Foreign Pathogens Research Articles

Recreating Human Skin In Vitro: Should the Microbiota Be Taken into Account?

Skin plays crucial roles in the human body: besides protecting the organism from external threats, it acts as a thermal regulator, is responsible for the sense of touch, hosts microbial communities (the skin microbiota) involved in preventing the invasion of foreign pathogens, contains immunocompetent cells that maintain a healthy immunogenic/tolerogenic balance, and is a suitable route for drug administration. In the skin, four defense levels can be identified: besides the physical, chemical, and immune barriers that are inherent to the tissue, the skin microbiota (i.e., the numerous microorganisms living on the skin surface) provides an additional barrier. Studying the skin barrier function or the effects of drugs or cosmetic agents on human skin is a difficult task since snapshot evidence can only be obtained using bioptic samples where dynamic processes cannot properly be followed. To overcome these limitations, many different in vitro models of human skin have been developed that are characterized by diverse levels of complexity in terms of chemical, structural, and cellular composition. The aim of this review is to summarize and discuss the advantages and disadvantages of the different human skin models so far available and to underline how the insertion of a proper microbiota would positively impact an in vitro human skin model in an attempt to better mimic conditions in vivo.

Current status and future prospective of breast cancer immunotherapy.

The immune system is complicated, interconnected, and offers a powerful defense system that protects its host from foreign pathogens. Immunotherapy involves boosting the immune system to kill cancer cells, and nowadays, is a major emerging treatment for cancer. With the advances in our understanding of the immunology of cancer, there has been an explosion of studies to develop and evaluate therapies that engage the immune system in the fight against cancer. Nevertheless, conventional therapies have been effective in reducing tumor burden and prolonging patient life, but the overall efficacy of these treatment regimens has been somewhat mixed and often with severe side effects. A common reason for this is the activation of molecular mechanisms that lead to apoptosis of anti-tumor effector cells. The competency to block tumor escape entirely depends on our understanding of the cellular and molecular pathways which operate in the tumor microenvironment. Numerous strategies have been developed for activating the immune system to kill tumor cells. Breast cancer is one of the major causes of cancer death in women, and is characterized by complex molecular and cellular events that closely intertwine with the host immune system. In this regard, predictive biomarkers of immunotherapy, use of nanotechnology, personalized cancer vaccines, antibodies to checkpoint inhibitors, engineered chimeric antigen receptor-T cells, and the combination with other therapeutic modalities have transformed cancer therapy and optimized the therapeutic effect. In this chapter, we will offer a holistic view of the different therapeutic modalities and recent advances in immunotherapy. Additionally, we will summarize the recent advances and future prospective of breast cancer immunotherapies, as a case study.

Herbal Drugs Inducing Autophagy for the Management of Cancer: Mechanism and Utilization.

When compared to chemical medicines, herbal medicines have the greatest therapeutic benefit while having fewer harmful side effects. Many different components in herbs have an anticancer impact, but the exact mechanism of how they work is unknown. Some herbal medicines have even been shown to trigger autophagy, a process that has shown promise as a potential cancer treatment. In the past ten years, autophagy has come to be recognised as a crucial mechanism in the maintenance of cellular homeostasis, which has led to the discovery of its implications in the pathology of the majority of cellular environments as well as human disorders. Autophagy is a catabolic process that is used by cells to maintain their homeostasis. This process involves the degradation of misfolded, damaged, and excessive proteins, as well as nonfunctional organelles, foreign pathogens, and other cellular components. Autophagy is a highly conserved process. In this review article, several naturally occurring chemicals are discussed. These compounds offer excellent prospects for autophagy inducers, which are substances that can hasten the death of cells when used as a complementary or alternative treatment for cancer. It requires additional exploration in preclinical and clinical investigations, notwithstanding recent advances in therapeutic medications or agents of natural products in numerous cancers. These advancements have been made despite the need for further investigation.

Systemic immune response of burns from the acute to chronic phase.

