Immunology - Immunology of the Skin

Question 1

What 4 factors contribute to the skin as an immunological system?

Answer 1

Genetics
Structure (keratin layer, stratification)
Cell types (immune cells, keratinocytes)
Chemical signals/ molecules (cytokines, chemokines, eicoanoids, antimicrobial peptides

Question 2

What are cytokines?

Answer 2

Proteins that are involved in cell communication

Question 3

What are chemokines?

Answer 3

Chemical messengers that induce chemotaxis

Question 4

What are eicosanoids?

Answer 4

Signalling molecules made by oxidation of 20-Carbon fatty acids

Question 5

What is an antigen?

Answer 5

a protein/ peptide or polysaccharide that elicits an immune response

Question 6

What is hypersensitivity?

Answer 6

over reaction to antigen

Question 7

What is autoimmunity?

Answer 7

Reaction to host tissue

Question 8

What is the stratum corneum made up of?

Answer 8

Corneocytes (terminally differentiation keratinocytes)

Question 9

What are 3 important structural proteins in the keratin layer?

Answer 9

Filaggrin
Involucrin
Keratin

Question 10

What is filaggrin?

Answer 10

Filament-associated protein that binds to keratin

Question 11

What does involucrin do?

Answer 11

Contributes to formation of cell envelope that protects corneocytes

Question 12

How do keratinocytes in the epidermis sense pathogens?

Answer 12

Via cell surface - then help mediate an immune response

Question 13

What 2 things (other than pathogens) can activate keratinocytes in the epidermis leading to an immune response?

Answer 13

UV

Sensitisers (e.g. contact dermatitis)

Question 14

What can keratinocytes in the epidermis produce that can kill pathogens directly?

Answer 14

Anti-microbial peptides (AMPs)

Question 15

In what condition are AMPs found in high levels in the skin?

Answer 15

Psoriasis

Question 16

What do keratinocytes in the epidermis produce that recruit and regulate cells of the adaptive and innate immune system?

Answer 16

Cytokines and chemokines

Question 17

Where are Langerhans cells found?

Answer 17

Interspersed with keratinocytes in the epidermis

Question 18

What is the main skin resident immune cell?

Answer 18

Langerhans cells

Question 19

What organelle is characteristic of Langerhans cells?

Answer 19

Birbeck granule

Question 20

What type of immune cell are Langerhans cells?

Answer 20

Dendritic cells - antigen presenting cells

Question 21

What shape are Birbeck granules?

Answer 21

“tennis-racket” cytoplasmic organelle

Question 22

What do Langerhan cells do?

Answer 22

“Keep watch” in the epidermis
Process lipid Ag and microbial fragments and present them to effector T cells
Help to activate T cells

Question 23

What type of T lymphocytes are located in the epidermis?

Answer 23

Mainly CD8+ (Killer) T cells

Question 24

What type of T lymphocytes are located in the dermis?

Answer 24

CD4+ and CD8+ T cells

Other subsets of T cells are also found e.g. NK cells

Question 25

What type of CD4+ Th cells are associated with psoriasis?

Answer 25

Th1 and Th17

Question 26

What type of CD4+ Th cells are associated with atopic dermatitis?

Answer 26

Th2 and Th17

Question 27

What interleukin does Th17 produce?

Answer 27

Interleukin 17

Question 28

What are interleukins?

Answer 28

A group of cytokines expressed by WBCs

Question 29

Where are T cells produced?

Answer 29

Bone marrow

Question 30

Where are T cells sensitised?

Answer 30

Thymus

Question 31

What does Ag recognition and T cell activation involve integration with?

Answer 31

T cell receptor (TCR) and major histocompatibility complex (MHC) - this is enhanced by co-receptors

Question 32

What do Th1 T cells do? what do they release (2)?

Answer 32

Activate macrophages to destroy micro-organisms - release IL2 and IFNgamma

Question 33

What do Th2 cells do? What do they release (3)?

Answer 33

Help B cells to make Ab, release IL4, IL5 and IL6

Question 34

What is the purpose of CD8+ cytotoxic T cells?

Answer 34

To kill infected cells directly | Important protection against viruses and cancer

Question 35

What are 2 examples of dendritic cells found in the dermis?

Answer 35

Dermal dendritic cell | Plasmacytoid dendritic cell (pDC)

Question 36

What are dermal dendritic cells involved in?

