Bafl Exam 1: Embryo, Immune System And Growth/differentiation

Front 1

TWO, FOUR, SIX, EIGHT WHO DO WE APPRECIATE?!

SKIN! SKIN! SKIN!! What happens embryologically at weeks 4, 6, 8, (1)2?

Back 1

4 Weeks: epidermis is a single layer of flattened cells (ectoderm)

6 Weeks: epidermis becomes bilayered with inner basal layer an douter non keratinizing periderm

8 Weeks: epidermal stratification begins and the stratum intermedium is produced (p63 is responsible for this); appearance of melanocytes, langerhans cells, merkel cells (Jain says Merkels are at 8-12 weeks, lecture says they start at 12 weeks)

12 Weeks: formation of DEJ (starts at 12 per Jain, fully formed at week 19 per lecture), nail bed starts to keratinize, proximal nail fold forms

Front 2

All the sweet embryologic skin stuff happens pretty early on, but some fun things happen at weeks 20-26, what are they?

Back 2

Week 20-22: granular layer is present, Melanin starts to transfer at 22

Week 24-26: all 4 layers present and mature epidermis is complete!, forehead is the first interfollicular surface to keratinize (nail bed is the first nonfollicular surface)

Front 3

By the end of what trimester does the dermis shift from non scarring to scarring wound repair?

Back 3

BY THE END OF THE SECOND TRIMESTER

Front 4

What is the ration of collagen III: collagen I in early embryogenesis? Adults?

Back 4

Embryo collagen III: collagen I --> 3:1

Adult collagen III: collage I --> 1:3

Front 5

Barrie function of neonatal skin is not complete until when?

Back 5

3 weeks post partum

Front 6

Melanocytes are derived from what origin? What about keratinocytes? Merkel cells?

Back 6

Melanocytes are from neural crest cells

Keratinocytes are from ectoderm

Merkel cells are from ectoderm

Front 7

buzz word: birbeck granules

Back 7

langerhans cells

Front 8

Keratinocytes comprise 80-85% of epidermal cells. What is their estimated turn over time?

Back 8

Lecture: 47 days = 19 days of basal cell division + 14 days from basal to granular layer + 14 days to migrate through corneum

Jain: 45-60 days = 30-50 days from basal to stratum corneum + 14 days to migrate through corneum

Front 9

As keratinocytes move up the epidermis, they flattn, lose their organielles, and acquire higher MW keratins. What are the two subtypes of keratins?

Back 9

Type I: K9-K20, acidic, smaller MW( 40-57kDa)... terrible, but I think of a small dog drinking acid... he's number 1 right?

Type II: K1-K8, basic, larger MW (52-67kDa)

Front 10

Memorize the chart on keratin parings and diseases

Back 10

I like the one in Jain better than the lecture one... remember the dance

Front 11

Disease associated with: K1/K10

Back 11

Epidermolytic hyperkeratosis, Unna-Thost palmoplantar keratoderma

Front 12

Disease associated with: K1/K9

Back 12

Palmoplantar expression: Vorner PPK

Front 13

Disease associated with: K2/K10

Back 13

granular/upper spinous layer: Icythyosis bullosa of Siemens

Front 14

Disease associated with: K3/K12

Back 14

cornea: Meesman corneal dystrophy

Front 15

Disease associated with: K4/K13

Back 15

Mucosa: white sponge nevus

Front 16

Disease associated with: K5/K14

Back 16

basal keratinocytes: EBS, Dowling-Degos disease

Front 17

Disease associated with: K6a/16

Back 17

outer root sheath: Pachyonychia congenita I

Front 18

Disease associated with K6b/17

Back 18

nail bed: Pachyonychia congenita II

Front 19

Disease associated with K8/18

Back 19

simple epithelium: Cryptogenic cirrhosis

Front 20

What are the three locations o fepidermal stem cells?

Back 20

hair bulge, sebaceous glands, basal layer

bulge stem cells are the most primitive and are capable of replenishing the stem cells of th eentire pilosebaceous unit

Front 21

Where does new synthesis of K1/K10 occur?

Back 21

Stratum spinosum

Front 22

Stratum granulosum is responsible for producing the corneal envelope. What is the corneal envelope and what is it used for?

