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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?

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
What PAMPs are recognized by TLR-10?
profilin-like proteins
26
TLR-9 turns on transcription factors for the production of what?
* Proinflammatory cytokines * IFN-alpha * via activation of IRF7
27
TLR-10 turns on transcription factors for the production of what?
Proinflammatory Cytokines
28
What is congenital neutropenia?
* 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
What is chronic granulomatous disease?
* Inability to produce hydrogen peroxide and hypochlorous acid * Inability to kill phagocytosed bacteria
30
What is Leukocyte Adhesion Deficiency?
* 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
What is the result of complement defects (various types)?
* Increased susceptibility to bacterial infections * Reduced ability to remove immunocomplexes
32
What da fuck is Chediak-Higashi Syndrome?
* Defect in gene LYST (CHS1) * a lysosomal trafficking gene that affects lysosomes and melanosomes * Increased susceptibility to bacterial infections
33
What is "the Mother of all immune system transcription factors"?
NF-KB
34
What are the four steps in leukocyte movement into the vascular circulation?
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
What cytokine inputs lead a macrophage to differentiate?
* GM-CSF * IL-3 * M-CSF
36
What cytokine inputs activate a macrophage to M1 ("angry") status?
* IFN-alpha * TNF-alpha
37
What cytokine inputs activate a macrophage to M2 ("healing") status?
* IL-4 * IL-3
38
What cytokine input deactivates a macrophage?
IL-10
39
What cytokines help hematopoietic stem cells differentiate into myeloid precursors?
IL-3 & GM-CSF
40
What cytokines help myeloid precursors differentiate into either basophil progenitors, eosinophil progenitors, OR granulocyte/macrophage progenitors?
* IL-3 * GM-CSF
41
What cytokines help basophil progenitor cells differentiate into mature basophils?
* GM-CSF * IL-3 * IL-4
42
What cytokines help eosinophil progenitor cells differentiate into eosinophils?
* GM-CSF * IL-3 * IL-5
43
What cytokines help granulocyte/macrophage progenitor cells differentiate into neutrophils?
* GM-CSF * G-CSF * IL-3
44
What cytokines help granulocyte/macrophage progenitor cells differentiate into monocytes?
* GM-CSF * M-CSF * IL-3
45
What cytokines help Monocytes (in the blood) differentiate into Dendritic Cells?
* GM-CSF * IL-4
46
What cytokines help Monocytes (in the blood) differentiate into Macrophages?
* GM-CSF * M-CSF
47
What cytokine outputs does a macrophage release after TLR's bind a ligand and transcriptional reprogramming occurs?
* IL-1 * TNF-alpha
48
What type of cells can also interact with a macrophage presenting MHC II in the blood venule?
CD4+ T-cells
49
What are the four functions of a Macrophage according to Dr. Diebel?
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
What are the two functions of a Dendritic Cells according to Dr. Diebel?
1. Antigen presentation to naive T-cells 2. Modulation of T-cell differentiation

IHO: Week 1 - WLB (8 decks)

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