Immune responses that occur following burn injury comprise a series of reactions that are activated in response to damaged autologous tissues, followed by removal of damaged tissues and foreign pathogens such as invading bacteria, and tissue repair. These immune responses are considered to be programmed in living organisms. Developments of modern medicine have led to the saving of burned patients who could not be cured previously; however, the programmed response is no longer able to keep up, and various problems have arisen. This paper describes the mechanism of immune response specific to burn injury and the emerging concept of persistent inflammation, immunosuppression, and catabolism syndrome.

TCR Signals Controlling AdaptiveImmunity against Toxoplasmaand Cancer.

T cells play a crucial role in adaptive immunity by recognizing and eliminating foreign pathogens and abnormal cells such as cancer cells. T cell receptor (TCR), which is expressed on the surface of T cells, recognizes and binds to specific antigens presented by major histocompatibility complex (MHC) molecules on antigen-presenting cells (APCs). This activation process leads to the proliferation and differentiation of T cells, allowing them to carry out their specific immune response functions. This chapter outlines the TCR signaling pathways that are common to different T cell subsets, as well as the recently elucidated TCR signaling pathway specific to CD8+ T cells and its role in controlling anti-Toxoplasma and anti-tumor immunity.

An Introduction to the Native and Non-Native Plant-Insect Interactions and Potential Pollinators of Puerto Williams and Yendegaia, Cabo de Hornos, Chile.

The Magellanic sub-Antarctic ecoregion of southern Chile represents one of the last remaining pristine areas on Earth, but there are knowledge gaps concerning the biodiversity and interactions of the regions' flora and fauna. Non-native insect species like Bombus terrestris and Vespula vulgaris are known to have detrimental influence on native populations through competition for resources/nesting habitat, larvae predation, and foreign pathogen introduction. However, their interactions with the native and non-native plants in the region and between introduced species are unknown. This study highlights the importance of further investigations documenting the region's biodiversity, native and non-native species interactions, and local pollinators.

Non B Cell-Derived Immunoglobulins in Lung Epithelial Cells and Lung Cancer.

As the locus for air exchange, lung tissue is perpetually exposed to a significant quantity of foreign pathogens. Consequently, lung has developed a refined and intricate immune system. Beyond their physical and chemical barrier roles, lung epithelial cells can contribute to immune defence through the expression of Toll-like receptors (TLRs) and other pattern recognition receptors, along with the secretion of cytokines. Emerging evidence demonstrates that lung epithelial cells can generate and secrete immunoglobulins (Igs), including IgM, IgA, or IgG, thus performing antibody function. Moreover, malignantly transformed lung epithelial cells have been discovered to produce high levels of Ig, predominantly IgG, which do not fulfill the role of antibodies, but instead carries out tumour-promoting activity. Structural analysis has indicated that the biological activity of IgG produced by lung cancer cells differs from that of Igs produced by normal lung epithelial cells due to the unique glycosylation modification. Specifically, the sialylated IgG (SIA-IgG), characterised by a non-traditional N-glycosylation modification at the Asn162 site of Igγ CH1, is highly expressed in tumour stem cells. It has been demonstrated that SIA-IgG relies on this unique sialylation modification to promote tumorigenesis, metastasis, and immune evasion. Current results have proven that the Ig produced by lung epithelial cells has multifaceted biological activities, including immune defence functions under physiological conditions, while acquiring tumour-promoting activity during malignant transformation. These insights possess potential for the diagnosis and treatment of lung cancer as novel biomarkers and targets.

A Thermally Stable Recombinant Human Fibronectin Peptide-Fused Protein (rhFN3C) for Faster Aphthous Ulcer (AU) Healing.