Back 22

Corneal envelope is a highly crosslinked , lipid rich flexible structure enveloping corneocytes that serves as an insoluble exoskeleton and rigid scaffold for internal keratin filaments

Assembly of CE begins in the granular layer where several proteins are crosslinked by transglutaminase into an insoluble structure

The CE contains keratohyalin granules that give you a lot of LIP: loricrin, involucrin, profilagggrin

Front 23

Which component of the cornified envelop is upregulated in psoriasis?

Back 23

Involucrin

Front 24

Mutations in what part of the corneal envelope could be a risk factor for atopic dermatitis?

Back 24

FILLAGRIN! one mutation increases risk of AD x 6, two mutations increases risk x 15

Front 25

What is Vohwinkel syndrome? What mutations are present in Vohwinkel syndrome?

Back 25

Vohwinkel syndrome (aka Keratoderma hereditaria mutilans, Mutilating palmoplantar keratoderma) is a diffuse AD keratoderma with onset in early infancy characterized by a honeycombed keratoderma and starfish keratosis involving the palmoplantar surfaces. Mild to moderate sensorineural hearing loss.

LORICRIN, GJB2

Front 26

What is an average epidermal melnin unit?

Back 26

1 melanocyte feeds 36 keratinocytes --> melanosomes are membrane organelles made within melanocytes, transported into dendritic processes via actin/dynein dependent transport and are phagocytized by neighboring KCs

Once melanosomes enter the KC, they are distributed as a cap over the nucleus, protecting it from UV damage

Front 27

What are the two types of melanin produced by melanocytes?

Back 27

Eumelanin- brown/black, ellipitcal and lamellar

Pheomelanin- yellow/red, spherical, less organized

Front 28

What is piebalism?

Back 28

c-kit mutation, features white forelock, depigmented patches with islands of sparing

Front 29

What stains are used for langerhans cells? Why are they so important?

Back 29

LC are the antigen presenting cells in the epidermis, they stain with CD1a, S100, Langerin, peanut agglutinin

These are reduced in psoriasis, sarcoidosis, and contact derm

**functionally impaired by UV radiation (UVB)

Front 30

Where are eccrine glands located? Control?

Back 30

located everywhere except vermillion lips, nail bed, labia minora and glans deep at the dermal/SQ junction

Under sympathetic cholinergic control stimulated by acetylcholine by postganglionic sympathetic fibers

Front 31

Apocrine glands are located where?

Back 31

Coiled glad in the dermis/SQ, straight duct empties into the isthmus of hair follicle

Take your eyes and ears to the PTA meeting:

eyelids (Moll's), external auditory canal, pits, tits, ass

Front 32

Where are sebaceous glands located?

Back 32

everywhere except palms and soles

associated with hair follicles except on nipple (montgomery), labia minora and prepuce (tysons), vermillion border, buccal mucosa (fordyce spots), eyelids (meibomian glands)

Front 33

What are the 4 areas of the BMZ?

Back 33

1. Basal keratinocyte

2. Lamina lucida- transmembrane portion of the HD interacts with laminins via integrins and BPAG-2

3. Lamina densa- Laminins 5, 6, 10 and interaction with type IV collagen

4. Sublamina densa- transition zone between BM and dermis, anchoring fibrils composed of type VII collagen

Front 34

What is the most common amino acid in collagen?

Back 34

GLYCINE

Front 35

Collagen types I-VII. What diseases can happen if they are messed up?

Back 35

I: STRONG, mc collagen in body, bones, scars, messed up in OI

II: cartilage and vitreous humor of the eye (slippery), messed up in polychondritis

III: vascular endothelium, keloids, early wound healing, messed up in EDS

IV: basal lamina/BM, messed up in Alports and Goodpastures

V: most interstitial tissue and adult dermis, messed up in EDS

VI: interstitial tissue, messed up in AD

VII: anchoring fibrils in DEJ, messed up in dystrophic epidermolysis bullosa

Front 36

What cross links collagen peptide chains?

Back 36

LYSYL OXIDASE

Front 37

Elastin is intertwined among collagen. There are two types of elastic fibers, what are they?

Back 37

Oxytalan- run perpendicular to DEJ

Elaunin- run parallel to DEJ

Front 38

What is ground substance?

Back 38

amorphous material that fills the space between collagen bundles, consists of glycosaminoglycans

Front 39

Accumulation of glycosaminoglycans occurs in many conditions... name a few

Back 39

lupus, myxedema, follicular mucinosis

Front 40

What are the differences between Meissner's corpuscles and Pacinian corpuscles?

