More than 2500 immunologists braved all weather in the "Mile High" city of Denver for the 90th Annual Meeting of the American Association of Immunologists. Their presentations revealed the dynamic and progressive nature of immunology research, taking advantage of some of the latest technologies to address both long-standing mysteries and new questions.

Even after trudging through snow on the last day, delegates warmed enthusiastically to a stunning visualization of early stages of autoimmune arthritis. And assuming that they'd had a stress-free time, their memories of the week and immune defenses would stay intact for the return home.

Increasingly, the innate immune system has entered the limelight, as researchers define the receptors and signals of this rapid defense force. Rare cases of people with severe recurrent infections have served as human models for investigating innate immunity, with the identification of mutations in the IRAK4 signaling protein that account for vulnerability to bacterial infection. Meanwhile, a new mutant mouse range has revealed the common action of an adaptor protein in the response to viruses and bacteria by TLR3 and TLR4 receptors.

The mucosal immune system is also getting more attention, leading to new insights into the balancing act between tolerance and immunity in the gut. The FcRn receptor, for years believed to be important solely for the transport of maternal IgG in newborns, now appears to be important into adulthood for the transport of tolerizing immune complexes. Meanwhile, Philippe Sansonetti of the Pasteur Institute has identified how epithelial cells respond to bacteria such as Shigella, via the cytoplasmic protein NOD1 that binds to a tripeptide of bacterial peptidoglycan.

Another type of sensor on the surface of CD11c+/CD11b-lo dendritic cells of the gut picks up reovirus and possibly other viruses, and presents them to T cells, and may serve as a new target for the design of vaccines that work specifically at mucosal surfaces. These surfaces are now a particularly desirable goal in HIV research, as 90% of HIV infection occurs across mucosal surfaces.

Moving from basic research and into the clinic, dendritic cells are increasingly finding application in the ex vivo manipulation of T cells for cancer immunotherapy, as described by Carl June, and for use in cancer vaccines. These studies help set the stage for the future direction of the immunology field, which according to Ralph Steinman of the Rockefeller University, New York, is now sufficiently well equipped to pursue human investigation. The use of tumor vaccines may also benefit from further knowledge of what controls the trafficking of tumor-specific T cells into lesions.

But tumors also have ways of trying to evade immunity. Pamela Ohashi told delegates that at least for her mouse SV40 tumor model, T cells are somehow impaired even though they may infiltrate tumors in large numbers, together with dendritic cells.

Pathogens too have ways of escaping resistance. Anthrax bacteria, for example, reduce the capacity of dendritic cells to activate T cells, whilst HIV may be able to counteract the anti-inflammatory action of tyrosine kinase receptor RON. This is part of a negative feedback process that inhibits HIV replication by dampening pro-inflammatory signals, for example in macrophages. HIV also benefits by being sequestered away by follicular dendritic cells, ready to reappear upon cessation of drug therapy.

On a public-health level, concerns are also mounting that the devastating impact of HIV on the immune system may also manifest itself in a new epidemic if the recently identified SARS virus gains a significant foothold in Africa and other developing countries where HIV is prevalent.

For those interested in the more basic concepts, such as T- and B-cell development, tolerance in peripheral tissues - most of the time - and the nature of autoimmunity, there was no shortage of new findings. T-cell development is far more plastic than was previously thought, with T cells developing from other sources besides the common lymphoid progenitor cell, whilst the mechanisms behind B-cell fate determination and receptor expression are also being elucidated.

As Paul Kincade noted in his presidential address, AAI prides itself in providing a supportive and educative environment for researchers throughout their careers, including the presentation of awards senior scientists. But one investigator who was sadly missed was Charlie Janeway, who died on 12 April, after a career spanning 40 years of research, teaching, and writing.