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ABAI 2020 REVIEW > Cells Involved in Immune Response > Flashcards

Cells Involved in Immune Response Flashcards

1
Q

NKT Cells

A

These are not NK cells

Limited T cell receptor repertoire Vα24/Jα18 and Vβ11

CD1-restricted

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2
Q
A

Monocyte

  • Express IgG, IgA, IgE
  • Monoblast → (GM-CSF, IL-6) → Monocyte
  • CD14 (a component of TLR4 and an LPS receptor)
  • Mature ⇒ CD16 (produce TNFαandIL-12)
  • Chemokines (attract monocytes to the lungs): CCL2, CCL3, CCL4, CCL5.
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3
Q
A

Macrophage

  • Express: CD14, CD16, CD11b/CD18 (Mac-1), CD33, and CD36
  • Develop in response → GM-CSF
  • Classical M1 (LPS and/or Th1 → INFγ) ⇒ secrete TNFα, IL6, IL-1β → Activate T cells
  • Alternative M2 (steroids and/or Th2 → IL-4, IL-13, IL-10)
  • TNFα promotes granuloma formation
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4
Q

HLH

A

Uncontrolled activation of macrophages with a marked increase in circulating cytokines.

  • Clinical characteristics: High fever, HSmegaly, high ferritin and TG, low fibrinogen, and NK cells.
  • Hemophagocytosis in BM biopsy.
  • Dx Criteria (5 of 8): 1) fever, 2) splenomegaly, 3) cytopenia (≥2 lines), 4) hyperTG or hypofibrinogenemia, 5) hemophagocytosis, 6) hepatitis, 7) Low or absent NK cell activity, 8) ferritin >500, and soluble CD25 (sI-2 recptor) >2,400.
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5
Q
A

Dendritic Cells

  • Key fact: pDC lack CD11c, express CD123
  • Develop: GM-CSF and IL-4
  • Most important APCs (critical in starting germinal centers reactions)
  • Express B7-1/B7-2 (CD80/CD86) interacts with CD28 (costimultion/2nd signal)
  • DCs interact with epithelial cells (especially Der p1 and Th2 polarization)
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6
Q

Langerhans Cell Histiocytosis

A
  • Rare malignancy of Langerhans cells
  • Eczema and/or seborrhea
  • 1/2 cases: Limited to lytic bone lesions. Other 1/2: Multisystem involvement.
  • Dx: Bipsy to confirm LC (CD1a, CD207)
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7
Q
A

Mast Cell

  • Essential receptor: CD117 (KIT); essential cytokine: SCF; transcription factor: GATA2
  • Life-span: weeks-months
  • Surface receptors: FCεRI, FCεRII, FCεRIIa, FcγRI, C5aR, C3aR, Leukotriene receptors; ch__emokine: CCR3, CCR5, CXCR2, CXCR4; c__omplement: C5aR, C3a; PG: PGE2R; LT: CysLT1R, CysLT2R.
  • Preformed mediators (<15 min): Histamine, proteases, carboxypeptidase A, proteoglycans, TNFα; lipid-derived mediators (~10 - 30 min): PGD2, LTB4, LTC4, LTD4, LTE4; chemokines: IL-3,4, 5, 6, 8, 13, GM-CSF, TNFα, MIP-1α (CCL-3), RANTES (CCL-5)
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8
Q
A

Basophil

  • Essential receptor: CD123 (IL-3R); essential cytokine: IL-3; transcription factor: GATA2
  • Life-span: Days
  • Surface receptors: FCεRI, FCεRIIb, CRTH2 (PGD2 receptor); chemokine: CCR2, CCR3; complement: CD11b, CD11c, CD35, CD88; PG: CRTH2 (PGD2 receptor)
  • Preformed mediators (<15 min): Histamine; lipid-derived mediators (~10 - 30 min): LTC4, LTD4, LTE4; chemokines: IL-3, 4, 5, 13, GM-CSF, TNFα, MIP-1α (CCL-3)
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9
Q
A

Eosinophils (life-span: days-week)

  • Essential receptor: IL-5R, CCR3
  • Essential cytokine: IL-5, IL-3, GM-CSF
  • Transcription factor: GATA1
  • Surface receptors: FcγRII, FcαRI, CCR3, CRTH2 (PGD2 receptor), leukotriene receptors; chemokine: CCR1, CCR3; complement: CR1/CD25, CR3, CD88; PG: PGD2 type 2 receptor; LT: CysLT1R, CysLT2R
  • Preformed mediators (<15 min):
    • Primary granules: CLC
    • Secondary granules: MBP, eosinophilic cationic protein, eosinophil peroxidase, the eosinophil-derived neurotoxin, lysosomal hydrolase, lysophospholipase
  • Lipid-derived mediators (~10 - 30 min): PGE2, LTC4, LTD4, LTE4
  • Cytokines/chemokines: IL-3, 4, 5, 8, 10, 12, 13, 16, 18, TGFβ, TNFα , CCL-5, CCL-11
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10
Q

Arachidonic Acid Pathway

A
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11
Q

Mast Cell Activation and Signaling

A

IgE Receptor/FcεR:

  • Tetrameric: one α chain (binding site for IgE), one β chain (four transmembrane domains and one ITAM), two γ chains (covalently linked, each one contains one ITAM; main signaling component)
  • Trimeric: one α chain and two γ chains (DC, monocytes, and eosinophils)
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12
Q

Where does Derp-p-1 cleaves?

