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)
2
Q
What level of the epidermis are keratohyaline granules found?
A
Stratum granulosum
3
Q
What substances do keratohyaline granules (present in stratum granulosum) contain?
A
Profilaggrin, loricrin, and involucrin
4
Q
Where is fillagrin located?
A
Stratum Granulosum
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)
6
Q
Where is filaggrin located?
A
In the keratohyaline granule in the stratum granulosum
7
Q
Keratins found in the stratum granulosum
A
K2 and K10 (K11)
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
9
Q
What is the major protein component of the cornified envelope?
A
Loricrin
10
Q
What enzyme crosslinks all the protein peptide bonds loricrin and involucrin to make the cornified envelope?
A
Transglutaminase 3
11
Q
What are the two major proteins that make up the cornified envelope?
A
Involucrin and loricrin (fillagrin is the glue)
12
Q
Which cornified envelope protein is the substrate for transglutaminase
A
Involucrin (this is the one that is upregulated in psoriasis)
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)
14
Q
Substrate for transglutaminase in the cornified envelope
A
Involucrine
15
Q
Upregulated in all layers in Psoriasis except basal
A
Involucrin
16
Q
Components of the basal layer (as a part of the DEJ)
A
Keratins K5/K14
17
Q
K5/K14
A
Basal layer keratinocytes, part of the BMZ complex/DEJ
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)
19
Q
Collagen XVII
A
Same thing as BPAG II
20
Q
What collagen is found in the lamida Lucida/basal layer
A
Collagen XVII - same thing as BPAG II
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)
22
Q
What type of collagen is found in the lamida densa?
A
Collagen IV
23
Q
Type IV collagen found where?
A
Lamina Densa
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)
25
Major components of the sublamina densa
```
Type VII collagen
Type III collagen
Type I collagen
Elastin
Fibrillin
Latent TGB-beta proteins
```
26
Where is type VII collagen found?
Sublamina densa
27
Major protein comprising Anchoring Fibrils?
Type VII Collagen
28
What are anchoring fibrils made of and where are they found?
Made of Type VII collagen and they are found in the sublamina densa
29
What protein connects the lamida lucida to the lamina densa?
Laminin 332 (Laminin 5)
30
Members of the plakin family
```
Plectin
BPAG 1
BPAG 2
Envoplakin
Desmoplakin
Periplakin
```
31
Major function of plectin
Attaches keratin filaments in the basal layer to the anchoring filaments in the hemidesmisome
32
Mutation in plectin causes what disease
EB with muscular dystrophy
33
How many kD is BPAG1?
230kD
34
Which is intracellular and which is a transmembrane protein:
BPAG 1
BPAG 2
BPAG 1 - intracellular
| BPAG 2 -transmembrane
35
How many kD is BPAGII?
180kD
36
How many kD is the EXTRACELLULAR portion of BPAGII?
120kD
37
Name 4 diseases that target BPAG2?
Bullous Pemphigoid
Pemphigoid Gestationis
Linear IgA Bullous Dermatosis
Cicatricial Pemphigoid
38
Which part of the BPAG2 protein does BP, Pemphigoid Gestationis, and Linear IgA target?
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
39
Which disease targets the carboxy terminus of BPAGII?
Cicatricial pemphigoid
40
What genetic disease has a defect in BPAG2 (BP180)
Non-Herlitz Junctional EB (widespread bulla at birth, heals with atrophic scarring, alopecia, improves with time)
41
Aquired disease, and genetic disease caused by mutation in integrin subunit beta-4
Aquired disease - cicatricial pemphigoid with ocular involvement
Congenital - Junctional EB with pyloric atresia
42
Genetic & Aquired disease caused by mutation in Laminin-5 (332)
Genetic - Junctional EB, Herlitz type
| Aquired - anti-epiligrin cicatricial pemphigoid
43
Type VII Collagen genetic and aquired disorders
Genetic: ALL Dystrophic EBs
Aquired: EB Aquisita, Bullous lupus
44
What is the only type of protein that is present in both adherents junctions AND desmosomes?
