immunology and the skin Flashcards
two immune systems in the body
innate (eoisnophils, basophils, NKCs, chemokines, neutrophils etc.); adaptive (B + T cells)
what is an allergy
a bad clinical reaction by the immune system to environmental antigens (allergens)
what is autoimmunity
Autoimmunity: a bad clinical reaction by the immune system to self-antigens (autoantigens)
what are 5 types of hypersensitivity reactions
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
how does type I hypersensitivity occur and what can it lead to
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
how does type II hypersensitivity occur and what can it lead to
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
how does type III hypersensitivity occur and what can it lead to
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
how does type IV hypersensitivity occur and what can it lead to
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
how does type V hypersensitivity occur and what can it lead to
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
3 general rules to hypersenitivity reactions in the skin
- immunological reactions cause disease by promoting inflammation;
- inflammation leads to different clinical patterns of disease;
- a pattern of disease may be caused by more than one type of immunological reaction
what is urticaria
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)
autoantibodies for what have been seen in urticaria and what does the binding cause
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
how do weals occur
mast cell degranulation (due to allergen/antibody binding + histamine release) leading to temporary leakage of plasma from capillaries
what hypersensitivity reaction causes urticaria
type I (immediate hypersensitivity due to allergen) and type V (stimulatory hypersensitivity due to an autoantibody)
what is bullous pemphigoid
an acquired blisteing condition of the skin (and sometime mucous membranes too)
what autoantibodies are involved in bullous pemphigoid and how do they react
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
what type of hypersensitivity reaction is bullous pemphigoid
Type II reaction where autoantibodies and complement lead to cytotoxic damage of living cells causing disease
if vasculitis affects the skin, what kind of BVs are normally affected
capillaries + venules i.e. small vessel vasculitis
4 possible triggers for vasculitis
drug, infection, cancer or an autoantibody
vasculitis pathophysiology
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
what 4 classical symptoms are seen in Henoch-Schonlein purpura (a small vessel vasculitis)
rash, arthritis, abdominal pain, and haematuria -> small vessel vasculites generlaly affect the skin, joints, kidneys and gut
what type of hypersensitivity reaction is vasculitis
type III
how does allergic contact dermatitis occur (pathway)
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
what type of hypersensitivity reaction is allergic contact dermatitis
type IV - delayed reaction
