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Microbes & Immunity Pulmonary immunity: Pathogens versus protectors

(i) Immunotherapies: Monoclonal antibodies and domain-like receptor protein 3 inflammasome and type I
immune checkpoint inhibitors are increasingly used interferon (IFN) responses – that influence the outcomes
to treat lung cancer and chronic respiratory infections of pulmonary infections. 17,18
(ii) Vaccines: Advances in mRNA vaccine technology, c. Advanced computational simulations
highlighted by the success of COVID-19 vaccines, Alongside experimental approaches, advanced
offer promising potential for preventing respiratory computational simulations have transformed the study of
infections pulmonary immune responses. By integrating data from
(iii) Gene Editing: Clustered regularly interspaced short both in vitro and in vivo studies, these simulations can
palindromic repeats (CRISPR)-based techniques are model complex immune networks and predict outcomes
being explored to correct genetic defects in immune across various scenarios. For example, agent-based models
cells or enhance their protective functions within the simulate the interactions of individual immune cells and
lungs. pathogens within the pulmonary microenvironment,
(iv) Nanotechnology: Engineered nanoparticles enable providing valuable insights into spatial and temporal
targeted delivery of drugs or vaccines directly to dynamics that are difficult to capture experimentally.
lung tissues, improving therapeutic efficacy while Similarly, systems biology approaches utilize large-scale
minimizing side effects. omics datasets to construct predictive models of immune
a. In vitro models of lung epithelial cells signaling pathways, aiding the identification of potential
In vitro models of lung epithelial cells have become therapeutic targets. Together, these computational tools not
essential tools for investigating the early stages of pathogen only enhance our understanding of pulmonary immunity
invasion and the subsequent immune response. These but also facilitate the development of personalized
models, typically derived from primary human bronchial treatment strategies
or alveolar epithelial cells, closely replicate the structural d. Innovative perspectives on pulmonary immune
and functional characteristics of the lung epithelium. By responses
exposing these cells to pathogens – such as Mycobacterium The human respiratory system is a continuous
tuberculosis, 15,16 influenza virus, or Pseudomonas aeruginosa battleground where pathogens and the immune system
– researchers can monitor real-time cellular responses, engage in a complex interplay of attack and defense. Recent
including the release of pro-inflammatory cytokines, advances in computational biology have transformed our
disruption of the epithelial barrier, and activation of understanding of these pulmonary immune responses,
innate immune signaling pathways. In addition, these offering innovative insights into how the body defends itself
models facilitate high-throughput screening of potential against invading microorganisms. Advanced computational
therapeutics, offering a controlled platform to evaluate simulations have become powerful tools for dissecting
drug efficacy and toxicity before evaluation in more and analyzing immune responses with unprecedented
complex systems. detail. By utilizing high-performance computing and
b. In vivo murine infection studies machine learning algorithms, researchers can now model
While in vitro models of lung epithelial cells provide the dynamic interactions between pathogens and immune
valuable insights into the early stages of pathogen invasion cells within the lung microenvironment. These simulations
and the subsequent immune response, they cannot fully provide valuable insights into the spatial and temporal
capture the complex interactions among immune cells, dynamics of immune responses, revealing how factors such
tissue architecture, and systemic responses present in a as cytokine signaling, cellular migration, and pathogen
living organism. In vivo murine infection studies address evasion strategies influence infection outcomes. For
this limitation by allowing researchers to examine instance, computational models have simulated the behavior
pulmonary immune responses within the context of a whole of alveolar macrophages – the lung’s first line of defense –
organism. Mice – with their well-characterized immune and their interactions with bacterial or viral invaders. Such
systems and genetic manipulability – serve as ideal models models can predict how variations in immune cell activity
for investigating host–pathogen interactions. For instance, or pathogen virulence may shift the balance between
studies using murine models have highlighted the role effective clearance and chronic infection. 19,20
of alveolar macrophages in clearing bacterial infections In addition, advanced computational approaches
and the contribution of T-cell subsets in controlling viral facilitate the integration of multi-omics data – including
replication. In addition, transgenic and knockout mouse genomics, transcriptomics, and proteomics – to construct
models have been pivotal in identifying key immune comprehensive models of pulmonary immunity. These
signaling pathways – such as the nucleotide oligomerization models help identify key molecular pathways and

Volume 2 Issue 4 (2025) 31 doi: 10.36922/MI025100019