Approximately 59.4-100% of head and neck cancer patients receiving radiotherapy or radio chemotherapy suffer from aphthous ulcers (AUs), which seriously affect the subsequent treatment. At the same time, AUs are a common oral mucosal disease with a high incidence rate among the population, often accompanied by severe pain, and affect both physical and mental health. Strategies to increase the ulcer healing rate and relieve pain symptoms quickly is a long-term clinical objective. Oral mucosal discontinuity is the main histological hallmark of AUs. So, covering the inner mucosal defect with an in vitro engineered oral mucosal equivalent shows good prospects for AU alleviation. Fibronectin (FN) is a glycopeptide in the extracellular matrix and exhibits opsonic properties, aiding the phagocytosis and clearance of foreign pathogens through all stages of ulcer healing. But native FN comes from animal blood, which has potential health risks. rhFN3C was designed with multi-domains of native FN, whose core functions are the recruitment of cells and growth factors to accelerate AU healing. rhFN3C is a peptide-fused recombinant protein. The peptides are derived from the positions of 1444-1545 (FNIII10) and 1632-1901 (FNIII12-14) in human native FN. We optimized the fermentation conditions of rhFN3C in E. coli BL21 to enable high expression levels. rhFN3C is thermally stable and nontoxic for L929, strongly promotes the migration and adhesion of HaCaT, decreases the incidence of wound infection, and shortens the mean healing time by about 2 days compared to others (p < 0.01). rhFN3C may have great potential for use in the treatment of AUs. The specific methods and mechanisms of rhFN3C are yet to be investigated.

The Relationship of Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase-Stimulator of the Interferon Gene Pathway With Other Immunity Signaling Pathways in Apoptosis

Natural immunity, the first defensive mechanism of the body against pathogen invasion, relies on nucleic acid recognition systems to detect the presence of pathogens. The cyclic GMP–AMP synthase-stimulator of interferon (IFN) gene (cGAS-STING) signaling pathway is a crucial pattern recognition and effector pathway in the innate immune system. Its primary function is to detect DNA molecules in the cytoplasm and initiate downstream signaling pathways, resulting in the production of type I IFNs and other inflammatory factors. STING, a pivotal transmembrane protein in the innate immune system, plays a vital role in the host’s ability to resist invasion by foreign pathogens. An increasing amount of evidence suggests that the cGAS-STING pathway induces apoptosis in addition to stimulating inflammatory responses and producing type I IFN. Many previous studies have so far focused on investigating the mechanisms of apoptosis induced by the cGAS-STING pathway as well as the effects that ensue. The relationship between the cGAS-STING pathway and apoptosis has been extensively examined in this article. Through endoplasmic reticulum stress, nucleotide oligomerization domain-like receptor protein-3, nuclear factor-κB (NF-κB), IFN regulatory factor 3, and IFN signals, the cGAS-STING pathway may cause apoptosis. Conversely, apoptosis could affect how the cGAS-STING pathway is regulated. It may release mitochondrial DNA to boost the process or activate caspases to suppress it. The cGAS-STING pathway plays a critical role in controlling innate immune responses, fighting off infections, and stopping the growth of tumors by stopping apoptosis.

Prospects for Stimulating Autoimmunity and Developing New T Cells in Cancer Treatment

Any adverse problem or weakening of the body's immunity, such as HIV infection, long-term physical and mental stress, nutritional deficiencies, chemotherapy or major surgery, will make cells prone to cancer. The body's immune system also deteriorates with age, which may help understand how people's risk of developing cancer increases significantly as they age. If the body's immune system is no longer strong enough to completely destroy cancer cells, then we move from "eliminating" cancer to "balancing."The immune system is the body's protective network, consisting of immune cells, immune organs, and immune substances. It fights against foreign pathogens and mutated cells in the body to maintain the health of the human body's internal environment.&#x0D; Strictly speaking, patients with better physical conditions have higher and more powerful T cells, and the more T cells awakened by immune drugs, they are relatively more effective in eliminating tumor cells. Currently, T cell-based immunotherapy includes CAR-T therapy, TCR-T therapy, TILs therapy, and CTL therapy.

Teleost Eye Is the Portal of IHNV Entry and Contributes to a Robust Mucosal Immune Response.

