Hypersensitivity Flashcards
Type I hypersensitivity immune reactant
IgE
Hypersensitivity
An excessive immune response against foreign, often innocuous, antigens - which may result in tissue damage or death
Sensitization
The initial exposure to an antigen that primes the immune system to elicit a reaction to a subsequent exposure to that antigen
Allergen
Antigen that elicits immediate hypersensitivity
Allergy
A reaction caused by an allergen
Atopy
Familial predisposition (genetic) reaction to allergen
Cells involved in type I hypersensitivity
Mast cells, basophils, and eosinophils
Histamine
An amine derivative of histidine that is involved in vasodilation and increase capillary permeability
Where is histamine released from?
Exosomes; means immediate result (no transcription/translation)
What do mast cells and basophils release to mediate type I hypersensitivity reaction?
- Histamines
- Lipid mediators: Leukotrines and prostaglandins
- Cytokines
Leukotrienes function
Smooth muscle contraction, increase capillary permeability, and mucus secretion
Prostaglandins function
Vasodilation and increase capillary permeability, PMN recruitment
Cytokines involved in type I hypersensitivity with mast cells/basophils and their functions
TNF-alpha: proinflammatory cytokine
IL-4, IL-5, IL-13: Th2 response
Sensitization response
- ) Prior to the hypersensitivity reaction, the individuals must have been exposed to the allergen
- ) Prototypical immune response for adaptive immunology takes place
- ) Production of plasma cells that secrete allergen-recognizing IgE
- ) IgE associates with the Fc receptor (FcεRI) on mast cells and primes, or sensitizes it for quick activation
2 phases of immediate reaction
Effector or elicitation phase and late-phase reaction
Effector/elicitation phase in immediate reaction
- ) Exposure to the antigen again is immediately recognized by the IgE-bound antibody on mast cells (crosslinking of the FcεRI receptors activate mast cells)
- ) Activation of mast cells result in degranulation and release of mediators (the vasoactive amines and lipid mediators result in the immediate reaction)
Late-phase reaction in immediate reaction
- Cytokines result in this a few hours after exposure
- Few hours post exposure
- Accumulation of PMNs, eosinophils, basophils, T helper cells, and their mediators
- May occur without prominent immediate reaction
Immediate reaction in immediate hypersensitivity
- Seconds to minute exposure
- Histamine and lipid mediators increase vascular permeability
- Wheal-and-flare response
Wheal
Redness and local swelling due to initial vessel dilation
Flare
Subsequent dilation promotes red rim
Chronic allergic inflammation
repeated exposure that results in persistent inflammation – may alter tissue (asthma, eczema, hay fever)
Immediate hypersensitivity anaphylaxis
Systemic activation of mast cells (such as from a bee sting) can lead to severe anaphylaxis
Anaphylaxis leads to…
Widespread vascular permeability and fluid leaving blood, may cause BP to drop
Clinical features of anaphylaxis
Resp: nasal obstruction, increased mucus, dyspnea, wheezing
CV: hypotension, shock
Skin: urticaria, angioedema, pruritus, erythema
GI: pain, nausea, diarrhea
Hematological: thrombocytopenia, DIC
How does epinephrine counteract the disease state during anaphylaxis?
