Lec 3 - hypersensitivity Flashcards
Contrast the mechanisms of Types I, II, III and IV hypersensitivity.
- Define the roles of allergen, IgE, mast cells, inflammatory cells, mediators and cytokines in Type I hypersensitivity.
- Explain the pathophysiology of early and late phase allergic reactions.
- Define atopy.
- Illustrate the clinical effects of Type I Hypersensitivity.
1) Define the roles of antibody, complement, Fc receptor bearing cells and ADCC in Type II hypersensitivity.
2) Illustrate the clinical effects of Type II hypersensitivity.
- Define the pathophysiology of immune complex formation in localised and systemic Type III hypersensitivity.
- Explain the factors involved in formation of abnormal immune complexes.
- Illustrate the clinical effects of Type III hypersensitivity.
- Define the roles of haptens, carrier proteins, Th1 cells, Th17 cells, antigen presenting cells and monocytes/macrophages in Type IV hypersensitivity - SEE SLIDE 8 AGAIN
- Illustrate the clinical effects of Type IV hypersensitivity
Describe type 1 hypersensitivity
- AKA …
- inappropriate response to an
- the inappropriate response arises from the foreign antigen being presented to what kind of T cell which then induces B cells to inappropriately synthesise which Ig
- Above Ig triggers what cells to produce allergic reaction
- response time
AKA allergy
ALLERGEN
Presented to Th2 cell which induces cytokine (IL-4) release –> IgE by B cells
Mast cells and eosinophils to degranulate
Within minutes of exposure
Elements involved in type I hypersensitivity
Allergen IgE, Mast cell/ basophil, Th2 cells Eosinophils Genes
Types of allergens in type 1 hypersensitivity
AIRBORNE - pollens, house dust mite
INGESTED - nuts, seafood
OCCUPATIONAL - latex, drugs (hospital), industrial
Type 1 hypersensitivity is caused by a combo of what factors
Genetic factors
Environmental influences
Immune reactivity
What genetic factor is imposed in type 1 hypersensitivity + describe this
Atopy - genetic tendency to produce IgE to normally innocuous allergens (not everyone with atopy gets allergies)
Type 1 hypersensitivity presentations
Rhinitis
Asthma
Anaphylaxis
Dermatitis
Angioedema
Urticaria
Eczema
What cytokine is produced by Th2 cells in type 1 hypersensitive to induce IgE production by B cells
IL-4
Difference between EARLY and LATE phase allergic reaction
IgE production in type 1 hypersensitivity bind to mast cells and trigger them to release mediators which differentiate the early and late phase
What mediators are released in the
-early
-late
phase
Early (within minutes) - histamine, heparin
(preformed granules)
Late (within hours) - leukotrienes, prostaglandins
(new mediators)
The genetics of allergies has been associated with polymorphisms of a gene encoding what protein
Fillagrin (expressed by keratinocytes and involved in maintaining epithelial barriers and moisturising surfaces)
Physiological effects of mediators released by mast cells in anaphylaxis
Vasodilation
Increased vascular permeability
Fluid shift from vascular to extravascular spaces –> severe fall in BP
Physiological effects of mediators released by mast cells in allergic rhinitis
Vasodilation
Oedema
Increased mucus secretion
Smooth muscle contraction within lungs –> airflow reduction
Treatment options for type 1 hypersensitivity
AVOID ALLERGEN
Pharma: B2 agonists, e.g. salbutamol Antihistamines Sodium cromoglycate Steroids Leukotriene antagonists, e.g. montelukast Desensitisation immunotherapy
Tests for type 1 hypersensitivity
Skin prick test IgE levels (RAST test)
Describe type 2 hypersensitivity
- mediated by which 2 immunoglobulins
- what is the mechanism of each of the above 2 immunoglobulins once it has bound to the antigen
IgG or IgM reacting with antigens on surface of self or foreign cells
IgM activates complement and IgG binds its Fc portion to antigen which stimulates phagocytes
Once antibody has bound to the relevant antigen in type 2 hypersensitivity, damage can arise in what 4 ways
Complement activation
Fc binding and stimulation of phagocytes
