Hypersensitivity Flashcards
Define hypersensitivity
The Ag-specific immune responses that are either inappropriate or excessive and result in harm to host
Outline the diff types of hypersensitivity reactions
(A) Type 1 = Allergy, Ab mediated, IgE, membrane bound Ag
(B) Type 2 = Ab mediated, IgG/M, soluble Ab
(C) Type 3 = immune complex mediated, IgG/M
(D) Type 4 = cell mediated, delayed
What are the phases of hypersensitivity reaction?
Sensitisation phase = first encounter with Ag, activation of APCs and memory effector cells
Effector phase = pathologic reaction on re-exposure
Define type 1 hypersensitivity
immediate <30mins
Allergy
IgE = MAST CELL ACTIVATION
Abnormal TH2 response
Give examples of allergens that will set off an type 1 hypersensitivity reaction
Pollens
Dust mites, cats, dogs
Fungal spores
Insect venom
Medicines
Latex
Food: milk, nuts
What is the mechanism for type 1 hypersensitivity?
Abnormal adaptive immune response = TH2, IgE prod
Mast cell activation = sensitised pts, location determines disorder
What is the hygiene hypothesis?
Children exposed to animals, pets, microbes in the early postnatal period appear to be protected against certain allergic diseases
What is the biodiversity hypothesis?
Western lifestyle induces alternation of the symbiotic relationships with parasites and bacteria leading to dysbiosis (compositional and functional alterations of microbiome) of the microbiome at mucosal surfaces
What is a mast cell?
Activated by IgE cross linked BY ALLERGEN
MEDIATORS =
- histamine = vasodilation, increased V permeability
- heparin = increased V permeability
- leukotrienes = increased V permeability, mucus prod
- tryptase = remodel CT matrix
- platelet-activating factor = attract leukocytes
- TNF alpha = promotes inflam
Location = GI, skin, resp, CT surrounding blood cells
Outline the immune mechanism of an allergic reaction
Allergen 1st exposure - TH2 response
Allergen 2nd response = IgE cross-linking BY ALLERGEN
= mast cell degranulation
= increased vascular permeability, vasodilation, bronchial constriction
When is urtucaria seen?
Activation of mast cell in the EPIDERMIS
When in angioedema seen in allergic reactions?
Activation of mast cells in the DEEP DERMIS
Describe the manifestations of anaphylaxis
systemic activation of mast cells =
- Hypotension, cardiovascular collapse
- Generalised urticaria
- Angioedema
- Breathing problems
What therapy is available for type 1 hypersensitivity?
Allergen desensitisation
Anti-IgE monoclonal Ab
Against mast cell activation
- Anti-histamine
- Leukotriene receptor antagonist
- Corticosteroids
ADVICE = avoid allergen, carry anti-histamines, consider desensitisation, regular cleaning, do not smoke
Define allergen desensitisation
Increasing doses of allergen extracts over a period of years
given to pts by injection or drops/tablets under the tongue (sublingual)
Outline type 2 hypersensitivity reactions
5-12 hrs
IgG/M Ab
Targets cell bound Ag (exogenous: blood group Ag, rhesus A Ag) (endogenous: self Ag)
Induced diff outcomes = tissue/cell damage, physiological change
Outline the type 2 hypersensitivity mechanism
Compliment activation = MAC, neutrophil activation, opsonisation
Ab-dependent cell cytotoxicity = IgG
Give an example of tissue/cell damage caused by type 2 hypersensitivity
Haemolytic transfusion reaction = incompatibility in ABO group or rhesus D
Haemolytic disease of the newborn = rhesus D incompatibility
How can haemolytic disease of the newborn be prevented?
Give IgG anti-RhD after 1st preg
Outline therapeutic approaches for tissue/cell damage caused by T2 hypersensitivity
Immune suppression
Plasmapheresis
Splenectomy
Intravenous immunoglobulin
Outline type 3 hypersensitivity reactions
3-8hrs
Immune complexes between IgG/M and Ag
Targets soluble Ag
Tissue damage caused by immune complex deposition
In T3 hypersensitivity where can IC be deposited?
Joints
Kidney
Small vessels
Skin
What key actors affect immune-complex pathogenesis?
Complex size = small and large cleared, intermediate persist
Host response
Local tissue factors
Give an examples of diseases caused by type 3 hypersensitivity
RA
Glomerulonephritis
SLE
Outline type 4 hypersensitivity
Delayed = 24-72 hrs
Involves lymphocytes, macrophages
Subtypes: contact (epidermal reaction), tuberculin (dermal reaction), granulomatous (persistent Ag, wall of the infected cell)
Outline the mechanism of tissue destruction in type 4 hypersensitivity
Sensitisation phase = APCs activating TH1
Effector phase = TH1 activating macrophages
What diseases are caused by type 4 hypersensitivity to exogenous Ags?
Granulomatous = Tb, leprosy
Contact = nickel, poison ivy
What disease are caused by type 4 hypersensitivity to endogenous Ags?
Autoimmune = DM, hashimotos
Outline the therapy available for type 3 and type 4
Anti-inflam drugs
Monoclonal Abs
How is anaphylaxis managed?
epipen = adrenaline = vasoconstriction
oxygen
IV anti-histamines
