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IHO: Week 1 - WLB > Innate Immunity - Diebel > Flashcards

Innate Immunity - Diebel Flashcards

1
Q

What are the four functions of Activated Innate Immunity?

A
  • Complement activation
  • Inflammation
  • Cell activation
    • cytokine and chemokine production
    • phagocytosis and other killing microbes
  • Priming of the adaptive immune response
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2
Q

What are defensins?

A
  • Major family of antimicrobial peptides
    • Beta-strand peptides connected by disulfide bonds
    • positively charged (cationic antimicrobial peptides)
  • Expressed in a variety of epithelial cells and sometimes leukocytes
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3
Q

What role do defensins and cathelicidins play in Innate Immunity?

A
  • Antimicrobial, chemotactic, and regulatory activities
  • Protect against bacteria, fungi, viruses, & parasites
  • Interact with microbial cell membrane components to increase cellular permeability resulting in cell death
    • membrane destruction
    • tissue barrier response to slow down pathogen
  • Also modulate the inflammatory response
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4
Q

What are the two main classes of defensins?

A
  • Two main classes based on the linking pattern of the cysteines
    • Alpha - 6 types: 29-35 AA’s long
    • Beta - 4 types: 38-42 AA’s long
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5
Q

Where do alpha-defensins 1-6 reside?

A
  • Highly concentrated in the granules of PMNs and Paneth cells of the small intestine
    • Human neutrophil peptide (HNP) 1-4 are primarily expressed in PMNs, monocytes, and lymphocytes
    • Human defensins (HD) 5-6 are mainly expressed in Paneth cells (epithelium of small intestine)
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6
Q

What are cathelicidins?

A
  • Alpha-helical cationic antimicrobial peptides
  • CATionic HELIcal bacteriCIDal proteIN
  • highly expressed by PMNs and numerous mucosal and epithelial cell types
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7
Q

Where do beta-defensins 1-4 reside?

A
  • Secreted by mucosal surface epithelia, including cells of the eye, skin, oral mucosa, urogenital and respiratory systems
    • Human beta defensing (HBD) 1-4 are mainly expressed by various epithelial tissues, but can also be expressed by monocytes, macrophages, and dendritic cells
      • HBD4 is more linked to the testes and epididymis
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8
Q

What PAMP does TLR-1 recognize?

A
  • Peptidoglycans (Gm +)
  • Lipopolysaccharides (Gm -)
  • Triacylated lipoproteins
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9
Q

TLR-1 turns on transcription factors for the production of what?

A
  • Proinflammatory Cytokines
    • TNF-alpha
    • IL-6
    • IL-12
  • via activation of AP-1 & NF-KB
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10
Q

What PAMPs are recognized by TLR-2?

A
  • When paired with TLR-1:
    • Triacylated lipoprotein
  • When paired with TLR-6:
    • Diacylated lipoprotein
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11
Q

TLR-2 turns on transcription factors for the production of what?

A
  • Proinflammatory Cytokines
    • TNF-alpha
    • IL-6
    • IL-12
  • via activation of AP-1 & NF-KB
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12
Q

What PAMPs are recognized by TLR-3?

A
  • double-stranded RNA (dsRNA), a molecular pattern associated with viral infection
    • in endosome
  • tRNA
  • siRNA
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13
Q

TLR-3 turns on transcription factors for the production of what?

A
  • Proinflammatory Cytokines
    • IFN-beta
  • via IRF3 activation
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14
Q

What PAMPs are recognized by TLR-4?

A
  • Lipopolysaccharides
  • Paclitaxel
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15
Q

TLR-4 turns on transcription factors for the production of what?

A
  • Proinflammatory cytokines
    • via activation of IRF3
      • IFN-beta
    • via activation of AP-1/NF-KB
      • TNF-alpha
      • IL-6
      • IL-12
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16
Q

What PAMPs are recognized by TLR-5?

A

Flagellin

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17
Q

TLR-5 turns on transcription factors for the production of what?

A
  • Proinflammatory Cytokines
    • TNF-alpha
    • IL-6
    • IL-12
  • via activation of AP-1/NF-KB
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18
Q

TLR-6 turns on transcription factors for the production of what?

A
  • Proinflammatory cytokines
    • TNF-alpha
    • IL-6
    • IL-12
  • Via activation of AP-1 & NF-KB
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19
Q

What PAMPs are recognized by TLR-6?

A

Diacylated lipoproteins

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20
Q

What PAMPs are recognized by TLR-7?

A
  • ssRNA (viral)
  • Guanosine analogs
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21
Q

TLR-7 turns on transcription factors for the production of what?

A
  • Proinflammatory cytokines
    • IFN-alpha
  • via activation of IRF7
22
Q

What PAMPs are recognized by TLR-8?

A

ssRNA

23
Q

TLR-8 turns on transcription factors for the production of what?

