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Cell Structure Flashcards

1
Q

What special structure is present in the stratum granulosum that binds keratin filaments together?

A

Keratohyaline granules (they are filled with histidine and cysteine rich proteins which bind the keratin filaments together)

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2
Q

What level of the epidermis are keratohyaline granules found?

A

Stratum granulosum

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3
Q

What substances do keratohyaline granules (present in stratum granulosum) contain?

A

Profilaggrin, loricrin, and involucrin

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4
Q

Where is fillagrin located?

A

Stratum Granulosum

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5
Q

What does filaggrin do?

A

Binds Keratin (like K 6/16) intermediate filaments and organizes into fibrils (like the glue that binds the keratins)

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6
Q

Where is filaggrin located?

A

In the keratohyaline granule in the stratum granulosum

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7
Q

Keratins found in the stratum granulosum

A

K2 and K10 (K11)

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8
Q

What enzyme crosslinks peptide bonds in the cornified envelope to make it into the insoluble compound y-glutamic lysine isopeptide bonds

A

Transglutaminase

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9
Q

What is the major protein component of the cornified envelope?

A

Loricrin

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10
Q

What enzyme crosslinks all the protein peptide bonds loricrin and involucrin to make the cornified envelope?

A

Transglutaminase 3

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11
Q

What are the two major proteins that make up the cornified envelope?

A

Involucrin and loricrin (fillagrin is the glue)

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12
Q

Which cornified envelope protein is the substrate for transglutaminase

A

Involucrin (this is the one that is upregulated in psoriasis)

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13
Q

What two cell proteins are upregulated in psoriasis, and which is downregulated?

A

Involucrin and K6/16 is upregulated
Loricrin is downregulated

(P5 in Jain)

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14
Q

Substrate for transglutaminase in the cornified envelope

A

Involucrine

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15
Q

Upregulated in all layers in Psoriasis except basal

A

Involucrin

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16
Q

Components of the basal layer (as a part of the DEJ)

A

Keratins K5/K14

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17
Q

K5/K14

A

Basal layer keratinocytes, part of the BMZ complex/DEJ

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18
Q

Hemidesmosome anchoring filament proteins

A 
BPAG 1
BPAG 2 (Collagen XVII)
Plectin
Alpha-6, beta-4 integrin
Tetraspan CD151
Laminin 332 (Laminin 5)
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19
Q

Collagen XVII

A

Same thing as BPAG II

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20
Q

What collagen is found in the lamida Lucida/basal layer

A

Collagen XVII - same thing as BPAG II

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21
Q

Plectin

A

A Heim-desmosome anchoring filament protein - found in the basal layer/lamida lucida along with BPAG I,II, integrin, and laminin 5 (332)

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22
Q

What type of collagen is found in the lamida densa?

A

Collagen IV

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23
Q

Type IV collagen found where?

A

Lamina Densa

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24
Q

Major components of lamina densa?

A 
Type IV Collagen
Heparin Sulfate proteoglycans
Laminin 311 (6) Laminin 511 (10)
Nitrogen
(Also tecnically some of laminin 5(332)
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25
Q

Major components of the sublamina densa

A 
Type VII collagen
Type III collagen 
Type I collagen 
Elastin
Fibrillin
Latent TGB-beta proteins
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26
Q

Where is type VII collagen found?

A

Sublamina densa

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27
Q

Major protein comprising Anchoring Fibrils?

A

Type VII Collagen

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28
Q

What are anchoring fibrils made of and where are they found?

A

Made of Type VII collagen and they are found in the sublamina densa

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29
Q

What protein connects the lamida lucida to the lamina densa?

A

Laminin 332 (Laminin 5)

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30
Q

Members of the plakin family

A 
Plectin
BPAG 1 
BPAG 2
Envoplakin
Desmoplakin
Periplakin
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31
Q

Major function of plectin

A

Attaches keratin filaments in the basal layer to the anchoring filaments in the hemidesmisome

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32
Q

Mutation in plectin causes what disease

A

EB with muscular dystrophy

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33
Q

How many kD is BPAG1?

