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
Give some examples of hypersensitivity to exogenous antigens
- Non infectious substances (innocuous) e.g. allergens to pollen, dust, food …
- Infectious microbes e.g. over reaction of system
- Drugs e.g penicillin
Give some examples of hypersensitivity to intrinsic antigens
- Infectious microbes (mimickry)
- Slef antigens (auto-immunity)
What is mimickry?
When the host triggers an immune reaction to an infectious microbes but due to host similarities the immune system begins to attack the host too e.g. Rheumatic fever
What are the 4 types of hypersensitivity reactions?
-
Type 1 (immediate) Allergy
- IgE mediated
-
Type 2 antiBody mediated
- IgG driven
- Membrane bound antibdoies → organ specific
-
Type 3 or immune Complex mediated
- IgG driven
- Soluble antibodies → more systemic
-
Type 4 or cell mediated (Delayed)
- environmental infectious agents and self antigens
What 2 phases must hypersensitivity reactions go through?
- Sensitisation phase
- Effector phase
What happens in the sensitisation phase of a hypersensitivity reaction?
- First encounter with the antigen
- APCs are activated and create memory effector cells
- Previously exposed individal to the antigen is ‘sensitised’
What happens in the effector phase of a hypersensitivity reaction?
Pathological reactivation upon re-exposure to the same antigen and activation of the memory cells of the adaptive immunity
How long does it take for type 2 sensitivity reactions to develop after re-exposure?
5-12 hours
What antibodies are involved in type 2 hypersensitivity reactions
IgG (smaller) or IgM (larger)
Give some examples of type 2 hypersensitivity reactions that occure due to complement activation
-
Haemolytic disease of the newborn
- Antigen to Rhesus D
-
Transfusion reactions
- ABO blood system
Explain the mechanism of type 2 hypersensitivity reaction
Give examples of type 2 hypersensitivity reactions that occur due to antibody-dependent cell cytotoxicity
- Autoimmune haemolytic anaemia (warm and cold)
- Immune thrombocytopenia purpura
- Goodpasture’s syndrome (Kidney glomerular nephritis)
Explain what happens in a haemolytic transfusion reaction
- Type 2 hypersensitivity IgM related
- Incompatibility in the ABO or rhesus D antigens leads to RBC lysis
- Life threatening condition
- Causes shock, kidney failure, circulatory collapse and even death
Which blood type is the universal donor?
O -
Which blood group is the universal plasma donor?
AB
(lacks A/B antibodies in plasma)
Explain the mechanism behind haemolytic disease of the newborn
- Rhesus negative mother pregnant by a Rh+ father → first baby is Rh+
- Mother develops antigens to the Rh D antigen from the developing fetus that can enter mothers blood during delivery → first baby is fine
- These antibodies at IgG and can cross the placenta
- On the 2nd pregnancy Rh+ baby, the anti-Rh antibodies can cross the placenta and attack the RBC of the fetus
Why does haemolytic disease of the newborn not occur in mismatch of mother and fetal ABO blood groups?
As ABO is IgM antibodies and these cannot cross the placenta
What symptoms happen to the baby in Haemolytic disease of the newborn?
What is kernicterus?
When bilirubin crosses the blood brain barrier
Can cause brain damage if not treated
Signs: increased tone, epilepsy, always tired
What tests can be performedduring pregnancy to confirm destruction of red blood cells (of the fetus)
Amniocentesis: Hb, Reticulocytes, LFT, Bilirubin
Non invasive: Doppler ultrasound can tell you if baby is aneamic (measure middle cerebral artery)
What can be given to pregnancy mothers who are Rh-?
RhoGAM administered 72hrs after birth
Stops the mother from becoming sensitised to Rh+ antigen
Explain what the Coomb’s test is
A test for haemolytic anaemia, looks for agglutination of RBC
Direct: looks for antibodies on RBC
Indirect: looks for antibodies in serum
What are the 2 types of haemolytic anaemia?
Warm: IgG mediated (optimally active at 37ºC)
Cold: IgM mediated (optimally active at 4ºC)
Explain how type II hypersensitivity reactions can cause pysiological changes to receptors
Receptor stimulation: e.g GRAVE’s DISEASE
- Increased thyroid activity
- antigen TSH receptor
Receptor blockage: e.g. MYASTHENIA GRAVIS
- antigen to Acetylcholine receptor
- Impaired neuromuscular signalling
Give some therapeutic approaches to dealing with the tissue damage caused by type II hypersensitivity reactions
- Anti-inflammatory drugs
- Plasmapheresis
- Splenectomy → end up immuno compromised
- Intravenous immunoglobin (IVIG)
- IgG degredation provides temporary relief
What is plasmapharesis therapy?
