to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the “fertile field” hypothesis, terms defined in our review. On the flip side, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the “hygiene hypothesis”, also defined here. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototypes showing that the interaction of our immune system with viruses can either accelerate or prevent autoimmunity. Studies using mouse models of LCMV have helped conceive and establish several concepts that we today know and explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established during the course LCMV are described in this short review.

Viral Infections and Autoimmune Disease: Roles of LCMV in Delineating Mechanisms of Immune Tolerance

Viral infections are a natural part of our existence. They can affect us in many ways that are the result of the interaction between the viral pathogen and our immune system. Most times, the resulting immune response is beneficial for the host. The pathogen is cleared, thus protecting our vital organs with no other consequences. Conversely, the reaction of our immune system against the pathogen can cause organ damage (immunopathology) or lead to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the “fertile field” hypothesis (terms defined in our review). In contrast, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the “hygiene hypothesis”, also defined here. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototypes showing that the interaction of our immune system with viruses can either accelerate or prevent autoimmunity. Studies using mouse models of LCMV have helped conceive and establish several concepts that we now know and use to explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established during the course of LCMV infection are described in this short review.

Viral Infections and Autoimmune Disease: Roles of LCMV in Delineating Mechanisms of Immune Tolerance

Viral infections make a natural part of our existence. They can affect us in hundreds of different ways that are the result of the interaction between the viral pathogen and our immune system. Most times the resulting immune response is beneficial for the host. The pathogen gets cleared protecting our vital organs with no other consequences. Sometimes, things go wrong and the reaction of our immune system against the pathogen causes organ damage (immunopathology) or leads to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the “fertile field” hypothesis. On the flip side, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the “hygiene hypothesis”. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototype viral systems showing that the interaction of our immune system with the viruses can either accelerate or prevent autoimmunity. Studies using LCMV have helped conceive and establish several concepts that we today know and explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established in LCMV are described in this short review.