A

230kD

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34
Q

Which is intracellular and which is a transmembrane protein:
BPAG 1
BPAG 2

A

BPAG 1 - intracellular

BPAG 2 -transmembrane

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35
Q

How many kD is BPAGII?

A

180kD

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36
Q

How many kD is the EXTRACELLULAR portion of BPAGII?

A

120kD

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37
Q

Name 4 diseases that target BPAG2?

A

Bullous Pemphigoid
Pemphigoid Gestationis
Linear IgA Bullous Dermatosis
Cicatricial Pemphigoid

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38
Q

Which part of the BPAG2 protein does BP, Pemphigoid Gestationis, and Linear IgA target?

A

NC16 terminus (which is the most superficial extracellular portion of the BPAGII protein)

Vs cicatricial pemphigoid which targets the distal carboxy-terminus which inserts through the lamina lucida into the lamina densa

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39
Q

Which disease targets the carboxy terminus of BPAGII?

A

Cicatricial pemphigoid

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40
Q

What genetic disease has a defect in BPAG2 (BP180)

A

Non-Herlitz Junctional EB (widespread bulla at birth, heals with atrophic scarring, alopecia, improves with time)

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41
Q

Aquired disease, and genetic disease caused by mutation in integrin subunit beta-4

A

Aquired disease - cicatricial pemphigoid with ocular involvement
Congenital - Junctional EB with pyloric atresia

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42
Q

Genetic & Aquired disease caused by mutation in Laminin-5 (332)

A

Genetic - Junctional EB, Herlitz type

Aquired - anti-epiligrin cicatricial pemphigoid

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43
Q

Type VII Collagen genetic and aquired disorders

A

Genetic: ALL Dystrophic EBs
Aquired: EB Aquisita, Bullous lupus

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44
Q

What is the only type of protein that is present in both adherents junctions AND desmosomes?

A

Plakoglobin (mutated in Naxos)

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45
Q

What cell transmembrane protein do Langerhans Cells use to connect with keratinocytes

A

E Cadherins

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46
Q

Name the armadillo proteins

A

B-Catenin
Plakoglobin
Plakophilin

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47
Q

Name the caderhins

A 
Desmogleins 
Desmocollin
E caderhin
P cadeherin
N caderhins
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48
Q

Which are quick but weak cellular adhesions

A

Adherens junctions

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49
Q

Which are slow but strong intracellular junctions

A

Desmosomes

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50
Q

DSG4 is mutated in what disease

A

AR Monolethrix

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51
Q

Do antibodies of mothers with Pemphigus vulgaris cross the placenta?
How about pemphigus foliaceous?

A

Yes PV antibodies cross the placenta and cause blisters

NO in Pemphigus foliaceous they do not cross the placenta

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52
Q

What desmogleins are expressed in neonatal skin

A

DSG3

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53
Q

Most common sites of PV involvement in the mouth?

A

Buccal mucosa and palatal mucosa

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54
Q

What is mutated in Striate PPK 1

A

DSG-1

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55
Q

Mutation in Striate PPK 2

A

Desmoplakin

56
Q

Mutation in Striate PPK3

57
Q

Substrate for IIF for PV

A

Monkey esophagus

58
Q

Substrate for IIF for Pemphigus Foliaceous

A

Guinea pig

59
Q

Substrate for IIF for Paraneoplastic Pemphigus

A

Rat bladder

60
Q

Does ELISA measurement of desmogleins in a patient’s blood correlate with disease severity?

A

YES (so you can use it to monitor treatment)

61
Q

Species transmitting fogo de selvagem

A

Black fly (simulium spp)

62
Q

Black fly transmits what disease

A

Pemphigus Foliaceous fogo de selvagem type

63
Q

Most common associations with Paraneoplastic pemphigus (IN ORDER)

A

NHL > CLL > Castlemans > Thymoma

64
Q

Most common associated with Paraneoplastic Pemphigus in children

A

Castlemans disease

65
Q

Most common cause of death in paraneoplastic pemphigus

A

Death from malignancy OR Bronchiolitis obliterans (BOOP)

66
Q

Desmocollin targeted in:

A

IgA Pemphigus Subcorneal pustular dermatosis type

67
Q

Most common site of involvement of cicatricial pemphigoid

A

Oral >conjuctival

68
Q

What is Brunsting-Perry variant?

