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A/I Board Review > Cytokines, Chemokines, Receptors > Flashcards

Cytokines, Chemokines, Receptors Flashcards

1
Q

How is TNF secreted from cells?

A

TACE cleaves mTNF to create sTNF. ligands of TNF family are trimers.

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2
Q

What cytokines are in the IL-1 family?

A

IL-1alpha, IL-1beta, IL-18, IL-33

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3
Q

A patient has fever, hypoalbuminemia, elevated serum IgG, elevated CRP, mild anemia. A “tumor plop” is heard on exam. What is the diagnosis?

A

Atrial Myxoma - neoplastic atrial cells produce high IL-6. Can treat by removing myxoma.

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4
Q

Which cytokine is essential for supporting NK cells differentiation?

A

IL-15

This cytokine is also needed by CD8 and NKT cells.

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5
Q

The receptor for TSLP shares its alpha-chain with the receptor for which cytokine?

A

IL-7

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6
Q

Which cytokine promotes differentiation of CD4 helper T cells into IFNgamma producing Th1 cells?

A

IL-12
AND
IL-18 + IFNγ also help do this

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7
Q

What are the type 1 interferons and what do they do?

A 
IFNalpha and IFNbeta
Inhibit viral replication, increase expression of class I MHC molecules, stimulate Th1 development
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8
Q

Which cytokine inhibits production of IL-12 from macrophages and dendritic cells, inhibits expression of costimulatory receptors, and helps to maintain tolerance to allergens?

A

IL-10

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9
Q

Mutations in IL-12Rβ1 cause susceptibility to what type of infections?

A

intracellular bacteria, notably Salmonella and atypical mycobacteria

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10
Q

Which cytokine promotes differentiation and maintenance of T cells that produce IL-17?

A

IL-23

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11
Q

Hyperproduction of IL-6 suggests what disease?

A

Castleman’s disease (angiofollicular lymph node hyperplasia)
Fever
Microcytic anemia with normal BM iron
Hypoalbuminemia
Elevated CRP
All from elevated IL-6 hyperproduction
If confined to single lymph node, removal of node is curative

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12
Q

What cells depend on IL2?

A

T lymphocytes, Tregs, NK cells

*IL2 binds IL2R and engages Jak3-STAT5 pathways

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13
Q

What cytokine is important for Th2 differentiation, B lymphocyte class-switching to IgE, and inhibition of Th1 and Th17 development?

A

IL-4

*IL4 receptor signals through Jak-STAT6

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14
Q

What cytokine activates immature eosinophils, stimulates growth and differentiation of eosinophils, and stimulates production of IgA?

A

IL-5

*IL5 receptor signals through Jak2-STAT3

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15
Q

Which cytokine promotes differentiation of naive CD4 T cells to the Th1 subset (via T-bet), activates macrophages to kill phagocytosed microbes, promotes IgG class switching, stimulates expression of MHC molecules on APCs, and inhibits differentiation of Th2 cells?

A

IFNγ

  • Receptor is Type II cytokine receptor family: IFNγR1 and IFNγR2.
  • IFNγR1 associates with Jak1
  • IFNγR2 associates with Jak2
  • leads to STAT1 signaling
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16
Q

Which cytokine inhibits proliferation and effector functions of T cells, inhibits activation of macrophages, and also can induce apoptosis?

A

TGFβ

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17
Q

Which cytokine is secreted by stromal cells, can promote APCs towards Th2 responses, suppresses Th1 and Th17 responses, AND has a receptor that contains IL7Rα?

A

TSLP

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18
Q

What are the 3 receptors are in the common β chain family?

A

Receptors for IL-3, IL-5, GM-CSF

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19
Q

What is the cytokine that is a mast cell growth factor?

A

Stem Cell Factor (SCF), which is a c-kit ligand

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20
Q

Which cytokine promotes growth and development of mast cells from bone marrow, and also promotes differentiation of basophils?

A

IL-3

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21
Q

Which cytokines upregulate anti-apoptotic protein Bcl-2 activation of NFkB, leading to powerful stimulation of B cells and B cell survival?

A

BAFF and APRIL

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22
Q

Which cytokine is known as “IFNγ-inducing factor” because it promotes Th1 differentiation and response, and also is known for inhibiting IgE synthesis and induction of adhesion molecules like ICAM-1 to enhance leukocyte recruitment?

A

IL-18

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23
Q

Which chemokine/receptors are associated with HIV/AIDS?

A
  1. CCR5 (mono/macro) - homozygotes - no infection, heterozygotes - slow progress of infection
  2. CXCR4 - T cell trophic
  3. CCL3L1 - low level = higher HIV acquisition, high viral load, worse disease
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24
Q

Which chemokine/receptors are associated with WHIM syndrome? Heparin-induced thrombocytopenia?

