Allergy and hypersensitivity Flashcards
What are the three ways the immune system can go wrong?
React to innocuous agent
Being deficient and not working
Reacting to self during autoimmunity
Define hypersensitivity
Damage to the host arising from an immune response
Causes of hypersensitivity
Autoimmunity
Side effect of response to pathogen
Transplantation
How many types of hypersensitivity are there?
6
Features of type I hypersensitivity
Mast cells
IgE
Generally allergies
Immediate
Which cells are involved in type I hypersensitivity?
Mast cells
B cells
Why is type I hypersensitivity immediate?
Since all the components involved are preformed
All you need is for the allergen to bind to its receptors
What is the half-life of IgE?
2.5 days in serum
12 weeks if bound to mast cells
IgE lasts longer when bound to its receptor
When does IgE become elevated?
Certain parasitic diseases
Hyper IgE syndrome
Allergy
What agents promote class switching to IgE in B cell immunoglobulins?
IL-4
IL-13
What agent inhibits IgE?
Interferon-y
What is the main mechanism underlying Type I hypersensitivity?
IgE-mediated mast cell degranulation
Describe the organ affected and the symptoms caused due to type I sensitivity
Upper respiratory tract - hay fever
Lower respiratory tract - atopic asthma
Skin - allergic eczema
Systemic - peanuts
Infection - worm
Which inflammatory granules are released by mast cells?
Histamine
Serotonin
TNFa
Prostaglandins
Leukotrienes
First two = stored, released immediately
Last three = newly synthesised, chronic effects
What is necessary for Type I hypersensitivity to take place?
IgE antibody acting on mast cells and eosinophils
Th2 cells releasing IL4, IL5 and IL13 to cause IgE class switching
What are the two main components describing the predisposition to allergies?
Genes
Environment
Which genes are related to allergy sensitivity?
FcRe
HLA-DQ
IL-2R
IL-4R
What are the three ways to treat allergies?
Allergen avoidance
Pharmacotherapy
Immunotherapy
Describe some drugs used to treat allergies
Corticosteroids - suppress transcription of proinflammatory genes
Sodium cromoglycate - blocks mediator release from mast cells, reducing IgE []
Anti-histamines
Motelukast - leukotriene receptor antagonist
Describe immunotherapes used to treat allergies
Omalizumab - anti-IgE and anti-FcER
Repeated low dose antigen over a period of years
What is type II hypersensitivity?
Antibody mediated killing
What are the two ways type II hypersensitivity manifests?
Antibody-mediated killing
Formation of antibodies that block physiological function
Describe how type II hypersensitivity causes antibody-mediated killing
- Antibody binds to target due to loss of tolerance or increased antigenicity of the cell (foreign antigen embeds into the cell)
- Fc from antibody (IgG) activates anything with an Fc receptor
- Complement cascade leads to killing and damage
When does type II hypersensitivity occur?
Transplantation - hyperacute transplant rejection
Haemolytic disease of the newborn
Autoimmune diseases
When does haemolytic disease of the newborn take place?
When the mother is Rhesus factor negative, but the baby is Rhesus factor positive
Describe the process behind Haemolytic disease of the newborn
- First pregancy, nothing happens to the baby
- During birth, the mother may come in contact with the RhD+ child
- The mother mounts an immune response against this protein, and forms anti-D antibodies
- In the second baby. the antibodies are ready
- The antibodies cross the placenta and coat the blood cells of the RhD+ baby
What is a possible treatment of Haemolytic disease of the newborn?
Overloading the system to mask out anti-D to prevent mother from being sensitised
What does a newborn who suffered haemolytic disease look like?
Blue
Blood cells are killed by mothers immune cells
Example of an autoimmune disease with type II hypersensitivity
Goodpasture’s
Antibody attacks type IV collagen
Especially damages kidneys
What is another example of type II hypersensitivity?
