Hypersensitivity Reactions Flashcards
What is a hypersensitivity reaction
An antigen specific immune response that is either inappropriate or excessive and results in harm to the host
What are the types of hypersensitivity reactions
Type I - immediate, antibody dependent. Allergy. IgE drives reaction
Type II - antibody mediated. IgG or IgM drives reaction. Triggered by self-antigen
Type III - immune complex mediated. IgG or IgM drives reaction. Triggered by self-antigen
Type IV - cell mediated. Delayed. Triggered by self-antigen
Describe the two phases in a hypersensitivity reaction
Sensitisation phase - first encounter with antigen. Have activation of APCs and memory effector cells. No clinical manifestation
Effector phase - pathological reaction upon re-exposure to same antigen. Activation of memory cells of adaptive immunity. Clinical manifestation
Describe what causes type I hypersensitivity reactions
Type I is caused by an antigen/allergen. Either local or systemic reaction. Antigens are enviromental
Have abnormal, adaptive immune response against allergens
Have TH2 activation instead of TH1 activation against the allergen whihc results in TH2 sending signals to produce IgE against the antigen
IgE causes mast cell activation - sensitisation
Describe the immune mechanism in type I hypersensitivity reactions
On first exposure to the allergen, there is production of IgE specfiic antigen by plasma cells
IgE binds to mast cells, arming them for re-exposure
Upon re-exposure of the antigen, the antigen cross links the IgG bound to the mast cell which stimulates signals in the cell to cause degranulation
What does the release of inflammatory mediators from mast cells
Increased vascular permeability
Vasodilation
Bronchial constriction
Name some manifestations of an allergic reaction
Urticaria - ithcy, raised wheals surrounded by erythema. Caused by mast cell activation within the epidermis
Angioedema - caused by mast cell activation deep in the dermis
What is anaphylaxis and what are some signs and symptoms
Anaphylaxis - systemic manifestation of an allergic reaction
Sudden and rapid progression and involves more than 2 body systems
Signs and symptoms: hypotension, cardiovascular collapse, angioedema, breathing difficulty, generalised urticaria
How does adrenaline help to treat anaphlyaxis and what mechanisms does it act by
Reverses peripheral vasodilation, reduces oedema and allervaites hypotension by acting on alpha-1 receptors
Reverses airway obstruction/bronchospams - beta-2 receptors
Increases force of heart contraction - beta-1 receptors
Inhibits mast cell activation and degranulation
What is the treatment for type I hypersensitivty
Anti-IgE monoclonal antibody
Immunotherapy - inhibit TH2 response
Anti-histamines, leukotriene receptor antagonists, corticosteriods - inhibit mast cell activation
What are the two outcomes from type II hypersensitivity reactions and name some conditions in each outcome
Tissue/cell damage
- Exogenous - haemolytic disease of newborn, transfusion reaction
- Endogenous - autoimmune haemolytic anaemia, thrombocytopenia purpura, Goodpasture’s disease
Physiological changes
- Receptor stimulation - Grave’s disease
- Receptor blockade - Mysathenia gravis
How does tissue/cell damage occur with type II hypersensitivity reactions
Antibody (IgG/IgM) binds to the antigen to cause complement activation
This causes cell lysis via membrane attack complexes, neutrophil recruitment/activation and opsonisation
There is also antibody-dependent cell cytotoxicity by natural killer cells
What is haemolytic transfusion reaction
Life threatening condition caused by incompatibility in the ABO or rhesus D antigens that results in RBCs being destroyed by the recipients immune system
Describe haemolytic disease of the foetus and newborn
A condition where the mother is rhesus negative while the father is rhesus positive
The Rh -ve mother carrys a Rh +ve foetus and then during delivery, Rh antigens from developing foetus enter mother’s blood
Mother produces anti-Rh antibodies - IgG
If women becomes pregnant with another Rh +ve foetus then her anti-Rh antibodies can cross the placenta and damage the foetal RBCs causing cell lysis so baby is born with HDFN
What is given to mothers to prevent HDFN
RhoGam/Anti-D is given to mothers after their baby is born
Anti-D isolates the Rh D antigen and clears it away by activating the innate immune system against the Rh D antigen so the body clears it before an acquired immune response can develop
What is the treatment for type II hypersensitivity reactions
Tissue/cell damage - anti-inflammatory drugs, IVIG, plasmapheresis, splenectomy
Physioloical change - correct metabolism and replacement therapy
Describe type III hypersensitivity reactions
Usually develop within 3-8hrs and is caused by immune complexes between IgG/IgM and antigens
Complexes circulate in the blood and are deposited in host tissue resulting in tissue damage and inflammation
The immune complexes are deposited in tissues, activating complement which causes neutrophil chemotaxis, adherence and degranulation
Name some factors affecting the pathogenesis of type III hypersensitivity reactions
Immune complex size - intermediate complexes cannot be cleared by the body so have increased risk of causing type III hypersensitivity reaction
Host response - low affintiy antibodies favour production of intermediate immune complexes
Local tissue factors - complexes often deposited in areas with high blood flow
Name some conditions caused by a type III hypersensitivity reaction
Rheumatoid arthritis - rheumatoid factor which deposits everywhere
Glomerulonephritis
Systemic lupus erythematosus - antigen is Ds-DNA. Have multi-organ inflammation
Describe type IV hypersensitivity reactions
Usually develops within 24-72hrs
Involves lymphocytes and macrophages
Different subgroups - contact, tuberculin and granulomatous hypersensitivity
In sensitisation phase there is production of TH1 cells against trigger/antigen and then upon re-exposure, TH1 cells recognise trigger and produce inflammatory factors that trigger macrophage activation which then causes localised tissue damage
What is contact hypersensitivity and give some examples
Type IV hypersensitivity reaction where there is an epidermal reaction in response to haptens that bind to endogenous proteins to cause a reaction
E.g. nickel, poision ivy, organic chemicals
What is granulomatous hypersensitivity and give some examples of some diseases of this type
Occurs 21-48 days post exposure where there is tissue damage as a result of a large number of granuloma formation in the tissue
E.g. TB, schistosomiasis, sarcoidosis
What is the treatment for type III and type IV hypersensitivity reactions
Anti-inflammatory drugs - non-steriodals corticosteroids
Monoclonal antibodies - against B and T cells, cytokine network or APCs
What is myasthenia gravis and describe the pathophysiology behind it
An autoimmune neuromuscular condition characterised by skeletal muscle weakness
There are antibodies against AChR produced which bind to nicotinic receptors on muscle end plates and prevent ACh binding so the end plate cannot be activated
This means no action potential can occur in the muscle so there is no muscle contraction
New-borns will have symptoms if mother has myasthenia gravis as anti-AChR antibodies from mother can cross placenta during pregnancy
What is given to treat myasthenia gravis and how does it work
Pyridostigmine
It is an acetylcholinesterase inhibitor that binds to AChesterase to reduce degradation of ACh so its levels in the synaptic cleft can rise high enough to cause an AP in the muscle
Name some signs and symptoms of myasthenia gravis
Droopy eyelids
Muscle fatigue quickly during exercise
Symmetrical weakness with normal muscle tone
Normal sensation and normal tendon reflexes
Difficulty chewing and swallowing
Slurred speech
Shortness of breath
Name some signs and symptoms of systemic lupus erythematosus
Butterfly rash and red patches on skin
Endocarditis
Pleuritis
Haematuria
Anaemia
Hypertension
Muscle and joint pain
Swollen joints
Severe abdominal pain
Alopecia
High fever
Headache
