Lecture 2: Intro To Innate Immunity Flashcards

1
Q

The mechanical barriers involved in innate immunity include epithelial cells joined by _______ ________, along with the longitudinal flow of air or fluid, movement of mucus by ___________, as well as tears and nasal cilia.

A

Tight junctions; cilia

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2
Q

What chemical barrier defenses exist in the skin?

A

Fatty acids
Beta-defensins
Lamellar bodies
Cathelicidin

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3
Q

What chemical barriers exist in the gut?

A

Low pH (pepsin)
Alpha-defensins (cryptidins)
RegIII (lecticidin)
Cathelicidin

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4
Q

What chemical defenses exist in the lungs?

A

Alpha-defensins
Cathelicidin
Pulmonary surfactant

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5
Q

What chemical defenses exist in the eyes/nose/oral cavity?

A

Enzymes in tears and saliva = lysozyme

Histatins, beta-defensins

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6
Q

What is the microbiological barrier associated with the first line of defense against pathogens?

A

Normal microbiota

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7
Q

___________ is a peptide that comes from neutrophils, mast cells, epithelia (skin, lung, GI, GU, oral), sweat, and seminal fluid that has antimicrobial and chemotactic action

A

Cathelicidin

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8
Q

____________ are peptides that come from neutrophils and have antimicrobial action

A

Alpha-defensins

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9
Q

__________ are peptides that come from neutrophils and epithelia (skin, oral, mammary, lung, urinary, eccrine, occular), and participate in antimicrobial, chemotactic and histamine release

A

Beta-defensins

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10
Q

Fatty acids and lactic acid are chemical barriers to infection that are primarily found in what bodily fluids?

A

Sweat

Sebum

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11
Q

Destructive enzymes like lysozyme and phospholipase are primarily found in what bodily secretions?

A

Tears
Saliva
Nasal secretions

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12
Q

Where does an acidic pH play a role as a chemical barrier to infection?

A

Stomach
Skin
Vagina

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13
Q

The lungs secrete surfactant proteins ___ and ___ as chemical barriers to infection

A

A

D

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14
Q

Defensins are found in what 3 major areas?

A

Lungs
GI tract
Skin

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15
Q

What are the 3 types of granulocytes?

A

Eosinophils
Basophils
Mast cells (tissue residents)

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16
Q

The main role of granulocytes in general is in _______ disease

A

Atopic

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17
Q

Natural killer cells express which 2 CD molecules?

A

CD16

CD56

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18
Q

NK cells provide innate immunity against __________ infections like viruses and cancer

A

Intracellular

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19
Q

What cell type is also known as polymorphonuclear cells and makes up 54-62% of white blood cells?

A

Neutrophils

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20
Q

Neutrophils are released from _______ ________ into the blood and migrate 7-10 hours then home to the tissue where they have a ______ day lifespan

A

Bone marrow

3

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21
Q

In response to an infection, neutrophils will be released from bone marrow in greater numbers in a process called ___________ ___________

A

Neutrophil leukocytosis

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22
Q

True or false: Neutrophils are the FIRST to the site of the infection, and are HIGHLY phagocytic

A

True

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23
Q

Neutrophils are a large component of pus/abscesses, meaning they are ___________

They express ______ and ______ CD markers

A

Pyogenic
CD15
CD16b

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24
Q

Neutrophils serve one purpose: professional killers. They are summoned from the bloodstream by what 3 cytokines?

A

IL-1
TNF-a
IL-8

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25
Q

Once neutrophils have been recruited by IL-1, TNF-a, and IL-8, endothelial cells near the site of infection begin expressing __________ proteins (adhesion molecules) that help capture the neutrophils attention

A

Selectin

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26
Q

_________ is the cell surface marker of macrophages, which recognizes and binds ________

A

CD14 (TLR4)

LPS

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27
Q

__________ respond to sites of inflammation in 1-2 days, but survive longer than neutrophils. Levels may be inreased in chronic inflammation, various immune-mediated diseases, stress response, and necrosis

A

Monocytes/macrophages

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28
Q

What are the 3 primary functions of monocytes/macrophages?

A
Garbage collecters (resting)
APCs (activated/primed)
Vicious killers (hyperactivated)
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29
Q

True or false: M1 macrophages have anti-inflammatory effects and participate in wound repair and fibrosis

A

False, this is a description of M2 (alternative) macrophages

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30
Q

M2 macrophages are induced by _____ and ______

A

IL-4

IL-13

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31
Q

Macrophage activity can be enhanced by ___ cytokines

A

T Helper cell

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32
Q

Activated macrophages have:

Increased phagocytic activity.

Increased ability to activate _____ cells.

Higher levels of _______on the cell surface

A

T helper

Class II MHC

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33
Q

What type of cell constitutively expresses high levels of class II HLA/MHC and CD80?

A

Dendritic cells

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34
Q

What makes dendritic cells an important bridge between innate and adaptive immunity?

A

They are professional APCs

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35
Q

What makes dendritic cells better APCs than macrophages and B cells?

