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HDM Midterm > Lecture 2: Intro To Innate Immunity > Flashcards

Lecture 2: Intro To Innate Immunity Flashcards

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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
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
Selectin
26
_________ is the cell surface marker of macrophages, which recognizes and binds ________
CD14 (TLR4) | LPS
27
__________ 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
Monocytes/macrophages
28
What are the 3 primary functions of monocytes/macrophages?
``` Garbage collecters (resting) APCs (activated/primed) Vicious killers (hyperactivated) ```
29
True or false: M1 macrophages have anti-inflammatory effects and participate in wound repair and fibrosis
False, this is a description of M2 (alternative) macrophages
30
M2 macrophages are induced by _____ and ______
IL-4 | IL-13
31
Macrophage activity can be enhanced by ___ cytokines
T Helper cell
32
Activated macrophages have: Increased phagocytic activity. Increased ability to activate _____ cells. Higher levels of _______on the cell surface
T helper Class II MHC
33
What type of cell constitutively expresses high levels of class II HLA/MHC and CD80?
Dendritic cells
34
What makes dendritic cells an important bridge between innate and adaptive immunity?
They are professional APCs
35
What makes dendritic cells better APCs than macrophages and B cells?
Their constitutive expression of class II MHC and CD80
36
__________ are molecules/structures that are shared by various classes of microbes but are not present on self
PAMPs (pathogen associated molecular patterns)
37
__________ are molecules released by stressed cells undergoing necrosis that act as endogenous danger signals to promote and exacerbate the inflammatory response
DAMPs (damage associated molecular patterns)
38
Binding of PAMP ligands to _______ induces intracellular signaling in the phagocytes leading to their ___________
PRRs | Activation
39
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
TLRs
40
Is the following TLR intracellular or extracellular and what type of PAMP does it recognize: TLR-8
Intracellular ssRNA
41
Is the following TLR intracellular or extracellular and what type of PAMP does it recognize: TLR-2
Extracellular Peptidoglycan
42
Is the following TLR intracellular or extracellular and what type of PAMP does it recognize: TLR-1:TLR-2
Extracellular Bacterial Lipopeptides
43
Is the following TLR intracellular or extracellular and what type of PAMP does it recognize: TLR-3
Intracellular dsRNA
44
Is the following TLR intracellular or extracellular and what type of PAMP does it recognize: TLR-2:TLR-6
Extracellular Bacterial Lipopeptides
45
Is the following TLR intracellular or extracellular and what type of PAMP does it recognize: TLR-4
Extracellular LPS
46
Is the following TLR intracellular or extracellular and what type of PAMP does it recognize: TLR-5
Extracellular Bacterial flagellin
47
Is the following TLR intracellular or extracellular and what type of PAMP does it recognize: TLR-7
Intracellular ssRNA
48
Is the following TLR intracellular or extracellular and what type of PAMP does it recognize: TLR-9
Intracellular TLR-9
49
Binding of ligand to a TLR results in phagocytosis, production and secretion of _____________, increased ________, and increased cytoskeletal changes
Cytokines | ROS
50
______________ 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
Opsonization
51
What are the 2 primary intracellular killing mechanisms?
Oxygen-independent killing | Oxygen-dependent killing
52
What is the oxygen-independent killing mechanism?
Lysozyme, defensins, lactoferrin, and hydrolytic enzymes contained in the lysosome
53
What 2 enzymes does the oxygen-dependent killing mechanism depend on?
NADPH oxidase Myeloperoxidase
54
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.
Autosomal recessive Albinism Pyogenic Granules
55
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.
NADPH oxidase Catalase-positive Granuloma
56
What neonatal finding may be indicative of chronic granulomatous disease?
Omphalatis (failed or delayed separation of the umbilical cord)
57
If chronic granulomatous disease results from a deficiency in NADPH oxidase, why is immunity only affected in terms of catalase-positive organisms?
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
What are the 3 principle cell sources of tumor necrosis factor (TNF)?
Macrophages T cells Mast cells
59
What effect does TNF have on the following: Endothelial cells Neutrophils Hypothalamus
Endothelial cells: activation (inflammation, coagulation) Neutrophils: Activation Hypothalamus: fever
60
What effect does TNF have on the following: Liver Muscle Many cell types
Liver: synthesis of APPs Muscle: fat catabolism (cachexia) Many cell types: apoptosis
61
What 5 cell types secrete IL-1?
