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Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. It is typically associated with extensive and progressive fibrosis, and is fatal and has limited treatment options. Characteristically IPF patients display large lymphocyte aggregates composed of CD3+ T cells and CD20+ B cells within the lung tissue that are located near sites of active fibrosis. In addition, IPF patients can have autoantibodies to a range of host antigens, suggesting a breakdown in immunological tolerance. In this review, we examine the role of T and B cells in IPF pathogenesis and discuss how loss of self-tolerance to lung-specific proteins could exacerbate disease progression in IPF. We discuss what these results mean in terms of future prospects for immunotherapy of IPF. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that intranasal (i.n.) administration of an immunodominant peptide (p1 111–139) derived from the house dust mite (HDM) allergen Der p 1 inhibits antigenspecific CD4+ T cell responses in H-2b mice. Here we report that i.n. peptide induced a rapid but transient activation of MHC class II restricted CD4+ T cells that peaked 4 days after peptide treatment and was of similar magnitude to that induced by parenteral immunization with antigen in adjuvant. During the early phase of the response lymph node and splenic T cells secreted a range of lymphokines when re-stimulated in vitro with p1 111–139; however, by day 14 IL-2 and IFN-γ secretion by T cells were down-regulated. Mice deficient in CD8+ T cells became tolerant by i.n. treatment with peptide, suggesting that CD8+ T cells are not involved in down-regulating the CD4+ T cell response. Rechailenging mice with a single dose of p1 111–139 21 days after the initial treatment elicited a further transient T cell response, which was subsequently down-regulated over time. Although the i.n. peptide induced a strong transient CD4+ T cell response, only low levels of peptide-specific antibodies were detected either after the initial or subsequent in. exposures to p1 111–139. Our findings address the mechanisms underlying peripheral T cell tolerance following i.n. administration of a high dose of Immunogenic peptide and have implications for understanding the consequences of peptide immunotherapy. [ABSTRACT FROM AUTHOR]

A major key to successful immunotherapy may depend on altering the qualitative nature of the immune response in allergic patients. In this reveiew we examine how immune responses to environmental allergens are regulated, and the mechanisms used by the immune system to prevent allergic sensitization. We also discuss future prospects of using allergen-derived peptides in immunotherapy and the possibility of 'reprogramming' the immune responses by immunizing under conditions that promote Th1 responses instead of Th2 responses. [ABSTRACT FROM AUTHOR]

• Mesothelial and immune cell interactions play a crucial role in tissue homeostasis in the serosal cavities such as the pleura. • Mesothelin is viewed as an attractive target for solid tumors, including malignant mesothelioma. • Checkpoint inhibitor therapy has shown variable efficacy against malignant mesothelioma. • CAR T cell therapies are being evaluated for malignant mesothelioma. • Treatment of malignant mesothelioma will require multimodality approaches with immunotherapy central to future therapies. The mesothelium when first described was thought to function purely as a non-adhesive surface to facilitate intracoelomic movement of organs. However, the mesothelium is now recognized as a dynamic cellular membrane with many important functions that maintain serosal integrity and homeostasis. For example, mesothelial cells interact with and help regulate the body's inflammatory and immune system following infection, injury, or malignancy. With recent advances in our understanding of checkpoint molecules and the advent of novel immunotherapy approaches, there has been an increase in the number of studies examining mesothelial and immune cell interaction, in particular the role of these interactions in malignant mesothelioma. This review will highlight some of the recent advances in our understanding of how mesothelial cells help regulate serosal immunity and how in a malignant environment, the immune system is hijacked to stimulate tumor growth. Ways to treat mesothelioma using immunotherapy approaches will also be discussed. [ABSTRACT FROM AUTHOR]

The pathogenesis of pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF) and other forms of interstitial lung disease, involves a complex interplay of various factors including host genetics, environmental pollutants, infection, aberrant repair and dysregulated immune responses. Highly variable clinical outcomes of some ILDs, in particular IPF, have made it difficult to identify the precise mechanisms involved in disease pathogenesis and thus the development of a specific cure or treatment to halt and reverse the decline in patient health. With the advent of in-depth molecular diagnostics, it is becoming evident that the pathogenesis of IPF is unlikely to be the same for all patients and therefore will likely require different treatment approaches. Chronic inflammation is a cardinal feature of IPF and is driven by both innate and adaptive immune responses. Inflammatory cells and activated fibroblasts secrete various pro-inflammatory cytokines and chemokines that perpetuate the inflammatory response and contribute to the recruitment and activation of more immune cells and fibroblasts. The balance between pro-inflammatory and regulatory immune cell subsets, as well as the interactions between immune cell types and resident cells within the lung microenvironment, ultimately determines the extent of fibrosis and the potential for resolution. This review examines the role of the innate and adaptive immune responses in pulmonary fibrosis, with an emphasis on IPF. The role of different immune cell types is discussed as well as novel anti-inflammatory and immunotherapy approaches currently in clinical trial or in preclinical development. [ABSTRACT FROM AUTHOR]