Skin Immunology and Biochemistry

Question 1

what 4 factors contribute to the skin’s effectiveness as a first line defence system?

Answer 1

structure - stratification, keratin layer
cell types - immune cells, keratinocytes
cytokines, chemokines, antimicrobial peptides
genetics

Question 2

what are the 2 components of immune defence?

Answer 2

non-specific (innate)
- first line
specific (adaptive)
- self limiting

Question 3

name 3 types of pathogenic immune responses

Answer 3

hypersensitivity
autoimmunity
immunodeficiency
autoinflammation

Question 4

what is the difference between autoimmunity and autoinflammation

Answer 4

autoimmunity = problem with adaptive immune system where it senses part of self as harmful and attacks
autoinflammation = problem with innate immune system where it reacts without cause or stimulation

Question 5

how does the keratin layer form?

Answer 5

lipid rich barrier formed by differentiation of keratinocytes to corneocytes

Question 6

what is present in the keratin layer?

Answer 6

filaggrin, involucrin, keratin,

Langerhans cells

Question 7

what are keratinocytes and where are they mainly found?

Answer 7

structural and functional cells of the epidermis

Question 8

what are 3 functions of keratinocytes?

Answer 8

• sense pathogens via receptors on cell surface and mediate an immune response
• produce antimicrobial peptides that directly kill pathogens
• produce cytokines and chemokines

Question 9

what are Langerhans cells?

Answer 9

type of dendritic cell found amongst keratinocytes in epidermis
main skin immune cell

Question 10

what is the function of Langerhans cells and how are they characterised?

Answer 10

antigen presenting cells

characterised by birbeck granules

Question 11

what type of T cells are found in the epidermis and the dermis?

Answer 11

epidermis = mainly CD8 T cells
Dermis = CD4 and CD8 T cells
other T cells like NK cells also found

Question 12

CD4 T cells become helper T cells, which ones are associated with psoriasis and atopic dematits?

Answer 12

psoriasis = TH1
atopic dermatitis = TH2
Combination of both = TH17

Question 13

where do T cells come from and where do they mature?

Answer 13

produced in the bone marrow

mature in the thymus

Question 14

what is involved in antigen recognition and T cell activation?

Answer 14

interaction with T cell receptor and MHC which is enhanced by co-receptors CD4 and CD8

Question 15

what is the role of CD4 cells?

Answer 15

helper T cells
TH1 = activate macrophages, IL2, IFN gamma
TH2 = help B cells make antibodies, IL4, IL5, IL6

Question 16

what is the role of CD8 cells?

Answer 16

cytotoxic T cells
directly kill infected cells
protect against viruses and cancer

Question 17

what is the role of interleukins?

Answer 17

communication between cells of the immune system

Question 18

what types of dendritic cells are found in the dermis and what do they do?

Answer 18

dermal DCs - Antigen presenting, secreting cyto/chemokines

plasmacytoid DCs - produce IFN alpha in diseased skin

Question 19

what cells are found in the dermis?

Answer 19

macrophages
neutrophils
mast cells
dendritic cells
T cells

Question 20

what do mast cells do in the dermis?

Answer 20

effectors of IgE mediated immunity (allergy) by releasing inflammatory mediators upon binding of IgE/drugs etc (eg - histamine)

Question 21

which chromosome encodes for major histocompatibility complex?

Answer 21

6

Question 22

what does MHC class I do?

Answer 22

found on all cells and presents proteins (either self or foreign antigens) on surface of cell which are detected by cytotoxic T cells

Question 23

what does MHC class II do?

Answer 23

found only on antigen presenting cells

presents foreign antigens to T helper cells

Question 24

what benefits and problems can occur with MHC?

Answer 24

benefits = anti-cancer mechanism
problem = transplant rejection

Question 25

name some skin conditions associated with inappropriate immune response

Answer 25

``` psoriasis atopic dermatitis eczema contact dermatitis urticaria SLE bullous pemphigoid skin infections/tumours ```

Question 26

what triggers the onset of psoriasis?

Answer 26

environmental trigger (trauma, stress, infection, drugs) in people who are genetically susceptible

Question 27

what are the hallmarks of psoriasis?

Answer 27

skin inflammation causing reversible plaques (red skin with overlying white scales) joint pain

Question 28

is psoriasis associated with immune defence?

Answer 28

yes | psoriasis = non-ending, accelerated immune response (mainly phase 2) resulting in plaques loaded with natural antibiotic

Question 29

describe the pathogenesis of psoriasis?

Answer 29

keratinocytes under stress release interleukins, TNF and factors that stimulate dendritic cells to produce IFN alpha these signals activate DCs which migrate to skin draining lymph node to present to T cells T cells are attracted to the dermis by chemokines and secrete ILs which stimulate keratinocyte proliferation

Question 30

what other factors play a role in psoriasis pathogenesis?

Answer 30

``` CD8 cells dermal fibroblasts (release growth factors for keratinocytes and epidermis) ```

Question 31

what 2 symptoms must be present in a diagnosis of eczema?

Answer 31

dry skin and overactive immune response to microbes causing itching etc

Question 32

what causes eczema?

Answer 32

impairment of skin barrier - mutation in filaggrin gene = cant bind water = dry skin - reduced anti-microbial peptide in skin allows access to allergen and promotes microbe colonisation

Question 33

what cells are involved in eczema?

Answer 33

``` TH2 dendritic cells keratinocytes macrophages mast cells ```

Question 34

give 3 autoimmune skin conditions

Answer 34

psoriasis vitiligo SLE

Question 35

what are the 2 types of immunodeficiency and give examples

Answer 35

``` primary = inherited defect (genetic) - DiGeorge syndrome Secondary = acquired - AIDS - malignancy - aging ```

Question 36

describe type 1 hypersensitivity

Answer 36

allergy (IgE mediated) 1st exposure produces IgE which binds to FcεR1 receptors on mast cells 2nd exposure = receptor crosslinking , signal transduction and mast cell degranulation

Question 37

what hypersensitivity is important in autoimmunity and transplantation?

Answer 37

type 2

Question 38

what mediates type 2 hypersensitivity?

Answer 38

antibodies | IgM and IgG

Question 39

what mediates type 4 hypersensitivity and what happens?

Answer 39

TH1 cells | T cell mediated response which then recruits other cells to site

Question 40

give examples of type 4 hypersensitivity

Answer 40

tuberculin reaction contact allergy (nickel) drugs