Formation of antibodies that block cell receptors
No killing is involved, but prevents the organ from functioning correctly
Example of type II hypersensitivity not caused by cell death
Myasthenia gravis
Blocking of the receptors to ACh
What is type III hypersensitivity mediated by?
Immune complex mediated
What makes it different from type II is that the antigens are NOT embedded to the cell wall, but rather are soluble
Describe the process of type III hypersensitivity
- Soluble antibody binds to soluble antigen, causing an immune complex
- Antigen-antibody complexes deposit in skin, kidney or lungs where the blood flows slower
- Macrophages try to eat them, but the complexes are unable to
- Macrophages carry out frustrated phagocytosis
What is frustrated phagocytosis?
Macrophages are activated and releasing their inflammatory factors without degrading the antibody-antigen complex
Where is type III hypersensitivity seen?
Allergies: Farmer’s lung (hay exposure)
Infections: post-streptococcal glomerulonephritis
Autoimmune diseases: SLE
What is post-streptococcal glomerulonephritis?
Following infection with streptococci, cross-reactivity can lead to kidney damage
What mediates Type IV hypersensitivity?
T cells
Both CD4+ and CD8+ subclasses
Cause symptoms through separate mechanisms
Which cytokines are increased during type IV hypersensitivity?
TNFa
IFN-y
When does type IV hypersensitivity take place?
Allergy - contact dermatitis
Tuberculin skin reaction to mycobacterial antigens
Infections - TB granuloma
How does type IV hypersensitivity cause skin rashes?
Immune cells migrate to the surface
Travel to the lymph nodes
T cells become activated and migrate to the site on the skin where they replicate
What test screens for latent TB infection?
Mantoux test
Involves injection of tuberculinin in the skin
How does type IV hypersensitivity cause granulomas in TB?
Continuous activation of T cells in chronic local TB
Leads to the accumulation of large numbers of macrophages
Macrophages cannot clear it and join up to make giant cells
Giant cells form granuloma to corner the infection
What did type V hypersensitivity used to be a subclass of?
Type II hypersensitivity
What molecule is involved in type V hypersensitivity?
Antibodies
What is the mechanism behind type V hypersensitivity?
Formation of antibody which acts as an agonist on the cell surface receptors
Causing the stimulation of that cell to carry out their function
Example of a condition caused by type V hypersensitivity
Grave’s disease
Agonist to TSHR on thyroid gland
Increases thyroid hormone release
What is innate hypersensitisation?
Hyperactivation of the innate immune system
Examples of innate hypersensitisation
Sepsis
Toxic shock syndrome
Describe the mechanism behind toxic shock syndrome
It is caused by a superantigen
This does not bind to a specific TCR on T cells, but rather lots of cells through the outside of the receptor at once
What conditions is chronic inflammation linked to?
Atherosclerosis
Alzheimer’s
Type II diabetes
Inflammageing
What test is done to look for allergies?
Skin prick allergy test
Describe the process behind a skin prick allergy test
Scratch with needle dipped into different allergens
Wait for 20 minutes for the test response
Some responses are more delayed, requiring more time = T cell mediated
What causes dust allergy?
Fecal pellets of D. Farinae
Each pellet contains 0.2 ng of the allergen
What is the main difference between type II and type III hypersensitivity?
Unlike type II hypersensitivities, antigen-antibody complexes in type III are not membrane-bound
Describe how CD4+ cells become activated in type IV hypersensitivity
APC displays antigen on MHC II receptor
IL-12 expression by APCs induces Th1 maturation
Th1 secrete IL-2 and IFN-y
Macrophage and T cell proliferation
Th17 activated and secrete IL-17, leading to neutrophil recruitment
Macrophages promote inflammation and leaky endothelium
What autoimmune conditions are caused by type IV hypersensitivity?
Type I diabetes
Multiple sclerosis
Hashimoto’s thyroiditis
Features of innate hypersenstivities
Chronic inflammation
Innapropriate responses
Overactivation of macrophages
