Session 1 - Hypersensitivity Reactions Flashcards
What is the main role of the adaptive and innate immune system?
Protection and prevention against infection = success
What can lead to failure of the immune system?
- non-self, Infection, altered self (e.g. cancer)
- immunodeficiency (primary and secondary Disorders)
- autoimmune disease
- allergies
Give the definition of hypersensitivity.
The antigen (or antigen driven) specific immune responses that are either inappropriate or excessive, and result in harm to host.
What are the 2 types of antigenic triggers?
Hypersensitivity to exogenous antigensm
- non infectious substances (innocuous)
- infectious microbes
- Drugs (penicillin)
Hypersensitivity to intrinsic antigens:
- infectious microbes (mimicry)
- self antigens (autoimmunity)
What are the different types of hypersensitivity reactions?
Type I = immediate (allergy) = environmental non infectious antigens. IgE mediated.
Type II = antibody mediated = against cell bound antigen (on tissue). IgG/IgM mediated.
Type III = immune complex mediated = against soluble antigen (can deposit). IgG/IgM mediated.
Type IV = Cell mediated (delayed) = environmental infectious agents and self antigens.
What are the common features of hypersensitivity reactions?
- sensitisation phase
- effector phase
What is the sensitisation phase?
First encounter with the antigen. Activation of APCs and memory effector cells. A previously exposed individual to the antigen is said to be sensitised. No clinical manifestation = no signs/symptoms
What is the effector phase?
Pathological reaction upon re-exposure to the same antigen and activation of the memory cells of the adaptive immunity. Get clinical manifestation = signs/symptoms.
Give the characteristics of a type II hypersensitivity reaction.
- usually develops within 5 - 12 hrs
- involves IgG or IgM antibodies
- targets cell bound antigens = exogenous (blood Group antigens, rhesus D antigens), endogenous (self antigens)
- induces different outcomes = tissue/cell damage or physiological change (change in organ function = bad)
What are the mechanisms of type 2 hypersensitivity reactions in relation to tissue/cell damage?
1) complement activation:
- Cell lysis (macrophages)
- neutrophil recruitment/activation (C3a/C5a)
- Opsonisation (C3b)
- e.g. haemolytic Disease Of The newborn (Rheus D antigen), transfusion reactions (ABO)
2) Antibody dependent cell cytotoxicity = natural killer cells
- e.g. autoimmune haemolytic Anaemia (warm and cold), immune thrombocytopenia purpura (lose platelets), goodpastures syndrome
Why is complement pathway important in type II hypersensitivity reactions?
Complement regulate innate and adaptive immune system.
Also clears immune complexes
Explain the process by which haemolytic disease if the newborn occurs.
1) Rh+ father
2) Rh- mother carrying her first Rh+ foetus. Rh antigens from the developing foetus can Exeter the mother’s blood during delivery.
3) in response to the foetal Rh antigens the mother will produce anti-Rh antibodies.
4) if the woman becomes pregnant with another Rh+ foetus, her anti-Rh antibodies will cross the placenta and damage foetal red blood cells.
Immunoglobulin against Rh factor given within 72hrs of delivery.
What are the mechanisms of Type II hypersensitivity reactions in relation to physiological change?
1) Receptor stimulation
- e.g. Graves’ disease = increased thyroid activity (antigen = TSH receptor)
2) receptor blockade
- e.g. Myasthenia gravis = impaired neuromuscular signalling (antigen = acetylcholine receptor)
What are the therapeutic approaches to type II hypersensitivity reactions?
Tissue/cell damage:
- anti inflammatory drugs = complement activation
- plasmapheresis = circulatory antibodies and inflammatory mediators
- splenectomy = opsonisation/phagocytosis
- intravenous immunoglobulin (IVIG) = IgG degradation
Physiological change:
- correct metabolism = antithyroid Drugs In Graves’ disease
- replacement therapy = Pyridostigimine (inhibits ACh esterase) in MG
What type II hypersensitivity Conditions would plasmapheresis be used for?
Myasthenia gravis
Goodpastures syndrome
Graves’ disease
Name some characteristics of type III hypersensitivity reactions.
- usually develops within 3-8 hrs
- involves immune complexes between IgG or IgM antigens
- targets soluble antigens = foreign (Infection) and endogenous (self antigens)
- tissue damage caused by the deposition of immune complexes in host tissues
What are the key factors affecting IC pathogens is in type III hypersensitivity reactions?
1) complex size:
- small and large ICs cleared
- intermediate size ICs
2) host response:
- low affinity antibody
- complement deficiency
3) local tissue factors:
- haemodynamic factors
- physio chemical factors
What can persistence of ICs in type III hypersensitivity reactions lead to?
Deposition = joint, kidney, small vessels, skin
Multisystem disease
What is the mechanism of type III hypersensitivity reactions?
1) intermediate sized immune complexes deposited in the tissue
2) complement activated
3) neutrophil chemotaxis
4) neutrophil adherence and degranulation
Give some examples of diseases caused by type III hypersensitivity reactions.
1) rheumatoid arthritis = immune complex deposition in areas of high blood flow e.g. kidney, knee, liver
2) glomerulonephritis (infectious) = bacterial endocarditis, hepatitis B infection
3) systemic lupus erythematous
Name some of the characteristics of type IV hypersensitivity reactions.
- usually develops within 24-72 hrs
- involves lymphocytes and macrophages
- different subtypes (clinical outcomes) = contact hypersensitivity, tuberculin hypersensitivity, granulomatous hypersensitivity
Give some examples of diseases caused by type IV hypersensitivity reactions to exogenous antigens.
Contact hypersensitivity:
- epidermal reaction
- require endogenous proteins
- e.g. nickel, poison ivy, organic chemicals
2) granulomatous hypersensitivity:
- 21 - 48 days post exposure
- tissue damage
- e.g. tuberculosis, leprosy (tuberculoid), schistomiasis, sarcoidosis
Give some examples of diseases caused by type IV hypersensitivity reactions to endogenous antigens.
- pancreatic islet Cell = insulin-dependent Diabetes mellitus
- thyroid gland = Hashimoto’s thyroiditis
- Fc portion of IgG = rheumatoid arthritis
What is the treatment of type III and type IV hypersensitivity reactions?
1) anti-inflammatory Drugs:
- non-steroidal
- corticosteroids (oral prednisolone )
- second Drugs as steroid sparing agents = azathioprine, mycophenolate mofetil, cyclophosamide
2) monoclonal antibodies:
