Hypersensitivity Flashcards
What is hypersensitivity?
Hypersensitivity is more commonly known as
allergy or autoimmunity
When immune system responds in an exaggerated or inappropriate way
resulting in harm
Usually occurs on second or subsequent
exposure to antigen
Hypersensitivity is a characteristic of the
individual (genetic susceptibility)
Hypersensitivity is a growing problem in the general population
- large ↑ in children suffering from asthma in children children suffering suffering from asthma
- large ↑ in allergic diseases among adults
Hypersensitivity is a growing problem in the dental surgery
Dentists and nurses becoming increasingly sensitised to: Latex Dental materials Patients increasingly sensitised to: Latex Dental materials Drugs used in the surgery
Acquired immunity consists of
Antibody Response (humoral humoral response)
Cell-mediated response
Both involved in Hypersensitivity reactions
Antibody responses
Antigen uptake Antigen processing Antigen presentation T cell help B cells proliferate -form plasma cells -produce antibody
Properties of antibody responses
Occur quickly Are often systemic or widespread This is because antibodies are soluble proteins that can reach most parts of proteins proteins that can reach most parts of the body quickly via: Blood Tissue fluids Body secretions
Cell mediated immunity - 1st exposure to antigen
1st exposure to antigen
Antigen uptake
Antigen processing
Antigen presentation in the context of MHC
T cell binds and becomes activated
Activated T cell proliferates
To form many antigen specific memory T cells that patrol the body
Cell mediated immunity - 2nd exposure to antigen
T cell recognises antigen expressed on target cell in context of MHC
T cell responds by releasing cytokines and/or killing the target cell (apoptosis)
Cell mediated immunity directed mainly against
Cellular targets e.g.
- tumour cells
- virally transformed cells
- foreign cells
Cellular immune responses tend to be
- localised
- slow to develop
- slow to resolve
Failure of the immune system
Fail to produce an adequate immune response Immunodeficiency Produce an overactive, damaging response Hypersensitivity Hypersensitivity - allergy
Hypersensitivity is divided into
4 Types (I - IV) Type I - Immediate/ anaphylaxis Type II - Cytotoxic Type III - Immune complex -type I, II, III antibody mediated Type IV - Delayed -cell mediated -examples of all 4 may occur in the dental setting
Type I or immediate hypersensitivity
Acute hypersensitivity (anaphylaxis)
Rapid onset
IgE mediated
-people susceptible to type 1 hypersensitivity have high IgE levels
Type I hypersensitivity: allergen
Is an Ag that give rise to Type 1 Hypersensitivity
Most allergens are small (10 -40 kDa) proteins
Examples of type 1 hypersensitivity allergens
Proteins Der p 1&2 - dust mite faeces Fel d 1 - cats Rat n1 - rats Pollen - grass
Type I hypersensitivity cells
Mast cells and basophils
- FCE receptors on surface
- histamine granules inside cells
- ->IgE binds to FcE receptor
- ->on second exposure to antigen, antigen cross-links that Fc receptors
- ->histamine released –> IL-5 –>eosinophils
Mast cell degranulation
Histamine and enzyme release (tryptase and chymase)
Histamine release causes
Vascular dilation ↑ Vascular permeability i.e. oedema Bronchospasm Urticarial rash – nettle rash nettle rash ↑ nasal and lacrimal secretions
Type I hypersensitivity responses most commonly present as
Hay fever Asthma Acute allergic responses: Angiodema/ anaphylaxis e.g. Latex allergy Local anaesthetic allergy Bee venom Peanut
Type I hypersensitivity responses most commonly present as
Hay fever Asthma Acute allergic responses: Angiodema/ anaphylaxis e.g. Latex allergy Local anaesthetic allergy Bee venom Peanut
Diagnosis of type I hypersensitivity
Wheel and Flare Skin Test -apply small amount of allergen just under skin using prick test. -skin response is fast (5 min) WHEEL caused by extravasation of serum into skin due to histamine – angio-odema. FLARE (erythematous red patch) caused by axon reflex. Late Phase (6 h+) due to leukocyte infiltrate + more odema
Type I hypersensitivity - Asthma
Allergen e.g. pollen leads to mast cell degranulation and mass histamine release
- chemotactic factors (TNFalpha and IL-5) lead to release of substances in blood stream
- spasmogens (histamine, leukotrienes, postaglandins) lead to bronchocontriction
- cell infiltrate from blood stream leads to mucus hypersecretion, increased muscle and chronic bronchospasm
Type I hypersensitivity - management
Adrenaline (epinephrine)
Antihistamines
Corticosteroids
Avoidance of allergen
Type II hypersensitivity
Antibody mediated hypersensitivity -antibodies target cell surface self antigens (auto-antibodies) Usually IgG or IgM The antibodies induce Cell damage Inflammation
Type II hypersensitivity mechanism ***
Antibodies target self antigen (auto-antibodies)
Autoantibodies activate either:
-ADCC (antibody dependent cell cytotoxicity) - K cell, Neutrophil, Macrophage
–>cell death and inflammation
-complement
–>complement activation results in inflammation and cell death (MAC)
Type II hypersensitivity responses are important in
Acute transplant rejection / blood transfusion Haemolytic Disease of the Newborn Autoimmune diseases e.g. Pemphigus Pemphigoid
Type II hypersensitivity - Haemolytic Disease of the Newborn
- First Pregnancy - RhD+ foetal blood enters RhD maternal
circulation - Baby born BUT mother raises Ab to RhD
- Second Pregnancy – If foetus is foetus is RhD+ mother + mother IgG crosses placenta and
will destroy foetal
erythrocytes - SO – preformed anti-RhD Ab given to Rh- mothers immediately after delivery of RHD+ infants.
