immunology and the skin

Question 1

two immune systems in the body

Answer 1

innate (eoisnophils, basophils, NKCs, chemokines, neutrophils etc.); adaptive (B + T cells)

Question 2

what is an allergy

Answer 2

a bad clinical reaction by the immune system to environmental antigens (allergens)

Question 3

what is autoimmunity

Answer 3

Autoimmunity: a bad clinical reaction by the immune system to self-antigens (autoantigens)

Question 4

what are 5 types of hypersensitivity reactions

Answer 4

Type I: IgE-mediated immediate hypersensitivity reactions;
Type II: Antibody and complement-mediated cytotoxic reactions;
Type III: Immune complex-mediated disease;
Type IV: Cell-mediated delayed hypersensitivity reactions;
Type V: Antibody-mediated stimulatory hypersensitivity

Question 5

how does type I hypersensitivity occur and what can it lead to

Answer 5

allergy - caused by the binding of exogenous proteins (e.g. foods, drugs, plant or animal) to allergen-specific IgE fixed to tissue mast cells or circulating basophils causing release of proinflammatory mediators, including histamine;
Leadsto immediate swelling reactions such as urticaria or anaphylaxis

Question 6

how does type II hypersensitivity occur and what can it lead to

Answer 6

specific IgG or IgM antibody binding antigens on the cell surface leading to cell damage by terminal components of complement (e.g. thrombocytopenia due to drugs), phagocytes or NK cells;
This is a less common cause of skin problems

Question 7

how does type III hypersensitivity occur and what can it lead to

Answer 7

complexes of specific IgG or IgM antibody aggregating with an antigen (e.g. drug, autoantigen or infection) and lodging in the walls of small blood vessels causing complement activation, inflammatory cell infiltration and tissue damage;
leads to vasculitis

Question 8

how does type IV hypersensitivity occur and what can it lead to

Answer 8

primed T-lymphocytes attracted by the presence of specific antigen to the site of inflammation;
Examples of this include allergic contact dermatitis, some drug reactions and the Mantoux test

Question 9

how does type V hypersensitivity occur and what can it lead to

Answer 9

applied to autoimmune thyroid disease where the antibody stimulates rather than inhibits the receptor for TSH and also to autoimmune urticaria where mast cell degranulation is stimulated by an antibody against the IgE receptor

Question 10

3 general rules to hypersenitivity reactions in the skin

Answer 10

1. immunological reactions cause disease by promoting inflammation;
2. inflammation leads to different clinical patterns of disease;
3. a pattern of disease may be caused by more than one type of immunological reaction

Question 11

what is urticaria

Answer 11

characterised by short-lived itchy swellings that may be superficial (weals) or deep (angio-oedema); it may last a few days (in which case it may be allergic) or many months (usually autoimmune)

Question 12

autoantibodies for what have been seen in urticaria and what does the binding cause

Answer 12

bind either the high affinity IgE receptor (FcεRI) on mast cells or basophils or IgE bound to the FcεRI, causing release of histamine and other mediators of inflammation

Question 13

how do weals occur

Answer 13

mast cell degranulation (due to allergen/antibody binding + histamine release) leading to temporary leakage of plasma from capillaries

Question 14

what hypersensitivity reaction causes urticaria

Answer 14

type I (immediate hypersensitivity due to allergen) and type V (stimulatory hypersensitivity due to an autoantibody)

Question 15

what is bullous pemphigoid

Answer 15

an acquired blisteing condition of the skin (and sometime mucous membranes too)

Question 16

what autoantibodies are involved in bullous pemphigoid and how do they react

Answer 16

autoantibodies (mainly IgG4) in junctional adhesion complexes called hemidesmosomes holding the epidermis and dermis -> Bind to BP180 or 230 antigens -> complement activation with attraction of N and Eos -> damage the basement membrane zone and lead to separation of the epidermis from the dermis -> blister

Question 17

what type of hypersensitivity reaction is bullous pemphigoid

Answer 17

Type II reaction where autoantibodies and complement lead to cytotoxic damage of living cells causing disease

Question 18

if vasculitis affects the skin, what kind of BVs are normally affected

Answer 18

capillaries + venules i.e. small vessel vasculitis

Question 19

4 possible triggers for vasculitis

Answer 19

drug, infection, cancer or an autoantibody

Question 20

vasculitis pathophysiology

Answer 20

antibody binds the antigen to form soluble immune complexes -> circulate in the blood until they adhere to the lining of small blood vessels due, perhaps, to changes in blood flow -> cascade of events leading to complement activation with formation of anaphylatoxins C3a and C5a -> degranulate nearby skin mast cells -> recruitment of white blood cells -> damage to the blood vessel wall and leakage of RBCs into the skin causing bruising

Question 21

what 4 classical symptoms are seen in Henoch-Schonlein purpura (a small vessel vasculitis)

Answer 21

rash, arthritis, abdominal pain, and haematuria -> small vessel vasculites generlaly affect the skin, joints, kidneys and gut

Question 22

what type of hypersensitivity reaction is vasculitis

Answer 22

type III

Question 23

how does allergic contact dermatitis occur (pathway)

Answer 23

chemicals/metal salts absorbed into the skin -> internalised and presented via APCs (Langerhans cells) -> activated APC travels in lymphatics to a regional lymph node -> presents processed antigen via its MHC class II receptor -> promotes activation and maturation of effector cells (predominantly CD8+ in ACD -> clonal expansion of these lymphocytes occurs -> circulate in the blood ready to move into the skin because they now express the skin homing marker, cutaneous lymphocyte antigen (CLA) -> MCH I presenting with this antigen causes activation and release of cytokines that cause inflammation and activate other cells e.g. karatinocytes -> allergic dermatitis

Question 24

what type of hypersensitivity reaction is allergic contact dermatitis

Answer 24

type IV - delayed reaction

Question 25

what can exacerbate vasculitis

Answer 25

cold temperatures

Question 26

What GI condition can present with rash

Answer 26

Coeliac’s - dermatitis herpitiforimis