Immunological Reviews
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A bacteriophages journey through the human body Summary The human body is colonized by a diverse collective of microorganisms, including bacteria, fungi, protozoa and viruses. The smallest entity of this microbial conglomerate are the bacterial viruses. Bacteriophages, or phages for short, exert significant selective pressure on their bacterial hosts, undoubtedly influencing the human microbiome and its impact on our health and well‐being. Phages colonize all niches of the body, including the skin, oral cavity, lungs, gut, and urinary tract. As such our bodies are frequently and continuously exposed to diverse collections of phages. Despite the prevalence of phages throughout our bodies, the extent of their interactions with human cells, organs, and immune system is still largely unknown. Phages physically interact with our mucosal surfaces, are capable of bypassing epithelial cell layers, disseminate throughout the body and may manipulate our immune system. Here, I establish the novel concept of an “intra‐body phageome,” which encompasses the collection of phages residing within the classically “sterile” regions of the body. This review will take a phage‐centric view of the microbiota, human body, and immune system with the ultimate goal of inspiring a greater appreciation for both the indirect and direct interactions between bacteriophages and their mammalian hosts.
Immunological Reviews - Tập 279 Số 1 - Trang 106-122 - 2017
Of <scp>CAR</scp>s and <scp>TRUCK</scp>s: chimeric antigen receptor (<scp>CAR</scp>) T cells engineered with an inducible cytokine to modulate the tumor stroma Summary Adoptive T‐cell therapy recently achieved impressive efficacy in early phase trials, in particular in hematologic malignancies, strongly supporting the notion that the immune system can control cancer. A current strategy of favor is based on ex vivo‐ engineered patient T cells, which are redirected by a chimeric antigen receptor (CAR ) and recognize a predefined target by an antibody‐derived binding domain. Such CAR T cells can substantially reduce the tumor burden as long as the targeted antigen is present on the cancer cells. However, given the tremendous phenotypic diversity in solid tumor lesions, a reasonable number of cancer cells are not recognized by a given CAR , considerably reducing the therapeutic success. This article reviews a recently described strategy for overcoming this shortcoming of the CAR T‐cell therapy by modulating the tumor stroma by a CAR T‐cell‐secreted transgenic cytokine like interleukin‐12 (IL ‐12). The basic process is that CAR T cells, when activated by their CAR , deposit IL ‐12 in the targeted tumor lesion, which in turn attracts an innate immune cell response toward those cancer cells that are invisible to CAR T cells. Such TRUCK s, T cells redirected for universal cytokine‐mediated killing, exhibited remarkable efficacy against solid tumors with diverse cancer cell phenotypes, suggesting their evaluation in clinical trials.
Immunological Reviews - Tập 257 Số 1 - Trang 83-90 - 2014
An Analysis of the Murine NK Cell as to Structure, Function and Biological Relevance
Immunological Reviews - Tập 44 Số 1 - Trang 165-208 - 1979
Tolerance and near‐tolerance strategies in monkeys and their application to human renal transplantation Summary: Studies in non‐human primates to evaluate tolerance strategies in organ transplantation have led to innovation in human transplantation. The two strategies we have studied in detail in non‐human primates are T‐cell depletion by anti‐CD3 immunotoxin and co‐stimulation blockade. Each of these strategies has been extended into early human trials in renal transplantation. The results of these human and non‐human primate studies are summarized. Continued progress in better and safer immunosuppressive methods remains closely linked to research using non‐human primates. However, there has not been a one‐to‐one correspondence between efficacy in the primate and efficacy in humans. Rather, principles can be derived from non‐human primate studies that can be extended into human trials with the knowledge that regimens will likely differ in humans compared to non‐human primates.
Immunological Reviews - Tập 183 Số 1 - Trang 205-213 - 2001
Calcium signaling in cells of the immune and hematopoietic systems
Immunological Reviews - Tập 231 Số 1 - Trang 5-9 - 2009
Inflammasomes: guardians of cytosolic sanctity Summary: The innate immune system is critical in recognizing bacterial and viral infections to evoke a proper immune response. Certain members of the intracellular nucleotide‐binding and oligomerization domain (NOD)‐like receptor (NLR) family detect microbial components in the cytosol and trigger the assembly of large caspase‐1‐activating complexes termed inflammasomes. Autoproteolytic maturation of caspase‐1 zymogens within these inflammasomes leads to maturation and secretion of the pro‐inflammatory cytokines interleukin‐1β (IL‐1β) and IL‐18. The NLR proteins ICE protease‐activating factor (IPAF), NALP1b (NACHT domain‐, leucine‐rich repeat‐, and PYD‐containing protein 1b), and cryopyrin/NALP3 assemble caspase‐1‐activating inflammasomes in a stimulus‐dependent manner. Bacterial flagellin is sensed by IPAF, whereas mouse NALP1b detects anthrax lethal toxin. Cryopyrin/NALP3 mediates caspase‐1 activation in response to a wide variety of microbial components and in response to crystalline substances such as the endogenous danger signal uric acid. Genetic variations in Nalp1 and cryopyrin/Nalp3 are associated with autoinflammatory disorders and increased susceptibility to microbial infection. Further understanding of inflammasomes and their role in innate immunity should provide new insights into the mechanisms of host defense and the pathogenesis of autoimmune diseases.
Immunological Reviews - Tập 227 Số 1 - Trang 95-105 - 2009
What brought the adaptive immune system to vertebrates? ‐ The jaw hypothesis and the seahorse Summary: A hypothesis is discussed that the adaptive immune system of vertebrates evolved in the gastrointestinal regions of primitive jawed fish (placoderms) due to increased localized injuries and infections which were inadvertently brought about by the novel jaw structures and the predatory life style. The question whether the modern jawless fish, cyclostomes, have adaptive immunity or not is briefly but critically reviewed. The discovery that the gut‐associated immune tissues in mammals constitute the primary immune tissues for the local T cells and that some epithelial γσ T cells have a unique propensity is summarized and discussed in relation to the jaw hypothesis. Initial study of the seahorse (Hippocampus) indicates that the gut‐associated immune tissues may be absent in this teleost species, suggesting an evolutionary link between the adaptive immune system and the jaw structure or eating habit.
Immunological Reviews - Tập 166 Số 1 - Trang 177-186 - 1998
Idiotypic Networks and Other Preconceived Ideas “Mirrors would be well‐advised to think twice before reflecting images.” The progress of science consists partly of replacing preconceived ideas by better ones, and partly of collecting experimental data relevant to these ideas. The latter exercise facilitates the former. The more fundamental the ideas are, the more rewarding is their replacement. In the present paper I shall reconsider some basic questions related to the function of idiotypic networks in the immune system.
Immunological Reviews - Tập 79 Số 1 - Trang 5-24 - 1984
The Follicular Dendritic Cell: Long Term Antigen Retention During Immunity
Immunological Reviews - Tập 53 Số 1 - Trang 29-59 - 1980
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