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FD9 > 13 - Basic Principles of Immunologic Diseases in Skin (Pathophysiology of Immunologic/Inflammatory Skin Diseases) > Flashcards

13 - Basic Principles of Immunologic Diseases in Skin (Pathophysiology of Immunologic/Inflammatory Skin Diseases) Flashcards

1
Q

Typically low-molecular-weight chemicals and metals, which interact with endogeneous proteins to form immunogenic (complete) antigens

A

Haptens

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2
Q

Y/N: Evidence suggesting that genetic susceptibility to ACD is important is strong

A

No - not strong

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3
Q

Initial exposures to haptens that commonly elicit ACD inpatients signal via 2 major pathways involved in innate immunity

A

Inflammasomes and/or

Toll-like receptors

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4
Q

Phases of acute contact dermatitis/contact hypersensitivity

A
  1. Sensitization
  2. Elicitation
  3. Resolution
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5
Q

Cytokine, toll-like receptor and inflammasome-mediated activation of APCs
No skin inflammation

A

Sensitization

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6
Q

Cytokine, toll-like receptor and inflammasome-mediated activation of APCs
Skin inflammation elicited by T cells

A

Elicitation

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7
Q

Resident memory T cells poised for subsequent exposure

A

Resolution

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8
Q

Y/N: Because haptens easily penetrate epidermis and reach the dermis, both Langerhans cells and dermal dendritic cells encounter contact allergens

A

Yes

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9
Q

CD8alpha+ (DCs and DDCs/LCs), but not (DCs and DDCs/LCs), contribute to CD8+ T-cell responses during antiviral responses

A

DCs and DDCs

LCs

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10
Q

_____ T cells appear to be the primary mediators of skin inflammation in ACD, but _____ T-cell activation may be required for optimal _____ T-cell responses

A

CD8+
CD4+
CD8+

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11
Q

_____ T cells mediate rapid cutaneous hypersensitivity responses, whereas _____ T cells cause delayed responses

A

Resident memory

Central memory

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12
Q

_____ T cells are thought to play major roles in attenuation or termination of inflammation in cutaneous hypersensitivity

A

Regulatory

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13
Q

Severe cutaneous adverse reactions include

A

SJS
TEN
DiHS/DRESS

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14
Q

Commonly included as SCAR, but is, in general, less severe than SJS/TEN and DiHS/DRESS

A

AGEP

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15
Q

In cohorts of Han-Chinese patients, SJS/TEN that is caused by allopurinol and carbamazepine is strongly associated with the HLA haplotypes _____ and _____, respectively

A

B*58:01

B*15:02

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16
Q

Dapsone hypersensitivity syndrome, a form of DiHS/DRESS has been associated with the _____ haplotype in Asians

A

HLA-B*13:01

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17
Q

_____ T cells can be readily detected in SJS/TEN lesions, suggesting that these cells are pathogenic

A

Cytotoxic

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18
Q

Probably reflects the existence of clones of drug-reactive CD8+ resident memory T (TRM) cells that reman at sites of previous skin lesions where they are poised to respond if offending drugs are readministered

A

Fixed drug eruptions

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19
Q

Y/N: Cytotoxic responses are more prominent in DiHS/DRESS

A

No - less prominent

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20
Q

Hallmark feature of DiHS/DRESS

A

Peripheral eosinophila

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21
Q

Expansion of regulatory T cells may result in immunocompromise in the initial stage of DiHS/DRESS, allowing reactivation of _____ infections

A

Herpes virus

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22
Q

EB virus-specific CD8+ T cells are reported to be increased in the circulation and cause tissue damage in EB virus-infected tissues, including _____, that is typical of DiHS/DRESS

A

Liver

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23
Q

B cells, which serve as a reservoir for EB virus, also may be targeted because patients with DiHS/DRESS frequently experience

A

Hypogammaglobulinemia

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24
Q

_____ patients exhibit immunologic abnormalities long after resolution of the acute phase and may develop autoimmune diseases such as Hashimoto thyroiditis, SLE, and type I DM

A

DiHS/DRESS

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25
Q

Accentuated immune responses against herpes viruses and the occurrence of autoimmune diseases suggest that breakdown of peripheral tolerance is a major contributor to

A

DiHS/DRESS

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26
Q

Posits that drugs bypass classic antigen-processing mechanisms and trigger immune responses through direct, noncovalent interactions with human leukocyte antigen alleles and/or T-cell receptors that are expressed on cell surfaces

A

Pharmacologic interaction with immune receptors (p-i) concept

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27
Q

Could explain why drug reactions occur within hours to few days in patients after initial exposure to causative drugs

A

Pharmacologic interaction with immune receptors (p-i) concept

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28
Q

Proposes that drugs bind directly to T-cell receptors and promote inappropriate T-cell reactivity to self-antigens

A

Altered TCR repertoire model

29
Q

Serum levels of IgE and CCL17 (TARC), both of which are characteristic of type 2 immune responses, are increased in

A

Atopic dermatitis

30
Q

Atopic dermatitis patients harbor loss-of-function mutations in the gene encoding the structural protein

A

Filaggrin

31
Q

Netherton syndrome, a disease with eczematous dermatitis as a prominent feature, is caused by mutations in the cell surface protease inhibitor

A

SPINK5

32
Q

(Presence/Loss) of SPINK5 leads to increased activity of cell surface serine proteases that compromises the barrier function of the stratum corneum

