Barrington- Lung Immunity Flashcards
____ and ____ airways together are largest exposed epithelial surface to inorganic and organic compounds, and microbes
upper and lower airways
different ways microbes can get into lungs
commensal microbes
microbes in the inhaled air
occurs within 12 hours of exposure to antigen
innate immunity
occurs within days of being exposed to antigen
adaptive immunity
_____ particles bind to dendritic cells and instruct immune response to become tolerant to those molecules
important for the airways (inflammation will impair gas exchange—-don’t want to invoke an immune response against just anything)
inert
upper airway immune defense
epithelial layer (cilia and mucus); immune cells
lower airway immune defense
surfactant and alveolar macrophages
PRRs on innate immune cells recognize _____ on pathogens, and migrate to regional lymph nodes where they can activate cell-mediated response
PAMPs
_____ triggers a cascade of events that result in activation of transcription factors (NFkB and IRF) which will go to nucleus and activate expression of different genes (inflammatory)
PRRs recognizing and binding to PAMPs
important in chemoattracting neutrophils
IL-8, CXCL8, MCP1
intracellular TLRs recognize what
nucleic acids
TLR4 recognizes what
LPS on gram - bacteria
antibody response directed by B cells is what immunity
humoral immunity
microbe has been phagocytosed and recognized by PRRs; presents to helper T cells and activates them
further activate macrophage—making it a better clearing cell of invading microbe
(is what immunity)
cell-mediated immunity
: taken up by APCs like dendritic cells and macrophages can present antigen to cytotoxic T cells leading to their activation and need 2 signals
signal 1: antigen peptide MHC and costimulatory signal (signal 2)
once activated CD8 T cell can go to infection site and start killing infected cells (what immunity)
cell-mediated immunity
2 major lung defenses
airways and their mucosa
alveolar spaces
prevents entry of larger particulates from traveling further in the lung
anatomical barriers
a way to get material out of lungs
cough
used to transport material from bronchi to trachea
mucociliary transport
____ in mucus combat bacteria
anti-microbials
can degrade bacterial cell walls
lysozyme
chelates iron
lactoferrin
produces ROS which can be lethal to bacteria
peroxidase
forms a pore in bacteria and kills through osmotic lysis
defensins
transcytosed across epithelial cells, neutralizes toxins, viruses, bacteria
secretory IgA
major site for IgA production in mucosa of GI and Res. tracts
mucosal lymphoid tissue in lamina propria
______receptor binds dimeric IgA and transports it to lumenal surface; where the IgA is released by proteolytic cleavage
Poly-Ig
predominate defense mechanism is neutralizing pathogens
IgA
____cells have PRRs (TLRs) so can mount an inflammatory response
epithelial
chemokine produced that recruit neutrophils to site of infection
CXCL8
blood-derived cell of mucosa
Dendritic cells
lymphocytes (during an infection)
eosinophils, mast cells, basophils
immune defense in alveolar space
alveolar macrophages
lymphocytes
type I and II pneumocytes (surfactant)
neutrophils
IgG and opsonins
not seen in the lungs usually unless there is an infection
neutrophils and lymphocytes
immunoglobin predominant in the lungs in general
IgA
immunoglobin most abundant in alveoli
IgG
C3b produced by _________ and lead to complement activation (microbe that has activated complement, get C3b on that microbe and that allows C3b to be recognized by receptors on macrophages and that will induce phagocytosis of microbe)
tissue macrophages
produced by the liver but can find it in lung in case of infection (a good opsonin)
CRP
key soluble PRRs in alveolar spaces
surfactants
less _____, macrophages less able to provide defenses against foreign threat
surfactant
surfactant in steady state
inhibits inflammatory response
surfactant interacting with PAMP and CD91
stimulates inflammatory response
____ leads to activation of alveolar macrophage (either directly or with CD91 interaction)
PAMPs
____ activation produces pro-inflammatory cytokines and recruits neutrophils to site of infection
NF-kB
when activated, can ingest a large number of microbes
destroy them with oxygen independent mechanisms
produce ROS and proteases that lead to tissue damage
neutrophils
professional phagocytes
neutrophils
release chromatin rich material, it is sticky and will bind microbes and prevent them from disseminating and facilitate phagocytosis
neutrophils releasing NETs
adaptive immune response in the lung is initiated in _______
draining lymph nodes
cells enter through ________ and inside there are B cell zones and T cell ones
B cell zones have germinal centers (where B cells undergo class switch recombination)
differentiate into plasma cells (start making antibodies)
afferent lymphatics into lymph node
CD4 cells can differentiate into what
Th1, Th2, Th17
kill virally infected cells
CD8 (cytotoxic) T cells
depends on this cytokine for clonal expansion of T cells
IL-2
produces IFNgamma (can also lead to macrophage activation) CD40 ligand and bind to CD40 on macrophages and activate them really good phagocytes
Th1
more important in driving antibody responses
interact with B cells
produce cytokines that will instruct B cell to differentiate and class switch into IgG or IgA
Th2 and Th17
T cell receptor peptide and MHC interaction as well as costimulatory molecule
2 signals for T cell activation
needs 2 signals to become activated, but once activated, just needs 1 signal to kill
CD8 T cells
similar structure as lymph node w/out afferent lymph
found at bifurcations in bronchus
bronchus-associated lymphoid tissue (BALT)
microbes and antigens can pass through (endocytosis or phagocytosis) into the associated lymphoid tissue
through M cells
large # of microbes
PRRs stimulated and innate immune system activated and steers response towards pro-inflammation; leads to clearance of microbes and tissue damage
infection
seasonal infection that can lead to pneumonia
viral influenza
- virus-induced damage to pulmonary epithelium
- influenza neuraminidase and upregulation of platelet-activating factor receptor expression
- cytokines (e.g. interferons)
increase susceptibility to secondary bacterial infection after influenza virus
engagement of alveolar macrophages -production of pro-inflammatory cytokines and recruitment of neutrophils to site of infection
get rid of microbe
normal lung exposed to pneumonia
some of the innate immune cells and alveolar macrophages are not able to recognize some of the bacteria during an active viral infection, turn on adaptive immunity and get IFNgamma produced
IFN gamma can lead to down regulation of PRRs on alveolar macrophage
patient with pre-existing viral infection exposed to pneumonia
