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VMPM (Immunology) > Lecture 5 and 6 > Flashcards

Lecture 5 and 6 Flashcards

1
Q
A
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2
Q

Which leukocytes are considered the professional phagocytes?

A

Macrophages and neutrophils

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3
Q

How long do monocytes circulate in the blood stream before migrating to the tissues?

A

1-2 days

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4
Q

What is the prominent leukocyte present in acute inflammation?

A

Neutrophil

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5
Q

What is the prominent cell type present in chronic inflammation?

A

Macrophage

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6
Q

True or false: Macrophages are longer-lived than neutrophils.

A

TRUE

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7
Q

Both neutrophils and macrophages have Fc receptors and C3b receptors. What are these receptors used for?

A

Detecting pathogens opsonized with antibody (Fc receptor) and/or complement (C3b receptor), triggering phagocytosis.

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8
Q

Macrophages possess a killing molecule that neutrophils do not. Which molecule is this?

A

Nitric oxide (NO)

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9
Q

What kind of signal activates a macrophage?

A

Cytokine signaling

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10
Q

True or False: Macrophages are polymorphonuclear, like neutrophls.

A

FALSE

Macrophages are mononuclear.

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11
Q

What kinds of cells do macrophages mature from?

A

Monocytes circulating in the blood stream.

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12
Q

True or False: Unlike neutrophils, macrophages can regenerate their cellular components.

A

TRUE

The macrophage nucleus is not condensed like a neutrophil’s, so can still be transcribed.

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13
Q

What is the macrophage type that resides in the lung? (2 types)

A

Pulmonary alveolar macrophage (PAM)

Pulmonary intravascular macrophage (PIM)

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14
Q

What is the macrophage type that resides in the liver?

A

Kuppfer cell

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15
Q

What is the macrophage type that resides in the bone marrow?

A

Osteoclast

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16
Q

What is the macrophage type that resides in the brain?

A

Microglia

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17
Q

What is the macrophage type that moves freely within the peritoneal and pleural cavities?

A

Histiocyte

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18
Q

What are the main functions of resident macrophages?

A

Defense against pathogens

Antigen presentation

Removal of dead cells

Removal of foreign objects/debris

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19
Q

If a pulmonary alveolar macrophage ingests a particle too large to digest, what will it do?

A

Migrate out of the alveolus to the ciliary escalator, where it will be transported up the trachea and swallowed for digestion.

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20
Q

If a pulmonary alveolar macrophage ingests and destroys a pathogen, what will it do?

A

Migrate out of the alveolus and drain into a bronchial lymph node for antigen presentation to lymphocytes.

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21
Q

Which organ contains the only capillary bed that receives 100% of cardiac output?

A

Lung.

Thus, the lung is an excellent blood filtration site.

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22
Q

What kind of pneumonia can result from an inhaled pathogen?

A

Bronchial pneumonia

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23
Q

What kind of pneumonia can result from a pathogen circulating in the blood (i.e. septicemia)?

A

Interstitial pneumonia

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24
Q

One type of resident lung macrophage is fixed, while the other type is mobile. Which is which?

A

Pulmonary alveolar macrophage (PAM) - Mobile

Pulmonary interstitial macrophage (PIM) - Fixed

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25
Q

What will happen if the resident macrophages of the lung are overwhelmed with particulate matter?

A

Accumulation of particulates in the lung, resulting in decreased function and inflammation. Depeding on the particle, can result in silica lung, smoker’s lung, etc.

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26
Q

What will happen if the resident macrophages of the lung are overwhelmed with pathogens?

A

Infection

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27
Q

What is meant by the term “angry macrophage?”

A

An activated macrophage with increased killing capacity

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28
Q

What is CMI?

A

Cell mediated immunity

Immunity that does not involve antibodies. Involves phagocytic cells, cytotoxic T cells, and the release of cytokines.

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29
Q

How is a macrophage activated?

A

Cytokines

Th1 (a class of T helper cells) release interleuken 1 to activate a macrophage.

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30
Q

Activated macrophages are better at killing. Name some pathogens that activated macrophages are capable of killing.

(Note: on this one, I would pick one pathogen to know)

A

Brucella

Salmonella

Listeria

Mycobacterium

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31
Q

What is the role of the macrophage in initial defense against a pathogen?

