Allergy week 3 Flashcards
What immune cells mediate/cause type IV hypersensitivity reactions? Be specific.
What is the time frame of this reaction?
What are these types of hypersensitivity reactions in response to?
How is this type of hypersensitivity reaction used clinically?
In addition to type IV hypersensitivity reactions being involved in autoimmune diseases (recall Hashimoto’s thyroiditis), this type of hypersensitivity reaction is evoked against foreign antigens. This type IV reaction participates in reactions against Mycobacterium tuberculosis, which leads to granuloma formation.
- Cytokine-mediated inflammatory reaction due to activation of CD4+ Th1 lymphocytes.
- Reaction evolves during a 24-48 hour period. This is why these reactions are also known as delayed type hypersensitivity (DTH)
- 4 hours after injection antigen, neutrophils accumulate in the post- capillary venules at site.
- 12 hour, T lymphocytes and monocytes infiltrate, venules leak plasma and fibrinogen (converted to fibrin)
- 18 hours edema and firmness (induration) due to fibrin deposition becomes detectable.
- 24-48 hours, induration becomes maximal.
- Used clinically to detect Mycobacterial sensitization, and contact sensitivity to metals
Give examples of clinical type IV hypersensitivity reactions.
Type IV reactions are involved in contact sensitivity to chemicals and metals. The most common contact sensitivity is to nickel, which manifests as a erythematous cutaneous rash where the skin comes into contact with the metal present in jewelry, watches, cosmetics, etc. The severity of reaction depends on the degree of sensitization and amount of exposure.
• Allergic contact dermatitis
– Ex. Nickel allergy
- Poison ivy
- Purified Protein Derivative (PPD)- Used in tuberculin skin testing.
When are PPD tests administered?
Explain what a PPD test is.
When are PPD tests read? Why?
- Evaluation of possible recent Mycobacterial infection (tuberculosis).
- Used to screen healthcare workers.
- Utilized purified protein derivative (PPD), a protein antigen of Mycobacterium tuberculosis
- 1-2 weeks after sensitization (primary infection or immunization), perform intradermal skin testing with PPD. If this time frame was shorter, may get false negative.
- Skin tests are read at 48 hours, reflecting time required for lymphocyte transit.
Explain how a skin biopsy would look after a type IV hypersensitivity reaction.
- Activated endothelial cells by inflammatory cytokines become plump.
- Space between endothelial cells widens allowing leukocytes to migrate into tissue (peri-vascular infiltrate)
- Macrophages and Th1 cells dominate delayed-type hypersensitivity reactions
What is the time frame for type I hypersensitivity reactions?
What stimulates these types of hypersensitivity reactions?
Explain the immune cells involved and what occurs when these cells are stimulated by antigen. Be specific.
When (in relation to number of exposures to antigen) do these types of hypersensitivity reactions occur?
Type I hypersensitivity, also called immediate hypersensitivity, reactions are clinically characterized by rapid reaction (within minutes) after an antigen exposure. It is thought that this type of hypersensitivity evolved to protect against helminthic parasites (worms). An antigen that can induce an immediate reaction is also called an allergen. Some examples of allergens are proteins from the eggs of helminths, cat dander, dust mites, peanuts and cow’s milk. These are proteins do not denature with heat and tend to have a high molecular weight. Some chemicals, such as penicillin, bind as haptens to carrier self‐proteins, which this complex can stimulate an allergic response. These proteins need to have been exposed to previously, to induce the production of immunoglobulin E (IgE). Upon re‐exposure, the allergen is recognized by IgE, which is bound to the high‐affinity IgE receptor located on the surface of mast cells and basophils. Upon binding, these two cells rapidly degranulate vasoactive amines (ex. histamines), enzymes (ex. tryptase, chymase) and lipid mediator (ex. leukotrienes, prostaglandins).
T helper (Th) cells that are activated and preferentially produce cytokines associated with Type I hypersensitivity (ex. IL-4, IL-5, IL-13).
- These skewed T helper cells are called Th2 cells.