A

Their constitutive expression of class II MHC and CD80

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36
Q

__________ are molecules/structures that are shared by various classes of microbes but are not present on self

A

PAMPs (pathogen associated molecular patterns)

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37
Q

__________ are molecules released by stressed cells undergoing necrosis that act as endogenous danger signals to promote and exacerbate the inflammatory response

A

DAMPs (damage associated molecular patterns)

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38
Q

Binding of PAMP ligands to _______ induces intracellular signaling in the phagocytes leading to their ___________

A

PRRs

Activation

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39
Q

The largest family of PRRs are the __________, which have receptors with specificities for different microbial products, respond to both exogenous and endogenous antigens, and are present on macrophages, dendritic cells, and neutrophils

A

TLRs

40
Q

Is the following TLR intracellular or extracellular and what type of PAMP does it recognize:

TLR-8

A

Intracellular

ssRNA

41
Q

Is the following TLR intracellular or extracellular and what type of PAMP does it recognize:

TLR-2

A

Extracellular

Peptidoglycan

42
Q

Is the following TLR intracellular or extracellular and what type of PAMP does it recognize:

TLR-1:TLR-2

A

Extracellular

Bacterial Lipopeptides

43
Q

Is the following TLR intracellular or extracellular and what type of PAMP does it recognize:

TLR-3

A

Intracellular

dsRNA

44
Q

Is the following TLR intracellular or extracellular and what type of PAMP does it recognize:

TLR-2:TLR-6

A

Extracellular

Bacterial Lipopeptides

45
Q

Is the following TLR intracellular or extracellular and what type of PAMP does it recognize:

TLR-4

A

Extracellular

LPS

46
Q

Is the following TLR intracellular or extracellular and what type of PAMP does it recognize:

TLR-5

A

Extracellular

Bacterial flagellin

47
Q

Is the following TLR intracellular or extracellular and what type of PAMP does it recognize:

TLR-7

A

Intracellular

ssRNA

48
Q

Is the following TLR intracellular or extracellular and what type of PAMP does it recognize:

TLR-9

A

Intracellular

TLR-9

49
Q

Binding of ligand to a TLR results in phagocytosis, production and secretion of _____________, increased ________, and increased cytoskeletal changes

A

Cytokines

ROS

50
Q

______________ is another way to recognize and respond to pathogens. Phagocytes have membrane receptors for IgG and C3b which facilitate the enhancement of phagocytosis up to 4000-fold

A

Opsonization

51
Q

What are the 2 primary intracellular killing mechanisms?

A

Oxygen-independent killing

Oxygen-dependent killing

52
Q

What is the oxygen-independent killing mechanism?

A

Lysozyme, defensins, lactoferrin, and hydrolytic enzymes contained in the lysosome

53
Q

What 2 enzymes does the oxygen-dependent killing mechanism depend on?

A

NADPH oxidase

Myeloperoxidase

54
Q

Chediak-Higashi syndrome results from microtubule defect affecting phagosome-lysosome fusion.

Genetically, it is _____________ ____________.

It is characterized by partial oculocutaneous ____________, recurrent _____________ infections, and the presence of giant _________ in leukocytes.

A

Autosomal recessive

Albinism
Pyogenic
Granules

55
Q

Chronic granulomatous disease results from an inherited deficiency in __________ _____________, leading to decreased production of reactive oxygen species.

Clinically, it results in chronic, recurrent infections with ____________-______________ microorganisms like Staphylococcus, Klebsiella, Serratia, and Aspergillus.

Chronic inflammatory symptoms like gingivitis, enlarged lymph nodes, and tumor-like ___________ masses.

A

NADPH oxidase

Catalase-positive

Granuloma

56
Q

What neonatal finding may be indicative of chronic granulomatous disease?

A

Omphalatis (failed or delayed separation of the umbilical cord)

57
Q

If chronic granulomatous disease results from a deficiency in NADPH oxidase, why is immunity only affected in terms of catalase-positive organisms?

A

The patient still has adequate myeloperoxidase, which is able to continue killing most bacteria.

However, catalase-positive organisms can neutralize H2O2 species that your body is trying to utilize to kill them, and thus survive in the phagosome.

58
Q

What are the 3 principle cell sources of tumor necrosis factor (TNF)?

A

Macrophages
T cells
Mast cells

59
Q

What effect does TNF have on the following:

Endothelial cells
Neutrophils
Hypothalamus

A

Endothelial cells: activation (inflammation, coagulation)

Neutrophils: Activation

Hypothalamus: fever

60
Q

What effect does TNF have on the following:

Liver
Muscle
Many cell types

A

Liver: synthesis of APPs

Muscle: fat catabolism (cachexia)

Many cell types: apoptosis

61
Q

What 5 cell types secrete IL-1?

A
Macrophages
Dendritic cells
Endothelial cells
Epithelial cells
Mast cells
62
Q

What effect does IL-1 have on the following:

Endothelial cells
Hypothalamus
Liver
T cells

A

Endothelial cells: activation (inflammation, coagulation)

Hypothalamus: fever

Liver: synthesis of APPs

T cells: Th17 differentiation

63
Q

What 6 cell types secrete chemokines?