Separation of the cells and plasma to remove the circulating antibodies
Useful in:
- Myaesthenia gravis
- Goodpasture’s syndrome
- Grave’s disease
What can you give to treat myaesthenia gravis?
Pyridostigmine
AChesterase inhibitor → increases levels of ACh at NMJ
What happens in myaesthenia gravis?
- Autoantibodies to the AChR produced and bind to nicotinic receptors at muscle end plates
- ACh cannot bind and cause normal depolarisation → action potentials
How long does it take for a type III hypersensitivity reaction to develop?
Usually 3-8 hours after exposure
Explain what happens in a type III hypersensitivity reaction?
- Immune complexes of IgG or IgM
- Targets soluble antigens
- immune complex will travel to target either foreign antigens (infection) or endogenous (self antigens)
- Causes tissue damage by deposition of the immune complexes in host tissue
How does the size of the immune complex alter its ability to create a reaction?
- Small and large size immune complexes are cleared
- Intermediate sized immune complexes aren’t → difficult to get rid of → clinically problematic
What kind of reaction will you always get if you have a deficiency in complement?
Type III reactions → cannot opsonise large complexes for degredation
Which body systems do immune complexes usually affect?
Multisystemic:
- Joint
- Kidney
- Small vessels
- Skin
Give 3 examples of dieases caused by type 3 hypersensitivity reactions?
- Rhemuatoid Arthritis (self-antigen)
- Glomerulonephritis (infectious)
- Bacterial endocarditis
- Hepatitis B infection
- Systemic lupus erythematosus
Explain the immune background of Rheumatoid arthritis
- Antigen to the Fc portion of IgG (Rheumatoid Factor)
- Get articular and extra-articular features
- Episodes of inflammation and remission
What factors give poorer prognosis of rheumatoid arhritis?
- <30 years old
- High titre of rheumatoid factor
- Female
- DR4 allele
- Joint erosions
What is the immune background to systemic lupus erythematosus?
- Antigen to Ds-DNA
- Most prevelant immune complex disease
- Affected Females: Males 9:1
- 40-60% of patients have cardiac, respiratory, joint, neurological features
- Repeated miscarriage
What are some of the common symptoms of systemic lupus erythematosus?
What is a type 4 hypersensitivity reaction?
- Cell mediated reaction that develops within 24-72hrs
- Involves lymphocytes and macrophages
What are the different subtypes of type IV hypersensitivity reactions?
- Contact hypersensitivity
- Tuberculin hypersensitivity
- Granulomatous hypersensitivity
How do type IV hypersensitivity reactions cause tissue destruction?
-
Sensitisation phase
- APCs present antigen to TH cells
- Causes a TH1 response
-
Effector phase
- TH1 cells activate resting macrophages
- Macrophage activation recruit more TH1 → granuloma
What is contact hypersensitivity?
- Occurs 48-72hr post exposure
- Epidermal reaction
- Requires endogenous proteins
- Examples
- Nickel
- Poison ivy
- Organic chemicals
What happens in granulomatous hypersensitivity reaction?
- Occurs 21-48 days post-exposure
- Granuloma forms when host can’t get rid of the microbe → helps seal off infection as long as granuloma is intact
- Tissue damage
- Examples
- TB
- Leprosy
- Schistosomiasis
- Sarcoidosis
What diseases can be caused by type 4 hypersensitivity reactions?
- Pancreatic islet cells → insulin dependent diabetes mellitus
- Thyroid gland → Hashimoto’s thyroiditis
- Fc portion of IgG→ Rheumatoid arthritis
What is the difference immunologically between Grave’s and Hashimotos disease?
Hashimotos: B cell and CD8 T cell activation causes necrosis/ apoptosis of thryroid cells → hypothyroidism
Grave’s: CD4+ tell cell reaction causes overstimulation of the TSH receptor → hyperthyroidism
How can you treat type III and IV hypersensitivity reactions?
Anti-inflammatory drugs
- Non steroidals
- Corticosteroids
- Steroid sparing agents
- Azathioprine
- Mycophenolate mofetil
- Cyclophosphamide
Monoclonal antibodies
- B and T cells
- Cytokine network
- APCs
Newborn infants from mothers with myaesthenia gravis can exhibit symtpoms of myaesthenia ravis at birth. Explain the immune mechanism why and why the disease eventually dissapears?
- Mother transfers antibodies to nAChR across the placenta to the baby
- Maternal antibodies will dissapear on their own as they are replaced by babies own antibodies
What are some of the side effects of treating myaesthenia gravis with an AChesterase inhibitor?
- stomach pain
- muscle cramps
- twitching
- sweating
- blurred vision
- cough with mucus