A

Variant of cicatricial pemphigoid without any mucosal involvement and alopecia

69
Q

What is the variant of cicatricial pemphigoid that has no mucosal involvement but has alopecia and is limited to the head and neck

A

Brungsting-Perry variant

70
Q

In which type of pemphigus/pemphigoid is IIF obsolete bc there are not a lot of circulating antibodies?

A

Cicatricial pemphigoid

71
Q

Treatment of choice for severe ocular cicatricial pemphigoid

A

Cyclophosphamide

72
Q

Most common cause of linear IgA

A

Vancomycin

73
Q

Antigen in Linear IgA

A

LAD1 (120kD cleaved protein of BPAG2)
AND
LABD97 (97kD cleaved protein of BPAG2)

74
Q

IgA in children

A

Chronic Bullous Dermatosis of Childhood

75
Q

What do you see on path for linear IgA

A

Neutrophils lined up along the DEJ

76
Q

Do indirect immunoflouresence levels correlate with disease activity in BP or PV?

A

PV - it does NOT correlate at all in BP

77
Q

Members of the Plakin family

A

Desmoplakin I,II
Envoplakin
Periplakin
BPAG1

(BPAG2 is a collagen)

78
Q

Where are Merkel cells located in the epidermis?

A

Stratum Basale

79
Q

This is a marker for proliferation activity located in the stratum basale

A

Ornithine decarboxylase

80
Q

Which keratins are expressed in the stratum basale?

81
Q

Mast cells express which cell markers

A

C-kit (Receptor and ligand)
CD34+ (derived from bone marrow)
CD13
C-KIT receptor (CD117)

82
Q

Which two cell types share a common progenitor cell type from the bone marrow of CD34?

A

Mast cells
Monocytes(blood)/Macrophages(skin)
Dermal dendrocytes

83
Q

Macrophage cell markers

A

CD11a
CD6
Fc receptor for IgG

84
Q

All TLRs except which one use the myd88 signaling pathway following activation

85
Q

Pain is detected by what kind of fibers?

A

Alpha-type fibers (large) or C-type fibers

86
Q

Are Merkel cells capsuleted or noncapsulated nerve ending fibers?

A

No encapsulated

87
Q

Merkel cells found in what cell layer?

A

Basal layer

88
Q

Which type of nerve endings are increased in concentration in the palms/soles/nipples/anogenital region?

A

Pasinian corpuscle (encapsulated nerve ending) which detect vibration

89
Q

Which nerve ending in non-encapsulated, looks like a pine cone, and detects LIGHT TOUCH

A

Meissner corpuscle

90
Q

Which nerve ending is encapsulated and detects continuous pressure

A

Ruffini corpuscle

91
Q

How long after an injury does it take for re-epithelialization to begin?

92
Q

How long after an injury does it take for fibroblasts to migrate to the wound?

93
Q

What type of collagen is the first to be formed in a healing wound?

94
Q

After a wound occurs, how long does it take for the TISSUE REMODELING phase to begin?

A

After the 3rd week

95
Q

The final strength of a healed wound has what percent strength of the original skin?

A

70-80% strength

96
Q

What is the strength of a scar at:
One week
Three weeks
One year?

A

One week: 5%
Three weeks: 20%
One year: 80%

97
Q

TLR activate which nucleolar pathway?

A

NFkB pathway (protein complex that controls transcription of DNA

98
Q

Corticosteroids downregulate which interleukin?

A

IL-1 (a proinflammatory cytokine)

99
Q

Name the 4 pro-inflammatory cytokines (as listed in Jain)

A

IL-1, IL-6, IL-18, TNF-alpha

100
Q

Which proinflammatory cytokine secreted by lymphoid cells and endothelial cells produces acute phase reactants, stimulates B cells into plasma cells, and increases neutrophil production?

101
Q

Which proinflammatory cytokine produced by activated T cells is an IFN-gamma inducing factor?

102
Q

What does IL-18 do?

