Commentary in 2007

We will never have a better opportunity to improve public health globally. The question is whether we are shrewd enough, bold enough, and committed enough to make it happen.

As part of the Global Theme Issue on Poverty and Human Development, Frances Gotch and Jill Gilmour describe the development of laboratory capacity to support HIV vaccine trials as a model for technology transfer in the developing world.

Relatively few studies have used live tissue microscopy to evaluate how the immune system responds to pathogens. In this commentary we discuss the challenges of imaging infectious processes and the questions that can be addressed with these dynamic approaches.

Modern cellular and molecular studies have made great progress in characterizing the mechanisms that control immune responses. Now it is time to broaden the present views to accommodate evidence from epitope-specific and other immunoregulatory systems, which were well studied some years ago and are still highly relevant to contemporary work.

Mutations have been the driving force behind some of the most important discoveries in immunology, and the growing speed with which they can be found has impelled the use of random mutagenesis to create new immunological phenotypes in mice. Here we describe how phenotypes are created, detected and ascribed to genetic change.

Conditional gene targeting based on excision or inversion of loxP-flanked DNA segments by Cre recombinase is a powerful technology for the analysis of gene function, but unexpected expression patterns of cre transgenes, variability of recombination efficiency depending on the target gene and potential toxicity of Cre recombinase represent serious challenges for the experimenter.

There is general appreciation that 'genetic background effects' can profoundly affect the immune phenotypes of congenic, transgenic and knockout mice. We suggest that attributing phenotypes to genetic background effects is outmoded and that new databases containing single-nucleotide polymorphisms obtained with a group of inbred mouse strains can be used to define the flanking DNA of nearly all mouse genes.

Investigations of immune recognition in nonmammalian species provide new insights into the evolution of immunity and the inner workings of the mammalian immune system. Very diverse mechanisms are used by different multicellular organisms to recognize and cope with the rapidly evolving microbial world.

Maternal-infant transmission provides a useful model for the study of immune factors associated with protection against the acquisition of human immunodeficiency virus and has emphasized the importance of CCL3 in protective immunity to this virus.

There have been enormous advances in the field of immunology over the past 3 decades, and those advances have had a positive effect on many subspecialties of medicine. Opportunities for even more notable advances remain. However, present and projected budget constraints for the National Institutes of Health have created formidable challenges. This commentary addresses the opportunities and challenges for the field of immunology during a period of restricted budgets.

Immune responses to microbial challenge in various tissues are not the same. Organ-specific immune responses are adapted to maintain organ physiology.

In their own defense, tissues send a panoply of signals that initiate immunity and guide the choice of effector class. T_H1-T_H2 and T_reg is far too simple a representation of the breathtaking variety of the resulting responses.

The immune system has co-evolved with microbes that cause acute infectious disease. Immune responses must be appropriate to allow survival of both the individual and the species. These responses involve complex interactions that often go unmeasured.

Communicating about and comprehending immune responses and immunity will be facilitated by greater attention to semantic precision and consistency and increased willingness to engage with the full dimensionality and quantitative nature of immunological phenomena.