The Inducible System: History of Development of Immunology as a Component of Host-Parasite Interactions
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
The most dramatic example of this has been the successful elimina tion of the scourge of small pox from the human population in the mid 1970s by a massive immunization program. In the fields of human and veterinary medicine, the study of how parasites induce a specific immune response in their hosts has overshadowed the study of all other aspects of host-parasite interactions. The field of cellular immunology has changed dramatically since Metchnikoff worked to elucidate the role of the phagocytic cells in the cellular response. The cells that successfully transferred immunity were lymphocytes, not macrophages, extending the scope of cellular immunology to another cell type. Our understanding of cellular immunology was further advanced in the 1950s and 1960s when it was shown that lymphocytes were also largely responsible for organ graft rejection. Congenie mice have been extremely powerful research tools in the study of the roles of histocompatibility and other genes in immunology.
Role of Macrophages in the Immune Response
A. Arthur Gottlieb in Developments in Lymphoid Cell Biology, 2018
This chapter points out some of the unexplored areas in the macrophage-research field. It first deals with the phagocytosis and "processing" of antigen by macrophages. Subsequently, the evidence which suggests that macrophages are indeed involved in many immunological reactions, both humoral and cell-mediated, is presented. Macrophage-independence of antigens may be related to the size or molecular dimension of the antigen. It also happens that polymerized polymerized flagellin (POL) is a thymus-independent antigen whereas sheep red blood cells (SRBC) is thymus-dependent. The chapter considers the evidence for the role of macrophages in the induction of the immune response to hapten-carrier conjugates. The available data suggest that macrophages bearing antigen in some form interact with "T" cells prior to involvement of bone marrow precursors of antibody-producing cells. Macrophages as well as lymphocytes appear to have the capacity to destroy foreign tumor cells.
Exercise and Age-Related Decline in Immune Functions
Ronald R. Watson, Marianne Eisinger in Exercise and Disease, 2020
A program of regular aerobic exercise has been shown to elicit beneficial outcomes in both the prevention and rehabilitation of many disease states, including heart disease, stroke, hypertension, diabetes, and cancer. Fundamental to an effective immune response is proper function of macrophages. Macrophages attack and process antigens before presentation to T-cells for recognition. Despite the age-associated involution of the thymus, T-cell numbers appear to be maintained with age in peripheral blood and in lymphoid organs. However, the percentage of T-cells capable of entering mitosis/replication cycle, necessary for complete immune responsiveness, has been reported to decline with advancing age. Endurance training is well known to elicit significant improvements in many cardiovascular and musculoskeletal variables including maximal oxygen consumption, stroke volume, local blood flow, and proliferation of mitochondrial enzymes.
Intravenous immunoglobulin suppresses the polarization of both classically and alternatively activated macrophages
Published in Human Vaccines & Immunotherapeutics, 2020
Chaitrali Saha, Prathap Kothapalli, Veerupaxagouda Patil, Gundallahalli Bayyappa ManjunathaReddy, Srini V Kaveri, Jagadeesh Bayry
Intravenous immunoglobulin (IVIG) is one of the widely used immunotherapeutic molecules in the therapy of autoimmune and inflammatory diseases. Previous reports demonstrate that one of the anti-inflammatory actions of IVIG implicates suppression of macrophage activation and release of their inflammatory mediators. However, macrophages are highly plastic and depending on the microenvironmental signals, macrophages can be polarized into pro-inflammatory classic (M1) or anti-inflammatory alternative (M2) type. This plasticity of macrophages raised additional questions on the role of IVIG towards macrophage polarization. In the present report, we show that IVIG affects the polarization of both classically and alternatively activated macrophages and this process is F(ab’)2-independent. Our data thus indicate the lack of reciprocal regulation of inflammatory and non-inflammatory macrophages by IVIG.
Effects of STING stimulation on macrophages: STING agonists polarize into “classically” or “alternatively” activated macrophages?
Published in Human Vaccines & Immunotherapeutics, 2018
Takayuki Ohkuri, Akemi Kosaka, Toshihiro Nagato, Hiroya Kobayashi
Stimulator of interferon genes (STING) was defined as an important molecule for promoting antitumor immunity through mediating type I interferon (IFN) production by sensing its ligands such as cyclic GMP-AMP (cGAMP). Our recent study indeed demonstrated that intratumoral injection of cGAMP showed effective antitumor responses via accumulating activated macrophages in the tumor microenvironment in a STING-dependent manner. Because the antitumor effect of cGAMP was abrogated when macrophages were depleted, the existence of the activated macrophages in the tumor site would be important for effective antitumor immune responses. Macrophages show phenotypic diversity and plasticity and are categorized into several groups by stimulation factors, e.g. IFN-γ and IL-4 for M1 and M2 macrophages, respectively. However, the impact of STING stimulation on the macrophage activation status remains to be evaluated. Here we summarize the complex polarized status of macrophages and the signaling cascade triggered by STING stimulation and also discuss the impact of STING signaling on the macrophage activation status for future directions.
Macrophages and Recently Identified Forms of Cell Death
Published in International Reviews of Immunology, 2014
Ana B. Sanz, Maria D. Sanchez-Niño, Maria C. Izquierdo, Liliana Gonzalez-Espinoza, Alvaro C. Ucero, Jonay Poveda, Olga Ruiz-Andres, Marta Ruiz-Ortega, Rafael Selgas, Jesus Egido, Alberto Ortiz
Recent advances in cell death biology have uncovered an ever increasing range of cell death forms. Macrophages have a bidirectional relationship with cell death that modulates the immune response. Thus, macrophages engulf apoptotic cells and secrete cytokines that may promote cell death in parenchymal cells. Furthermore, the presence of apoptotic or necrotic dead cells in the microenvironment elicits differential macrophage responses. Apoptotic cells elicit anti-inflammatory responses in macrophages. By contrast macrophages may undergo a proinflammatory form of cell death (pyroptosis) in response to damage-associated molecular patterns (DAMPs) released from necrotic cells and also in response to pathogen-associated molecular patterns (PAMPs). Pyroptosis is a recently identified form of cell death that occurs predominantly in subsets of inflammatory macrophages and is associated to the release of interleukin-1β (IL-1β) and IL-18. Deregulation of these processes may result in disease. Thus, failure of macrophages to engulf apoptotic cells may be a source of autoantigens in autoimmune diseases, excessive macrophage release of proapoptotic factors or sterile pyroptosis may contribute to tissue injury and failure of pathogen-induced pyroptosis may contribute to pathogen survival. Ongoing research is exploring the therapeutic opportunities resulting this new knowledge.