Localized Immune Memory in the Lung

Antibody-forming cells (AFC) produced in the lung-associated lymph nodes after lung immunization enter the blood and accumulate mainly in the Immunized lung. In lung interstitial tissues and alveoli, AFC mature into plasma cells and produce specific antibody. In addition to AFC, published data suggest that memory cells are also recruited to and/or are produced in immunized lung lobes, and that these memory cells can respond in the alveoli to secondary antigen challenges. The purpose of this study was to determine if memory cells induced in the lung by multiple antigen exposures could respond in vivo to challenges with low doses of antigen. The degree of inflammation produced by antigen doses that would allow the accumulation of AFC from the blood was evaluated. Beagle dogs were anesthetized, and a fiberoptic bronchoscope used to instill 106, 107, 108, 109, or 1010 sheep red blood cells (SRBC) into individual lung lobes. Of these doses, only 109 and 1010 SRBC significantly increased inflammation (increased number of neutrophils) or vascular permeability (increased total protein). The number of specific IgM AFC and concentration of anti-SRBC IgG antibody were significantly elevated only in lavage fluid from the lung lobes immunized with 109 and 1010 SRBC. Four lung lobes were then given two additional challenges with 1010 SRBC. In third and fourth challenges, these lung lobes received doses of SRBC of 104, 105, 106, 107, 108, and 109 SRBC. The results showed that significantly increased numbers of specific IgM AFC and concentrations of IgG antibody were found even at the lowest dose of antigen (104 SRBC) in the absence of increased inflammation or vascular permeability. The challenge of a control lung lobe that had not been previously exposed to antigen with 106 SRBC did not induce specific AFC or measurable anti-SRBC antibody. These results suggest that immune memory cells are recruited to and/or are produced in individual lung lobes after immunization and challenge, and that these memory cells can respond in vivo to low doses of antigen. Because challenge with low doses of antigen produced positive immune responses with minimal changes in inflammation or vascular permeability, immune cells and antibody were likely produced locally rather than being recruited from the blood.