A
  • Proinflammatory cytokines
    • IFN-alpha
  • via activation of IRF7
24
Q

What PAMPs are recognized by TLR-9?

A
  • CpG-DNA
  • CpG oligodeoxynucleotides (CpG ODN) or bacterial DNA
25
Q

What PAMPs are recognized by TLR-10?

A

profilin-like proteins

26
Q

TLR-9 turns on transcription factors for the production of what?

A
  • Proinflammatory cytokines
    • IFN-alpha
  • via activation of IRF7
27
Q

TLR-10 turns on transcription factors for the production of what?

A

Proinflammatory Cytokines

28
Q

What is congenital neutropenia?

A
  • Lack of GM-CSF
    • involved in the differentiation of basophils, eosinophils, neutrophils, macrophages, & dendritic cells
    • no defense against bacteria
  • Frequent bacterial infections
  • Retain Lymphocyte properties
    • can fight viral attacks with CD8+ & NK’s
29
Q

What is chronic granulomatous disease?

A
  • Inability to produce hydrogen peroxide and hypochlorous acid
  • Inability to kill phagocytosed bacteria
30
Q

What is Leukocyte Adhesion Deficiency?

A
  • Lack of integrin subunit (common beta chain)
  • Inability to recruit innate immune cells to site of inflammation
  • Increased susceptibility to bacterial, fungal, and viral infections
31
Q

What is the result of complement defects (various types)?

A
  • Increased susceptibility to bacterial infections
  • Reduced ability to remove immunocomplexes
32
Q

What da fuck is Chediak-Higashi Syndrome?

A
  • Defect in gene LYST (CHS1)
    • a lysosomal trafficking gene that affects lysosomes and melanosomes
  • Increased susceptibility to bacterial infections
33
Q

What is “the Mother of all immune system transcription factors”?

A

NF-KB

34
Q

What are the four steps in leukocyte movement into the vascular circulation?

A
  1. Rolling - leukocyte rolls along endothelium of a venule
  2. Tethering - endothelial cells present E-selectin & leukocyte CD15 grabs on (endothelial cell releases IL-8)
  3. Adhesion - endothelial cells release chemokines that activate integrins and leukocyte CR3 (complement receptor) binds ICAM-1 (endothelial cell adhesion molecule)
  4. Migration - leukocyte squeezes through endothelial cell jxn
35
Q

What cytokine inputs lead a macrophage to differentiate?

A
  • GM-CSF
  • IL-3
  • M-CSF
36
Q

What cytokine inputs activate a macrophage to M1 (“angry”) status?

A
  • IFN-alpha
  • TNF-alpha
37
Q

What cytokine inputs activate a macrophage to M2 (“healing”) status?

A
  • IL-4
  • IL-3
38
Q

What cytokine input deactivates a macrophage?

A

IL-10

39
Q

What cytokines help hematopoietic stem cells differentiate into myeloid precursors?

A

IL-3 & GM-CSF

40
Q

What cytokines help myeloid precursors differentiate into either basophil progenitors, eosinophil progenitors, OR granulocyte/macrophage progenitors?

A
  • IL-3
  • GM-CSF
41
Q

What cytokines help basophil progenitor cells differentiate into mature basophils?

A
  • GM-CSF
  • IL-3
  • IL-4
42
Q

What cytokines help eosinophil progenitor cells differentiate into eosinophils?

A
  • GM-CSF
  • IL-3
  • IL-5
43
Q

What cytokines help granulocyte/macrophage progenitor cells differentiate into neutrophils?

A
  • GM-CSF
  • G-CSF
  • IL-3
44
Q

What cytokines help granulocyte/macrophage progenitor cells differentiate into monocytes?

A
  • GM-CSF
  • M-CSF
  • IL-3
45
Q

What cytokines help Monocytes (in the blood) differentiate into Dendritic Cells?

A
  • GM-CSF
  • IL-4
46
Q

What cytokines help Monocytes (in the blood) differentiate into Macrophages?

A
  • GM-CSF
  • M-CSF
47
Q

What cytokine outputs does a macrophage release after TLR’s bind a ligand and transcriptional reprogramming occurs?

A
  • IL-1
  • TNF-alpha
48
Q

What type of cells can also interact with a macrophage presenting MHC II in the blood venule?

A

CD4+ T-cells

49
Q

What are the four functions of a Macrophage according to Dr. Diebel?

A
  1. Tissue homeostasis
  2. Antigen presentation to activated T-cells
  3. With IFN-gamma = Effector cell of cell-mediated immunity
  4. Restore tissue homeostasis by clearing apoptotic neutrophils and promoting wound repair
50
Q

What are the two functions of a Dendritic Cells according to Dr. Diebel?

A
  1. Antigen presentation to naive T-cells
  2. Modulation of T-cell differentiation

IHO: Week 1 - WLB (8 decks)

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