PUlm defense mechanisms Flashcards
Effects of chronic alcohol consumpotm
1) incr gram negative organisms
2) blunted cough and gag reflex = aspiration
3) decr mucocilliary clearance
4) impaired alveolar macrophage function
how does alcohol affect oropharynx
1) bacterial colonization (gram neg)
2) poor dentition
how does alcohol affect glottis and airway
1) incr aspiration
2) decr mucocilliary function
how does alcohol affect innate immunity
vs. adaptive immunity
1) decr macrophage and neutrophil function
__
1) decr T cells and cytokines
2) decr B cells and airspace IgG
when should asthmatics exercise
NOT IN afternoon because peak ozone concentration
what should you tell patients about ozone during ozone alert
1) transient
2) stay inside b/c irritant
3) exercise early in morning
Air contains what kinds of things?
1) pollutants
2) oxidants
3) dust pollens
4) toxins
5) bacteria and LPS
6) viruses
what is airway clearance mechanism
1) air turbulence created by nasal passages trachea and large airway
2) large particle deposit on mucous surface of airway
3) mucus project to surface by beating cilia on epith cell
4) cleared by coughin, sneezing, swallowing
how do we clear large particles deposit on mucous surface of airways
1) mucous project to surface via beating of cilia
2) cleared by cough, sneeze, swallow
what are ciliary function
1) coordinate movement of particles from airways
what are examples of things that make it hard to clear form lungs
1) air pollution/ozone
2) viral infection (sloughing of epithelial cell)
3) cigarette smoke (poison cilia
Genetic disorders assoc with abnormal ciliar function
1) primary ciliary dyskinesia (immotile ciliary syndrome) AKA…
- inheritance
- due to ?
- symptoms
1) AR
2) defect in dynein arms
3) sinusitis, bronchiectaissi, situs inversus, infertility (KARTAGENER’S when assoc with situs inversus)
components of airway epithelial fluid (4)
1) antimicrobial peptides and proteins (defensins, cathelicidin, lysoszyme)
2) antioxidants
3) antiproteases
4) IgA
Sarcoidosis
effects on
1) endocrine/renal
2) MSK
3) skin
4) spleen
1) diabetes insipidous rarely due to pituitary/hypothalamic involvement
2) musculoskeletal (sausage digits, bony erosions)
3) erythema nodosum/lupus pernio around eye fold
4) granulomatous inflamm
what is function of innate
= early host defense against (3)
relies on ….
1) early host defense against virus, fungi, bacteria
2) PAMPs are recog by secreted, cell surface or intracellular PRR (
3) recruitment of phagocytes,
4) kill microbes + inflamm
components of adaptive immunity
what does memory allow for?
1) B and T cells for antigen specificity
2) memory allows for more rapid and greater secondary response
how do we clear small particles from lower airways
1) ingested by resident alveolar macrophages and/or dendritic
2) bind to lung collectins and surfactant protein A and D (secreted PRR)
3) PRR bind PAMP
4) opsonization and phagocytosis by macs and dendritic cell
macrophages are a critical part of innate immunity located where?
in alveolar part of lung
what is role of macrophage in host defense
1) suppress adaptive immune response
2) clear particles, bugs, debris, apoptotic cells
3) initiate inflamm response
4) transport particles and bugs to lymph nodes
5) clear alevoelar surfactant
what is major component of normal bronchoalveolar lavage
how does that change with smoking
what is normal CD4:Cd8
1) macrophages
2) incr macrophages b/c eat tar granules can look black
3) 2:1
what happens when you inhale harmless particle
1) inhale harmless particle
2) bind to epithelial cell and mucus
3) mucociliary escalator to mouth to sneeze, cough
4) some particles bind to dendritic cell (projection between epithelial cell to sample airway)
5) if particle does not have a PAMP, then dendritic cell will go to draining lymph node —> not activated to induce adaptive immune response
tonic suppression of inflammation
tonic suppression of adaptive immunity
(what we normally inhale during day)
what happens when you inhale virus
1) inhale virus
2) virus has PAMP
3) PAMP bind to epithelail cell —> activ —> chemokine/cytokine to recruit
neutorphils and induce microbial killing
4) PAMP bind to DC upregul CD8 and MHC
5) DC traffick to lymph node to present to T cells and induce adaptive immune response
activation of dendritic cell
PMN recruitment and adaptive immune response
what is mechanism of innate immune protect in lung
1) cytokine/chemokine recruit
2) PMN recruit
3) microbial killing
4) dendritic cell maturation
5) monocyte recruit
TL4 mutations associated with ___ in humans
endotoxin hyporesponsiveness (incr infection)
less likely to develop ARDS/ALI
TLR2 bind to gram positive
TLR4 binds gram negative
TLR7 and TLR8 bind HIV
TLR9 binds DNA
a
where are TLR mostly expressed
innate immune system
granulocytes/macrophages (mostly)
dendritic cells too
what does TLR stimulation do?