A

CXCR4 for WHIM syndrome

CXCL4 for HIT

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25
Q

Which chemokine ligands and receptors are important for naive T cell homing?

A

CCL19/CCL21 –> CCR7 = lymphocyte homing

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26
Q

Which chemokine ligands and receptors are important for pro-Th2 response?

A

CCL17/CCL22 –> CCR4

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27
Q

What is the chemokine naming designation for “Eotaxin”? What is the receptor?

A 
Eotaxin = CCL11;
Receptor = CCR3
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28
Q

What is the chemokine naming designation for “IL-8”? What is the receptor? What is the purpose of this chemokine?

A

CXCL8 = IL-8 (“neutrophil chemotactic factor”);
Receptor = CXCR 1, CXCR2;
-Proinflammatory chemotactic factor that recruits neutrophils, basophils, and T cells to site of infection

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29
Q

What is the chemokine naming designation for “TARC”? What is the receptor?

A 
CCL17 = TARC;
Receptor = CCR4
30
Q

What is the chemokine naming designation for “RANTES”? What is the receptor?

A

CCL5 = RANTES;

Receptors: CCR 1,3,5

31
Q

What are the general family of chemokines is associated with neutrophil/lymphocyte migration?
How about monocyte/eos/basophil migration (allergic response)?

A

CXC family for neutrophil migration (example: CXCL8 attracts neutrophils through receptor CXCR 1,2);
CC family for monos/eos/basos (example: CCL2 attracts monocytes through receptor CCR2B)

32
Q

What are the 3 major types of selectins and where are they generally located?

A
  • P Selectin - located on platelets and Weibel-Palade bodies of the endothelium, help with binding PMNs, T cells, and monocytes;
  • E Selectin - located on endothelium and help T cell homing to inflammation;
  • L selectin - located on lymphocytes/leukocytes and help with homing to lymph node HEV;
33
Q

α4β7 does what?

A

Integrin that is a mucosal addressin that binds to cell adhesion molecule (MAdCAM) and is important for gut homing.

34
Q

What is the cluster of differentiation name for ICAM1, and what does ICAM1 bind to?

A

CD54 - binds LFA1, MAC1, and rhinovirus

35
Q

What are the cluster of differentiation names and binding targets for:

  1. VCAM1
  2. PECAM
  3. NCAM
A
  1. CD106 –> binds vascular VLA4 (α4β1, think V = “vascular”)
  2. CD31 –> binds to CD31 and CD38 (think P = “platelets”)
  3. CD56 –> binds neuronal VLA4 (α4β1, think N = “neuronal”)
36
Q

What chemokines are implicated in atherosclerosis?

A

CX3CL1 - fractalkine;

CX3CR1 - fractalkine receptor

37
Q

Which complement receptor binds C3d and provides a second signal for B-lymphocyte activation by antigen in conjunction with CD19 and CD81?

A

CR2 (CD21)

38
Q

Which complement receptor is a marker for dendritic cells, and known to function only for phagocytosis by binding C3b on bacterial surfaces?

A

CR4 (CD11c/CD18 aka αXβ2)

39
Q

Which complement receptor stimulates phagocytosis by binding to C3b on bacterial surfaces, and is also important for leukocyte adhesion and migration by binding ICAM-1?

A

CR3 (CD11b/CD18 aka αMβ2)

40
Q

Which complement receptor regulates complement activation, stimulates phagocytosis of bacteria coated with complement components, and helps RBCs transport and clear immune complexes?

A

CR1 (CD35)

41
Q
  1. Which membrane-bound receptors disrupt formation of the MAC complex (C5-C9)? If they are defective, what disease occurs?
  2. What soluble protein inhibits MAC complex formation?
A
  1. CD55 (Decay-accelerating factor or DAF) and CD59 (Protectin) - if defective leads to Paroxysmal Nocturnal Hemoglobinuria (PNH).
  2. Protein S (vitronectin) - binds MAC complexes and inhibits their random insertion into cell membranes
42
Q

What membrane-bound receptor is a cofactor for Factor I, allowing decreased formation of C3 convertase?

A

CD46 (Membraine-cofactor protein or MCP) - factor I is a serine protease that cleaves C3b and C4b

43
Q

What does Factor I do? What does Factor I deficiency cause?

A

Factor I is a serine protease that cleaves C3b and C4b to stop complement activation. Deficiency of Factor I causes uncontrolled complement activation, leading to depletion of C3, pyogenic infections, hemolytic uremic syndrome

44
Q

Defects in what regulatory protein is associated with age-related macular degeneration and atypical hemolytic uremic syndrome?

