Current status of immunology research in India

Rudimentary studies on aspects of biochemistry in India date back to 1927. But, in the field of Immunology, such studies were started by scholars only during early 1970s at the All India Institute of Medical Sciences, New Delhi, India. Science and Technology was not an immediate priority until 1961 due to domestic and political conditions in the country. We were then 11 years old since independence and our focus was on economic and social developments. Gradually, improvements were made in the field and now we have 15 to 20 major groups (small in size) of immunologists in the country, who have made significant contribution in the field during the last 8 to 10 years. Hence, we anticipate improvements in manpower and infrastructure in the near future

Status sorológico e de infecção canina em área endêmica de leishmaniose visceral

OBJECTIVE This study investigated the serological status of dogs living in a visceral leishmaniasis-endemic area and its correlation with the parasitological condition of the animals. METHODS Canine humoral response was evaluated using the sera of 134 dogs by enzyme-linked immunosorbent assay and immunohistochemistry to detect parasites in the skin, lymph node, and spleen of the animals. The specific antibodies investigated were IgG, IgG1, IgG2, and IgE. RESULTS According to the parasitological, laboratory, and clinical findings, the dogs were placed into one of four groups: asymptomatic with (AP+, n = 21) or without (AP-, n = 36) Leishmania tissue parasitism and symptomatic with (SP+, n = 52) or without (SP-, n = 25) parasitism. Higher IgG and IgE levels were positively correlated with the infection condition and parasite load, but not with the clinical status. In all groups, total IgG was the predominant antibody, which occurred at the expense of IgG2 instead of IgG1. Most of the infected dogs tested positive for IgG (SP+, 98.1%; AP+, 95.2%), whereas this was not observed with IgE (SP+, 80.8%; AP+, 71.2%). The most relevant finding was the high positivity of the uninfected dogs for Leishmania-specific IgG (SP-, 60.0%; AP-, 44.4%), IgE (SP-, 44.0%; AP-, 27.8%), IgG1 (SP-, 28.0%; AP-, 22.2%), and IgG2 antibodies (SP-, 56.0%; AP-, 41.7%). CONCLUSIONS The serological status of dogs, as determined by any class or subclass of antibodies, did not accurately distinguish dogs infected with L. (L.) infantum chagasi from uninfected animals. The inaccuracy of the serological result may impair not only the diagnosis, but also epidemiological investigations and strategies for visceral leishmaniasis control. This complex serological scenario occurring in a visceral leishmaniasis-endemic area highlights the challenges associated with canine diagnosis and points out the difficulties experienced by veterinary clinicians and coordinators of control programs.OBJETIVO Foi investigado o status sorológico de cães, em área endêmica de leishmaniose visceral, e sua correlação com a infecção parasitológica dos animais. MÉTODOS A resposta humoral canina foi avaliada no soro de 134 cães pelo método ELISA e pela imuno-histoquímica, para detectar parasitos na pele, linfonodo e baço desses animais. Os anticorpos específicos investigados foram IgG, IgG1, IgG2 e IgE. RESULTADOS De acordo com os achados parasitológicos, laboratoriais e clínicos, os cães foram alocados em um dos quatro grupos: assintomáticos com (AP+, n = 21) e sem (AP-, n = 36) parasitismo tecidual por Leishmania e sintomáticos com (SP+, n = 52) ou sem (SP-, n = 25) parasitismo. Níveis mais elevados de IgG e IgE se correlacionaram positivamente com o status de infecção e a carga parasitária, mas não com a condição clínica. Em todos os grupos, IgG total foi o anticorpo predominante, com maior concentração de IgG2 que IgG1. O anticorpo IgG foi positivo em proporção elevada nos animais infectados (SP+ 98,1%; AP+ 95,2%), mas não o IgE (SP+ 80,8%; AP+ 71,2%). O achado mais relevante refere-se aos cães não infectados que apresentaram elevada positividade para anticorpos IgG anti-Leishmania (SP- 60,0%; AP- 44,4%), IgE (SP- 44,0%; AP- 27,8%), IgG1 (SP- 28,0%; AP- 22,2%) e IgG2 (SP- 56,0%; AP- 41,7%). CONCLUSÕES O status sorológico dos cães, determinado por qualquer classe ou subclasse de anticorpos, não distinguiu com acurácia cães infectados por L. (L.) infantum chagasi daqueles não infectados. A imprecisão do resultado sorológico pode prejudicar não só o diagnóstico, mas também as investigações epidemiológicas e as estratégias para o controle da leishmaniose visceral. Esse complexo cenário sorológico observado na área endêmica mostra quão desafiador é o diagnóstico canino, e aponta a dificuldade enfrentada pelos médicos veterinários e coordenadores dos programas de controle