A

Act as sentinel cells

Release pro-inflammatory cytokines

Antigen presentation to T cells

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32
Q

What are some functions of an activated macrophage?

A

Cytokine secretion

Attack and kill tumor cells

Phagocyose and kill microbes

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33
Q

At any one time, what percentage of circulating leukocytes are monocytes?

A

1-3%

34
Q

Macrophages are normally found in the lungs. Are neutrophils?

A

NO

The presence of neutrophils represents an inflammatory response

35
Q

What is the role of microglia in the brain?

A

Mostly the removal of dead cells and maintenance of normal physiological function.

Note that because of the blood-brain barrier, pathogens normally do not enter the brain. If they do, there will be an inflammatory repsonse.

36
Q

What is the function of a pulmonary intravascular macrophage (PIM) in the lung?

A

Removal of microbes from the blood. In some species, these cells are important microbial filters.

37
Q

Where are microbes primarily filtered in dogs, rodents, and humans?

A

Kuppfer cells in the liver and spleen

38
Q

Where are microbes primarily filtered in the cat, calf, sheep, pig, and horse?

A

Pulmonary intravascular macrophages (PIMs) in the lungs

39
Q

List some effects of pro-inflammatory cytokines on the hypothalamus

A

Fever (attempts to kill microbes, increases metabolism)

“Sick Feeling” (no appetite, lethargy, removing self from the herd)

40
Q

List some effects of pro-inflammatory cytokines on the liver

A

Induce production of acute phase proteins

41
Q

List the effects of pro-inflammatory cytokines on the bone marrow

A

Increased production of neutrophils, resulting in neutrophlia

42
Q

When an animal feels sick, it tends to be lethargic and separate itself from the herd. Why is this?

A

Prevent the spread of infection to other herd members

43
Q

What is a PRR?

A

Pattern recognition receptor

“Signaling receptors of the innate immune system that recognize PAMPs and DAMPs, and thereby activate innate immune responses.”

44
Q

What is a TLR?

A

Toll-like receptor

45
Q

What is an NLR?

A

Nod-like receptor

46
Q

Where are TLRs located?

A

Cell surfaces, intracellular membranes

47
Q

What is the effect of binding to a TLR on a macrophage?

A

Production of pro-inflammatory cytokines

Produce IL-2, which stimulates the adaptive immune system

Produciton of nitric oxide (NO)

48
Q

Of these species, which has the most pulmonary intravascular macrophages?

Dog

Rat

Sheep

A

SHEEP

Dogs and rats rely primarily on Kuppfer cells in the liver for microbial filtration.

Cats, calves, sheep, pigs, and horses rely on pulmonary intravascular macrophages (PIMs) for microbial filtration.

49
Q

What is LPS?

A

Lipopolysaccharide, or endotoxin

A molecule found in gram-negative bacteria. Released upon the death of a bacterium. Though it does not cause direct cellular damage, it is a powerful stimulator of pro-inflammatory cytokines.

50
Q

LPS is released from dead gram-negative bacteria. If LPS is free-floating in the blood stream, which class of macrophage pattern recognition receptor (PRR) is it likely to bind with?

A

Toll-like receptor (TLR)

TLRs are important for detecting PAMPs outside the cell membrane.

51
Q

A common effect of sickness is muscle pain and weakness. Why is this?

A

Amino acids are being mobilized from the muscles to assist in the inflammatory response.

52
Q

What are the effects of pro-inflammatory cytokines on the vasculature?

A

Vasodilation

Upregulation of leukocyte adhesion proteins

53
Q

Where are acute phase proteins produced?

A

Liver

54
Q

What is septic shock?

A

Massive release of pro-inflammatory cytokines.

Can result in decreased blood pressure and cardiac output, vascular damage and thrombosis, and pulmonary edema.

Endotoxin is a common cause of septic shock.

55
Q

What are the 5 cardinal signs of acute inflammation?

A

Redness

Heat

Pain

Swelling

Loss of function

56
Q

True or False: For a vaccine to be effective, it must induce the release of pro-inflammatory cytokines.

