16: Hypersensitivity Reactions Flashcards
Hypersensitivity
A state of heightened reactivity to antigen
Hypersensitivity reactions
Immune responses to innocuous antigens that lead to symptomatic reactions upon re-exposure
Hypersensitivity disease
Damage to host tissue caused by hypersensitivity reactions to typically innocuous antigens
Who classified hypersensitivity reactions into 4 types based on the types of antigens that are recognized and the types of immune responses involved?
Coombs and Gel
What does Type I hypersensitivity involve?
IgE-dependent triggering of mast cells
What does Type II hypersensitivity involve?
IgG antibody that is reactive with cell-surface or matrix antigens
What does Type III hypersensitivity involve?
Production of antigen:antibody complexes
What does Type IV hypersensitivity involve?
T cell-mediated hypersensitivity
Antigens that selectively stimulate TH2 cells that drive an IgE response are known as ______.
Allergens
What are the features that many allergens have in common? (4)
- Small proteins
- Highly soluble
- Carried on desiccated particles
- Upon contact with mucosa of airways, soluble antigens elute from the delivery particles and diffuse into the mucosa
Antigens presented to TH0 cells at low doses tend to elicit differentiation into ________.
TH2 CD4 cells
T or F: All common allergens have enzymatic activity.
F: most but not all
What is the prerequisite for type I hypersensitivity?
The initial response to an allergen must be an IgE response
What cytokines do TH2 cells produce that favor class switching to IgE?
IL-4, IL-5, and IL-13
What do TH2 cells do to favor class switching to IgE?
- Produce and secrete IL-4, IL-5, and IL-13
2. Upregulate expression of CD40L and CD23
What kind of cells primarily initiate type I hypersensitivity reactions?
Mast cells
What types of cells have FCeRI receptors?
Mast cells, eosinophils, and basophils
What is atopy?
A predisposition to allergy
T or F: Atopic individuals have higher levels of soluble IgE and more circulating eosinophils than non-atopic individuals.
T
Genes encoded on chromosomes ____ and ___ appear to be involved in allergic predisposition.
5 and 11
Chromosome 11 encodes a gene for _______.
The beta subunit of FCeRI
Chromosome 5 encodes a cluster of genes that encode _____________.
Proteins involved in isotype switching, eosinophil survival, and mast cell proliferation (IL-3, IL-4, IL-5, IL-9, IL-13, and GM-CSF)
T or F: HLA Class II polymorphism affects the IgE response to certain allergens.
T
What is the wheal and flare reaction?
An inflammatory reaction produced immediately at the injection site that is a result of mast cell degranulation in the skin
- Swelling due to increased permeability produces the wheal
- Redness is the flare
The late phase reaction to an allergen is mediated by _________.
Leukotrienes, chemokines, and cytokines produced by mast cells following IgE-mediated activation
What differentiates the late phase reaction from the wheal and flare reaction?
Late phase reaction is 6-8 hours post injection and consists of more widespread swelling
Airborne allergens irritate _______ and food-borne allergens irritate _______.
Airborne: Irritate mucosa of respiratory tract
Food-borne: Irritate mucosa of GI tract
What mechanisms have developed as a means of expulsion of parasites from the body?
Coughing and sneezing, vomiting, diarrhea
What is systemic anaphylaxis?
Wide-spread activation of mast cell degranulation causing both an increase in vascular permeability and a widespread constriction of smooth muscle
What is the most common cause of anaphylaxis?
IgE-mediated allergy to penicillin or other drugs
What is the treatment for anaphylactic and anaphylactoid reactions?
Injection of epinephrine
How doe epinephrine treat anaphylactic and anaphylactoid reactions?
It stimulates reformation of tight junctions between endothelial cells, reducing permeability of blood vessels, diminishing tissue swelling, raising blood pressure, and stimulating the heart
What is allergic rhinitis?
Mild allergic response characterized by sneezing and runny nose in response to inhaled allergens; caused by allergens that diffuse across the mucous membranes of nasal passages and activate mucosal mast cells beneath the nasal epithelium
What is allergic asthma?
A serious condition where allergic reactions to commonly inhaled allergens cause chronic breathing difficulties
When is allergic asthma triggered?
When submucosal mast cells in the lower respiratory tract are stimulated by allergen/IgE interaction
What is the overall effect of an allergic asthmatic attack?
Trapping of air in the lungs, making breathing more difficult (can be fatal!)
What type of hypersensitivity reaction is chronic asthma?
Type IV because it can be exacerbated by immune responses to bacterial or viral infection of the respiratory tract (especially infections that elicit TH2 responses)
Urticaria
Hives – caused by release of histamine by mast cells in the skin
Angioedema
Inflammation caused by activation of mast cells in deep subcutaneous tissue – swelling is more diffuse than observed for urticaria
What are the 3 strategies used to reduce the effects of allergic disease?
- Modification of patient’s behavior and environment
- Pharmacological approach
- Immunological treatment
How do antihistamines work?
They prevent histamine from binding to H1 histamine receptors on vascular endothelium – reduce rhinitis and urticaria
How do corticosteroids work for hypersensitivity?
