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Immunology Jenny > 2. Innate immunity > Flashcards

2. Innate immunity Flashcards

1
Q

Receptors involved in tight binding of neutrophils

A
  • s-Le^x => E-selectin
  • CXCL8R (IL-8 R) => chemokine CXCL8 (IL-8)
  • LFA-1 (alphaL:beta2) (integrin) => ICAM-1
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2
Q

Involved in tethering and rolling of neutrophils

A

Selectins (E-selectin)

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3
Q

Involved in tight binding of neutrophils

A

Integrins (ICAM-1)

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4
Q

Anti-microbial effects of neutrophils

A

1) Phagocytosis (intravesical killing which can be oxygen dependent or independent, degrad. by lysosomal enzymes)
2) Degranulation (frustrated phagocytosis)
3) NETs (extracellular DNA trap
4) (Superoxide production)

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5
Q

Types of transendothelial migration

A

Paracellular and transcellular

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6
Q

Neutrophil swarm

A

Coordinated chemotaxis. Steps:

1) Scouting (DAMPs and/or PAMPs)
2) Amplification (Cluster of necrotic neutrophils, gets an ECM devoid region at the injury site)
3) Stabilization (Monocytes appear)

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7
Q

Immature dendritic cells

A
  • Reside in peripheral tissues
  • High phagocytic activity
  • Macropinosome
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8
Q

Mature dendritic cells

A

Appears when immature dendritic cell has taken up an antigen in case of pathogen invasion/inflammation

  • In deep cortex of lymph node
  • Present antigens to T cells
  • No phagocytic activity
  • Costimulation
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9
Q

Human dendritic cell populations

A

1) Myeloid
- Conventional DC1 (cDC1)
- Conventional DC2 (cDC2)
2) Plasmocytoid DC (pDC)
3) Monocyte derived DC

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10
Q

Monocyte derived DC functions

A
  • TNF
  • iNOS
  • Bacterial antigens
  • Secondary immune responses
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11
Q

Zipper hypothesis of Fc mediated phagocytosis

A

Fc receptor connected to actin, stretches and wraps around the pathogen

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12
Q

Frustrated phagocytosis

A
  • Phagocyte attaches to surface via Fc receptors
  • Lysosomes moves to attached surface
  • Lysosomal contents released into extracellular space
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13
Q

Maturation of phagosome

A

“Phagolysosome”
Fusion of phagosome with endosomes and lysosomes
- Endosome enters cell via endocytosis with a clathrin-coated pit
- Lysosomes from golgi, contains hydrolytic enzymes

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14
Q

Surface receptors of phagocytes

A
  • Opsonic receptors: Fc and complement receptors

- PRRs

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15
Q

Opsonization

A

Facilitation of phagocytosis by binding of antibody or a complement protein to the antigen
- Then phagocytic cells can take up antigen through complement receptor and/or Fc receptor

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16
Q

Used to split antibody

A

Papain (-> Fab and Fc)

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17
Q

Fc receptors

A
  • Fcg
  • Fce
  • PolyIg
  • FcRn (neonatal)
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18
Q

Fcg receptor

A
  • Bind IgG
  • Facilitate phagocytosis
  • Zipper mechanism, respiratory burst of macrophages
  • May suppress function of B cells (FcR IIb)
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19
Q

Fce receptor

A
  • Bind IgE
  • High affinity form on mast cells and basophils
  • Plays role in allergy
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20
Q

PolyIg receptor

A
  • Bind polymeric antibodies (IgA)

- Plays a role in transcytosis through epith. of mucus membrane

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21
Q

FcRn receptor

A
  • Neonatal
  • Bind IgG
  • Transfer of passive immunity to fetus
  • Protects IgG from degradation
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22
Q

Intravesical killing - Oxygen dependent microbicidal activity

A

1) Peroxidase-independent
- NADPH oxidase
2) Peroxidase dependent
- Lysosome with myeloperoxidase
- Catalase from peroxisomes

23
Q

Intravesical killing - The nitric oxide pathway

A

1) IFNγ -> activate inducible NOS -> NOS w/tetrahydrobiopterin -> L-arginine + O2 to NO
2) TNF skip first step, rest same as IFNγ

24
Q

Pus content

A

Alive + dead neutrophils and tissue debris

25
Q

CGD

A

Chronic granulomatosis disease

  • Phagocyte oxidase deficiency
  • Granuloma formation, skin infections, gingivitis
26
Q

Innate-like cells (between innate and adaptive)

A
  • iNKT cells
  • MAIT cells
  • γδ T cells
  • Innate like cells (ILCs)
  • B1 B cells
  • Marginal zone B cells
27
Q

NK cells

A
  • Kill virus infected and tumor cells
  • No B nor T cell receptor
  • Have activating and inhibitory receptors
  • Attacks cells with no MHC class I, that contain activating ligands
  • Might attack cells with MHC class I if they have activating ligands (depends on balance)
28
Q

Inhibitory NK cell receptor

A

NKG2A (ITIM receptor)