A

TRUE

57
Q

IL-6 is a pro-inflammatory cytokine. What is its effect on the liver?

A

Release of acute phase proteins

58
Q

C-reactive protein (an acute phase protein) is most similar in structure to which immunoglobulin?

A

IgM

59
Q

What is the function of C reactive protein?

A

Acts like an opsonin

Activates complement

60
Q

Mannose binding protein (an acute phase protein) is most similar to which complement molecule?

A

C1

61
Q

What kind of lesion is pictured here?

A

Granulomatous lesion. Note how the lesion is surrounded by macrophages. The macrophages have walled off the area, and fibroblasts have encased the area in fibrin. Caseous necrosis in the center.

This lesion is typical with Mycobacterium infections.

62
Q

How long after an infection does it take for acute phase proteins to be released?

A

Approximately 24 hours (assuming pro-inflammatory cytokines have been released)

63
Q

Metal-binding proteins are a class of acute phase protein. How do they fight infection?

A

Bacteria require iron and other metals for growth. Metal-binding proteins sequester the metal and prevent its uptake by bacteria.

64
Q

What is meant by “negative acute phase proteins?”

A

Proteins that decrease in the plasma because the liver is producing so many other acute phase proteins.

Albumin

Prealbumin

Transferrin

65
Q

True or False: There is such a thing as kicking too much ass on this test.

A

FALSE

I want you to set new records for ass-kicking.

66
Q

Name the three types of macrophage activation.

A

Innate activation

Immune activation

Alternative activation

67
Q

What causes innate activation of a macrophage?

A

Pattern recognition receptor detection of PAMPs and DAMPs

Enhanced functions include:

Lysosomal enzyme production

Phagocytosis

Membrane receptors for IgG and complement

68
Q

What causes immune activation of a macrophage?

A

Interferon gamma secretion by Th1 cells or NK cells

69
Q

Immune activation of a macrophage results in what kind of macrophage?

A

M1 macrophage or “angry macrophage”

Enhanced abilities:

Increased size, movement, membrane activity

Increased killing ability, especially with nitrous oxide

70
Q

What causes alternative activation of a macrophage?

A

IL4, IL10, and IL13 release from Th2 cells

71
Q

Alternative macrophage activation results in what kind of macrophage?

A

M2 macrophage

Enhanced abilities:

Tissue repair

Increased MHCII expression

(Decreased killing, decreased NO production)

72
Q

What kind of activated macrophage produces NO?

A

M1

73
Q

Which activated macrophage is better at killing?

A

M1

74
Q

Which activated macrophage promotes healing and tissue repair?

A

M2

75
Q

Which cells produce IFN gamma? What is its function?

A

Th1 and NK

Immune activation of macrophage to M1 (“angry”) macrophage

76
Q

True or False: Acute phase proteins are just as good at antibody at opsonization and complement activation.

A

FALSE

Acute phase proteins are non-specific. Even so, they are helpful at fighting infection.

77
Q

Listeria monocytogenes lives inside cells. How will the body kill this pathogen?

A

Cannot kill with antibody because the organism is intracellular.

Cell-mediated immunity (CMI) is the body’s main response. Th1 recognizes antigens and secretes IFNgamma to activate a macrophage.

78
Q

True or False: Chronic inflammation occurs when the immune system fails to remove antigenic material.

A

TRUE

79
Q

What is the result of chronic inflammation?

A

Macrophages encircle the inflamed area. Fibroblasts secrete fibrin to wall off the inflamed area, creating a granuloma.

80
Q

Why is NO cytotoxic (i.e. such a good killer)?

A

Free radical - causes membrane peroxidation, lysis.

81
Q

Which activated macrophage secretes NO?

A

M1

(“angry” macrophage)

82
Q

This graph illustrates survival time of Listeria monocytogenes in the presence of macrophages. Interpret the results.

A

When Listeria is growing by itself in culture, it has not activated its virulence factors.

Red line - normal macrophages kill a large percentage of the bacteria. However, the bacteria then activate their virulence factors, overwhelming the macrophages’ killing ability, leading to infection.

Blue line - activated macrophages are much better at killing (through phagocytosis and NO), and quickly dispatch all of the bacteria.

VMPM (Immunology) (15 decks)

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