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3.24 > Lecture 4: The lungs- immunology and inflammation > Flashcards

Lecture 4: The lungs- immunology and inflammation Flashcards

1
Q

What is the single largest infectious cause of death in children worldwide?

A

Pnuemonia

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2
Q

What are the stages in infection?

A
  1. Pathogens adhere to epithelium
  2. Local infection, penetration of epithelium
  3. Local infection of tissue
  4. Adaptive immunity
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3
Q

What protects pathogens from adhering to the epithelium?

A
  • Normal flora
  • Local chemical factors
  • Phagocytes (especially in lung)
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4
Q

What protects against local infection, penetration of epithelium?

A
  • Wound healing induced
  • Antimicrobial proteins and peptides, phagocytes and complement destroy invading microorganisms
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5
Q

What protects against local infections of tissues?

A
  • Complement, cytokines, chemokines Phagocytes, NK cells
  • Activation of macrophages
  • Dendritic cells migrate to lymph nodes to initiate adaptive immunity
  • Blood clotting helps limit spread of infection
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6
Q

What protects against adaptive immunity?

A
  • Infection cleared by specific antibody
  • T-cell dependanct macrophage activation and cytotoxic T cells
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7
Q

What is the first line of defence against infection?

A

Epithelial surface - epithelial cells held together by tight junctions form a seal against external environment

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8
Q

What do epithelial cells secrete?

A

Mucus - interferes with adhesion and results in expulsion resultin from beating of cilia

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9
Q

What do epithelial cells produce?

A

Antimicrobial peptides such as b-defensins that damage bacterial cell membranes and surfactant proteins A and D that facilitate phagocytosis

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10
Q

What does epitheliam penetration result in?

A

Recognition of pathogen surface molecules by macrophages and subsequent phagocytosis

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11
Q

What do activated macrophages secrete?

A

Cytokines and Chemokines

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12
Q

What do cytokines do?

A

Affect behaviour of other cells

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13
Q

What do chemokines do?

A

Attract other cells

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14
Q

Define inflammation

A

Heat, pain, redness and swelling due to effects of cytokines/other mediators on local blood vessels

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15
Q

Name the cytokines

A
  • Il-1B
  • TNF-a
  • IL-6
  • CXCL8
  • IL-12
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16
Q

What are the local effects of IL-1B

A
  • Activates vascular endothelium
  • Activates lymphocytes
  • Local tissue destruction increases access of effe tor cells
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17
Q

What are the local effects of TNF-a?

A
  • Activates vascular endothelium and increases vascular permeability, which leads to increased entry of IgG, complement, and cells to tissues and increased fluid drainage to lymph nodes
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18
Q

What are the local effects of IL6

A
  • Lymphocyte activation
  • Increased antibody production
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19
Q

What are the local effects of CXCL8?

A

Chemitactic factor recruits neutrophils, basophils and T cells to site of infection

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20
Q

What are the local effects of IL12?

A
  • Activates NK cells
  • Induces the differentiation of CD4 T cells into Th 1 cells
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21
Q

What are the systemic effects of IL-1B?

A

Fewer production of IL6

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22
Q

What are the systemic effects of TNF-a?

A
  • Fever
  • Mobilization of metabolites
  • Shock
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23
Q

What are the systemic effects of IL6?

A
  • Fever
  • Induces acute phase protein prodcution
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24
Q

What ingests pathogens in infected tissues?

A

Immature dendritic cells - this is dependant on Pathogen Recognition Receptors (PPRs) or macropinocytosis

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25
Q

What do dendritic cells mature and migrate to?

A

Peripheral lymphoid organs and present pathogen antigens to T cells

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26
Q

Where do immature dendritic cells reside?

A

In peripheral tissues

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27
Q

How do dedritic cells migrate?

A

Via lymphatic vessels to regional lymph noded

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28
Q

What do mature dendritic cells activate?

A

Naive T cells in lymphoid organs such as lymph nodes

29
Q

Name important cells in lung disease

A
  • Airway Epithelial Cell and Dendritic Cell
  • Type 2 Helper T Cell (Th2 Cell)
  • Type 1 Helper T Cell (Th1 Cell)
  • Type 2 Innate Lymphoid Cell (ILC2)
  • Eosinophil
  • Neutrophil
  • Mast cell
30
Q

What can activate epthelial cells directly?

A

molecules such as allergens via pattern recognition receptors or protease activated receptors

31
Q

What can decrease barrier function?

A

Allergenic proteases by cleaving epithelial cell tight junction proteins and gain access to underlying cells like DCs

32
Q

What causes migration and activation of DCs to induce T cell immune responses

A

Cytokines produced by epithelial cells including IL-25 and IL-33

33
Q

What are the features of airborne allegens that may promote the primimg of Th2 cells that drive IgE responses?