A

Proinflammatory cytokine
Produced by activated T cells
Stimulates IFN-gamma

103
Q

IL-18 is produced by what kind of cells?

A

Activated T cells

104
Q

What non-IL, proinflammatory cytokine induces fever and catabolism, and releases other proinflammatory cytokines like IL-1, IL-6?

105
Q

What does TNF-alpha do?

A

It is a proinflammatory cytokine
Produced by T cells, phagocytes, mast cells, keratinocytes
Stimulates the release of other proinflam cytokines like IL-6,IL-1
Causes fever
Causes cachexia

106
Q

Which two cytokines induce a TH-1 response?

A

IL-12, INFy (gamma)

107
Q

Name the cytokines involved in the TH1 response

A

IL-2
IL-12
INFy
TNFa/b

108
Q

Name the cytokines involved in a TH2 response?

A 
IL-4 (class switching to IgE)
IL-5 (IgA, eos)
IL-6 (proinflammatory, B to plasma cells)
IL-9
IL-10
IL-13
109
Q

What does IL-2 do?

A

TH1 cytokine

  • T cell stimulator
  • increased growth and activation of T, NK, and B cells
110
Q

Which cytokine induces the growth of mast cells and basophils?

111
Q

IL-3 does what?

A

Induces the growth of mast cells and basophils

112
Q

What does IL-4 do?

A

TH2 cytokine

  • induces B cell class switching to IgE
  • increases MHCII production
113
Q

Which cytokine induces B cell class switching to IgE??

114
Q

Which cytokine is an IFN-alpha inducing factor?

115
Q

What does IL-18 do?

A

Proinflammatory cytokine, stimulates IFN-alpha

116
Q

CD19, CD20, CD79 are all markers for what type of cell?

A

B cell surface markers

117
Q

What type of cells express CD45RA?

A

Naive T cells express CD45RA while memory T cells express CD45RO. (*ROte memorization)

118
Q

Name the preformed proinflammatory mediators vs the newly formed:

A

Preformed: histamine, proteases, heparin

Newly formed: prostaglandin D2, leukotrienes C4/D4/E4, platelet activating factor, cytokines

119
Q

What chemical associated with taking ACE-I causes urticaria?

A

The release of bradykinin

120
Q

What common medication should you avoid if you have chronic urticaria?

A

Aspirin! It exacerbates chronic urticaria in 30% of people

121
Q

Most common causes of acute urticaria in

  1. Adults
  2. Children
A
  1. Adults: Idiopathic >URI > drugs (beta lactams)

2. Kids: viral

122
Q

Name some other syndromes chronic urticaria is associated with

A 
**autoimmune thyroid disease
Vitiligo 
IDDM
RA
H pylori gastritis
Parasite infections
123
Q

Most common type of physical urticaria

A

Dermatographism

124
Q

Keratin filaments of Basal layer

125
Q

What two locations in the skin are the epithelial stem cells located?

A

Interfollicular Basal layer
&
Bulge area of the hair follicle (these are only activated following injury)

126
Q

What substance is expressed by the basal layer which is a marker for proliferation activity (and is stimulated by UVB, and blocked by retinoic acid/Vit d3)

A

Ornithine decarboxylase (ODC)

127
Q

Ornithine Decarboxylase

A

Substance which is expressed in the basal layer, and is a marker for epithelial expression

128
Q

Name the cell structure which connects the basal layer to the basement membrane

A

HEMIDESMOSOME

129
Q

What does the hemidesmosome do?

A

Connects the basal layer to the basement membrane

130
Q

What percentage of cells in the basal layer are made up of stem cells?

131
Q

Keratinopathy in Psoriasis

A

K6/16

Remember K6a/16 is Pach Cong type I, and K6b/17 is Pach Cong Type II

132
Q

What keratins are found in the Granular layer?

133
Q

K2/10 found in what layer

A

Granular layer

134
Q

Which cornified cell envelope protein is upregulated in psoriasis?

A

Involucrin

135
Q

Involucrin is upregulated in psoriasis in all the cell layers except which one?

A

Basal layer

DERMATOLOGY (16 decks)

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