22. Hypersensitivity Reactions: Type 1 and 2 Flashcards
1. Understand the fundamental differences in immunological mechanisms underlying type 1 and 2 hypersensitivity reactions 2. Explain how certain antigens elicit IgE leading to type 1 reactions, detailing the chemical mediators and cells involved 3. Describe how IgG and IgM antibodies interact with other components of the immune system to cause type 2 reactions 4. Provide examples of clinical manifestations of hypersensitivity (52 cards)
What does adaptive immunity provide?
Antigen specific protection against infection
What causes the immunopathology of hypersensitivity reactions?
adaptive immune response to harmless antigens
What is an autoimmune disease?
An excessive immune response to a self-antigen
What is a hypersensitivity reaction?
An excessive immune response to a foreign antigen.
How are hypersensitivity reaction classified?
Immune response to harmless environmental antigens that are divided into 4 types based on effector mechanisms.
The original classification has been modified and expanded as immunology has developed.
What are the 4 types of hypersensitivity reaction?
- Type 1 - immediate hypersensitivity
- Type 2 - Cytotoxic
- Type 3 - Immune complex
- Type 4 - delayed-type hypersensitivity
What hypersensitivity reactions are antibody mediated?
Type 1 - immediate hypersensitivity
Type 2 - Cytotoxic
Type 3 - Immune complex
What hypersensitivity reactions are T-cell mediated?
Type 4 - Delayed-type hypersensitivity
What causes type 1 hypersensitivity reactions?
Allergens
What are allergens?
- An antigen which elicits an immediate allergic reaction.
- Allergens can be derived from grass pollen, dust mites, food, and bee venom.
When do allergic reactions occur?
- When sensitisation to an allergen occurs and allergen-specific IgE develops.
- Type 1 hypersensitivity reactions occur upon re-exposure to these allergens.
What are the properties of an allergen?
- Highly soluble proteins
- have diverse biological functions though most are enzymes
- They must be small enough to be carried by airborne particles
What are examples of allergens?
- Der p1 from House dust mite faeces
- Lol p1 from grass pollen
What happens with most allergens?
Most people inhale 5-50ng of allergen a day without adverse effects.
What mediates type 1 hypersensitivity?
IgE
What receptors does IgE bind?
- FcεR1 = A high affinity receptor on mast cells and basophils.
- FcεR2 = A low affinity receptor on eosinophils and B cells
What is unusual about IgE FcεR1 binding?
IgE binds to FcεR2 in the absence of a bound antigen
Why is IgE an unusual antibody isotype?
- Serum concentrations are very low.
- It is produced in small quantities against a select group of antigens.
- It has a very short serum half-life.
- IgE is mostly found bound to the high affinity FcεR1 on mast cells and basophils.
- FcεR1 receptors are usually saturated with IgE despite low serum concentrations and this can prolong the half life.
What molecular mechanism causes type 1 hypersensitivity reactions?
- Mast cells with bound IgE reside in the tissue and orchestrate the response.
- An antigen comes along and binds the IgE crosslinking them.
- This triggers degranulation of mast cells.
- Preformed granules are rapidly released. These include histamine.
- Newly-synthesised inflammatory mediators are released more slowly.
What does histamine do?
It is a toxic mediator that causes vasodilation.
What does mast cell activation cause?
an inflammatory cascade that is amplified by the recruitment of other leukocytes.
What molecules are released by activated mast cells?
- Enzymes
- toxic mediators like histamine that cause vasodilation
- type 2 cytokines to promote a Th2 response.
- Other cytokines to promote inflammation.
- chemokines to recruit other immune cells.
- Lipid mediators that have a variety of functions.
What is the effect of allergen-specific IgE response on a patient?
- IgE antibodies to a sensitised antigen.
- local reaction at the point of exposure.
- Within 20 minutes an immediate hypersensitivity reaction (type 1). Mast cells release histamine cause swelling.
- Then becomes a generalised reaction called anaphylaxis.
- This causes fall in blood pressure, Hives, and Bronchospasm.
- Can lead to anaphylactic shock.
What is anaphylactic shock?
- Systemic vasodilation that causes a massive fall in blood pressure that could cause circulatory collapse.
- Can also cause Tracheal swelling a suffocation.
- These reactions can be unpredictable.
- A lot of people have these without knowing they are allergic.