A
Macrophages
Dendritic cells
Endothelial cells
T lymphocytes
Fibroblasts
Platelets
64
Q

What effect do chemokines have on leukocytes?

A

Increased integrin affinity, chemotaxis, activation

65
Q

What 2 cell types secrete IL-12?

A

Dendritic cells

Macrophages

66
Q

What effect does IL-12 have on the following cell types:

NK cells and T cells

T cells

A

NK cells and T cells: IFN-y production, increased cytotoxic activity

T cells: Th1 differentiation

67
Q

What 2 cell types secrete IFN-y?

A

NK cells

T cells

68
Q

What effect does IFN-y have on its cellular targets?

A

Activation of macrophages

Stimulation of some antibody responses

69
Q

What are the 2 principle cell sources for IFN-alpha?

A

Dendritic cells

Macrophages

70
Q

What is the principle cell source for IFN-beta?

A

Fibroblasts

71
Q

What effects do IFN-alpha and IFN-beta have on the following:

All cells

NK cells

A

All cells: antiviral state = increased class I MHC expression

NK cells: activation

72
Q

What are the 3 cell sources of IL-10?

A

Macrophages
Dendritic cells
T cells

73
Q

What effect does IL-10 have on macrophages and dendritic cells?

A

Inhibition of cytokine and chemokine production, reduced expression of costimulators and class II MHC molecules

74
Q

What are the 3 principle cell sources of IL-6?

A

Macrophages
Endothelial cells
T cells

75
Q

What effect does IL-6 have on the following:

Liver

B cells

A

Liver: synthesis of APPs

B cells: proliferation of antibody-producing cells

76
Q

What is the principle cell source of IL-15?

A

Macrophages

77
Q

What effect does IL-15 have on the following:

NK cells
T cells

A

NK cells: proliferation

T cells: proliferation

78
Q

What is the principle cell source of IL-18?

A

Macrophages

79
Q

What effect does IL-18 have on NK cells and T cells?

A

IFN-y synthesis

80
Q

TGF beta is secreted by many cell types. What is its generalized effect and what effect does it have on T cells?

A

Inhibition of inflammation

T cells: differentiation of Th17, regulatory T cells

81
Q

What cytokines are responsible for directly inhibiting viral replication?

A

Type I interferons (alpha and beta)

82
Q

How do type I interferons go about inhibiting viral replication?

A

They degrade viral mRNA which nonspecifically shuts down cellular protein synthesis

83
Q

What other role do type I interferons play in the protection of the cells surrounding an infected cell?

A

IFNs produced by virally infected cell protect neighboring cells via IFN receptors

84
Q

Natural Killer cells express _______ and ______, and provide innate immunity against intracellular infections (especially viral) and cancer

A

CD16; CD56

85
Q

NK cells have effector mechanisms similar to cytotoxic T cells in that they perform cell killing and secretion of cytokines.

They also secrete __________ and _________ which induce apoptosis in the target cell

A

Perforin

Granzymes

86
Q

What 3 cytokines serve to activate NK cells?

A

IL-12 (from macrophages)
IL-15
Type I IFNs

87
Q

What cytokine do NK cells secrete that is responsible for activating macrophages?

A

IFN-y

88
Q

NK cells destroy bacteria, parasites, fungi, tumor cells, and virus-infected cells by forcing them into apoptosis.

This is done by first secreting _________ proteins that deliver “suicide” enzyme _____________ into the target cell.

_____ ligand expressed on their cell surface binds death receptor on target cell to induce apoptosis

A

Perforin; granzyme B

Fas

89
Q

How do macrophages and NK cells work together to fight infection?

A

Macrophages that have phagocytosed microbes find NK cells and secrete IL-12 to activate them

Those NK cells then secrete IFN-y to further activate macrophages

90
Q

Why don’t NK cells target healthy cells?

A

They have an inhibitory receptor that binds to MHC class I (an indicator of healthy cells)

Viruses inhibit class I MHC expression, so the NK cell inhibitory receptor is not engaged and thus the infected cell will be killed.

91
Q

What would be the general result in a phagocyte deficiency?

A

Increased susceptibility to extracellular bacteria and fungi

92
Q

What would be the general result of an NK cell deficiency?

A

Increased susceptibility to viral infections, especially Herpes Simplex

93
Q

What type of deficiency would lead to widespread pyogenic bacterial infections?

A

Leukocyte adhesion deficiency

94
Q

What disease leads to intracellular and extracellular infections as well as large collections of cells that cannot be cleared?

A

Chronic Granulomatous Disease

95
Q

What deficiency results in defective respiratory burst and chronic infections?

A

G6PD deficiency

96
Q

What deficiency leads to defective intracellular killing and chronic infections?

A

Myeloperoxidase deficiency

97
Q

What syndrome results in intracellular and extracellular infections as well as granulomas, other than CGD?

A

Chediak-Higashi syndrome