A

Factor H, a soluble factor that regulates complement activation by displacing C3b from C5 convertase and acting as a cofactor to allow Factor I to inactivate C3b.

45
Q

What is the only known “positive regulator” of complement as it stabilizes factor B after factor B is cleaved by factor D, to form the C3 convertase (alternative pathway)?

A

Properdin

46
Q

What antibody is found in patients with hypocomplementemic urticarial vasculitis (HUVS)?

A

Anti-C1q antibody

47
Q

What is the name of the autoantibody that binds and stabilizes the alternative pathway C5 convertase, protecting the convertase from factor H-mediated dissociation and factor I-mediated inactivation, which can then lead to unregulated consumption of C3 that can cause membranoproliferative glomerulonephritis and partial lipodystrophy?

A

C3 nephritic factor.
-partial lipodystrophy occurs because adipose cells are the main source of factor D, which are present in higher concentration in the upper half of the body, and factor D is the first step in generating the alternative pathway C5 convertase. C3 nephritic factor-stabilized convertases lyse adipocytes.

48
Q

What are the possible complement deficiencies in the following scenarios?

  1. CH50 absent + AH50 is OK
  2. CH50 is OK + AH50 is absent
  3. CH50 absent + AH50 absent, and C3 is OK
  4. CH50 absent + AH50 absent, and C3 is absent
A
  1. Deficiency of any of the following: C1q/r/s, C2, C4 – leads to autoimmune disease (SLE, MPGN) > recurrent infections
  2. Deficiency of Factor B or Factor D or Properdin
  3. Deficiency of C5, C6, C7, C8, or C9 (Neisseria infections)
  4. Deficiency of Factor H or Factor I
49
Q

Which complement deficiency causes recurrent Neisserial infections but a normal CH50 test, and occurs only in males?

A

Properdin deficiency (the only X-linked complement deficiency!)

50
Q

Which cytokines stimulate class-switching to IgA?

A

IL-5 and TGFβ

51
Q
  1. What receptor do circulating naive B cells express that allow homing into lymphoid follicles or other lymph tissue?
  2. What is the ligand for this receptor and what cells produce it?
A
  1. CXCR5

2. CXCL13, produced by follicular dendritic cells

52
Q

What lipid molecule has chemotactic activity similar to chemokines, and acts through a concentration gradient to draw unactivated naive T cells expressing the conjugate receptor away from lymphoid tissues and back into circulation?

A

sphingosine-1-phosphate (S1P)

*S1PR1 (receptor) is internalized if naive T cell recognizes antigen:MHC complex, allowing it to stay in the lymph node to proliferate. After several days of proliferation and maturing into effector T cells, S1PR1 reappears and effector T cells can migrate out into circulation.

53
Q

Which receptor is highly expressed on monocytes and macrophages, and binds to LPS (it is a component of TLR4)?

A

CD14

54
Q

What cell surface markers help distinguish a plasmacytoid dendritic cell (pDC) from a conventional DC (cDC)?

A

pDC’s lack CD1, CD11b/c, and express CD123 (IL-3 receptor).

cDC’s have CD1, CD11b/c, CD14(coreceptor with TLR4), CD209 (DC-SIGN).

55
Q

What immunohistochemical staining markers identify Langerhans cells and are found in biopsy of bone lesions in Langerhans cell histiocytosis?

A

CD1a and CD207 (langerin)

56
Q

What are the essential receptors and transcription factors on 1. mast cells, 2. basophils, and 3. eosinophils?

A
  1. Mast cells - KIT (receptor for SCF and target of imatinib); GATA2
  2. Basophils - IL3R (CD123); GATA2
  3. Eosinophils - IL5R and CCR3; GATA1
57
Q

Which cytokines attract eosinophils into tissues?

A

RANTES (CCL5), eotaxin (CCL11), eotaxin-2 (CCL24), eotaxin-3 (CCL26)

58
Q

Which leukotriene attracts neutrophils into tissue?

A

LTB4

59
Q

Which cytokine uniquely promotes airway mastocytosis and mast cell progenitor development and localization to the airway?

A

IL-9 is produced by Th9 cells and is a growth factor for mast cells, involved in mucosal immunity.

60
Q 
Which family of cytokines are linked to autoimmune diseases including rheumatoid arthritis, inflammatory bowel diseases and multiple sclerosis, in addition to increased expression in asthmatic patients?
A. IL-16 family cytokines.
B. IL-17 family cytokines.
C. TNF-α.
D. IFN-γ.
A

B. IL-17 family cytokines
IL-17A to IL-17F, are linked with several autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis; in particular, IL-17E and IL-17F are of interest in asthma because their expression is increased in the airways of asthmatic
patients, and levels have been correlated with disease severity.