Plakoglobin (mutated in Naxos)
45
What cell transmembrane protein do Langerhans Cells use to connect with keratinocytes
E Cadherins
46
Name the armadillo proteins
B-Catenin
Plakoglobin
Plakophilin
47
Name the caderhins
```
Desmogleins
Desmocollin
E caderhin
P cadeherin
N caderhins
```
48
Which are quick but weak cellular adhesions
Adherens junctions
49
Which are slow but strong intracellular junctions
Desmosomes
50
DSG4 is mutated in what disease
AR Monolethrix
51
Do antibodies of mothers with Pemphigus vulgaris cross the placenta?
How about pemphigus foliaceous?
Yes PV antibodies cross the placenta and cause blisters
NO in Pemphigus foliaceous they do not cross the placenta
52
What desmogleins are expressed in neonatal skin
DSG3
53
Most common sites of PV involvement in the mouth?
Buccal mucosa and palatal mucosa
54
What is mutated in Striate PPK 1
DSG-1
55
Mutation in Striate PPK 2
Desmoplakin
56
Mutation in Striate PPK3
Keratin 1
57
Substrate for IIF for PV
Monkey esophagus
58
Substrate for IIF for Pemphigus Foliaceous
Guinea pig
59
Substrate for IIF for Paraneoplastic Pemphigus
Rat bladder
60
Does ELISA measurement of desmogleins in a patient's blood correlate with disease severity?
YES (so you can use it to monitor treatment)
61
Species transmitting fogo de selvagem
Black fly (simulium spp)
62
Black fly transmits what disease
Pemphigus Foliaceous fogo de selvagem type
63
Most common associations with Paraneoplastic pemphigus (IN ORDER)
NHL > CLL > Castlemans > Thymoma
64
Most common associated with Paraneoplastic Pemphigus in children
Castlemans disease
65
Most common cause of death in paraneoplastic pemphigus
Death from malignancy OR Bronchiolitis obliterans (BOOP)
66
Desmocollin targeted in:
IgA Pemphigus Subcorneal pustular dermatosis type
67
Most common site of involvement of cicatricial pemphigoid
Oral >conjuctival
68
What is Brunsting-Perry variant?
Variant of cicatricial pemphigoid without any mucosal involvement and alopecia
69
What is the variant of cicatricial pemphigoid that has no mucosal involvement but has alopecia and is limited to the head and neck
Brungsting-Perry variant
70
In which type of pemphigus/pemphigoid is IIF obsolete bc there are not a lot of circulating antibodies?
Cicatricial pemphigoid
71
Treatment of choice for severe ocular cicatricial pemphigoid
Cyclophosphamide
72
Most common cause of linear IgA
Vancomycin
73
Antigen in Linear IgA
LAD1 (120kD cleaved protein of BPAG2)
AND
LABD97 (97kD cleaved protein of BPAG2)
74
IgA in children
Chronic Bullous Dermatosis of Childhood
75
What do you see on path for linear IgA
Neutrophils lined up along the DEJ
76
Do indirect immunoflouresence levels correlate with disease activity in BP or PV?
PV - it does NOT correlate at all in BP
77
Members of the Plakin family
Desmoplakin I,II
Envoplakin
Periplakin
BPAG1
(BPAG2 is a collagen)
78
Where are Merkel cells located in the epidermis?
Stratum Basale
79
This is a marker for proliferation activity located in the stratum basale
Ornithine decarboxylase
80
Which keratins are expressed in the stratum basale?
K5/14
81
Mast cells express which cell markers
C-kit (Receptor and ligand)
CD34+ (derived from bone marrow)
CD13
C-KIT receptor (CD117)
82
Which two cell types share a common progenitor cell type from the bone marrow of CD34?
Mast cells
Monocytes(blood)/Macrophages(skin)
Dermal dendrocytes
83
Macrophage cell markers
CD11a
CD6
Fc receptor for IgG
84
All TLRs except which one use the myd88 signaling pathway following activation
TLR-3
85
Pain is detected by what kind of fibers?
Alpha-type fibers (large) or C-type fibers
86
Are Merkel cells capsuleted or noncapsulated nerve ending fibers?