Answer 36

Ag presenting and secreting cyto/ chemokines

Question 37

What is the purpose of plasmacytoid dendritic cells?

Answer 37

Ag presenting and to produce IFNalpha -> found in diseased skin

Question 38

Apart from dendritic cells, what 3 other immune cells are present in the dermis?

Answer 38

Macrophages Neutrophils Mast cells

Question 39

What attracts circulating neutrophils to tissue?

Answer 39

Chemokines

Question 40

What cells are the effects of IgE-mediated immune response?

Answer 40

Mast cells

Question 41

What happens when IgE binds to mast cells?

Answer 41

Activation of the mast cell and release of inflammatory mediators

Question 42

What are 4 examples of pre-formed mediators released from mast cells?

Answer 42

Tryptase Chymase TNF Histamine

Question 43

What are examples of newly synthesised mediators released from mast cells?

Answer 43

IL (3, 5, 6, 8, 13, 16, 18), TNF, TGFbeta, PGD2, PGE2, LTB4, LTC4, VEGF, bFGF, IP-10, MIP-1alpha, MIP-1beta

Question 44

Apart from IgE, what else can activate mast cells? (3)

Answer 44

Physical trauma, certain drugs, micro-organisms

Question 45

What chromosome is the gene for MHC found?

Answer 45

Chromosome 6

Question 46

Where are class 1 MHC found?

Answer 46

On almost all cells

Question 47

What is the purpose of class 1 MHC?

Answer 47

To present Ag to cytotoxic T cells - present endogenous Ag

Question 48

What is the purpose of class 2 MHC?

Answer 48

To present exogenous Ag to Th cells

Question 49

Where are Class 2 MHC found?

Answer 49

On APC (B cells, macrophages)

Question 50

Skin conditions associated with inappropriate immune response/ inflammation? (9)

Answer 50

``` Skin infection Skin tumours Psoriasis Atopic dermatitis Bullous pemphigoid Contact dermatitis Morphea/ systemic sclerosis Urticaria Systemic lupus erythematous ```

Question 51

Give 3 examples of autoimmune skin conditions?

Answer 51

Psoriasis Vitiligo Systemic lupus erythematous

Question 52

What mediates type 1 hypersensitivity?

Answer 52

IgE - immediate

Question 53

What happens in type 1 hypersensitivity?

Answer 53

Early exposure to allergen causes the production of IgE, which binds to FceRI receptor on mast cells Laster exposure causes rapid cross linking of the receptors, signal transduction and degranulation of mast cell

Question 54

What 2 time frames of responses are involved in type 1 hypersensitivity?

Answer 54

Very rapid early response = minutes (wheal and flare) | Later réponse = hours (cellular infiltration, nodule)

Question 55

What mediates type 2 and 3 hypersensitivity?

Answer 55

Antibodies - IgG and IgM

Question 56

What conditions are type 2 hypersensitivity important in?

Answer 56

Auto-immunity and transplantation e.g. haemolytic disease the newborn

Question 57

What type of reaction does skin testing in type 3 hypersensitivity lead to?

Answer 57

Arthus reaction- slow than type 1 but faster than type 4

Question 58

What mediates type 4 hypersensitivity?

Answer 58

Th1 cells - delayed type hypersensitivity based on a t cell resoles which then recruits other cells to the site

Question 59

2 examples of a type 4 hypersensitivity reaction?

Answer 59

Tuberculin reaction | Contact allergy

Question 60

when does a type 4 hypersensitivity reaction peak?

Answer 60

24 - 48 hours after exposure

Question 61

How does ageing affect skin immunity?

Answer 61

Changes in skin structure = easier access Decreased ability to detect malignant cells Decreased ability to detect Ag = infection risk Decreased ability to detect self from non-self = autoimmunity

Question 62

Non-immune cells of the epidermis?

Answer 62

Keratinocytes | Melanocytes

Question 63

Immune cells of the epidermis?

Answer 63

``` Langerhans cells T cells (Esp. CD8+ cells) ```

Question 64

Immune cells in the dermis?

Answer 64

Dendritic cells Macrophages NK cells T cells (CD4+ and CD8+)

Question 65

Non-immune cells in the dermis?

Answer 65

Fibroblasts | Lymph/ vasculature