The ocular mucosa (OM) is an important and unique part of the vertebrate mucosal immune system. The OM plays an important role in maintaining visual function and defending against foreign antigens or microorganisms, while maintaining a balance between the two through complex regulatory mechanisms. However, the function of ocular mucosal defense against foreign pathogens and mucosal immune response in bony fish are still less studied. To acquire deeper understanding into the mucosal immunity of the OM in teleost fish, we established a study of the immune response of rainbow trout (Oncorhynchus mykiss) infected with the infectious hematopoietic necrosis virus (IHNV). Our findings revealed that IHNV could successfully infiltrate the trout's OM, indicating that the OM could be an important portal for the IHNV. Furthermore, qPCR and RNA-Seq analysis results showed that a large number of immune-related genes were significantly upregulated in the OM of trout with IHNV infection. Critically, the results of our RNA-Seq analysis demonstrated that viral infection triggered a robust immune response, as evidenced by the substantial induction of antiviral, innate, and adaptive immune-related genes in the OM of infected fish, which underscored the essential role of the OM in viral infection. Overall, our findings revealed a previously unknown function of teleost OM in antiviral defense, and provided a theoretical basis for the study of the mucosal immunity of fish.

Application of lateral flow immunochromatography assay, CRISPR/Cas12, and QDs-based biosensing for SARS-CoV-2 diagnosis

During the COVID-19 pandemic, scientists have developed many diagnostic techniques, such as biosensors, to detect whether a patient is infected by SARS-CoV-2. This could help the governments to plan an effective method to decrease the rate at which the illness is spreading across the globe. These diagnostic techniques are developed after the research of this foreign viral pathogen, SARS-CoV-2, by investigating the potential analytes that could be used and the various ways that the virus could infect a person after exposure. The three diagnostic techniques will be discussed in this paper, including lateral flow immunochromatography assay (LFIA), CRISPR/Cas12, and quantum dots (QDs)-based biosensing system. In addition, this research will also systematically discuss the advantages and disadvantages of these three monitoring and analysis methods. Although these three diagnostic techniques have very high selectivity and sensitivity, establishing a reliable result, there are pathogens that could result in similar symptoms of respiratory pneumonia just like SARS-CoV-2. The diagnostic techniques explained in this paper cant diagnose more than one pathogen or disease, therefore, it is essential to further develop a multiplexing assay to produce a more detailed result.

Transcriptional regulation of the HIV-1 inhibitory factor human mannose receptor 1 by the myeloid-specific transcription factor PU.1.

HIV-1 infection of human macrophages leads to the downmodulation of human mannose receptor 1 (hMRC1), a cell-surface glycoprotein that is involved in the host innate immune response. We previously reported that downmodulation of hMRC1 involves the transactivator of transcription (Tat)-dependent transcriptional silencing of the hMRC1 promoter. However, the inhibitory effect of Tat on hMRC1 transcription was indirect and involved inhibition of the transcriptional activator PU.1, which normally upregulates hMRC1 expression in macrophages and other myeloid cells. We cloned a 284-bp fragment of the hMRC1 promoter, and within it, we identified four PU.1 box elements. We assessed the relative contribution of each of the four PU.1 boxes to PU.1-dependent transcriptional regulation and, surprisingly, found that only one of the four PU.1 boxes [PU.1(b)] was critically required for PU.1-mediated upregulation of luciferase expression. Transfer of this PU.1 box to a heterologous promoter conferred PU.1 responsiveness to an otherwise PU.1 insensitive promoter. Electrophoretic mobility shift assays identified this PU.1 box as a direct binding site for PU.1 both in the context of the hMRC1 promoter and the heterologous promoter. Furthermore, mutational analysis of the PU.1 protein identified the C-terminal DNA-binding domain in PU.1 as the region responsible for interaction with the PU.1 box. Recombinant HIV-1 Tat protein did not bind to the hMRC1 promoter element but efficiently interfered with the binding of PU.1 protein to the hMRC1 promoter. Thus, Tat is likely to inhibit the formation of active PU.1 transcription complexes, presumably by binding to and depleting common transcriptional cofactors.IMPORTANCEHIV-1 infection of cells results in the modulation of cellular gene expression by virus-encoded proteins in a manner that benefits the virus. We reported that HIV-1 transactivator of transcription (Tat) dysregulates the expression of the human mannose receptor 1 (hMRC1). hMRC1 is involved in the innate immune response of macrophages to foreign pathogens. Tat does not act directly on the hMRC1 promoter but instead inhibits PU.1, a cellular transcription factor regulating hMRC1 gene expression. Here, we characterize the PU.1-dependent regulation of hMRC1 expression. We identified four potential PU.1 binding sites in the hMRC1 promoter region but found that only one, PU.1(b), functioned as a true binding site for PU.1. Transfer of the PU.1(b) box to a heterologous promoter did not activate this promoter per se but rendered it responsive to PU.1. Our results support the view that PU.1 acts as a transcriptional co-factor whose activity can be regulated by HIV-1 Tat.