Back 40

Meissners- responsible for fine touch, look like a pine cone, palms and soles

Pacinian- responsible for vibration and pressure, looks like pearl onion, palms and soles

Front 41

Which macromolecules are in the hemidesmosome of the BMZ?

Back 41

BPAG1 (230kDa), BPAG2 (180kDa), a6B4 integrin, plectin

Front 42

Which macromolecules are in the lamina lucida?

Back 42

Anchoring filaments! Laminin, portion of BPAG2

Front 43

What macromolecules are in the lamina densa?

Back 43

Anchoring plaques! Type IV collagen, laminins, heparin sulfate

Front 44

What macromolecules are in the sublamina densa?

Back 44

Anchoring fibrils! Type VII collagen, fibrillin, type IV collagen (anchoring plaque)

Front 45

How does tyrosine convert to pheomelanin or eumelanin?

Back 45

Tyrosine --> DOPA --> DOPAquinone --> pheomelanin or eumelanin

first two reactions catalyzed by copper and tyrosinase

Front 46

How does retinoic acid affect collagen synthesis?

Back 46

STIMULATES IT

Front 47

Make up of collagen?

Back 47

Triple helix contains Gly-x-y

Glycine is always the third residue, x frequently proline, y hydroxylysine or hydroxyproline

Front 48

Which neuropeptides are found in merkel cells?

Back 48

Neuron specific enolase (NSE), vasoactive intetinal peptide (VIP), calcitonin gene related peptide (CGRP), chromogranin A, synaptophysine, met-enkephalin

Front 49

Dermis is composed of:

Back 49

collagen

elastin

ground substance

glomus cells

Front 50

What is the difference between oxytalan fibers and eulanin fibers of elastic tissue?

Back 50

Oxytalan- thin fibers running perpendicular to skin surface in papillary dermis

Eulanin- thick fibers running parallel to skin surface in reticular dermis

Front 51

What are the nociceptors for pain in nerves that feed the skin?

Back 51

A(delta) bype fibers or C fibers

Front 52

How does the shape of the follicle dictate hair growth?

Back 52

Oval follicle gives curly hair

Round follicle gives straight hair

Front 53

What are the nonencapsulated nerve endings?

Back 53

Merkel cells- in basal layer, detects touch

Front 54

What are the encapsulated nerve endings?

Back 54

Pacinian corpuscles- deep pressure and vibration, palms/soles, nips, butt

Meissners corpuscles- light touch, highest density in palmoplantar skin

Ruffini- slow adapting receptors, detects continuous pressure

Front 55

Why are bacterial infections so much more common in AD than in psoriasis?

Back 55

levels of hBD-2 and LL37 are decreased in AD and increased in psoriasis

Front 56

What are the three stages of wound healing?

Back 56

1. Inflamation- first 6-8 hours, clot formation, then neutrophils and macrophages come in and debride wound

2. Granulation tissue formation- 5-7 days, keratinocyte re-epithelialization and granulation tissue formation and angiogenesis

3. Tissue remodeling- after third week, granulation tissue initially composed of type III collagen gradually replaced by type I

Front 57

What are the pattern recognition molecules?

Back 57

complement, toll like receptors, NOD-LRR domains (nucleotide oligomerization domains)

Front 58

What are toll like receptors?

Back 58

TLR are part of innate immunity, expressed on/in many immune cells, including keratinocytes, dendritic cells, monocytes, macrophages, B cells --> they are receptors that recognize PAMPs (pathogen associated microbial proteins), activation releases tons of cytokines

Front 59

What pathway do TLR typically use to generate inflammatory cytokines?

Back 59

MyD88/NFkB --> protein complex that controls transcription of DNA, involved in responses to stress, free radicals, UV

Front 60

What does TLR2 detect? What are our synthetic TLR7? TLR8?

Back 60

TLR2: p.Acnes

synthetic TLR7: imiquimod

synthetic TLR8: resiquimod

Front 61

What are NODs? What are they detecting specifically?

Back 61

Also recognize PAMPs (pathogen associated molecular pattern), but these detect INTRACELLULAR bacteria (opposed to TLRs)

Front 62

What disorder is due to a NOD2 deficiency? What about a NOD2 activating mutation?

Back 62

NOD2 deficiency: Listeria infections

NOD2 activation: Chrons

Front 63

What are the antimicrobial peptides? (learned 4 in lecture, there's probably tons)

Back 63

Antimicrobial peptides are small cationic peptides produced by immune cells that disrupt microbial membrane (death), increase inflammatory mediators, and upregulate CCR6, thereby calling in skin T cells

EXAMPLES:

- human beta defensins

- canthelicidins

- dermicidin

- psoriasin

Front 64

Most human beta defensins (antimicrobial peptide) are inducible when in the presence of microbes. Which is the only one that is constitutive?