Type II hypersensitivity - Pemphigus
Auto-antibodies against desmoglein-1&3
Ab prevents formation of gap junctions
between epithelial cells
Epithelial shedding – mainly mucosal
Type II hypersensitivity - pemphigoid
Auto-antibodies against hemidesmosomes
Ab prevents binding of epithelium with dermis at basement membrane
Epithelial shedding – skin and mucosal
Type III hypersensitivity
Immune complex-mediated hypersensitivity
Immune complexes form between antigen and antibodies
These complexes form in the serum
-so different from type II - which are cell-based
Type III hypersensitivity - immune complexes may deposit in
Lining of BVs
Glomeruli
Lung
Type III hypersensitivity - here they induce
Complement activation
Leukocyte binding
Inflammation
Type III hypersensitivity as trigger for > vascular permeability
- Immune complexes normally bind C’. This binds to CR1 on erythrocytes which are removed in the liver.
- In inflammation, immune complexes bind to BVs where they act on platelets and Basophils
- These are then activated and
release vasoactive peptides (histamine) - This > vascular
permeability
Type III hypersensitivity - deposition of immune complexes in BV walls
1. Increased vascular permeability allows more immune complexes to be deposited 2. Induced platelet aggregation and C’ activation – (C5a & C3a - leukocyte chemotaxis) 3. Neutrophils attracted but cannot ingest complexes 4. The secrete lysosomal enzymes causing further tissue damage
Type III hypersensitivity - immune complex mediated hypersensitivity is important in
Immune complex mediated vasculitis e.g.
- erythema multiforme
- systemic luous erythematosus (SLE)
Type III hypersensitivity treatment
Immunosuppression with steroids
Type III Type III Hypersensitivity - Erythema Multiforme
Common skin condition mediated by deposition of immune complex in superficial microvasculature of skin and oral mucous membrane that usually follows infection or drug exposure. Often has classical "target lesion" appearance.
Type IV hypersensitivity
Cell-mediated immunity/ delayed type hypersensivity Mediated by T cells As response is cellular it is usually -slow to develop (12-48hrs) -slow to resolve -localised
Type IV hypersensitivity mechanism
Cell mediated hypersensitivity T cell recognises antigen expressed on another cell in context of MHC T cell responds by: -releasing cytokines -killing targets cell
Type IV hypersensitivity cell mediated immune responses are important in
Delayed type hypersensitivity responses
Contact hypersensitivity - e.g. dermatitis
Lichenoid reactions to amalgam fillings and other materials
Type IV hypersensitivity - contact dermatitis
Sensitisation
- Ag gets into skin and is internalised by Langerhans cells - special APC in epidermis
- These travel to lymph nodes and rpesent Ag to CD4+ T cells
- These form memory CD4+ T cells
Type IV hypersensitivity steps (contact dermatitis)
1 Langerhans cells move from epidermis to dermis (Elicitation Phase)
2. They present Ag to memory CD4+ T cells
3. These are activated and
secrete IFNγ.
4. This > expression of ICAM-1 and MHCII on Keratinocytes
5. Causes secretion of proinflammatory
cytokines
6. More leukocytes attracted to site
7. Neutrophils arrive after 4 h, monocytes & T cells after monocytes and T cells after
12 h & secrete tissue
damaging cytokines
-tissue damage seen at post 12h (delayed)
-tissue damage resolved if Ag
removed
Type IV hypersensitivity tests
Skin patch testing
-samples applied to skin of back or arm for 72-96 hours
Denture acrylic allergy
Type IV reaciton to chemicals (Benzoyl peroxide + formaldehyde) that used to make dentures
Red areas due to uncontrolled inflammation and tissue damage
Epithelial thickening due to leukocytes, inflammation and proliferating keratinocytes trying to repair damage
Lichenoid reaction to amalgam
Type IV contact hypersensitivity response to mercury or amalgam Lesions closely associated with amalgam fillings Positive skin patch test response to mercury or amalgam Lesion resolves on removing filling