BLK positively regulates TLR/IL-1R signaling by catalyzing TOLLIP phosphorylation.

TLR/IL-1R signaling plays a critical role in sensing various harmful foreign pathogens and mounting efficient innate and adaptive immune responses, and it is tightly controlled by intracellular regulators at multiple levels. In particular, TOLLIP forms a constitutive complex with IRAK1 and sequesters it in the cytosol to maintain the kinase in an inactive conformation under unstimulated conditions. However, the underlying mechanisms by which IRAK1 dissociates from TOLLIP to activate TLR/IL-1R signaling remain obscure. Herein, we show that BLK positively regulates TLR/IL-1R-mediated inflammatory response. BLK-deficient mice produce less inflammatory cytokines and are more resistant to death upon IL-1β challenge. Mechanistically, BLK is preassociated with IL1R1 and IL1RAcP in resting cells. IL-1β stimulation induces heterodimerization of IL1R1 and IL1RAcP, which further triggers BLK autophosphorylation at Y309. Activated BLK directly phosphorylates TOLLIP at Y76/86/152 and further promotes TOLLIP dissociation from IRAK1, thereby facilitating TLR/IL-1R-mediated signal transduction. Overall, these findings highlight the importance of BLK as an active regulatory component in TLR/IL-1R signaling.

Vaccinating Against Cancer - How to Force the Quadrature of the Circle

There are compelling evidences that the immune system is to confer protection not only against foreign pathogens but also against cancer. But if the immune system can’t detect every malignant cell, and at the same time a suitable tumor microenvironment (TME) is formed by inflammatory processes, carcinogenesis is not longer to be blocked. Once the tumor cells have found their niche, the tumor cells are trained by immune cells turned inside out in how to deal with the immune system "out there". The TME is a training camp and protected space for tumor cells. The Corona crisis has revived a therapeutic approach that was thought to be almost dead: RNA vaccines. Despite decades of research and many clinical studies, no registered RNA cancer vaccine exists today. But the SARS-CoV-2 RNA vaccines against COVID-19 disease have demonstrated their dangerous weaknesses: RNA vaccines manipulate the innate immunity and make the body susceptible to any viral infection. There is also the possibility of integration into the genome. The few approved therapeutic cancer vaccines show little effect. Despite some successes, immunotherapies remain ineffective for most patients with cancer. Powerful therapeutic cancer vaccines remain an unfulfilled dream, a misconception.

Comparative analyses of functional antibody-mediated inhibition with anti-circumsporozoite monoclonal antibodies against transgenic Plasmodium berghei