``` Macrophages Dendritic cells Endothelial cells Epithelial cells Mast cells ```
62
What effect does IL-1 have on the following: Endothelial cells Hypothalamus Liver T cells
Endothelial cells: activation (inflammation, coagulation) Hypothalamus: fever Liver: synthesis of APPs T cells: Th17 differentiation
63
What 6 cell types secrete chemokines?
``` Macrophages Dendritic cells Endothelial cells T lymphocytes Fibroblasts Platelets ```
64
What effect do chemokines have on leukocytes?
Increased integrin affinity, chemotaxis, activation
65
What 2 cell types secrete IL-12?
Dendritic cells | Macrophages
66
What effect does IL-12 have on the following cell types: NK cells and T cells T cells
NK cells and T cells: IFN-y production, increased cytotoxic activity T cells: Th1 differentiation
67
What 2 cell types secrete IFN-y?
NK cells | T cells
68
What effect does IFN-y have on its cellular targets?
Activation of macrophages Stimulation of some antibody responses
69
What are the 2 principle cell sources for IFN-alpha?
Dendritic cells | Macrophages
70
What is the principle cell source for IFN-beta?
Fibroblasts
71
What effects do IFN-alpha and IFN-beta have on the following: All cells NK cells
All cells: antiviral state = increased class I MHC expression NK cells: activation
72
What are the 3 cell sources of IL-10?
Macrophages Dendritic cells T cells
73
What effect does IL-10 have on macrophages and dendritic cells?
Inhibition of cytokine and chemokine production, reduced expression of costimulators and class II MHC molecules
74
What are the 3 principle cell sources of IL-6?
Macrophages Endothelial cells T cells
75
What effect does IL-6 have on the following: Liver B cells
Liver: synthesis of APPs B cells: proliferation of antibody-producing cells
76
What is the principle cell source of IL-15?
Macrophages
77
What effect does IL-15 have on the following: NK cells T cells
NK cells: proliferation T cells: proliferation
78
What is the principle cell source of IL-18?
Macrophages
79
What effect does IL-18 have on NK cells and T cells?
IFN-y synthesis
80
TGF beta is secreted by many cell types. What is its generalized effect and what effect does it have on T cells?
Inhibition of inflammation T cells: differentiation of Th17, regulatory T cells
81
What cytokines are responsible for directly inhibiting viral replication?
Type I interferons (alpha and beta)
82
How do type I interferons go about inhibiting viral replication?
They degrade viral mRNA which nonspecifically shuts down cellular protein synthesis
83
What other role do type I interferons play in the protection of the cells surrounding an infected cell?
IFNs produced by virally infected cell protect neighboring cells via IFN receptors
84
Natural Killer cells express _______ and ______, and provide innate immunity against intracellular infections (especially viral) and cancer
CD16; CD56
85
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
Perforin | Granzymes
86
What 3 cytokines serve to activate NK cells?
IL-12 (from macrophages) IL-15 Type I IFNs
87
What cytokine do NK cells secrete that is responsible for activating macrophages?
IFN-y
88
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
Perforin; granzyme B Fas
89
How do macrophages and NK cells work together to fight infection?
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
Why don't NK cells target healthy cells?
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
What would be the general result in a phagocyte deficiency?
Increased susceptibility to extracellular bacteria and fungi
92
What would be the general result of an NK cell deficiency?
Increased susceptibility to viral infections, especially Herpes Simplex
93
What type of deficiency would lead to widespread pyogenic bacterial infections?
Leukocyte adhesion deficiency
94
What disease leads to intracellular and extracellular infections as well as large collections of cells that cannot be cleared?
Chronic Granulomatous Disease
95
What deficiency results in defective respiratory burst and chronic infections?
G6PD deficiency
96
What deficiency leads to defective intracellular killing and chronic infections?
Myeloperoxidase deficiency
97
What syndrome results in intracellular and extracellular infections as well as granulomas, other than CGD?
Chediak-Higashi syndrome

HDM Midterm (10 decks)

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