- Ligand: HLA-E with leader peptides from HLA-A, -B, -C and -G

29
Q

Activating NK cell receptor

A

NKG2D

- Ligand: MICA, MICB, ULBP

30
Q

γδ T cell effects

A
  • Lysis of infected and stressed cells
  • Cytokine and chemokine production
  • B cell help and IgE prod.
  • Priming of αβ T cells via antigen presentation
  • Dendritic cell maturation
  • Regulation of stromal cell function via growth factor production
31
Q

Innate lymphoid cells (ILCs)

A

Type I: IFNγ producers (NK cell)
Type II: Th2 cytokines producers
Type III: IL17 or IL22 producers

32
Q

Pattern recognition receptors (PRRs)

A

1) Membrane PRRs
2) Secreted PRRs
3) Intracellular PRRs
- Vesicular
- Cytosolic

33
Q

Membrane PRRs

A

1) Lectin R
2) NK cell R
3) Scavenger R
4) Complement R
5) Toll like R

34
Q

Membrane PRRs on macrophages

A
  • Mannose R
  • LPS R (CD14)
  • TLR-2 and -4
  • Glucan R
  • Scavenger R
35
Q

Toll-like receptors (TLR)

A
  • Horse-shoe shape
  • Leucine-rich repeats
  • PAMP recognition
  • Very conserved structures
36
Q

TLR signal transduction pathway

A
  • Ligand binds
  • > Binding of MyD88 adaptor
  • > Ser/Thr kinase cascade
  • > Phosphorylation of IB degradation
  • > NFB translocation to nucleus!
  • Induces expression of costimulatory molecules and cytokines (induces increased MHC- and B7 expression in T cells)
37
Q

Membrane-bound TLRs

A
  • Recognize bacteria
  • TLR1:TLR2
  • TLR2
  • TLR4 (recognize LPS, contains MD2)
  • TLR5
  • TLR2:TLR6
38
Q

Intracellular TLRs

A
  • Recognize viruses
  • TLR3
  • TLR7
  • TLR8
  • TLR9
39
Q

Secreted PRRs

A

Soluble lectins

  • Ficolins
  • Lung surfactant
  • MBL
  • Pentraxins (CRP, SAP)
  • Cationic peptides
  • Antimicrobial peptides (defensins)
  • Cathelicidines
  • Lipid transporter proteins
  • Mindin
  • Lipocalin
  • C type lectins: C1q, MBL
40
Q

Cytosolic PRRs

A
  • NOD-like receptors (NLR)

- RIG-I-like receptors

41
Q

RIG-I-like receptors

A
  • Cytosolic PRRs
  • Virus recognition
  • Helicase domain
  • Cytoplasmic dsRNA recognition
42
Q

NOD-like receptors (NLR)

A
  • Intracellular bacteria
  • Cytoplasmic peptidoglycan recognition
  • 20 members
  • 4 subfamilies: NLRA, NLRB, NLRC, NLRP
43
Q

Inflammasome constituents

A

Cytoplasmic multiprotein oligomer

  • NLR
  • ASC (CARD + pyrin domain)
  • Caspase 1
  • Activated by PAMPs or DAMPs
44
Q

Inflammasome secretions

A

IL-1β and IL-18 (and IL-33)
(RICK via NOD/IPAF)
-> Inflammatory response via NF-κB or MAPK pathways)

45
Q

Inflammasomopathies

A

Autoinflammatory disorders

  • IL-1β secretion
  • Ex: Gout, Type II Diabetes, Muscle-Wells Syndrome (MWS)
46
Q

TLR location on gut epithelial cells

A

Intracellularly on the basolateral surface

47
Q

Natural immunity of bacteria

A

Anti-nucleic acid defence

- Prod. restriction endonucleases (cut phage DNA into smaller, non-infectious fragments)

48
Q

Natural immunity of bacteria - Natural CRISPR Pathway

A

1) DNA invasion
2) Incorporation into CRISPR (of the invading DNA)
3) Pre-crRNA transcription
4) Guide RNA formation
5) Cas9 activation
6) Target binding
7) Target cleavage (of the invading DNA)

49
Q

Time course of immune response

A

0-4 hrs: Innate immunity
4-96 hrs: Early induced response
>96 hrs: Adaptive immune response (T/B cells)

50
Q

Innate immunity receptor characteristic

A

Fixed in genome

51
Q

Types of macrophages

A

1) Tissue-resident
- Osteoclasts, Kupffer cells, histiocytes, microglia
2) Recruited
- M1: Classically activated by IFNγ
- M2: Alternatively activated by IL-4 and IL-13

52
Q

M1 macrophage

A
  • Classically activated by IFNγ
  • Proinflammatory
  • Prod. IL-1, TNF and IL-12
  • Promote Th immunity
  • Antitumor immunity
53
Q

M2 macrophage

A
  • Alternatively activated by IL-4 and IL-13
  • Regulate wound healing
  • Prod. IL-1ra, decayIL-1RII, IL-10
  • Suppress T cell responses
  • Suppress host defense
  • Suppress antitumor immunity
54
Q

Elimination of apoptotic cells by macrophages

A

1) “Find me” (MCP-1, IL-8)
- Apoptotic cells send attraction signals
2) “Eat me” (Phosphatidylserine++)
- Receptors on phagocyte (bridging protein R, PS R++)
3) “Tolerate me”
- Ingest w/o starting huge reaction

Immunology Jenny (16 decks)

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