allergy Flashcards
HYPERSENSITIVITY
- There are four types of hypersensitivity reactions mediated by immunological
mechanisms that cause tissue damage: - Type 1: IgE-mediated
- Type 2: IgG towards cell surface- or matrix-associated
antigen - Type 3: IgG towards soluble antigen (immune complex)
- Type 4: T cell-mediated
ALLERGY (TYPE I)
IgE-mediated hypersensitivity ”Allergy”
* most often proteins e.g. pollen, house dust mite feces, dander from
cat or dog
* can also be triggered by chemical xenobiotics
initiation time: 2-30 min
Rhinitis: runny eyes, sneezes, itching
Anaphylaxis: rapid reaction, rashes, local swelling (edema), difficulties
breathing, may affect brain and heart, death
Atopy
genetic predisposition to develop allergy
Allergy
dysregulated immune response (Th2 and IgE) against otherwise harmless antigens in our environment
Allergen
an antigen that triggers allergic responses in an atopic individual
Type II: Antibodies to cell surface- or matrix-associated antigen
allergy to drugs like penicillin
* Example: The hapten penicillin (beta-lactam antibiotics) is chemically reactive and binds to proteins on the erythrocyte
(red blood cell) surface.
* Anti-penicillin IgG antibodies bind to hapten and are
recognized by phagocytes and NK cells that lyse the
erythrocytes by releasing toxic mediators.
* Leads to hemolytic anemia.
* Drug-induced granulocytopenia and thrombocytopenia are
also known.
Urticaria = Rashes and swelling of skin caused by release of
histamine, but many different types!
Ca. 50% of all patients with chronic urticaria have auto-IgG
against the alpha subunit of FcεRI or against IgE.
Initiation time: 5-8 h
what is type III allergy?
IgG towards soluble antigen (immune complex)
antibody-mediated (IgG), can activate complement-mediated and phagocytic effector mechanisms
Pathology caused by the deposition of Ag:Ab complex aggregates in particular sites and tissues (e.g. blood vessel walls), leukocyte activation, tissue injury
Can be caused by drugs containing a protein moiety of other species, or medication such as certain antibiotics, allopurinol, barbiturates
Arthus reaction = triggered in the skin of sensitized individuals who possess IgG antibodies towards the sensitizing antigen. Can occur for instance after tetanus toxoid–containing or diphtheria toxoid– containing vaccination.
What is type IV allergy?
Delayed hypersensitivity T cell-mediated
Allergic contact dermatitis (ACD)
- rashes, blisters, wheals, urticaria, itching
Initiation time: 24-72 h
More than 4000 chemicals are known to cause contact hypersensitivity (e.g. chemicals
in perfume, hair dyes, latex, and other consumer products…)
what are the TWO PHASES OF ALLERGIC IMMUNE RESPONSES?
- SENSITIZATION
- EFFECTOR PHASE (ELICITATION)– IMMEDIATE REACTION
Sensitization Phase
Allergen Exposure: The process begins when an individual is exposed to an allergen, which is a substance that can provoke an allergic reaction. Common allergens include pollen, pet dander, certain foods, and insect venom.
Antigen Presentation: The allergen is taken up by antigen-presenting cells (APCs), such as dendritic cells. These cells process the allergen and present its fragments (antigens) on their surface using molecules known as Major Histocompatibility Complex (MHC) class II.
T Cell Activation: The APCs migrate to lymph nodes, where they interact with naive T helper (Th) cells. The presentation of the allergen fragments, along with co-stimulatory signals, activates these Th cells and promotes their differentiation into Th2 cells.
B Cell Activation: The Th2 cells secrete cytokines, such as interleukin-4 (IL-4), IL-5, and IL-13, which play a crucial role in allergic responses. IL-4, in particular, induces the activation and differentiation of B cells that recognize the same allergen.
IgE Production: The activated B cells differentiate into plasma cells and produce allergen-specific Immunoglobulin E (IgE) antibodies. These IgE antibodies are released into the bloodstream.
Binding to Mast Cells and Basophils: The allergen-specific IgE antibodies bind to high-affinity IgE receptors (FcεRI) on the surface of mast cells and basophils. These cells are now sensitized to the allergen.
Summary
The sensitization phase is characterized by the initial exposure to an allergen and the immune system’s response to this exposure, resulting in the production of allergen-specific IgE antibodies. These IgE antibodies bind to mast cells and basophils, sensitizing them to the allergen.
- EFFECTOR PHASE (ELICITATION)– IMMEDIATE REACTION
It involves the actual allergic reaction that occurs upon subsequent exposure to the allergen.
Re-exposure to Allergen: When the sensitized individual is re-exposed to the same allergen, the allergen binds to the IgE antibodies that are already bound to the high-affinity IgE receptors (FcεRI) on the surface of mast cells and basophils.
Cross-linking of IgE: The allergen cross-links the bound IgE antibodies, which leads to the aggregation of the FcεRI receptors on the cell surface. This cross-linking is a crucial step that triggers the activation of the mast cells and basophils.
Degranulation: Upon activation, mast cells and basophils undergo degranulation, a process in which they release preformed granules containing various mediators. Key inflammatory mediators include:
Histamine: Causes vasodilation, increased vascular permeability, and smooth muscle contraction.
Leukotrienes: Increase vascular permeability, cause bronchoconstriction, and attract other immune cells.
Clinical Symptoms: The immediate reaction occurs within minutes of allergen exposure and results in the clinical symptoms of an allergic reaction.
Allergic symptoms:
swelling, congestion,
coughing, mucus secretion
- EFFECTOR PHASE – LATE REACTION
The late-phase reaction is a prolonged inflammatory response that occurs hours after the initial allergen exposure. It involves the recruitment and activation of various immune cells, leading to sustained inflammation and tissue damage. This phase is responsible for the chronic symptoms and complications associated with allergic diseases.
WHY DOES ALLERGIC CONTACT DERMATITIS EXIST?
Hypothesis: use of conserved immune mechanism to
distinguish between harmless/beneficial commensal
bacteria and potentially dangerous pathogenic
microorganisms
- Pattern recognition receptors (PRRs) engagement by
danger-associated molecular patterns (DAMPs)
e.g. Ni2+ <=> TLR4 (ROS, proinflammatory signal)
trinitrochlorobenzene activates TLR2/4 via hyaluronic
acid degradation
- Oxidative stress through production of reactive
oxygen species (ROS)
→ combination of antigen delivery with danger signals
MAST CELLS
Mast cells are a type of white blood cell that plays a crucial role in the immune system, particularly in allergic reactions and the defense against pathogens. They are found in various tissues throughout the body, especially in locations that interface with the external environment, such as the skin, respiratory tract, and gastrointestinal tract.
Mast cells are central players in allergic reactions. They express high-affinity receptors (FcεRI) for Immunoglobulin E (IgE).
Upon exposure to an allergen, IgE bound to the FcεRI receptors is cross-linked, leading to mast cell activation and degranulation.
Degranulation releases preformed mediators (e.g., histamine) that cause immediate allergic symptoms such as itching, swelling, and bronchoconstriction.
MAST CELL MEDIATORS
Preformed Mediators: These are stored in granules and released rapidly upon activation. They include:
Histamine: Causes vasodilation, increased vascular permeability, and smooth muscle contraction.
Proteases (e.g., tryptase, chymase): Contribute to tissue remodeling and inflammation.
Newly Synthesized Mediators: Produced after activation and released over a longer period.
Cytokines (e.g., TNF-α, IL-4, IL-5, IL-6): Attract and activate other immune cells.