BackgroundAcquired functional inhibitory antibodies are one of several humoral immune mechanisms used to neutralize foreign pathogens. In vitro bioassays are useful tools for quantifying antibody-mediated inhibition and evaluating anti-parasite immune antibodies. However, a gap remains in understanding of how antibody-mediated inhibition in vitro translates to inhibition in vivo. In this study, two well-characterized transgenic Plasmodium berghei parasite lines, PbmCh-luc and Pb-PfCSP(r), and murine monoclonal antibodies (mAbs) specific to P. berghei and Plasmodium falciparum circumsporozoite protein (CSP), 3D11 and 2A10, respectively, were used to evaluate antibody-mediated inhibition of parasite development in both in vitro and in vivo functional assays.MethodsIC50 values of mAbs were determined using an established inhibition of liver-stage development assay (ILSDA). For the in vivo inhibition assay, mice were passively immunized by transfer of the mAbs and subsequently challenged with 5.0 × 103 sporozoites via tail vein injection. The infection burden in both assays was quantified by luminescence and qRT-PCR of P. berghei 18S rRNA normalized to host GAPDH.ResultsThe IC50 values quantified by relative luminescence of mAbs 3D11 and 2A10 were 0.396 µg/ml and 0.093 µg/ml, respectively, against transgenic lines in vitro. Using the highest (> 90%) inhibitory antibody concentrations in a passive transfer, an IC50 of 233.8 µg/ml and 181.5 µg/ml for mAbs 3D11 and 2A10, respectively, was observed in vivo. At 25 µg (250 µg/ml), the 2A10 antibody significantly inhibited liver burden in mice compared to control. Additionally, qRT-PCR of P. berghei 18S rRNA served as a secondary validation of liver burden quantification.ConclusionsResults from both experimental models, ILSDA and in vivo challenge, demonstrated that increased concentrations of the homologous anti-CSP repeat mAbs increased parasite inhibition. However, differences in antibody IC50 values between parasite lines did not allow a direct correlation between the inhibition of sporozoite invasion in vitro by ILSDA and the inhibition of mouse liver stage burden. Further studies are needed to establish the conditions for confident predictions for the in vitro ILSDA to be a predictor of in vivo outcomes using this model system.

Host-pathogen coevolution promotes the evolution of general, broad-spectrum resistance and reduces foreign pathogen spillover risk.

Genetic variation for disease resistance within host populations can strongly impact the spread of endemic pathogens. In plants, recent work has shown that within-population variation in resistance can also affect the transmission of foreign spillover pathogens if that resistance is general. However, most hosts also possess specific resistance mechanisms that provide strong defenses against coevolved endemic pathogens. Here we use a modeling approach to ask how antagonistic coevolution between hosts and their endemic pathogen at the specific resistance locus can affect the frequency of general resistance, and therefore a host's vulnerability to foreign pathogens. We develop a two-locus model with variable recombination that incorporates both general resistance (effective against all pathogens) and specific resistance (effective against endemic pathogens only). With coevolution, when pathogens can evolve to evade specific resistance, we find that the regions where general resistance can evolve are greatly expanded, decreasing the risk of foreign pathogen invasion. Furthermore, coevolution greatly expands the conditions that maintain polymorphisms at both resistance loci, thereby driving greater genetic diversity within host populations. This genetic diversity often leads to positive correlations between host resistance to foreign and endemic pathogens, similar to those observed in natural populations. However, if resistance loci become linked, the resistance correlations can shift to negative. If we include a third linkage-modifying locus in our model, we find that selection often favors complete linkage. Our model demonstrates how coevolutionary dynamics with an endemic pathogen can mold the resistance structure of host populations in ways that affect its susceptibility to foreign pathogen spillovers, and that the nature of these outcomes depends on resistance costs, as well as the degree of linkage between resistance genes.

Delineation of the healthy rabbit tonsil by immunohistochemistry – A short communication

Situated in the oral cavity, the rabbit palatine tonsils are part of the mucosal immune system and help to defend the body against foreign pathogens. Expressed as two oval protrusions in the wall of the oropharynx, the rabbit palatine tonsils are characterized by excretory ducts and trabeculae. We here compare paraffin embedded and cryosections of the healthy rabbit tonsils. This analysis centers on evaluating the differential outcomes resulting from the application of these fixation methodologies in conjunction with immunohistochemical assays targeting collagen I, collagen III, fibronectin, α-smooth muscle actin (α-SMA), and ki67. Subsequent recommendations are provided based on our findings. Furthermore, we demonstrate the advantage of an antigen retrieval step in immunohistochemical labeling of paraffin sections. Basic classical histological stainings as HE, GT and elastin were also performed. Comparison of different stainings and labelings was furthermore performed in serial sections, showing that adjacent to the excretory ducts, the tonsillar tissue was particularly composed of collagen I and fibronectin, while the vessel walls were predominantly α-SMA positive. Moreover, PAR-2 immunohistochemical staining was performed, where a small fraction of the cells found in the tonsillar connective tissue were PAR-2 positive (probably a subpopulation of mast cells), as well as the lumen of some excretory ducts and trabeculae. Collagen III on the other hand was only weakly expressed in the tonsils. Proliferating ki67 positive cells were rare. This endeavor serves to furnish the scientific community with reference imagery pertinent to researchers opting for the rabbit palatine tonsil model. The diversity of staining techniques employed herein establishes a foundational repository of images, primed for comparative analysis against pathological conditions. Furthermore, these images hold the potential to illustrate inter-species variations. For instance, they can be juxtaposed against murine or rodent tonsils, or even offer insights into the human context.

