Hypersensitivity Flashcards
Major mediators of Type I hypersensitivity
IgE and Mast Cells or Eosinophils
Types of hypersensitivity reaction
Major mediators of Type II hypersensitivity
Autoreactive IgG/IgM and sometimes effector mediators of IgG (neutrophils, macrophages)
Major mediators of Type III hypersensitivity
Immune-complex-forming antibodies against soluble antigens, complement, and chronic inflammatory cells recruited to sub-endothelial immune-complex deposits.
Major mediators of Type IV hypersensitivity
CD4 and CD8 T cells and downstream effector cells driven by T-cell-derived cytokine production
Atopy
Presdisposition to developing allergies. Sometimes used synonymously with allergy.
Sensitization phase of allergy
Activation of Th2 and IL-4-secreting Tfh cells, which lead to ε heavy chain class-switching and IgE production in B cells. The IgE produced then binds to the surface of mast cells, basophils, and eosinophils via FcεRI.
Distinct phases of Type I hypersensitivity
The immediate effects are mediated by mast cell degranulation, but there is also a late-phase reaction.
This late-phase reaction happens several hours following exposure and is the characterized by infiltration of neutrophils and eosinophils in response to the mast cell signals. It is these cells which are the culprit in tissue damage associated with repeated bouts of allergic reactions.
Development of an allergy diagram
Kinetics of allergy
Genes with variants that predispose to development of allergies
IL-4
IL-4R
IL-13
IL-5
Filaggrin
Filaggrin
Protein required for barrier protection in skin. Mutations predispose to development of allergies early in life, especially atopic dermatitis.
FcεRI signaling
Principal cells involved in late-phase reaction
neutrophil
eosinophil
Th2
Late-phase reactions are stimulated by. . .
. . . IL-4 and TNF-α derived from mast cell degranulation.
Most of the actual tissue damage associated with allergy is caused by. . .
. . . eosinophil-derived proteases cleaving structural proteins.
hay fever
Allergic reaction to inhaled antigens, such as ragweed pollen antigens. This results in allergic sinusitis and rhinitis, initiated by mast cells in the nasal mucosa.
Increased mucus production and late-phase inflammation occur as a result of mast cell degranulation and Th2 activation locally.
food allergy
Ingested antigens trigger intestinal mast cell activation. Results in increased peristalsis which may cause diarrhea and vomitting.
More severe symptoms such as anaphylaxis may occur if the antigens are absorbed and become systemic.
asthma
Characterized by difficulty breathing, wheezing, coughing, and airway obstruction in response to a respiratory allergen which activates bronchial mast cells.
chronic asthma
In chronic cases of asthma, baseline eosinophilia of the airway is common, and mucus production in the airway is ramped up. Bronchial smooth muscle also hypertrophies and thus becomes hyper-reactive to various stimuli.
May be IgE-dependent or -independent, in which case cold or exercise may trigger asthma attacks.
Anaphylaxis
Systemic reaciton characterized by rapid edema in various tissues, including the larynx, and precipitous drop in blood pressure (anaphylactic shock), as well as bronchoconstriction.
A result of systemic mast cell degranulation.
Treatment for anaphylaxis
Epinephrine to contract vascular smooth muscle and relieve shock symptoms, as well as acting as a bronchodilator to counter bronchoconstriction symptoms.
Treatments for asthma
Corticosteroids, leukotriene antagonists, and β adrenergic receptor agonists.
Cromolyn
Inhibits mast cell degranulation
Isotypes of antibody which bind to Fcγ receptors on neutrophils and macrophages and promote activation
IgG1 and IgG3
Pernicious anemia
Anemia caused by B12 deficiency resulting from either diet or loss of intrinsic factor.
May be autoimmune in origin, if the immune system targets parietal cells for destruction or neutralizes intrinsic factor.
Type II vs Type III Hypersensitivity manifestations
Type II will usually be tissue localized depending on the antigens involved.
Type III will manifest as systemic vasculitis and will focus around tissues with turbulent flow that are susceptible to IC deposition, such as synovial joints and kidneys.
Serum sickness
First discovered Type III hypersensitivity disease. Occurs following administration of antiserum. Produces ciruclating immune complexes which then mediate disease.
This may result from host antibodies and injection of foreign antigen within the blood as well. Some humanized mAbs may also serve as antigens for serum sickness ICs.
Arthus reaction
A localized form of Type III hypersensitivity. Induced by subcutaneous administration of protein antigen. Results in local IC formation and local vasculitis.
In a small percentage of vaccine recipients who have previously been vaccinated or already have antibodies against the vaccine antigen, a painful swelling that develops at the injection site represents a clinically relevant Arthus reaction.
In human immune complex diseases, the antibodies may be specific for ___.
In human immune complex diseases, the antibodies may be specific for self antigens or microbial antigens
Systemic lupus erethymatosus as a Type III hypersensitivity disease
In systemic lupus erythematosus, immune complexes of anti-DNA antibodies and DNA can deposit in the blood vessels of almost any organ, causing vasculitis and impaired blood flow, leading to a multitude of different organ pathologies and symptoms
Example of bacterial antigen-induced Type III hypersensitivity from Microbiology
Poststeptococcal glomerulonephritis
Where does delayed-type hypersensitivity get its name?
Because it occurs 24 to 48 hours after an individual previously exposed to a protein antigen is re-challenged with the antigen (i.e., the reaction is delayed). The delay occurs because it takes several hours for circulating effector T lymphocytes to home to the site of antigen challenge, respond to the antigen at this site, and secrete cytokines that induce a detectable reaction.
Example of a purposefully induced Type IV Hypersensitivity reaction with clinical utility
Purified protein derivative tests
Think 48-72 hour followup appointments to read a tuberculosis PPD test.
