The vertebrate immune system has to solve a complex, multidimensional problem in space and time. It needs to protect the host against a wide variety of pathogens and tissue insults… Click to show full abstract
The vertebrate immune system has to solve a complex, multidimensional problem in space and time. It needs to protect the host against a wide variety of pathogens and tissue insults including malignant transformation, each of which has its own unique characteristics, to conduct these activities where the location of the problem within the body is not predetermined, and to be ready to provide a suitable response to these various challenges at unpredictable times. The evolutionary solution to this linked set of equations is to combine soluble mediators that can suffuse the entire body together with cellular elements capable of extensive migration between and within tissues. The latter responses are divided into broadly reactive immediate effectors (innate immunity) and more slowly differentiating and proliferating effectors dependent on selective recognition of finegrained rather than generic molecular features of the pathogen or tumor (adaptive immunity). The key cellular elements mediating innate and adaptive responses are myeloid and lymphoid cells whose capacity and need for migration are nearly unique among the cells of the adult organism. Further, the rare nature of the antigenspecific T and B lymphocytes that provide adaptive immunity places enormous demands on the system. It must be functionally and spatially organized to enable efficient interaction among these sparse elements in a timely manner. This is to insure that pathogen replication does not overwhelm the host before these defensive functions can be brought to bear through clonal expansion and differentiation of the few relevant cells.1 Understanding how the immune system facilitates the latter interactions and how innate cells conduct the search and destroy missions that hold invaders or malignant cells at bay until the adaptive effectors can join the fray clearly requires observing and measuring cell dynamics within diverse tissues and organs. It also demands highresolution mapping of cell content and spatial organization in secondary immune organs as well as in tissue sites of effector function. Such information can only be gathered at present using imaging based on advance microscopy methods. As several of the reviews in this volume point out, microscopic observation has been a part of immunological study for more than a century. However, it is only in the past 2 decades that methods and technologies have emerged that permit (a) in situ dynamic observation of immune cell behavior deep in tissues and (b) detailed mapping of immune system architecture with full attention to the increasing number of cell subsets and states that new methods for dissociated singlecell analysis have revealed. The major tipping point in terms of imaging immunity came in 2002, when a trio of copublished papers first reported immune cell dynamics in intact tissue samples.24 This was followed in short order by a seminal fourth paper employing true intravital imaging to establish what has become the existing kinetic paradigm for T cell responses to foreign antigen within lymph nodes.5 These early papers led to a great deal of excitement in the field and the rapid adoption of these new imaging methods by other laboratories. A previous volume of immunologic reviews contained articles summarizing the very early successes of this new way of visualizing the immune system and pointing out (correctly) the enticing prospects for future advances.6 On the decadal anniversary of publication of the original dynamic imaging papers, a major review highlighted the enormous progress made in the first 10 years of imaging, with its emphasis on dynamics of immune cells.7 We are now another decade into the steady growth of imaging as a major approach to exploration of immune system, and it is clearly time for another update of this burgeoning field. Although it was not possible to have all key investigators represented or all topics reviewed, the 19 contributions in the present volume cover many key aspects of this now quite large field. These articles provide a strong
               
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