Sunday, July 05, 2015


The study of immunology has revealed a complexity of immune cell types and prolific interactions that overwhelm even the experts. The emerging description of chemical signaling that occurs among immune cells and between immune cells and all other tissues of the body has become especially complicated. As the collected data become denser, even highly specialized researchers have difficulty visualizing what is actually occurring in a diseased body.

The MD examining a patient, using conventional medical tools, is hopelessly inadequate and does not understand what is really going on. Classifications and names have changed with advancing discoveries. There more than 30 members of the interleukin family, for example, subdivided into families. To make a complex matter simple, they can be sorted into pro-inflammatory and anti-inflammatory groups.

Cell Signals

Cytokines are soluble proteins that regulate immune responses. One idea is that cytokines are short range signals. For example, it was though that production in lymphoid tissues is tightly localized and signaling occurs between conjugate cells. Perona-Wright et al assessed cytokine signaling during infection by measuring in vivo phosphorylation of intracellular signal transducer and activator of transcription (STAT) proteins. They stated: We show that interferon-γ (IFN-γ) and interleukin 4 (IL-4) signaled to the majority of lymphocytes throughout the reactive lymph node and that IL-4 conditioning of naive, bystander cells was sufficient to override opposing T helper type 1 (TH1) polarization. Our results demonstrate that despite localized production, cytokines can permeate a lymph node and modify the majority of cells therein. Cytokine conditioning of bystander cells could provide a mechanism by which chronic worm infections subvert the host response to subsequent infections or vaccination attempts.

 Another idea is that cytokines provide long-range signalling and help to organize systemic responses to infection and injury. The nature series of scientific journals sponsors a data base that by 2006 listed over 3700 signaling proteins that carry messages among cells of the body. Dove described the state of signalling science: “Ask a cell biologist to explain signal transduction, and you are in for a long story. The science of understanding how individual cells sense their environments and respond to stimuli fills library shelves, occupies whole departments of colleges and inspires the careers of thousands of researchers around the world. Even so, the field sometimes seems woefully understaffed.

The advent of whole-genome sequencing and gene-expression profiling revealed what most biologists already suspected: we are just beginning to understand cell signaling. For example, cells rely heavily on surface receptor proteins to communicate with the outside world. Often, signals flows through receptors that are coupled to effector molecules called G proteins. Inside the cell, information flow often entails an enzyme finding a specific target protein and attaching or removing phosphates, lipid groups, or other chemical structures. The modified target commonly goes on to modify other targets and so on through baroque cascades of interactions.”

Scientists have described a bewildering complexity of cytokines and variable cytokine production in different humans. We know that humans are not created equal. One significant inequality lies in the ability to produce cytokines of different types. An individual’s cytokine profile will help to determine the response to antigen challenges, susceptibility to different diseases and the severity of the disease, once contracted. Advances in techniques of identifying ever larger numbers of signaling molecules have produced research papers dense with measurement data, often in a curious limbo, where the ephemeral dynamics of cell interactions are scarcely mentioned and not at all understood.

From Immunology Notes by Stephen Gislason MD