Antibody enhanced intracellular killing of Leishmania amazonensis: the role of soluble immune complexes and their effect on autophagy

Leishmania amazonensis is an intracellular protozoal parasite that causes cutaneous leishmaniasis in humans and other mammalian hosts. This disease affects people within tropical and subtropical countries. Generally a Th1 cell-mediated host immune response is thought to be important for the clearance of the parasite. However, throughout this work we have shown that a productive B cell response is important for the clearance of the parasite through the production of IgG2a isotype antibodies. These antibodies can form small soluble immune complexes that can stimulate the FcγR leading to the production of superoxide. Superoxide and nitric oxide are required to kill intracellular L. amazonenesis parasites. Our studies have also shown that macrophages can be activated to produce these required immune factors if they are stimulated with soluble immune complexes, IFN-γ, and Leishmania antigen (tripartite activation). We have also found that these three factors can lead to the upregulation of the autophagy pathway for the clearance of the parasite. These soluble immune complexes can be replaced by novel recombinant proteins that have similar morphology to murine IgG2a Fc. These Fc constructs have the ability to recapitulate killing of the parasite and superoxide production seen with tripartite activation. All of these factors are important for the development of a possible immunomodulating therapy that could be used to treat patients infected with this chronic, debilitating disease

The role of TLR2 in cutaneous leishmaniasis and as a target for vaccine adjuvants

After the introduction of clean water, vaccination is thought to be the most effective public health tool ever introduced, responsible for preventing millions of cases of disease, disability and death each year. Unfortunately there remain a number of important human diseases for which we have no vaccine, particularly parasitic diseases, such as leishmaniasis, which primarily affect poor communities in tropical regions. There are many complex reasons why we have failed to develop effective vaccines for parasitic diseases, but there is hope that with our improved understanding of the immune system alongside the development of a new generation of vaccines, we will soon develop new vaccines which are effective enough to prevent such diseases. Toll-like receptors (TLRs) are major targets for adjuvants and have been shown to be crucial for defence against a number of infections. TLR2 recognises bacterial lipopeptides in a heterodimer with either TLR1 or TLR6, and its function has been linked to protection against various bacterial infections and to the efficacy of the BCG vaccine. TLR2 has been shown to recognise surface glycoconjugates of Leishmania parasites in vitro, particularly lipophosphoglycan (LPG). In this study, in vivo experimental infections show that TLR2 has a protective role in controlling cutaneous leishmaniasis (CL), as shown by increased lesion sizes and parasite burdens in TLR2-/- mice infected with L. major and L. mexicana. Furthermore, it appears that LPG is not the major mediator of TLR2 activation during infection with L. mexicana, as parasites lacking LPG also resulted in exacerbated disease in TLR2-/- mice. Mice lacking TLR2 co-receptors TLR1 and TLR6 did not show increased susceptibility to infection, suggesting either mono-TLR2 function or alternative co-receptor involvement. Infected TLR2-/- mice show a skewed Th2 immune response to Leishmania, as demonstrated by elevated IL-4, IL-13 and IL-10 production by draining lymph node (DLN) cells in response to antigen. These results suggest that TLR2 is involved in promoting protective immune responses to Leishmania parasites during primary infection in vivo, and is a potential target for protective and therapeutic vaccine adjuvants. Paradoxically, however, TLR2-targeting lipopeptides Pam2 and Pam3 were ineffective adjuvants for use in a whole-cell vaccine to protect against CL, as whole-cell autoclaved L. major (ALM) vaccines containing lipopeptides resulted in exacerbated disease upon challenge when compared to unvaccinated controls and in contrast to effective vaccination when CpG adjuvants were used. The ratio of antigen specific IgG1:IgG2c antibody isotypes, which is a marker of the type of adaptive immune response (Th1 or Th2), was elevated in mice that received vaccines containing lipopeptide adjuvants, suggesting that these adjuvants drive non-protective Th2 responses to Leishmania. In a Th2-dependent vaccine model using Brugia malayi, the use of Pam2 as an adjuvant resulted in an enhanced protective phenotype with similar efficacy to the Th2-driving adjuvant Alum. Thus, in the context of CL infection TLR2 has a protective role in late-stage primary infections with L. major and L. mexicana, yet when targeted with lipopeptide adjuvants in whole-cell vaccines promotes exacerbated disease in challenge infections, through driving Th2 immune responses. Lipopeptides that target TLR2, such as Pam2, are therefore more appropriate for use as adjuvants in vaccines where Th2 protective immunity is required