They suppress leukocyte function and are used to treat chronic inflammation of asthma, rhinitis, or eczema
How does cromolyn sulfate work for hypersensitivity?
It’s used as a prophylactic inhalant and it prevents degranulation of activated mast cells and granulocytes
How does desensitization work?
It modulates the immune response to shift it to an IgG response. Give a series of injections with increasing doses of allergen to change the TH2 response to a TH1 response
What type of vaccine would you give to someone to reduce hypersensitivity?
Vaccination with allergen-derived peptides that are known to be presented by HLA class II molecules to TH2 CD4 cells in an attempt to induce anergy
T or F: Most IgE induced is parasite-specific.
F: only a small percentage is parasite-specific, the remainder is highly heterogeneous and represents the product of a non-specific polyclonal B and T cell activation by the parasite
Who wins in competition for binding to FCeRI receptors: nonspecific IgE or parasite-specific IgE?
Nonspecific IgE
Type II hypersensitivity reactions can be associated with the administration of what drugs?
Penicillin, quinidine, and methyldopa
How do drugs cause type II hypersensitivity?
The chemically active drugs bind to the surface of RBCs or platelets and create new epitopes to which the immune system is not tolerant
In penicillin-induced hypersensitivity, new epitopes generated by penicillin stimulate the production of ____ and ____ antibody specific for the new epitopes.
IgG and IgM
What is the end result of penicillin-induced type II hypersensitivity?
Destruction of RBCs
Type III hypersensitivity reactions are caused by __________.
Immune complexes formed from IgG and soluble antigens
What is more efficient at fixing complement: large immune complexes or small immune complexes?
Large immune complexes
Small immune complexes tend to ___________.
Remain in circulation and become deposited along blood vessel walls
What is an Arthus reaction?
An inflammatory response created by a type III hypersensitivity reaction
How can systemic type III hypersensitivity reactions be caused?
By IV administration of large quantities of antigen
How do you get serum sickness?
From immune responses to non-self material administered into the bloodstream as a treatment for a variety of illnesses. It is caused by a systemic accumulation of immune complexes.
What are the 6 characteristics of serum sickness?
- Chills
- Fever
- Rash
- Arthritis
- Vasculitis
- Glomerulonephritis (sometimes)
What do transplant patients often receive to prevent rejection of transplanted tissues?
Large doses of monoclonal anti-T cell antibodies
Heart attack patients receive large injections of _______ to help degrade blood clots.
Streptokinase
Type III hypersensitivity can result from continual inhalation of antigens that ________.
Elicit IgG instead of IgE antibody responses
What are examples of type III hypersensitivities that result from workers being exposed to the same airborne antigens daily.
Farmer’s lung and bird-breeders disease
Type IV hypersensitivity reactions are mediated by _______.
Antigen-specific effector T cells
Type IV hypersensitivity reactions are also known as _____________.
Delayed-type hypersensitivity (DTH) – different than Ab-mediated hypersensitivities which are apparent within a couple minutes of antigen exposure
T or F: DTH reactions require much larger quantities of antigen due to inefficiency of antigen processing/presentation.
T
What are the most common antigens that elicit DTH responses?
Mycobacterial proteins, insect venoms, penadecacatechol (poison ivy), and small metal ions
What is the most well studied example of a type IV hypersensitivity reaction?
Tuberculin reaction (to test is someone has been infected with mycobacteria tuberculosis)
What is the response to initial contact with poison ivy?
Production of effector T cells and immunological memory, but little if any inflammatory response
What does penadecacatechol do upon initial contact with a poison ivy plant?
It penetrates the outer layers of the skin and forms covalent bonds with EC proteins and skin cell surface proteins, forming new antigens that are recognized as non-self. APCs take up the new antigens, return to secondary lymphoid tissues, and present peptide antigens on MHC Class II to naive CD4 cells. (or CD8 cells too!)
After initial exposure to poison ivy, each subsequent contact results in a rash that is mediated by _________.
Antigen-specific effector CTLs and antigen-specific TH1 cells that produce cytokines for macrophage activation and induction of inflammation
Why is poison ivy an example of contact sensitivity?
Because contact of the allergen with the skin is required to initiate the allergic response
What biological effects do tryptase, chymase, cathepsin G, and carboxypeptidase have?
Remodeling of connective tissue matrix
What do IL-4 and IL-13 do?
Stimulate and amplify the TH2-cell response
What do IL-3, IL-5, and GM-CSF do?
Promote eosinophil production and activation
What does TNF-alpha do?
Pro-inflammatory cytokine
What does CCL3 do?
It’s chemotactic for monocytes, macrophages, and neutrophils
What do LTC3, LTD4, and LTE4 do?
Cause smooth muscle contraction, increase vascular permeability, and cause mucus secretion
What does PAF do?
It’s chemotactic for leukocytes, amplifies production of lipid mediators, activates neutrophils, eosinophils, and duhhh platelets
What does mast cell granule release do in the GI tract?
Causes increased fluid secretion and peristalsis –> vomiting, diarrhea
What does mast cell granule release do to airways?
Decreases diameter and increases mucus secretion
