Skin & Immune Mediated Disease 2

Question 1

what are the cells and effector mechanisms in innate immunity

Answer 1

cells: sentinel cells –> macrophages, mast cells, dendritic cells

effector mechanims: inflammation, complement activation

Question 2

what are the important cells and effector mechanisms

Answer 2

cells: antigen presenting cells: dendritic cells, macrophages

effector mechanism: antibody-mediated (humoral immunity), cell-mediated, immunological memory

Question 3

how are innate and adaptive immunity linked

Answer 3

pathogens can be phagocytosed via primitive “non-specific” mechanisms

mononuclear phagocytes (monocyte/macrophages) can process antigen and “present” it to the immune system (ex. antigen presentation)

antigen presentation triggers the activation and expansion of –> 1. B cells producing antibody specific for the antigen 2. cytotoxic T cells are able to lyse cells infected with the pathogen

Question 4

what are the 2 key attributes that adaptive (acquired) immunity develops in response to antigens present on invading organisms

Answer 4

1. specificity
2. memory

Question 5

what are the skin immune systems

Answer 5

1. physicochemical barriers (stratum corneum, surface lipids, antimicrobial peptides –> defensins, cathelicidins)
2. skin microbiome (the commensal microorganisms in the skin, have an anti-inflammatory role, affect T cell maturation –> educate T cells, priming them to respond to similarly marked pathogenic cousins)

Question 6

how does the cornified envelope form

Answer 6

loricrin (80%), involucrin

filaggrin breaks down to amino acids (natural moisturizing factor)

Question 7

how does the lipid bilayer form

Answer 7

forms lipids –> extruded from lamellar bodies

Question 8

what rivets the corneocytes together

Answer 8

corneodesmosomes –> structural integrity

Question 9

what does filaggrin form from

Answer 9

profilagrin (keratohyalin granules) –> causes keratins to aggregate

lipids for in lamellar bodies

Question 10

what % of healthy stratum contains lipid

Answer 10

85% lipid

sphingolipids (ceramide)

cholesterol

free fatty acids

Question 11

what do sphingolipids and fatty acids contribute to

Answer 11

1. physical barrier
2. permeability barrier
3. immunologic barrier

Question 12

which cutaneous lipids have antimicrobial properties

Answer 12

sphingoid bases derived from epithelial sphingolipids

mechanisms are not fully understood

Question 13

what produces antimicrobial peptides

Answer 13

ex. defensins, cathelicidins

produced by neutrophils, macrophages, epithelial cells and by bacteria

Question 14

what is the function of antimicrobial peptides

Answer 14

1. activate and recruit inflammatory cells
2. alarm and arm keratinocytes

Question 15

what is the skin microbiome

Answer 15

the skin like the gut needs microbial signals and proper immune function

commensal microbes (ex. staph epidermidis) stimulate skin and immune cells to produce IL-1

IL-1 activates T cells which become more responsive to invading organisms

Question 16

what are the factors affecting skin microbiome

Answer 16

1. host physiology (sex, age, site)
2. environment (climate, geographical location)
3. immune system (previous exposures, inflammation)
4. host genotype (susceptibility genes such as filaggrin)
5. lifestyle (occupation, hygiene)
6. pathobiology (underlying conditions such as diabetes)

Question 17

what is the role of commensal bacteria (microbiome) in innate immunity

Answer 17

1. facrtors produced by commensal bacteria modulate the skin immune system
2. staphylococcus epidermidis produces –> antimicrobial peptides, small molecules which enhance expression of defensins

Question 18

what are the cells of the skin immune system

Answer 18

1. keratinocytes (squames)
2. dendtritic cells
3. mast cells
4. lymphocytes (T cells)

Question 19

what are the functions of keratinocytes (squames)

Answer 19

account for the majority of epidermal cells

mitosis of stem cells in s. basale

important in keratin production

Question 20

what are the function of dendritic cells

Answer 20

major role in antigen presentation

epidermal (Langerhan cells)

dermal

Question 21

what are the functions of mast cells

Answer 21

release histamine

Question 22

what are the function of lymphocytes (T cells)

Answer 22

various T-helper subsets

Question 23

what are chemokines and cytokines

Answer 23

chemokines: critical in T cell and macrophage recruitment
cytokines: arm effectors and direct the immune response

Question 24

what are the roles for keratinocyte

Answer 24

1. sentinel cell activate in host defence –> express pattern recognition receptors (PRRs) respond to DAMPs and PAMPs (associated with microbial invasion)
2. pro-inflammatory effector cell –> reacts to harmful insult –> producing a complex mixture of AMPs, pro-inflammatory cytokines and chemokines
3. non-proffessional antigen-presenting cell –> expresses MHC class II molecules can interact with antigen-experienced T cells