A

Low-affinity IgE receptor /FcεRII/CD23

C-type lectin found on mature B-cells, activated macrophages, eosinophils, dendritic cells, and platelets

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13
Q

Primary immunodeficiencies with elevated IgE

A

Hyper IgE syndrome, Wiskott-Aldrich Syndrome, Omenn syndrome, IPEX, atypecal complete DGS

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14
Q

Unlike mast cells, basophils do not produce:

A

Tryptase, chymase, carboxypeptidase, heparin, PGD2, and LTB4

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15
Q
A

Charcot-Leyden Crystals

Eosinophils → Primary Granules

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16
Q

Eosinophils Secondary Granules

A
  1. MBP
  2. Eosinophil cationic protein
  3. Eosinophil peroxidase
  4. Eosinophil-derived neurotoxin
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17
Q

Infections most commonly responsible for CGD infection

A
  1. S aureus
  2. Aspergillus spp.
  3. Chromobacterium violaceum
  4. Pseudomonas cepacia
  5. Nocardia spp.
  6. Salmonella typhimurium
  7. Serratia marcescens
  8. Mycobacterium fortuitum
  9. Klebsiella spp.
  10. E coli
  11. Actinomyces spp.
  12. Legionella bosmanii
  13. C difficile
18
Q

Eosinophils migrate to tissue in response to:

A
  • RANTES (CCL-5)
  • Eotaxin (eotaxin-1, CCL-11, eotaxin-2, CCL-24)
19
Q

Eosinophils release cytokines:

A
  • IL-1
  • IL-2
  • IL-4
  • IL-5
  • IL-6
  • IL-8
  • IL-13
  • TNF
20
Q

Infections with high eosinophils (remember most bacterial/viral infections suppress eosinophils)

A
  1. HIV (secondary to adrenal insufficiency, HIV medications, or HIV itself)
  2. Parasitic infections, especially those that invade the tissue (Strongyloides)
  3. Isospora belli and Sarcocystis, but not other protozoa
  4. Chronic TB
21
Q
A

Neutrophil

  • Attracted to tissue by IL-8 (CXCL-8)
    • ​Also, INFγ, fMLP, MIP-1, LTB-4, C5a, and interactions between Sialy-Lewis X, E-/P-selectins, and LFA-1/ICAM-1
  • Express surface receptors for IgG and IgA
  • Survival/differentiation/proliferation: G-CSF, GM-CSF, and IL-3
22
Q
A

Platelet

  • Formation regulated by thrombopoietin (secreted by liver and kidney)
  • Surface receptor: IgG and CD23
  • ​Activated: Exposed collagen and vWF
  • Thromboxane A2 → Activates more platelets
  • Release: ADP/ATP, calcium, serotonin, TGFβ, PF4, PDGF, vWF, and fibrinogen
  • Clump: vWF ⇔ GPIIb/IIIa
23
Q

Drug-induced thrombocytopenia (autoantibody?)

A

Antibody against platelet antigen PF4

24
Q

ITP (autoantibody?)

A

GP2b3a

25
Q

TTP (autoantibody?)

A

ADAMTS13

26
Q

Wiskott-Aldrich syndrome

A

Triad: Eczema, infections, thrombocytopenia (as well as small platelets)

Defect: WASp used in cell signaling

Remember: Elevated IgE

27
Q

Receptor Rhinovirus

A

ICAM-1

28
Q

Receptor Influenza

A

Glycans

29
Q

Receptor Adenovirus

A

Integrins and CD80/86

30
Q

Produce by epithelial cells

A

TSLP, GM-CSF, IL-25, and IL-33

31
Q

Suppression of β defensins and cathelicidins

A

Atopic dermatitis, IL-4, and IL-13 expression

32
Q

Bullous Skin Disorders

A

1

33
Q

Pemphigus Vulgaris

A

Intercellular IgG and IgM to Desmoglein 3 (desmosome)

34
Q

Pemphigus Foliaceous

A

Intercellular IgG to Desmoglein 1 (desmosome)

35
Q

Bullous Pemphigoid

A

Linear IgG at basement membrane zone to BPAg1 (BP 230) and BPAg2 (BP 180) [hemidesmosome]

36
Q

Pemphigoid gestationis (herpes gestationis)

A

Linear IgG at basement membrane zone to BPAg1 (BP 230) and BPAg2 (BP 180) [hemidesmosome]

37
Q

Dermatitis Herpetiformis

A

Granular IgA in dermis to Transglutaminase (subepidermal)

38
Q

Linear IgA dermatosis

A

Linear IgA in basement membrane zone to BPAg2 (BP 180)

[hesmidesmosome]

39
Q

Adhesions Molecules Used for Transmigration of Leukocytes

A
40
Q

Anti-SMA (IgG autoantibody)

A

Type I autoimmune hepatitis

41
Q
A

ABAI 2020 REVIEW (10 decks)

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