History of the development of the science of the immune system

The immune system is a large network of organs, white blood cells, proteins (antibodies), and chemicals. This system works in concert to protect the body from foreign pathogens (bacteria, viruses, parasites, and fungi) that cause infection, disease, and illness. The human immune system works hard to stay healthy. Its task is to prevent the invasion of pathogens, destroy them or limit the extent of their damage if they enter. When the immune system is working properly, it can distinguish which cells are "own" and which substances are foreign to the body. It activates, mobilizes, attacks and kills foreign organisms that can harm human health. It is believed that the term "immunity" was used for the first time by Thucydides - a prominent ancient Greek philosopher, historian, political scientist and military leader. For the first time, he discovered the resistance of a recovered person to a recurrence of the disease. Since that time, hundreds of outstanding scientists have devoted their lives to the study of extremely complex processes that occur in the human immune system during invasion. The invention of the vaccine became a significant impetus in the development of immunology as a science. In 1885, Pasteur administered the first vaccine to a human, a young boy who had been repeatedly bitten by a rabid dog. Immunology made significant progress in the late 19th century due to rapid developments in the study of humoral immunity and cellular immunity. In 1903, a humoral component known as an opsonin was discovered that makes target bacteria suitable for phagocytosis. Particularly important was the work of Paul Ehrlich, who proposed the side chain theory to explain the specificity of the antigen-antibody reaction. His contribution to the understanding of humoral immunity was recognized by awarding a joint Nobel Prize in 1908 together with the founder of cellular immunology, the Russian zoologist Ilya Mechnikov, who first formulated the phagocytic theory in 1880. Modern immunologists, using the tools of molecular and cellular biology, genomics, and proteomics, will take a step towards preventing fatal diseases. The world is expected to witness a further explosion of knowledge in the field of immunology in the coming decades. Collaborative efforts across subjects such as tumor immunology, autoimmunity, and vaccinology are needed to develop strategies to protect against multiple diseases.

On the path to predicting immune responses in the lung: Modeling the pulmonary innate immune system at the air-liquid interface (ALI)

Chronic respiratory diseases and infections are among the largest contributors to death globally, many of which still have no cure, including chronic obstructive pulmonary disorder, idiopathic pulmonary fibrosis, and respiratory syncytial virus among others. Pulmonary therapeutics afford untapped potential for treating lung infection and disease through direct delivery to the site of action. However, the ability to innovate new therapeutic paradigms for respiratory diseases will rely on modeling the human lung microenvironment and including key cellular interactions that drive disease. One key feature of the lung microenvironment is the air-liquid interface (ALI). ALI interface modeling techniques, using cell-culture inserts, organoids, microfluidics, and precision lung slices (PCLS), are rapidly developing; however, one major component of these models is lacking—innate immune cell populations. Macrophages, neutrophils, and dendritic cells, among others, represent key lung cell populations, acting as the first responders during lung infection or injury. Innate immune cells respond to and modulate stromal cells and bridge the gap between the innate and adaptive immune system, controlling the bodies response to foreign pathogens and debris. In this article, we review the current state of ALI culture systems with a focus on innate immune cells and suggest ways to build on current models to add complexity and relevant immune cell populations.