-
lung dz that are mediated primarily by innate immunity
acute respiratory distress syndrome
-
lung Diseases mediated by adaptive mechanisms of immunity
- Th1 mediated: Hypersensitivity pneumonitis
- Th2 mediated: Asthma
-
lung dz mediated by autoimmune mechanisms
- Wegener’s granulomatosis
- Goodpasture Syndrome
-
severe-life threatening respiratory insufficiency caused by diffuse alveolar capillary damage and influx of fluid into the alveoli
ARDS
-
collapsed or distended alveoli.
Many contain dense proteinaceous debris, desquamated cells and hyaline membranes
ARDS
-
triggers of ARDS
Sepsis, Diffuse pulmonary infections (viral, mycoplasma, pneumocystis, pneumonia and military tuberculosis), Gastric aspirations, Mechanical trauma
-
mechanism of ARDS from infectious insults
- Antigen (bacteria) LPS binds TLR4 on alveolar macs --> Activation of transcription factors, particularly NF- kB, that control pro-inflammatory gene expression --> Transcription of inflammatory cytokine genes --> TNF, IL-1, IL-12, IL-8 --> strong neutrophil chemoattractant and stimulates their recruitment from the
- microvasculature, thru the interstitium and into alveolus --> Once in air space, neutrophils produce leukotrienes, ROS and proteases, and platelet activating factor (vasodilation) --> loss of diffusion capacity and both Type I and II cells die & permeability increases
-
mechanism of ARDS from non infectious insults
Activation of transcription factors, particularly NF- kB, that control pro-inflammatory gene expression --> Transcription of inflammatory cytokine genes --> TNF, IL-1, IL-12, IL-8 --> strong neutrophil chemoattractant and stimulates their recruitment from themicrovasculature, thru the interstitium and into alveolus --> Once in air space, neutrophils produce leukotrienes, ROS and proteases, and platelet activating factor (vasodilation) --> loss of diffusion capacity and both Type I and II cells die & permeability increases
-
IFN gamma
produced by Th1 cells. Activates macs
-
Macs produce _____ to activate/differentiate more Th1 cells
IL 12
-
stimulates monocyte production by bone marrow
IL3/GM-CSF
-
cause local tissue destruction, incr expression of local adhesion molecules
TNF-alpha and TNF-beta
-
mechanism of granulmatous formation
Chronic CD4 T cell activation (by persistent antigen) and Th1 cytokine production (IFNg) continually stimulate macs --> macs develop incr cytoplasm & cytoplasmic organelles (epitheloid cells), and may fuse together to form multinucleated giant cells --> Clusters of activated macs surrounding persistent antigen --> granulomas
-
true granuloma is...
composed of an aggregation of macs that are transformed into epithelium-like (epithelioid) cells, surrounded by lymphocytes & fibroblasts
-
pathogenesis of TB
- Primary Tb infection is characterized by early proliferation of bacteria in pulmonary alveolar macrophages (Lasts about 3 weeks)
- By 3 wks a Th1 CD4 T cell response is mounted that activates macs to contain the M. Tb, by 1) formation of intracell phagolysosome, 2) production of NO, and 3)orchestrating formation of granulomas.
- TNFa, produced by activated macrophages, recruits monocytes, which differentiate into epithelioid cells, and in combo w/ formation of Giant cells form granuloma
-
differ from asthma cuz it involves alveoli instead of airways
hypersensitive pneumotitis. Farmer's lung and pigeon breeder's lung
-
caused by inhalation of spores of thermophilic actinomycete found in harvested hay
Farmer's lung (hypersensitivity pneumotitis)
-
caused by proteins from serum, excretions, or feathers of birds
pigeon breeder's lung (hypersensitive pneumotitis)
-
mechanism of hypersensitivity pneumotitis
Activated neutrophils release proteases, ROS, and vasodilator substances resulting in damage to alveolar epithelium and edema.
Activated alveolar macrophages produce IL-12, which promotes Th1 CD4 T cell production of IFNg, that further stimulates inflammatory cytokine production by alveolar macrophages and contributes to granuloma formation
-
type II hypersensitivity because immune complexes are not tissue bound
Wegener’s granulomatosus (cANCAs--PR3) and Goodpasture
-
Noncollagenous protein in basement membrane of lung alveoli and kidney glomeruli is antigen --> complement activation via immune complexes à neutrophil activation and degranulation
Goodpasture syndrome
-
high prevalence of certain HLA haplotypes (eg, HLA-DRB1) in a affected patients
diffuse pulmonary hemorrhage, glomerulonephritis, or both presenting simultaneously, in association with circulating
Goodpasture syndrome
-
anti-basement membrane antibodies. bind to type IV collagen. Destruction of alveolar basement membrane
results in intra-alveolar hemorrhage
Goodpasture syndrome
-
mechanism of Goodpasture syndrome
Bound antibody leads to activation of classical complement pathway and generation of C5a, which recruits neutrophils and monocytes --> Recruited cells bind to deposited antibodies via Fc receptors --> produce enzymes ROS that mediate tissue damage
-
Rheumatic fever mechanism
hypersensitivity reaction induced by group A streptococci , where antibodies directed against M proteins of certain strains of streptococci cross-react with glycoprotein antigens in the heart, joints and other tissues
-
molecular mimicry
In rheumatic fever. resemblance of pathogen and host antigens that leads to the targeting of host tissues
-
rheumatic fever is type ___ hypersensitivity rxn
II and IV
|
|
