Begell House Inc.
Critical Reviews™ in Immunology
CRI
1040-8401
39
3
2019
The Human Immune System against Staphylococcus epidermidis
151-163
10.1615/CritRevImmunol.2019031282
Mirzaei
Rasoul
Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Mohammadzadeh
Rokhsareh
Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Shokri Moghadam
Mohammad
Department of Microbiology, School of Health, Tehran University of Medical Sciences, Tehran, Iran
Karampoor
Sajad
Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Moradi
Ahmadreza
Department of Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
biofilm
immune system
neutrophil
phenol soluble modulin
polysaccharide intercellular adhesin
Staphylococcus epidermidis
Staphylococcus epidermidis is one of the major causes of nosocomial infections in humans. This organism can exist as a commensal on the skin. However, it can also lead to severe infections. The immune system has evolved mechanisms to deal with microorganisms and has strategies to combat bacteria. The initial defense against S. epidermidis infections includes the activation of complement complex, recruitment and then killing of the microorganism by effectors. The success of pathogenic S. epidermidis strains has been attributed to their capacity to evade innate immune cells. Extracellular matrix binding protein, polysaccharide intercellular adhesin, and accumulation-associated protein have been found to suppress killing of S. epidermidis by effector cells. PSM constitutes the only kind of exported toxins in S. epidermidis strains and has strong cytolytic features against leukocyte cells. The human innate immune system can be stimulated against S. epidermidis via toll-like receptors that enhance antibacterial reactions, trigger inflammation, and result in the stimulation of immune system effectors, e.g., type-1 interferon (IFN-alpha and IFN-beta), proinflammatory cytokines, and nitric oxide. Proinflammatory cytokines, e.g., interleukin-1, interleukin-6, and tumor necrosis factor are formed from resident human cells and result in migration of the lymphocyte and fever. In this review we will examine the immune system's response against S. epidermidis.
Back to the Light Side: The Role of Mechanotransduction in the Paradoxical Response to Checkpoint Inhibitors in Cancer Patients
165-173
10.1615/CritRevImmunol.2019031554
Eslam
Abbas
Dar El Salam Cancer Center, 987 Corniche El Nil, Al Manial, 11553 Cairo, Egypt
Tamer Z.
Salem
Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, October Gardens, 6th of October City, Giza 12578, Egypt
PD-1
hyperprogressive disease
checkpoint inhibitors
Fc-gamma receptor
T-cells
tumor-associated macrophages
tumor immune-escape
A growing number of studies and case series point to a dark side of immune checkpoint inhibitors, as they may cause rapid tumor growth with potentially deleterious effects. The pathophysiological mechanism of hyper-progressive disease (HPD) is still unknown; in addition, there are no reliable predictive biomarkers that facilitate the process of patient selection for immunomodulatory antibody-based therapy. The proposed model attempts to reveal the mechanism of such paradoxical response, in a subset of patients receiving anti-PD1/PD-L1 immunotherapy, depending on the biomechanistic properties of the crystal structure of PD-1 protein. PD-1 can exhibit a signaling pattern depending on mechanotransduction upon the formation of PD-1/monoclonal antibody (mAb)/Fc-gamma receptor (Fc-γR) axes resulting from the interaction between PD-1/mAb complex, on the surface of tumor-specific T-cells, and Fc-γR-bearing tumor-associated macrophages (TAMs) within the tumor microenvironment. The generated mechanical force activates ITIM and ITSM on the cytoplasmic endodomain of the PD-1 receptor, leading to suppression of the effector function of tumor-specific T-cells which effectively unleashes cancer cells from the cytotoxic barrier and causes HPD in affected patients. This model provides clues about why patients receiving anti-PD1/PD-L1 mAbs are more prone to develop HPD as well as the variability of the ICIs response among treated patients. Additionally, it features the effect of specific immunophenotypic dynamics, such as TAM infiltration, on the final outcome of antibody-based immunotherapy and gives new insights for designing next-generation immunomodulatory interventions.
CD4+ T Lymphocytes Subsets in Early Life: Does Exclusive Breastfeeding Promote Allergy?
175-187
10.1615/CritRevImmunol.2019031416
Augusto Lengler
Konrath
Medical Student at University of the Taquari Valley − Univates, Lajeado, RS, Brazil
Fernanda Scherer
Adami
Health and Medical Research Group, Medical Sciences Centre, School of Medicine, University of the Taquari Valley − Univates, Lajeado, RS, Brazil
Ioná
Carreno
Health and Medical Research Group, Medical Sciences Centre, School of Medicine, University of the Taquari Valley − Univates, Lajeado, RS, Brazil
André Anjos
da Silva
Health and Medical Research Group, Medical Sciences Centre, School of Medicine, University of the Taquari Valley − Univates, Lajeado, RS, Brazil
Ramatis Birnfeld
de Oliveira
Health and Medical Research Group, Medical Sciences Centre, School of Medicine, University of the Taquari Valley − Univates, Lajeado, RS, Brazil
adaptive immunity
breast feeding
eczema
hypersensitivity
Breastfeeding provides ideal nutrition and passive immunization for growing infants, protecting them from potentially fatal infectious diseases. Exclusive breastfeeding is recommended for at least six months and should be continued complementarity for another year. One of the justifications for this recommended practice is the prevention of allergic diseases, which has been controversial for many years. Here we reviewed data regarding breastfeeding practices and hypothesized that exclusive breastfeeding for long periods may affect the availability of helper T lymphocyte 1-polarizing antigens in babies. This fact could favor helper T lymphocyte 2 (TH2) phenotype development and consequently increase the incidences of allergies, although we have found no consistent evidence in the literature supporting or denying that breastfeeding plays a role in allergic diseases. The literature mostly presents inconsistencies and/or methodological issues precluding a final answer to this issue. The development of the adaptive immune system depends on exposure to antigens that elicit the production of specific cytokines and activates T lymphocyte populations. It is believed that a promotion of the TH2 phenotype to the detriment of another lymphocyte subset takes place, although the exact knowledge about when this process begins is still under investigation. Therefore, the recent increase in allergy incidence might be partly explained by breastfeeding practices in the world and by the hypothesis presented here, affecting the baby's immune system development through selective antigen availability.