61
Q

List alternative names and the corresponding ligands for the following leukocyte integrins:

  1. LFA-1
  2. Mac-1
  3. p150,95
  4. VLA-4
  5. α4β7
A
  1. LFA-1 or αLβ2 or CD11a:CD18; binds ICAM-1/ICAM-2
  2. Mac-1 or αMβ2 or CD11b:CD18 or CR3; binds ICAM-1 and iC3b
  3. p150,95 or αXβ2 or CD11b:CD18 or CR4; binds to iC3b
  4. VLA-4 or α4β1 ; binds to VCAM1 on endothelium
  5. α4β7; binds to MadCAM-1 for gut homing
62
Q

List the cluster of differentiation names and corresponding ligands for the following immunoglobulin superfamily cell adhesions proteins:

  1. ICAM-1
  2. ICAM-2
  3. VCAM-1
  4. PECAM
A
  1. ICAM-1 (CD54) - on endothelium, binds to LFA-1, Mac-1
  2. ICAM-2 (CD102) - on endothelium, binds to LFA-1
  3. VCAM-1 (CD106) - on endothelium, binds to VLA-4
  4. PECAM (CD31) - on leukocytes and endothelium tight junctions, binds to itself (CD31)
63
Q

If a naïve T cell is activated by antigen in the lymph node, which of the following proteins helps the
activated naïve T-cell to remain in the lymph node?
a. CD31
b. CD69
c. Albumin
d. Ficolin

A

b. CD69 - a protein that binds S1PR1 and reduces its cell surface expression. This prevents the naïve T cell from migrating from the low concentration of S1P in the lymph node to the high concentration of S1P in the blood.

64
Q

What receptor allows lymphocyte homing to CXCL12 (stromal cell derived factor 1 or SDF-1) found in bone marrow or germinal centers?

A

CXCR4 - allows homing to CXCL12 found in the bone marrow or stromal cells in germinal centers

- Germinal Centers (where somatic hypermutation occurs): rapidly proliferating B cells express both CXCR4 and CXCR5.  Stromal cells in the dark zone produce CXCL12, so these proliferating B cells migrate towards the stromal cells and form the Dark Zone. When these proliferating cells reduce their rate of proliferation and enter the growth phase, they downregulate CXCR4 and move into the light zone which contains fDCs that generate CXCL13. - T cell tropic HIV is associated with CXCR4
65
Q

What cells are known for expressing CD68?

A

Macrophages and monocytes

66
Q

Which subtype of mast cells have the CD88 receptor for C5a anaphylatoxin?

A

MCtc (connective tissue mast cells)

67
Q

Tissue-specific T-cell homing, can you name the corresponding ligand/receptor for:

  1. CCR4
  2. CCR7
  3. MAdCAM-1
  4. CCR9
  5. CCR10
  6. CLA
A
  1. CCR4: CCL17 (TARC) [skin homing], CCL22 [lymph node homing], think Th2 cells
  2. CCR7: CCL19, CCL21 [naive T cell lymph node homing]
  3. MAdCAM-1: α4β7 [gut homing]
  4. CCR9: CCL25 (TECK) [gut homing]
  5. CCR10: CCL27 (CTACK) [skin homing]
  6. CLA (cutaneous lymphocyte antigen): E-selectin [skin homing]
68
Q

T cell subset homing, can you name the corresponding receptor and ligands involved in homing for:

  1. naive T cell
  2. Th1
  3. Th2
  4. Th17
A
  1. CCR7: CCL19, CCL21 (naive T cell homing to lymph nodes)
  2. CCR5: CCL3, CCL4, CCL5, CCL8 (CCR5 expressed on monocytes/macrophages at sites of inflammation too)

3a. CCR4: CCL17 (TARC) [skin homing], CCL22 [lymph node homing]
3b. CCR3: eotaxins (CCL11, CCL24, CCL26) [Th2 and eos both using these for homing]

  1. CCR6: CCL20 [activated epithelium, Th17, and ILC3 all produce CCL20 to aid homing towards mucosal/skin]
69
Q

What is the cluster of differentiation name for:

  1. CTLA-4
  2. CD40L
  3. PSGL-1 (P-selectin glycoprotein ligand-1)
  4. FasL (Fas ligand)
A
  1. CTLA-4 is CD152
  2. CD40L is CD154
  3. PSGL-1 is CD162
  4. Fas ligand is CD178
70
Q

NKG2 is an NK receptor that modulates NK cell killing. What is it’s cluster of differentiation name?

A

CD159

71
Q

Do NK cells express CD3?

A

no

A/I Board Review (8 decks)

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