Antibody dependent cellular cytotoxicity (ADCC)
Effects on target cell function - inhibit/stimulate function
How does antibody dependent cellular cytotoxicity (ADCC) work in type 2 hypersensitivity
Effector cell of the immune system (probably NK cell) lyses the target cell, whose membrane surface antigens have been bound by specific antibodies
Clinical effects of type II hypersensitivity
Haemolytic reactions, e.g. after blood transfusion, autoimmune haemolysis, drug induced haemolysis
Haemolytic disease of the newborn
Hyperacute graft rejection
Some organ specific autoimmune diseases, e.g. Grave’s disease, pemphigus, goodpasture’s syndrome
Describe type 3 hypersensitivity
- AKA
- characterised by
- can also involve what Igs
- signs & symptoms generally manifest how long after antigen exposure
AKA immune complex disease
EXCESSIVE/ABNORMAL immune complexes of antigen and antibody that cause damage at the site of production or circulate and damage elsewhere
IgM or IgG
4-10 hours
Immune complex formation is a normal physiological process but it is pathological in type 3 hypersensitivity and causes symptoms due to predisposing factors in either the antigen involved or in the immune response to that antigen
The end result of abnormal immune complex formation is that the complexes precipitate out into tissues and cause inflammation
This inflammation tends to take one of two main forms:
Systemic illness where immune complexes are deposited throughout many tissues (SERUM SICKNESS)
Localised disorder where complexes form locally in tissues, rather than depositing in blood (ARTHUS REACTION)
Difference between serum sickness and arthus reaction in type 3 hypersensitivity
Serum sickness - systemic deposition of immune complexes
Arthus reaction - localised immune complexes
Small immune complexes form in type 3 hypersensitivity when antibody levels are … and antigen levels are …
Antibody low
Antigen high
Large immune complexes form type 3 hypersensitivity when antibody levels are … and antigen levels are …
Antibody high/normal
Antigen low/normal
How are immune complexes usually broken down
What happens to this process in type 3 hypersensitivity?
Transported (usually attached to red cells) to the liver and spleen where phagocytes such as Kupffer cells take up and destroy the complexes
This process fails and immune complexes are not cleared
Clinical effects of Type III hypersensitivity
- kidney
- systemic
- resp
Immune complex deposition in kidney
- GN, e.g. post-streptococcal
- Nephrotic syndrome
- Renal failure
Systemic
-SLE
Resp
- farmer’s lung
- bird fancier’s lung
Describe type 4 hypersensitivity
- AKA
- mediated by
- inappropriate response to
- how long for clinical response to occur
Delayed hypersensitivity
Th1 and/or Th17 cells and their CYTOKINES
Inert (unreactive) environmental substances, e.g. nickel, drugs, cosmetics) or as a reaction to infection with certain micro-organisms
48-72 hours
Define the roles of -haptens, carrier proteins -antigen presenting cells -Th1 cells -TNF in Type IV hypersensitivity
Haptens - in type 4 reactions, the antigen is usually of TOO LOW MOLECULAR WEIGHT TO EVOKE IMMUNE RESPONSE so…
Carrier proteins - …haptens. need to bind to a host protein called a CARRIER to produce sufficient antigenic bulk to stimulate immune response
APCs - macrophages and dendritic cells present antigen to T cells
Th1 cells - recognise foreign antigen upon presentation and stimulate cytokine production –> inflammation
TNF - secreted by macrophages and T cells and stimulates MOST OF THE DAMAGE IN TYPE 4
What substance produced by macrophages and T cells and stimulates much of the damage in delayed hypersensitivity
Tumour necrosis factor
What conditions can type 4 delayed hypersensitivity lead to
RA
MS
IBD
(all are affected by Th1/Th17 cells and macrophages causing inflammation)
Treatment options of type 4 hypersensitivity
Prevention/ avoidance of contact with antigen
Anti-inflammatory drugs
- corticosteroids
- NSAIDs
- drugs that block TNF, IL-6
- monoclonal antibodies against B cells