No encapsulated
87
Merkel cells found in what cell layer?
Basal layer
88
Which type of nerve endings are increased in concentration in the palms/soles/nipples/anogenital region?
Pasinian corpuscle (encapsulated nerve ending) which detect vibration
89
Which nerve ending in non-encapsulated, looks like a pine cone, and detects LIGHT TOUCH
Meissner corpuscle
90
Which nerve ending is encapsulated and detects continuous pressure
Ruffini corpuscle
91
How long after an injury does it take for re-epithelialization to begin?
HOURS
92
How long after an injury does it take for fibroblasts to migrate to the wound?
48 hours
93
What type of collagen is the first to be formed in a healing wound?
Type III
94
After a wound occurs, how long does it take for the TISSUE REMODELING phase to begin?
After the 3rd week
95
The final strength of a healed wound has what percent strength of the original skin?
70-80% strength
96
What is the strength of a scar at:
One week
Three weeks
One year?
One week: 5%
Three weeks: 20%
One year: 80%
97
TLR activate which nucleolar pathway?
NFkB pathway (protein complex that controls transcription of DNA
98
Corticosteroids downregulate which interleukin?
IL-1 (a proinflammatory cytokine)
99
Name the 4 pro-inflammatory cytokines (as listed in Jain)
IL-1, IL-6, IL-18, TNF-alpha
100
Which proinflammatory cytokine secreted by lymphoid cells and endothelial cells produces acute phase reactants, stimulates B cells into plasma cells, and increases neutrophil production?
IL-6
101
Which proinflammatory cytokine produced by activated T cells is an IFN-gamma inducing factor?
IL-18
102
What does IL-18 do?
Proinflammatory cytokine
Produced by activated T cells
Stimulates IFN-gamma
103
IL-18 is produced by what kind of cells?
Activated T cells
104
What non-IL, proinflammatory cytokine induces fever and catabolism, and releases other proinflammatory cytokines like IL-1, IL-6?
TNF-alpha
105
What does TNF-alpha do?
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
Which two cytokines induce a TH-1 response?
IL-12, INFy (gamma)
107
Name the cytokines involved in the TH1 response
IL-2
IL-12
INFy
TNFa/b
108
Name the cytokines involved in a TH2 response?
```
IL-4 (class switching to IgE)
IL-5 (IgA, eos)
IL-6 (proinflammatory, B to plasma cells)
IL-9
IL-10
IL-13
```
109
What does IL-2 do?
TH1 cytokine
- T cell stimulator
- increased growth and activation of T, NK, and B cells
110
Which cytokine induces the growth of mast cells and basophils?
IL-3
111
IL-3 does what?
Induces the growth of mast cells and basophils
112
What does IL-4 do?
TH2 cytokine
- induces B cell class switching to IgE
- increases MHCII production
113
Which cytokine induces B cell class switching to IgE??
IL-4
114
Which cytokine is an IFN-alpha inducing factor?
IL-18
115
What does IL-18 do?
Proinflammatory cytokine, stimulates IFN-alpha
116
CD19, CD20, CD79 are all markers for what type of cell?
B cell surface markers
117
What type of cells express CD45RA?
Naive T cells express CD45RA while memory T cells express CD45RO. (*ROte memorization)
118
Name the preformed proinflammatory mediators vs the newly formed:
Preformed: histamine, proteases, heparin
Newly formed: prostaglandin D2, leukotrienes C4/D4/E4, platelet activating factor, cytokines
119
What chemical associated with taking ACE-I causes urticaria?
The release of bradykinin
120
What common medication should you avoid if you have chronic urticaria?
Aspirin! It exacerbates chronic urticaria in 30% of people
121
Most common causes of acute urticaria in
1. Adults
2. Children
1. Adults: Idiopathic >URI > drugs (beta lactams)
| 2. Kids: viral
122
Name some other syndromes chronic urticaria is associated with
```
**autoimmune thyroid disease
Vitiligo
IDDM
RA
H pylori gastritis
Parasite infections
```
123
Most common type of physical urticaria
Dermatographism
