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Spr2015_Week7 > PUlm defense mechanisms > Flashcards

PUlm defense mechanisms Flashcards

1
Q

Effects of chronic alcohol consumpotm

A

1) incr gram negative organisms
2) blunted cough and gag reflex = aspiration
3) decr mucocilliary clearance
4) impaired alveolar macrophage function

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2
Q

how does alcohol affect oropharynx

A

1) bacterial colonization (gram neg)

2) poor dentition

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3
Q

how does alcohol affect glottis and airway

A

1) incr aspiration

2) decr mucocilliary function

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4
Q

how does alcohol affect innate immunity

vs. adaptive immunity

A

1) decr macrophage and neutrophil function

__

1) decr T cells and cytokines
2) decr B cells and airspace IgG

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5
Q

when should asthmatics exercise

A

NOT IN afternoon because peak ozone concentration

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6
Q

what should you tell patients about ozone during ozone alert

A

1) transient
2) stay inside b/c irritant
3) exercise early in morning

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7
Q

Air contains what kinds of things?

A

1) pollutants
2) oxidants
3) dust pollens
4) toxins
5) bacteria and LPS
6) viruses

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8
Q

what is airway clearance mechanism

A

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

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9
Q

how do we clear large particles deposit on mucous surface of airways

A

1) mucous project to surface via beating of cilia

2) cleared by cough, sneeze, swallow

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10
Q

what are ciliary function

A

1) coordinate movement of particles from airways

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11
Q

what are examples of things that make it hard to clear form lungs

A

1) air pollution/ozone
2) viral infection (sloughing of epithelial cell)

3) cigarette smoke (poison cilia

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12
Q

Genetic disorders assoc with abnormal ciliar function

1) primary ciliary dyskinesia (immotile ciliary syndrome) AKA…

  • inheritance
  • due to ?
  • symptoms
A

1) AR
2) defect in dynein arms
3) sinusitis, bronchiectaissi, situs inversus, infertility (KARTAGENER’S when assoc with situs inversus)

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13
Q

components of airway epithelial fluid (4)

A

1) antimicrobial peptides and proteins (defensins, cathelicidin, lysoszyme)
2) antioxidants
3) antiproteases
4) IgA

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14
Q

Sarcoidosis
effects on
1) endocrine/renal
2) MSK

3) skin
4) spleen

A

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

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15
Q

what is function of innate
= early host defense against (3)

relies on ….

A

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

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16
Q

components of adaptive immunity

what does memory allow for?

A

1) B and T cells for antigen specificity

2) memory allows for more rapid and greater secondary response

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17
Q

how do we clear small particles from lower airways

A

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

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18
Q

macrophages are a critical part of innate immunity located where?

A

in alveolar part of lung

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19
Q

what is role of macrophage in host defense

A

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

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20
Q

what is major component of normal bronchoalveolar lavage

how does that change with smoking

what is normal CD4:Cd8

A

1) macrophages
2) incr macrophages b/c eat tar granules can look black
3) 2:1

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21
Q

what happens when you inhale harmless particle

A

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)

22
Q

what happens when you inhale virus

A

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

23
Q

what is mechanism of innate immune protect in lung

A

1) cytokine/chemokine recruit
2) PMN recruit
3) microbial killing
4) dendritic cell maturation
5) monocyte recruit

24
Q

TL4 mutations associated with ___ in humans

A

endotoxin hyporesponsiveness (incr infection)

less likely to develop ARDS/ALI

25
Q

TLR2 bind to gram positive
TLR4 binds gram negative
TLR7 and TLR8 bind HIV
TLR9 binds DNA

A

a

26
Q

where are TLR mostly expressed

A

innate immune system

granulocytes/macrophages (mostly)
dendritic cells too

27
Q

what does TLR stimulation do?

A

1) induce proinflamm response
(activ epithelial, DCs, cytokines, type 1 IFN)

2) bridge between innate and adaptive imunity

28
Q

what is the function of MHC molecules?

A

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

29
Q

what are the major APC in the lung?

A

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

30
Q

Compare and contrast

Resident macrophages. vs monocytes vs. resident dendritic cells

major function

A

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

31
Q

which major cell types phagocytose inhaled particulates

A

resident macrophages and resident dendritic cells

32
Q

which major cell type suppress adaptive immunity/unwanted inflamm

A

resident macrophages

33
Q

which major cell type patrols vascular endothelium

A

monocytes

34
Q

which major cell type maintains tolerance

A

resident dendritic cell

35
Q

which major cell type activ by PAMPs

A

1) resident macrophage
2) monocytes
3) resident dendritic cells

36
Q

what is the trimolecular complex?

A

T cell receptor + antigen peptide + MHC

37
Q

Migratory DCs engulf antigen and traffic to __

A

mediastinal lymph nodes

38
Q

in response to harmless antigen,

A

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

39
Q

In response to virus/bacteria,

In response to allergen, cause DC to beocme activ via PAMP, maturation, and prolif of dendritic cell

A

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

40
Q

CD8+ T cell kinetics after acute LCMV infection of B6 mice

vs.

CD4+ T cell kinetics

A

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

41
Q

how do you initiate the granulomatous response

A

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

42
Q

what is essential initial step in generating granuloma

A

alveolitis

43
Q

T cells in lung are incr by 2 potential mechanisms after activation…

A

1) influx of Ag specific T cells from blood

2) local T cell prolif

44
Q

Adaptive immune response in lung process

A

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

45
Q

a

A

a

46
Q

what does BAL look like in sarcoidosis
(CD4+ /CD8+)
CD4:CD8 ratio

A

incr in number of CD4+ and CD8+ depending on severity

3-15:1 ratio rather than 2:1

47
Q

what major cell type increases in BAL of sarcoidosis

A

lymphocytes

48
Q

if you have greater CD8>CD4

A

hypersensitivity pneumonitis

49
Q

If IL-12 around to stim naive CD4+ t cell then become

A

Th1 CD4+ T cell for cell-mediated immunity and intracellular pathogens (TB and legionella)

50
Q

If IL-4 around to stim naive CD4+ t cell then become

A

Th2 CD4+ T cell for
IL-4, IL-5, IL-13
humoral immunity, helminth infection, atopy

51
Q

If IL-23, IL-6 around to stim naive CD4+ t cell then become

A

Th17 CD4+ T cells

clear bacterial pathogen/autoimmunity

52
Q

in chronic beryllium disease

main type of T cell produced?

A

Th1 cytokine secretion

Spr2015_Week7 (10 decks)

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