Skip to main content
. 2022 May 10;55(5):749–780. doi: 10.1016/j.immuni.2022.04.013

Figure 2.

Figure 2

Acute pulmonary inflammation and downstream responses

Initiation: Lung insults often involving infectious etiologic agents or vaccine components are recognized by structural cells, including epithelial and endothelial cells, along with tissue-resident antigen-presenting cells (airway macrophages and dendritic cells). Together, these cells recognize pathogen-associated molecular patterns (PAMPs), tissue damage-associated molecular patterns (DAMPs), or vaccine adjuvants via a complex network or surface, endosomal, and cytoplasmic sensors, collectively termed pattern recognition receptors (PRRs). Calibration: Detection of viral and bacterial PAMPs or vaccine-derived adjuvants initiates differential response pathways depending on the source (viral, bacterial, or adjuvant). Detection of viral PAMPS leads to production of IFN-I and/or IFN-III, TNFα, IL1β, IL6, IL8, IL12, MCP1, and inflammasome activation. Distinctive bacterial PAMPs (endotoxins, lipopolysaccharide [LPS], and peptidoglycan [PG]) trigger NF-κB signaling axis, leading to production of IL6, IL8, IL18, TNFɑ/β, and inflammasome activation. Detection and response to vaccine adjuvants can be tailored to promote type 1 or type 2 immune responses and specific development of cellular and humoral immunity. Trafficking: Specialized APCs capture and process protein components from pathogen or vaccine sources, traffic to airway-associated draining lymph nodes, and present antigen to naive T cells. Adaptive responses: Priming of adaptive responses begins around day 4 post-exposure and occurs in respiratory-associated lymphoid tissues. Following antigen-specific training, CD8+ T cell and CD4+ Th1 responses (IFNγ, TNF, IL1, IL12) are typically mounted against intracellular pathogens (antigens presented on MHC-I), while CD4+ Th2 (IL4, 5, 6, 10, 13), humoral (Tfh, B cells; antibody), and CD4 T helper (Th17, Th22) responses are increased in response to extracellular insults. Cross-presentation of external-derived antigens on MHC-I to CD8+ T cells allows development of cellular immunity to external insults. Figure created with BioRender.com.