Back 64

HBD1- kills gram negative organisms... this is probably why all that skin crap is gram positive

Front 65

Antimicrobial peptides are down regulated in what disease process? Up regulated?

Back 65

Antimicrobial peptides (specifically HBD2 and LL37) are down regulated in AD (that's why there are so many superficial infections)

Antimicrobial peptides (specifically HBD2 and LL37) are up regulated in psoriasis

Front 66

What specific human beta defensin is altered in AD? In Psoriasis?

Back 66

HBD2 is downregulated in AD, upregulated in psoriasis

Front 67

What specific canthelicidin is altered in AD? Psoriasis?

Back 67

LL-37 is downregulated in AD, upregulated in psoriasis

Front 68

There are three complement pathways... but what is the end goal?

Back 68

Complement consists of classical, alternative and lectin pathways, ALL of them activate C3convertase --> C5convertase --> MAC complex

Front 69

Keratinocytes are AWESOME!!! They produce antimicrobial peptides, pathogen receptor proteins and tons of cytokines and chemokines. What cytokines do keratinocytes NOT produce?

Back 69

they do NOT produce:

IL-2 (p/b activated T cells)

IL-4 (p/b Th2 cells)

INF-y (p/b T cells and NK cells)

They produce everything else, so it's easier to remember it like this

Front 70

Which interleukin is a potent stimulator of neutrophils?

Back 70

IL-8

Front 71

Which IL induces B cell class switching to IgE? Which one is an eosinophil stimulator?

Back 71

IL4 stimulated IgE class switch

IL5 stimulated eosinophils (and IgA)

Front 72

Which IL stimulated myeloid cells and basophil production?

Back 72

IL3

Front 73

How do NK cells determine which cells are the bad guys?

Back 73

MHC Class I molecules are often lost in tumor or viral infected cells --> NK targets this

Front 74

Langerhans cells are bound to keratinocytes by what?

Back 74

E-cadherin... this is the marker for immature LHC

Front 75

Which cell marker is exclusive to langerhans cells?

Back 75

CD1a

also has S100, langerin (CD207)

Front 76

What happens during langerhans cell maturation?

Back 76

- Upregulation of MHC class II on surface

- Upregulation of CD40, CD80, CD86

- Downregulation of E cadherin

- Migration to lymph nodes

Front 77

What APC express MHC I vs MHC II? Broadly, what type of pathogens do they go after?

Back 77

Vast majority of nucleated cells express MHC I molecules --> these are used for primarily endogenous and intracellular (virus, tumor) pathogens

MHC II is super dependent on LC, B cells, monocytes/macrophages --> primarily targets exogenous and extracellular (bacteria, parasites) pathogens

Front 78

What are the Th1 diseases?

Back 78

Make a PACT with Th1!

Psoriasis

Allergic contact dermatitis

Cutaneous leishmaniasis

Tuberculoid leprosy

Front 79

What are the Th2 diseases?

Back 79

LAPS D

Lepromatous leprosy

Atopic dermatitis

Parasitic infections

Sezary syndrome

Disseminated leishmaniasis

Front 80

All T cells express what CD? What is specific to helper and cytotoxic?

Back 80

All T cells express CD3

Cytotoxic express CD8 (MHC I)

Helper express CD4 (MHC II)

Front 81

There are several interactions between T cells and APC cells. What are the CD28 interactions?

Back 81

CD28 is on the T cell, it interacts with CD80 and CD86 on the APC and induces expression of antiapoptotic proteins and T cell proliferation

Front 82

There are several interactions between T cells and APC cells. What are the CD 2 interactions?

Back 82

CD2 is on the T cell, it interacts with LFA3 on the APC, promotes T cell prolifertion and cytotoxic activity

Front 83

There are several interactions between T cells and APC cells. What are the ICAM-1 interactions?

Back 83

ICAM-1 is on the T cell, it interacts with LFA-1 on the APC

Front 84

What is the CD40/CD40 ligand interaction? Why do we care?

Back 84

CD40 is on Th2 and mast cells, it binds to CD40L on B cells, APCs and endothelial cells, this promoted B cell proliferation and differentiation and isotype switching