1) induce proinflamm response
(activ epithelial, DCs, cytokines, type 1 IFN)
2) bridge between innate and adaptive imunity
what is the function of MHC molecules?
antigen presenting cell via MHC class 2 or MHC class 1
1) encounter bug
2) phagocytosed
3) via antigen processing pathway, chopped up into peptides
4) bind to either MHC class 2 and interact with CD4
binds to MHC 1 to interact with CD8
5) dendritic cell activated –> must upregul co-stim molec
must be costim
must have both signals for optimal immune response
what are the major APC in the lung?
dendritic cells
1) pathogen has PAMP
2) bind to PRR
3) activation of dendritic
cell
4) travel to lymph node
5) T cell area in lymph
node
6) small freq of T cells
specific for peptide on MHC
7) interaction btwn
antigen specific receptor
on TCR
to allow T cell activ
prolif and traffick to skin
Compare and contrast
Resident macrophages. vs monocytes vs. resident dendritic cells
major function
1) resident macrophage
suppress adaptive imm, unwanted inflamm, phagocytose particulates
2) diff into inflamm macs, DCs
patrol vascular endothelium
3) resident dendritic cell
phag inhaled particulates, migrate to lymph nodes, maintain tolerance
which major cell types phagocytose inhaled particulates
resident macrophages and resident dendritic cells
which major cell type suppress adaptive immunity/unwanted inflamm
resident macrophages
which major cell type patrols vascular endothelium
monocytes
which major cell type maintains tolerance
resident dendritic cell
which major cell type activ by PAMPs
1) resident macrophage
2) monocytes
3) resident dendritic cells
what is the trimolecular complex?
T cell receptor + antigen peptide + MHC
Migratory DCs engulf antigen and traffic to __
mediastinal lymph nodes
in response to harmless antigen,
1) no adaptive immune response, no inflamm
2) DCs sample harmless antigen —> migrate to lymph node —> no co-stim molec and induce IL-10 and ICOS-L
3) convert that T cell to become regulator and decr inflamm response
In response to virus/bacteria,
In response to allergen, cause DC to beocme activ via PAMP, maturation, and prolif of dendritic cell
cause DC to eat protein, become activ via PAMP stim —> DC migrate and amplify
to T cell area of lymph node and present 2 signals to develop CD4 immune response
CD8+ T cell kinetics after acute LCMV infection of B6 mice
vs.
CD4+ T cell kinetics
1) expansion of CD8+ T cells specific for LCMV, the maintenance of response
(amplification, contraction, maintenance)
2) amplification, contraction but then overall CD4+ count decr
how do you initiate the granulomatous response
1) inhale stim (MTB)
2) alveolitis, then granuloma formation to wall off
3) trigger CD4+ T cells by APCs
4) activ T cells and release Th1 cytokines (IL-2, IFNy)
5) accumulate immunocompetent cells
what is essential initial step in generating granuloma
alveolitis
T cells in lung are incr by 2 potential mechanisms after activation…
1) influx of Ag specific T cells from blood
2) local T cell prolif
Adaptive immune response in lung process
1) antigen ingested by DC and alveolar macrophage
2) primary immune response NOT IN LUNG
TRAFFIC TO MEDIASTINAL LYMPH NODE
TO ENGAGE CD4 (representing specific antigen
TCR
3) clonal prolfieration of T cell
4) traffic back to lung to decr immune response
a
a
what does BAL look like in sarcoidosis
(CD4+ /CD8+)
CD4:CD8 ratio
incr in number of CD4+ and CD8+ depending on severity
3-15:1 ratio rather than 2:1
what major cell type increases in BAL of sarcoidosis
lymphocytes
if you have greater CD8>CD4
hypersensitivity pneumonitis
If IL-12 around to stim naive CD4+ t cell then become
Th1 CD4+ T cell for cell-mediated immunity and intracellular pathogens (TB and legionella)
If IL-4 around to stim naive CD4+ t cell then become
Th2 CD4+ T cell for
IL-4, IL-5, IL-13
humoral immunity, helminth infection, atopy
If IL-23, IL-6 around to stim naive CD4+ t cell then become
Th17 CD4+ T cells
clear bacterial pathogen/autoimmunity
in chronic beryllium disease
main type of T cell produced?
Th1 cytokine secretion
