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CMOD- Block1 > Path: Inflammation 4 > Flashcards

Path: Inflammation 4 Flashcards

1
Q

Chronic inflammation is inflammation of how long?

A

prolonged duration: weeks to years

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2
Q

Chronic inflammation consists of what 2 aspects?

A
  1. active inflammation
  2. tissue destruction
  3. attempted repair
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3
Q

What are 4 example causes of chronic inflammation?

A
  1. persistent infections (ex: TB)
  2. prolonged toxin exposure (ex: silicosis)
  3. autoimmunity (ex: lupus)
  4. conditions of unknown etiology, such as atherosclerosis, sarcoidosis, Alzheimer’s
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4
Q

What cell is the key player in chronic inflammation?

A

macrophages

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5
Q

Macrophages secrete neutrophil chemotactic factor and growth factors such as ___, ___, and ___.

A

TGF-beta, PDGF, and FGF

*PDGF=platelet derived growth factor

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6
Q

Macrophages and lymphocytes have bi-directional communication. Macrophages present antigens and secrete ___, which stimulate T cells. In turn T cells secrete ___ which activates macrophages.

A

cytokines (IL-12); IFN-gamma

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7
Q

What draws macrophages to sites of inflammation?

A

chemotaxis by MCP-1, C5a, PDGF, TGF-alpha, fibronectin, and fibrinopeptide fragments

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8
Q

Examples of ____ predominant diseases include most forms of thyroiditis, rheumatoid arthritis, and myocarditis.

A

lymphocyte

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9
Q

Examples of ____ predominant diseases include atherosclerosis, subacute phase phenomena, Gaucher disease, gout, and usual interstitial pneumonia.

A

macrophage

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10
Q

Examples of ____ predominant diseases include osteomyelitis.

A

neutrophil

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11
Q

Examples of ____ predominant diseases include the fungal infection blastomycosis.

A

macrophage and neutrophil co-predominant

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12
Q

Resident macrophages in the liver are called ____ cells.

A

Kupffer

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13
Q

Resident macrophages in the spleen/lymph nodes are called ____ cells.

A

histiocytes

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14
Q

Resident macrophages in the brain are called ____ cells.

A

microglia

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15
Q

Resident macrophages in the lungs are called ____ cells.

A

alveolar macrophages

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16
Q

There are two pathways of macrophage activation. What are they?

A
  1. classical

2. alternative

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17
Q

The classical pathway of macrophage activation can start with what three options?

A
  1. microbial products sensed by TLRs
  2. cytokines, from T cells
  3. foreign substances, like crystals
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18
Q

What is the name of classically activated macrophages?

A

M1 macrophages

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19
Q

M1 macrophages upregulate production of what to fulfill their role as effector cells?

A

lysosomal enzymes, nitric oxide, reactive oxygen species

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20
Q

IL-1, IL-12, IL-23, and chemokines are inflammatory mediators secreted by what?

A

classically activated macrophages

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21
Q

The alternative pathway of macrophage activation can start with what?

A

cytokines (other than IFN-gamma) including IL-4 and IL-13

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22
Q

True or false: the alternative cytokines inhibits the classical pathway of macrophage activation.

A

true

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23
Q

What is the name of alternatively activated macrophages?

A

M2 macrophages

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24
Q

True or false: M2 macrophages are actively microbicidal.

A

False - they are instead activated to secrete anti-inflammatory factors like IL-10 and TGF-beta

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25
Q

M2 macrophages secrete ____ that promote angiogenesis and stimulate fibroblasts to make ____.

A

growth factors; collagen

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26
Q

It is presumed that ____ macrophage activation precedes ____ activation in dealing with chronic infections or injuries.

A

classical preceded alternative

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27
Q

True or false: the classical macrophage activation pathway makes them healers, while the alternative macrophage activation pathway makes them killers.

A

False - the other way around

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28
Q

What factors recruit lymphocytes to sites of chronic inflammation?

A

IL-1, TNF-1, and chemokines

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29
Q

True or false: Th1 lymphocytes secrete IFN-gamma, which activates macrophages by the classical pathway to promote killing of intracellular microbes, taking over from the first responder neutrophils.

A

True

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30
Q

Th2 lymphocytes secrete ____ and ____, which activates macrophages by the alternative pathway to promote healing from infection.

A

IL-4 and IL-13

31
Q

In addition to secreting IL-4 and IL-13 to activate macrophages, Th__ lymphocytes can also secrete ____ to recruit and activate eosinophils responding to parasitic infestations and inappropriately responding stimuli in allergies.

A

TH2 lymphocytes; IL-5

32
Q

TH17 lymphocytes secrete IL-17, which does what?

A

recruits neutrophils and monocytes to sites of chronric infammation

33
Q

Are plasma cells and activated B-cells often found at the site of chronic inflammation?

A

yes - not sure why

34
Q

Describe the process of lymphoid organogenesis in chronic inflammation.

A

sometimes in chronic inflammatory diseases the lymphocytes will form into germinal centers outside of lymphoid tissues; the resulting tissue is called tertiary lymphoid organs; this occurs in the synovium in RA and in the thyroid gland in Hashimoto thyroiditis

35
Q

What is a granuloma?

A

an aggregate of activated macrophages working together

36
Q

True or false: granulomatous conditions are always acute, never chronic.

A

False - because they are macrophages, they won’t even develop acutely, and they take time to form

37
Q

What are the two major forms of granulomas?

A
  1. foreign body granulomas

2. immune granulomas

38
Q

Describe foreign body granulomas.