- B-cells are activated and the cytokines produced by Th2 cells induce antibody class-switching to IgE production.
associated with Type I hypersensitivity (ex. IL-4, IL-5, IL-13).
Interaction btwn what ligand and receptor on Th2 and B cells allows for class switching to IgE?
What cytokine is released from Th2 cells to also stimulate this change?
What receptor does IgE bind to on mast cells and basophils to stimulate degranulation?
- Th2 lymphocytes provide:
- Cluster of differentiation 40 (CD40) to stimulate class-switching (CD40 on B cells must bind to CD40L on Th2 cells)
- Interluekin-4 (IL-4) to class-switch to the epsilon (e) heavy chain.
- IgE is released into blood and binds to the high-affinity IgE receptor (FcεRI) on mast cells and other cell types.
- IgE is specific for an epitope of an allergen.
- The epitope can be amino acid sequence (linear epitope) or,
- A shape of portion of the allergen (conformational epitope).
- On re-exposure, recognition and crosslinking of IgE molecules on mast cell, the mast cell degranulates.
Explain the two phases of type I hypersensitivity reactions.
Explain the physical symptoms that occur in type I hypersensitivity reactions.
These released immediate released mediators (histamines, leukotrienes, prostaglandins, enzymes such as tryptase) work in concert to cause vasodilation, vascular leak, bronchoconstriction, intestinal hypermotility, and tissue damage. These end effects explain the clinical symptoms of type I hypersensitivity reactions. In addition, to this immediate reaction, there is a late phase reaction that is due to new synthesis of cytokines (ex. tumor necrosis factor, TNF) which lead to killing of parasites and host cells. The immediate and late‐phase reactions together provide the two components of the bimodal distribution that is classic for Type I hypersensitivity reactions.
In what phase of the allergic reaction to eosinophils come into play? What recruits them to the site of inflammation?
What do eosinophils release and what are the effects?
Eosinophils are recruited to tissue by late‐phase cytokines (interleukin‐5, IL‐5) that are produced by Th2 cells. These eosinophils release granular proteins including major basic protein and eosinophilic cationic protein. These produce chemicals (hypochlorous acid, hypobromous acid) that are toxic to parasites (helminthes, protozoa) and the human host.
List types of Type I hypersensitivity reactions.
Food allergy
Anaphylaxis
Asthma
Allergic rhinitis, sinusitis (hay fever)
What are the symptoms that occur in food allergy/anaphylaxis?
How is it treated? Explain why/how the treatment works.
Food allergy anaphylaxis is an immediate‐onset severe systemic type I hypersensitivity reaction in response to a food allergen the individual is sensitized. In consists of cutaneous symptoms, including hives and non‐dependent asymmetric tissue edema (angioedema); laryngospasm, bronchospasm; and low blood pressure (hypotension). Treatment includes prompt administration of epinephrine and B‐adrenergic agonists (albuterol) for bronchospasm. Antihistamines and corticosteroids can be given to assist in management. Examples include peanut, shrimp, milk or egg allergy.
What are the symptoms of allergic rhinitis? How is it treated? Explain how the treatments work.
Allergic rhinitis is an immediate type I hypersensitivity reaction to allergens in the environment. Histamine released leads to itching, and vasodilation. The vasodilation leads to nasal congestion, increased mucous production and edema. Treatment includes avoidance of allergens, antihistamines (block histamines actions of vasodilation, vascular permeability, smooth muscle contraction), intransasal corticosteroids (reduced inflammation) and leukotriene receptor antagonists (relax bronchial smooth muscle and reduce inflammation). Examples include cat allergy, ragweed allergy.
What are the symptoms of asthma? How is treated in the short term? Long-term?
Asthma is a reversible airway obstruction. One of the possible triggers include type I hypersensitivity to allergens in the environment. Exposure leads to bronchospasm of the airway smooth muscles, leading to clinical signs of wheezing, coughing, and shortness of breath. Short‐term (acute) treatment includes B‐adrenergic agonists (albuterol). Long‐term (chronic) treatment includes inhaled corticosteroids, leukotriene receptor antagonists and omalizumab (Xolair) a humanized monoclonal anti‐IgE antibody.
