Hypersensitivity Reactions Flashcards
What is hypersensitivity?
The antigen-specific immune responses that are inappropriate or excessive and result in harm to host.
What are the 2 types of triggers?
Exogenous - innocuous substances, drugs, microbes
Intrinsic - auto-immune,mimicry
What is a type 1 hypersensitivity reaction?
Allergy - Immediate reaction
Environmental - non infectious antigens
Which antibody is present in a type 1 reaction?
IgE
What is a type II reaction mediated by?
Antibody mediated
IgM - cell bound antigens
What is a type III reaction mediated by?
Immune complex mediated
What type of antibody is present in type III reaction?
IgG - soluble antigens
What is a type IV reaction?
Cell-mediated - Delayed
Which 3 reaction types are antibody mediated?
Type I,II and III
What are the two phases of hypersensitivity reactions?
Sensitization phase - first encounter with antigen. Memory cells.
Effector phase - pathological reaction upon re-exposure and activation of memory cells
How long does type II hypersensitivity take to develop?
5-12 hours
Give an example of an endogenous and an exogenous cause of type II reaction.
Exogenous - blood group antigens, rhesus D antigen.
Endogenous - self-antigens
What 2 types of tissue damage occur from a type 2 reaction?
- Complement activation
- Antibody-dependent cell cytotoxicity
What are the effects of complement activation?
Cell lysis (MAC)
Opsonisation - C3b
Chemotaxis - C3a/5a
What is antibody- dependent cell cytotoxicity?
NK cells bind to antibody Fc receptor, release toxic radicals to kill target cells.
Give some examples of conditions caused by type 2 hypersensitivity.
- Haemolytic disease of the newborn
- Haemolytic transduction reaction
- Autoimmune haemolytic anaemia
- ITP
- Goodpastures
What are the physiological changes that can occur from type 2 hypersensitivity?
- Receptor stimulation - Graves’ disease
2. Receptor blockade - myasthenia gravis
What treatment is aimed at reducing tissue damage from type 2 hypersensitivity?
- Immune suppression - complement
- Plasmapheresis - short term relief, allows tissue healing
- Splenectomy
- IV immunoglobin
What is the cause of tissue damage in type 3 hypersensitivity?
Immune complex deposition
Complement activation
Neutrophil chemotaxis and degranulation
How does the size of the IC affect pathogenesis of type 3 hypersensitivity?
Small and large easily cleared.
Intermediate less so.
What factors affect pathogenesis of type 3?
- IC size
- Host response - affinity of antibody, complement deficiency
- Haemodynamic and physiochemical factors
Which areas are commonly affected by IC deposition?
Joints
Kidney
Small vessels
Skin
What are examples of diseases caused by type 3 hypersensitivity?
Rheumatoid Arthritis
Glomerulonephritis (infectious)
SLE
What is the antigen for rheumatoid arthritis, is it present in all cases?
Anti-rheumatic factor
No - 75%
What is the antigen in SLE?
Ds-DNA
How long after exposure does type IV hypersensitivity occur?
24-72 hours -delayed
Which cells are involved in type 4 hypersensitivity?
Macrophages + lymphocytes
What are the 3 types of type IV hypersensitivity?
Contact hypersensitivity
Tuberculin hypersensitivity
Granulomatous hypersensitivity - if persisting antigen,most severe, tissue damage
Give examples of granulomatous sensitivity.
TB
Sarcoidosis
Schistomiasis
Give examples of contact hypersensitivity.
Nickel
Poison Ivy
Organic chemicals
What is type 4 sensitivity used for?
Sensitization status-
Mantoux test for TB
What diseases are caused by type 4 reactions to endogenous antigens?
Type 1 diabetes
Rheumatoid arthritis
What can be used to treat type 3 + 4 hypersensitivity?
Anti-inflammatory - NSAIDs, corticosteroids
Monoclonal antibodies
What is the time-scale for type 3 reactions?
3-8 hours
What are poor prognostic factors of RA?
< 30yo
High RF titre
Female
What is the time scale for type IV hypersensitivity reactions, why?
24-72 hours
Involvement of macrophages + lymphocytes
Name 3 autoimmune diseases caused by type 4 hypersensitivity?
T1DM - pancreatic islet cells
Hashimoto’s
IgG RA
Which cell mediates granulomatous type IV reactions?
Macrophage - later become epithelioid and giant cells.
Give some examples of general presenting symptoms of lupus?
Myalgia Weight loss Weakness Fever Arthralgia in small joints