A

These are granulomas that form around a foreign body that is indigestible by one phagocyte (usually b/c too large), so many macrophages coalesce into one multinucleated foreign body giant cell; many of these cells come together and form a foreign body granuloma

39
Q

What are the subcategories of immune granulomas?

A
  1. those that are due to infection

2. those that are autoimmune

40
Q

True or false: immune granulomas can be induced by self-perpetuating positive feedback loops that stimulate T cell activation of themselves and macrophages.

A

True

41
Q

Immune granulomas tend to have a rim of _____ around the macrophages.

A

T lymphocytes

42
Q

What do epithelioid cells, or activated macrophages in granulomas, look like?

A

they have pink granular cytoplasm with indistinct cell boundaries and they resemble epithelial cells, hence the name “epithelioid cells”

43
Q

Giant cells in immune granulomas are often called ____ and have what characteristic appearance?

A

Langhans type cell; nuclei arranged in semi-circle around the periphery of the giant cell

44
Q

In granulomas due to TB and histoplasmosis, there is sometimes a central area of necrosis attributed to hypoxia + free radical injury. Because this area consists of amorphous, acellular, eosinophilic material without ghost cells, it is common to call this microscopic necrotizing granuloma ____.

A

caseating

45
Q

Please name the three distinct types of granulomas.

A
  1. foreign body
  2. infectious immune
  3. autoimmune
46
Q

Tuberculosis, syphilis, lupus, cat-scratch disease, and sarcoidosis are examples of ____ disease.

A

granulomatous

47
Q

TB starts in the ____ and spread to ____.

A

lungs; local lymph nodes

48
Q

Cat-scratch disease starts in the ____ and spreads to ____.

A

skin; nearby lymph nodes

49
Q

A granuloma described as “tiny potatoes (tubercles), especially cheesey (caseous) ones” would make you think of what disease?

A

tuberculosis

50
Q

A granuloma described as “round or stellate with central necrotic granular debris and neutrophils” would make you think of what disease?

A

cat-scratch disease

51
Q

What type of granulomas does sarcoidosis tend to have?

A

non-necrotizing, non-caseating, tight naked granulomas, without a rim of lymphocytes

52
Q

Inflammation of lymphatic channels is called ____.

A

lymphangitis

53
Q

Inflammation of lymph nodes is called ____.

A

lymphadenitis

54
Q

Enlargement of lymph nodes is called ____.

A

lymphadenopathy

55
Q

True or false: chronic inflammation has the same systemic effects on the patient as acute inflammation has.

A

False - it has similar but not the same systemic effects

56
Q

Compare and contrast the sedimentation rate in acute inflammation and chronic inflammation.

A

Both inflammation types will elevate the erythrocyte sedimentation rate, but:

  • chronic: elevated sed rate because Igs makes RBCs sticky
  • acute: higher sed rate because fibrinogen makes the RBCs very sticky.
57
Q

True or false: chronic inflammation causes anemia but acute does not.

A

True - acute inflammation will not usually cause anemia unless it’s complicated by hemolysis, DIC, or bleeding, but chronic inflammation will

58
Q

Why does chronic inflammation cause anemia?

A

the body thinks the inflammation is due to persistent microbial infection, so it takes up and hides all the iron - but ends up hiding it from RBCs as well

59
Q

What is ferroportin?

A

it’s the only iron export protein in iron-transporting cells

60
Q

What causes down-regulation of ferroportin?

A

IFN, LPS, TNF-alpha

61
Q

What does hepcidin do, and what stimulates hepatic production of it?

A

inhibits duodenal absorption of iron and macrophage iron recycling, as well as binds to ferroportin and leads to its degradation; production stimulated by IL-6 and LPS

62
Q

The storage and retention of iron within macrophages is stimulated by what factors, which also induce ferritin expression?

A

TNF-alpha, IL-1, IL-6, and IL-10

63
Q

___ and ___ inhibit production of erythropoietin in the kidney.

A

TNF-alpha and IFN-gamma

64
Q

Anemia of chronic disease will usually only reduce hemoglobin to ___g/dl–so if it’s lower than that, look for another cause of the anemia.

A

10g/dl

65
Q

Tuberculosis is cause by what microbe?

A

mycobacterium tuberculosis

66
Q

What is sarcoidosis?

A

multi-system probably autoimmune granulomatous disease

67
Q

What are the functions of TNF-alpha?

A
  • Downregulates ferroportin
  • Induces ferritin
  • Promotes retention of iron in macrophages
  • Inhibits erythropoietin production in kidney
68
Q

What are the functions of IFN-gamma?

A
  • Secreted by TH1 cells to activate macrophages by the classical pathway (killer cells)
  • Inhibits erythropoietin production in kidney
69
Q

What are the functions of IL-6?

A
  • Stimulates production of hepcidin
  • Induces ferritin
  • Promotes retention of iron in macrophages
70
Q

What are the functions of IL-1?

A
  • Inflammatory mediator secreted by M1 cells
  • Recruits lymphocytes to site of inflammation
  • Induces ferritin
  • Promotes retention of iron in macrophages
71
Q

What are the functions of IL-12?

A
  • Inflammatory mediator secreted by M1 cells

- Secreted by macrophages to induce T cells

72
Q

What are the functions of IL-4?

A
  • activates macrophages by the alternative pathway

* secreted by TH2 cells

73
Q

What are the functions of IL-5?

A
  • recruit and activate eosinophils responding to parasitic infestations and inappropriately responding stimuli in allergies
  • secreted by TH2 cells
74
Q

What are the functions of IL-13?

A
  • activates macrophages by the alternative pathway

* secreted by TH2 cells

CMOD- Block1 (36 decks)

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