Aspergillus spores are small (2–3 μm in diameter) and can penetrate deep into the respiratory system to the alveolar level. In healthy people, innate and adaptive immune responses are triggered by various immune cells (notably neutrophils, resident alveolar macrophages and dendritic cells) drawn to the site of infection by numerous inflammatory cytokines and neutrophilic attractants (such as CXCR2 receptor ligands). In this situation, mucociliary clearance is initiated and spores are successfully phagocytosed, clearing the infection from the host. In people with predisposing lung diseases—such as persistent asthma or cystic fibrosis (or rarer diseases such as chronic granulomatous disease or Hyper-IgE syndrome)—several factors lead to an increased risk of<unk> . These include immune factors (such as atopy or immunogenic HLA-restricted phenotypes), as well as genetic factors (such as CFTR gene mutations in both asthmatics and cystic fibrosis patients and a ZNF77 mutation resulting in a premature stop codon in asthmatics and<unk>  patients). By allowing Aspergillus spores to persist in pulmonary tissues, it permits successful germination which leads to hyphae growing in mucus plugs. There are hypersensitivity responses, both a type I response (atopic, with formation of immunoglobulin E, or IgE) and a type III hypersensitivity response (with formation of immunoglobulin G, or IgG). The reaction of IgE with Aspergillus antigens results in mast cell degranulation with bronchoconstriction and increased capillary permeability. Immune complexes (a type III reaction) and inflammatory cells are deposited within the mucous membranes of the airways, leading to necrosis (tissue death) and eosinophilic infiltration. Type 2 T helper cells appear to play an important role in<unk>  due to an increased sensitivity to interleukin (IL) 4 and IL-5. These cytokines up-regulate mast cell degranulation, exacerbating respiratory decline. Aspergillus also utilises a number of factors to continue evading host responses, notably the use of proteolytic enzymes that interrupt IgG antibodies aimed towards it. Another important feature is its ability to interact and integrate with epithelial surfaces, which results in massive pro-inflammatory counter-response by the immune system involving IL-6, IL-8 and MCP-1 (a CCL2 receptor ligand). Proteases released by both the fungus and neutrophils induce further injury to the respiratory epithelium, leading to initiation of repair mechanisms (such as an influx of serum and extracellular matrix (ECM) proteins) at the site of infection. Aspergillus spores and hyphae can interact with ECM proteins, and it is hypothesised that this process facilitates the binding of spores to damaged respiratory sites. As concentrations of Aspergillus proteases increase, the immunological effect switches from pro-inflammatory to inhibitory, and further reduces phagocytic ability to clear Aspergillus. Ultimately, repeated acute episodes lead to wider scale damage of pulmonary structures (parenchyma) and function via irreversible lung remodelling. Left untreated, this manifests as progressive bronchiectasis and pulmonary fibrosis that is often seen in the upper lobes, and can give rise to a similar radiological appearance to that produced by tuberculosis.
Allergic bronchopulmonary aspergillosis
Chronic pulmonary aspergillosis
Tuberculosis
Miliary tuberculosis
Fungal pneumonia
Primary pulmonary coccidioidomycosis
Cryptogenic organizing pneumonia
Atypical pneumonia