Question 25

what is the innate immune response to injury or pathogen invasion

Answer 25

1. release of primary cytokines --\> inflammation --\> upregulation of endothelial expression of adhesion molecules --\> recruitment of additional innate effector cells 2. activation of skin cells and resident innate immune cells --\> langerhan's cells & dermal dendritic cells carry antigen to draining lymph node

Question 26

what are the adaptive immune response in the skin

Answer 26

1. memory T cell carry TCRs specific for antigen previously encountered in skin 2. interaction of antigen specific T cells with APCs results in T cell activation 3. cytokines stimulate expression of T cell specific chemokine ligands on endothelium 4. T cells recruited by antigen non-specific mechanism

Question 27

what are langerhans cells and what is their function

Answer 27

epidermal dendritic cells dendritic cells link the innate and adaptive immune responses langerhans cells interact with skin resident memory T cells

Question 28

what is the response of the epidermis to injury

Answer 28

release of pro-inflammatory cytokines & growth factors by keratinocytes --\> altered proliferation & differention (hyperplasia, hyperkeratosis/parakeratosis)

Question 29

what is the response of the dermis to injury

Answer 29

stimulation of dermal inflammation (erythema, inflammatory edema, exudation) --\> release of secondary cytokines/growth factors promotes further change --\> antigen presenting cells interact with T cells

Question 30

what is the are epidermal responses to injury (7)

Answer 30

1. orthokeratotic hyperkeratosis 2. parakeratotic hyperkeratosis 3. hypergranulosis 4. acanthosis 5. hyperplasia 6. hyper- or hypopigmentation 7. lichenification

Question 31

what is orthokeratotic hyperkeratosis

Answer 31

increase in thickness of anuclear surface keratin

Question 32

what is this

Answer 32

orthokeratotic hyperkeratosis increase in thickness of anuclear surface keratin

Question 33

what is this

Answer 33

parakeratotic hyperkeratosis thickened keratin layer has retained nuclei

Question 34

what is this

Answer 34

hypergranulosis prominent granular layer associated with hyperkeratosis

Question 35

what is this

Answer 35

acanthosis broadening of the spinous (prickle cell) layer --\> often accompanies hyperplasia

Question 36

what is this

Answer 36

hyperplasia an increase in the number of cells often irregular

Question 37

what is this

Answer 37

altered pigmentation pigmentary incontinence

Question 38

what is this

Answer 38

lichenification hyperkeratosis, hyperplasia and dysplasia

Question 39

what are examples of direct traumatic skin disease

Answer 39

1. friction/pressure 2. chemical (irritant contact dermatitis) 3. heat (burns) 4. light (phototoxicity)

Question 40

what are the indirect causes of traumatic skin disease

Answer 40

metabolic (photosensitivity)

Question 41

what is self trauma

Answer 41

major contributing factor in the development and progression of skin disease in animals

Question 42

what is self-trauma a response to (2)

Answer 42

1. response to pruritus (or pain) --\> action of various mediators, epidermal & dermal sensory nerves 2. scratch reflex --\> spinal reflex, modulated by motor cortex neurons

Question 43

what is the itch-scratch cycle

Answer 43

Question 44

what is hairless plaques (acral lick dermatitis)

Answer 44

self trauma in skin disease also known as lick granuloma may reflect underlying pyoderma may be an indication of behavioural disturbance

Question 45

how do you distinguish orthokeratotic from parakeratotic hyperkeratosis

Answer 45

???

Question 46

are antimicrobial peptides good or bad

Answer 46

?

Question 47

what is the skin microbiome and how does it help

Answer 47

?

Question 48

what is this cell and what is its role in protection of the skin

Question 49

is this cell part of the innate or activated immune response

Answer 49

?

Question 50

which epidermal changes result in thickening of the skin

Answer 50

?

Question 51

which immune cell can be of myeloid or lymphoid origin

Answer 51

?

Question 52

what are the differential features of innate and adaptive immunity (self/non-self discrimination, lag phase, specificity, diversity, memory)

Answer 52

**innate:** self/non-self discrimination: present, reaction is against foreign lag phase: absent, response is immediate specificity: limited, the same response is mounted to a wide variety of agents diversity: limited, hence limited specificity memory: absent, subsequent exposures to agent generate the same response **adaptive:** self/non-self discrimination: present, reaction is against foreign lag phase: present, response takes at least a few days specificity: high, the response is directed only to the agents that initated it diversity: extensive, and resulting in a wide range of antigen receptors memory: present, subsequent exposures to the same agent induce amplified responses