Prevalence of Autoimmune Diseases and Its Challenges in Diagnosis
189-201
10.1615/CritRevImmunol.2019031798
Rajni
Chauhan
Molecular Genetics Laboratory, Medanta-The Medicity, Gurgaon, Haryana, India; Chimera Transplant Research Foundation, New Delhi, India; Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India
Vimarsh
Raina
Chimera Transplant Research Foundation, New Delhi, India
Shoma Paul
Nandi
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India
autoantibodies
autoimmunity
systemic lupus erythematosus
Autoimmune diseases (ADs) are the outcome of a malfunctioning immune system in which the immune system attacks self-antigens. These diseases are grouped into organ-specific and non-organ-specific types. Autoantibodies are important biomarkers used for confirming the diagnosis of ADs. Disease-specific autoantibodies are detected at a very early stage when typical clinical symptoms are not present in the patient, allowing prediction of the disease several years before the symptoms are visible. Diagnosis at an early stage is essential to decrease morbidity, disability, and mortality caused by ADs. Detection of autoantibodies, specific to particular phenotypes, helps to define these disorders as well as facilitate diagnosis, prognosis, and monitoring. In this review, we outline the present technologies used in autoimmune laboratories and the limitations of these methods along with future perspects of autoimmune diagnostics.
Evaluation of Serum Free Light Chain in Diagnosis and Monitoring of Plasma Cell Disorders
203-210
10.1615/CritRevImmunol.2019032260
Ayesha A.
Ansari
Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan
Hamid N.
Tipu
Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan
Dawood
Ahmed
Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan
Muhammad
Farhan
Armed Forces Bone Marrow Transplant Center, Rawalpindi, Pakistan
multiple myeloma
plasma cell disorders
serum free light chain assay
Objective: To determine diagnostic accuracy of serum free light chain assay compared to serum and urine protein electrophoresis in plasma cell disorders.
Study Design: Descriptive cross-sectional study.
Place and Duration of Study: This study was conducted in the Immunology Department, Armed Forces institute of Pathology (AFIP), Rawalpindi, from May 2017 to May 2018.
Methodology: Patients referred to AFIP for diagnosis of plasma cell disorders or for monitoring while receiving treatment were included in study. They were tested for serum protein electrophoresis (SPE), urine protein electrophoresis (UPE), immunofixation (IF), and serum free light chain assay (sFLC). IF was used as the reference standard. Test results were compared in terms of sensitivity, specificity, positive or negative predictive value, and accuracy index.
Results: During the study period 220 patients were tested for plasma cell disorders. One hundred and sixty-seven patients tested positive. One hundred twenty-nine patients had multiple myeloma, 13 plasmacytoma, 11 monoclonal gammopathy of undetermined significance, 6 amyloidosis, 6 POEMS, and 2 Waldenstrom macroglobulinemia. SPE had a sensitivity of 70.5%, specificity of 100%; sFLC had a sensitivity of 87%, specificity of 81%; and UPE had a sensitivity of 23.5%, specificity of 97%. Accuracy index was 80.5% for SPE, 85% for sFLC, and 54% for UPE. When taken together, SPE and UPE had a combined sensitivity of 72%, specificity 97%, and accuracy index 80.5%. SPE and sFLC had combined sensitivity of 98.6%, specificity 84.3%, and accuracy index 94%.
Conclusion: Combination of SPE and sFLC had the highest sensitivity and accuracy index for diagnosis and monitoring of plasma cell disorders compared with conventional tests.
Immunotherapy for Triple-Negative Breast Cancer: Latest Research and Clinical Prospects
211-221
10.1615/CritRevImmunol.2019030924
Rida Fatima
Ahmed
Department of Biotechnology, University of Sargodha, Sargodha 40100, Pakistan
Farwah
Jameel
Department of Bioinformatics and Biotechnology, Government College University, Faisalabad 38000, Pakistan
Muhammad
Irfan
Department of Biotechnology, University of Sargodha, Sargodha 40100, Pakistan
triple-negative breast cancer
immunotherapy
immune checkpoint
cancer treatment
Patients with triple-negative breast cancer (TNBC) do not express estrogen receptor (ER), HER2/neu, or progesterone receptor (PR) and generally have a poor prognosis with elevated chances of recurrence. They constitute about 15% of breast cancer patients. TNBC, when diagnosed at stage II, has a recurrence of about 60%, while the risk of recurrence for a hormone receptor-positive cancer is about 10-20%. This particular breast cancer has no targeted treatment at the molecular level; unlike other subtypes of breast cancer, patients have only chemotherapy and radiation to rely on. They cannot benefit from endocrine therapy. Research based on cancer immunology and translational immunotherapy has been supported by early trial successes. However, major questions still exist concerning these therapeutic approaches in practice. Promising new therapies hold the potential to cure a wide range of tumor types, including those which cannot be treated with conventional therapies. A better insight into the immunogenicity of TNBC has resulted in clinical studies of various immunotherapeutic agents. This review focuses on current immunotherapies for TNBC, including immune checkpoint inhibitors, dendritic cell therapy, adoptive cell therapy, and oncolytic viral therapy.