A
  • Protein, often with carbohydrate side chains
  • Low dose
  • Low molecular weight
  • Highly soluble
  • Stable
  • Contains peptides that bind host MHC class II
34
Q

What is the function of IL4?

A

promotes IgE production in B cells

35
Q

What is the function of IL5?

A

Drives eosinophil recruitment in lung tissue

36
Q

What is the function of IL-13?

A

Causes bronchial hyper-reactivity

37
Q

What does ILC2 secrete?

A

“large” amounts IL-5 and IL-13 and “small” amounts of IL-4

38
Q

What does IL-5 supports development of?

A

eosinophils in the bone marrow and recruitment to the circulation

39
Q

What supports recruitment of eosinophils to the lungs?

A

chemokines, eotaxin 1-3

40
Q

What do eosinophils synthesis?

A

Mediators such as cytokines and leukotrienes that amplify the inflammatory response

41
Q

What does Eosinophil peroxidase cause?

A

Bronchial hyper-reactivity and activation of DCs to drive Th2 polarisation

42
Q

What can damage structural cells of the lungs?

A

Eosinophil major basic protein

43
Q

What imparts characteristic orange colour in eosinophil stais?

A

eosin

43
Q

What imparts characteristic orange colour in eosinophil stais?

A

eosin

44
Q

What do mass cells express?

A

Express FceRI and so bind IgE with high affinity; cross-linking of IgE by allergens causes degranulation and release of inflammatory mediators

45
Q

What can infiltrate the bronchial smooth muscle layer and contribute to bronchial hyper-responsiveness?

A

Mast cells

46
Q

What leads to rapid release of inflammatory mediators?

A

IgE antibody cross-linking on mast-cell surfaces

47
Q

What does a resting mass cell contain?

A

Granules containing histamine and other inflammatory mediators

48
Q

What causes release of granule contents?

A

Multivalent antigen cross links bound IgE antibody

49
Q

Wha molecules are realeased by activated mast cells?

A
  • enzymes
  • Toxic mediator
  • Cytokine
  • Chemokine
  • Lipid mediator
50
Q

Name enzymes released by acativated mast cells

A
  • Tryptase
  • Chymase
  • Cathepsin G
  • Carboxypeptidase
51
Q

Name toxic mediators released by activated mast cells

A
  • Histamine
  • Heparin
52
Q

Name cytokines released by acativated mast cells

A
  • IL4
  • IL13
  • IL33
  • IL3
  • IL5
  • GM-CSF
  • TNF-A
53
Q

Name chemokine released by activated mast cells

A

CCL3

54
Q

Name lipid mediator released by activated mast cells

A
  • Prostaglandin D2, E2
  • Leukotrienes C4, D4, E4
  • Platelet activating factor
55
Q

What are the biological effects of enzymes produced by mast cells?

A

Remodel connective tissue matrix

56
Q

What are the biological effects of toxic mediators produced by mast cells?

A
  • Toxic to parasites
  • Increase vascular permeability
  • Cause smooth muscle contraction
  • Anticoagulation
57
Q

What are the biological effects of cytokine IL4, IL13, IL33?

A

Stimulate and amplify Th2 cell response

58
Q

What are the biological effects of cytokine IL3, IL5, GM-CSF?

A

Promote eosinophil prodcution and activation

59
Q

What are the biological effects of cytokine TNF-a?

A
  • Promotes inflammation
  • Stimulates cytokine production by many cell types
  • Activates endothelium
60
Q

What are the biological effects of chemokine CCL3?

A

Attracts monocytes, macrophages and neutrophils

61
Q

What are the biological effects of lipid mediators; Prostaglandin D2, E2 and leukotrienes C4, D4, E4?

A
  • Smooth muscle contraction
  • chemotaxis of eosinophils, basophils and Th2 cells
  • Increase vascular permeability
  • Stimulate mucus secretion
  • Bronchoconstriction
62
Q

What are the biological effects of lipid mediator - platelet activating factor?

A
  • Attracts leukocytes
  • Amplifies production of lipid mediators
  • Activates neutrophils, eosinophils and platelets
63
Q

What does IL17 do?

A

Increases airway remodelling by various methods, e.g., by promoting fibroblast proliferation

64
Q

Describe neutrophil predominant disease in asthma patients?

A
  • Some asthma patients have neutrophil (and not eosinophil)-prominent disease with absence of Th2 cytokines
  • This is usually more severe with increased airway remodelling and is also late onset and associated with steroid resistance
  • Neutrophils/IL-17 important in pathogenesis of COPD
65
Q

What are Th1 cells induced by?

A

IL-12

66
Q

What do Th1 cells produce

A

IFNy

67
Q

What is the role of Th1 cells?

A
  • Play a critical role in protection against mycobacterial disease
  • involved in protection against certain extracellular bacteria such as Klebsiella pneumoniae
  • involved in protection against respiratory viruses (e.g., influenza) and fungi (e.g., Aspergillus)

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