A

Loss

33
Q

Y/N: SPINK 5 polymorphisms have been associated not with AD, but with elevated IgE levels in patients with AD

A

Yes

34
Q

Characterized by dermatitis and impaired Th17 responses leading to increased susceptibility to Th17 responses leading to increased susceptibility to Staphylococcus aureus colonization or infections
Caused by loss of function mutations in STAT3

A

Job syndrome (hyperIgE syndrome)

35
Q

Commonly colonizes AD skin

A

S. aureus

36
Q

Although _____% of non-AD patients carry S. aureus as a commensal microbe, both the abundance and relative frequency of S. aureus representation in the skin microbiome is increased in AD patients, even when their disease is quiescent

A

20-30

37
Q

When patients experience acute exacerbation of AD, _____ become predominant in the skin microbiome

A

Staphylococci (primarily S. aureus)

38
Q

Cutaneous application of S. aureus in AD caused eczema, whereas commensal _____ species did not

A

Corynebacterium

39
Q

Humanized monoclonal anti-IgE antibody which effectively treats asthma, food allergies, and urticaria, but is not effective in AD

A

Omalizumab

40
Q

Blocks IL-4 and IL-13 signaling by binding to IL-4Ralpha

Effective in AD

A

Dupilumab

41
Q

Inhibit both JAK1 and JAK3

Have activity in inflammatory diseases including rheumatoid arthritis, psoriasis and alopecia areata

A

Tofacitinib

Ruxolitinib

42
Q

The calcineurin inhibitor _____ is a remarkably effective antipsoriatic agent
Ability to modulate keratinocyte growth and gene expression

A

Cyclosporine

43
Q

Lymphocyte-depleting agent: IL-2 receptor-directed cytotoxin

A

Denileukin diftitox

44
Q

Lymphocyte-depleting agent: CD2-binding LFA-3/Fc fusion protein

A

Alefacept

45
Q

Y/N: Denileukin diftitox and alefacept were too toxic to be routinely administered to psoriatic patients because they have broad-spectrum antilypmhocyte effects

A

Yes

46
Q

Anti-TNFalpha neutralizing antibody (one of the first widely used biologics)

A

Infliximab

47
Q

TNFalpha is coproduced by dermal dendritic cells that also produce _____, a cytokine that is required for Th-17 cell development

A

IL-23

48
Q

IL-23 is a heterodimeric protein composed of IL-23-specific p19 as well as p40, a polypeptide that is shared with the Th1-promoting cytokine

A

IL-12

49
Q

Anti-humn p40

A

Ustekinumab

50
Q

Anti-IL-7A monoclonal antibodies

A

Secukinumab

Ixekinumab

51
Q

Anti-IL-23 p19 monoclonal antibody

A

Guselkumab

52
Q

Single nucleotide polymorphisms in the _____ locus confer the largest amount of genetic risk in both European and Chinese psoriasis populations

A

MHC Class I

53
Q

Y/N: The accepted importance of Th17 cells in psoriasis would predict that variants of interest would occur in the MHC Class II locus, rather than the MHC Class I locus

A

Yes

54
Q

Scalp biopsies obtained from the (center/periphery) of expanding alopecia areata lesions feature lymphocyte-predominant inflammation

A

Periphery

55
Q

Preferential association of lesional lymphocytes with anagen hair _____, rather than the stem cell-containing bulge regions, is consistent with the characterization of AA as a nonscarring alopecia

A

Bulbs

56
Q

Inflammatory lesions in AA is thought to result from loss of “_____” that is a property of normal hair follicles
May depend on low-level expression of MHC Class I and Class II antigens by HF keratinocytes and local production of immunosuppressive cytokines and perhaps neuropeptides

A

Immune privilege

57
Q

_____ inhibitors can reverse hair loss by suppressing inflammation and by directly acting on hair follicles to induce hair growth

A

JAK

58
Q

The cytokine _____ is known to be important for CD8+ T-cell induction and/or persistence, so it is not surprising that neutralization of _____ also attenuates AA activity

A

IL-15

59
Q

Coadministration of CD4+ CD25- (helper) T cells with CD8+ (promotes/prevents) disease progression whereas coadministration of CD4+ CD25+ (regulatory) T cells with CD8+ T cells (promotes/prevents) disease induction

A

Promotes

Prevents

60
Q

Most common autoimmune blistering disorders

A

Pemphigus

Pemphigoid

61
Q

Desmoglein _____ is expressed in oral and esophageal mucosae

A

3

62
Q

Two major antigens targeted in BP

A

Collagen XVII/BPAG1/BP230

BPAG2/BP180

63
Q

Expressed on cell surfaces

Considered to be the major BP autoantigen

A

COL17

64
Q

Y/N: The pathophysiologic role of anti-BP230 antibodies in BP is uncertain because BP230 is an intracellular protein

A

Yes

65
Q

Caused by anti-COL7 antibodies

A

Epidermolysis bullosa acquisita

66
Q

In BP patients, the majority of anti-COL17 IgG autoantibodies target the _____ domain

A

NC16a

67
Q

_____ deposition in the basement membrane zone is universal in BP

A

C3

68
Q

The increased incidence of pemphigus (especially PF) in patients with _____ suggests that impairment of central tolerance relates to the onset of pemphigus

A

Thymoma

69
Q

Binds the cell surface protein CD20 that is expressed by B cells
Leads to depletion of both normal and autoreactive B cells in patients

A

Rituximab

FD9 (108 decks)

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