Vascular smooth muscle contraction, increased cardiac output, and inhibit mast cell degranulation
Hygiene hypothesis
- Allergy is on the rise in developed countries
- Treg cells and IL-10 production capacity are low
- skew towards Th2 response
- IgE, IL-4, IL-5, IL-13
Function of chemokines in type I hypersensitivity
Recruit PMNs, monocytes, and macrophages
Late-phase reaction in immediate hypersensitivity
- Few hours post exposure
- Accumulation of PMNs, eosinophils, basophils, T helper cells, and their mediators
- May occur without prominent immediate reaction
Immediate hypersensitivity clinical responses
- Food/drug allergies (hives, anaphylaxis, flushing, angioedema)
- Atopic dermatitis (eczema)
- Atopic urticaria (hives)
- Atopic rhinoconjunctivitis (allergic rhinitis, hay fever)
- Asthma
Genetics of atopy (reaction to allergen)
MHCII, TCR-alpha, IL-4, FcεRI, and Th1/2 balance
IL-10 function
- Elevated in helminth infested individuals
- Blocks mast cell degranulation
Type I hypersensitivity diagnostics
- Application (skin prick or intradermal injection) of allergen in skin to visualize wheal and flare
- Blood test to detect specific IgE (results take days)
Type I desensitization
To gradually decrease IgE-dominant response towards IgG or Treg response (IL-10)
Type II hypersensitivity
- Antibody mediated disease caused by anti-tissue antibody
- Main antibody – IgG, IgM
- Antibody targets tissues or extracellular matrix
- 2 - 24 hours
Effector mechanisms of type II hypersensitivity
- ) Opsonization and phagocytosis
- ) Complement and Fc receptor-mediated inflammation
- ) Abnormal physiologic response w/o injury
HDNB
Rh- mothers may carry an Rh+ fetus; fetal erythrocytes enter mother’s circulation during childbirth and anti-Rh antibodies produced in the mother; subsequent pregnancies in which the fetus is Rh+ may result in fetal erythrocyte destruction due to IgG crossing placenta (RhIG administration w/i 72 hours after first Rh+ birth)
Type II hypersensitivity reactions
Blood transfusions Autoimmune hemolytic anemias Autoimmune thrombocytopenic purpura Goodpasture syndrome Pemphigus vulgaris Penicillin sensitivity (non allergic) Acute rheumatic fever
Grave’s
receptor of thyroid gland targeted by TSI (triggers production of TSH); symptoms: irregular heartbeat, bulging eyes, anxiety, heat sensitivity, weight loss, goiter
Myasthenia gravis
- Autoantibody targets acetylcholine receptors
- Blocks acetylcholine binding, resulting in defective neuromuscular transmission
- Symptoms: muscle weakness, localized paralysis, strabismus (eye misalignment), ptosis (drooping eyelids), difficulty swallowing
Type III hypersensitivity
- Antibody mediated disease caused by immune complexes
- Main antibody – IgG, IgM
- Antibody targets soluble antigen
- Hours, days, weeks
Effector mechanisms of type III hypersensitivity
- Immune complex formation (normally cleared by classical complement and phagocytes)
- Certain immune complexes may get deposited on tissue
- Phagocytes (PMNs) recognize antibody via Fc receptors and complement via CRs (receptors activate cells to secrete inflammatory mediators»tissue inflammation and injury)
Most common sites of immune complex deposition
Small arteries (vasculitis) Renal glomeruli (nephritis) Joint synovium (arthritis)
Serum sickness
- Individuals w/ no prior exposure
- Antitoxin administration from horse serum
- Controls toxin but mounts response against horse antibodies
- Symptoms: fever, weakness, rash, edema (7-21 days later)
Arthus reaction
- Localized form of type III hypersensitivity that causes vasculitis
- Subcutaneous antigen is delivered to a previously immunized individual to that antigen
- Antibody-antigen complexes form in the area of injection
- Symptoms: inflammation, pain, and necrosis in severe cases
Type III hypersensitivity reactions
Systemic lupus erythematosus
Polyarteritis nodosa
Granulomatosis with polyangiitis (Wegener’s disease)
Farmer’s lung
Type IV hypersensitivity
-Type IV hypersensitivity is also delayed type hypersensitivity (DTH)
-Cell-mediated reaction
Th1
Th2
CTL (CD8+)
-2 days to weeks post exposure
Effector mechanisms of type IV
-Antigen processed by APC,
-Th1 activated (IFN-gamma, macrophage activation and inflammatory mediators released)»tissue damage
-Th2 cells are activated
IL-5 – Eosinophil activation and inflammatory mediators released»tissue damage
-Th17 cell are activated
IL-17 – PMN recruitment and activation»tissue damage
-CTL activation – direct cytotoxicity of recognized MHCI-antigen
Basis of tuberculin/PPD/Mantoux test
- Individuals who have had Mycobacterium tuberculosis infection have produced memory CD4+ T cells to mycobacterial antigens
- Exposure to PPD (tuberculin purified protein derivative) will activate these memory CD4+ T cells, release proinflammatory cytokines, and recruit macrophage, resulting in an indurated skin lesion 48-72 hours later
Allergic contact dermatitis
- skin inflammation including pruritic papules and vesicles on an erythematous base
- Upon first contact with an allergen, sensitization may take 10 - 14 days (Langerhans cells (DCs))
- Subsequent contact = hours to days (T cell mediated)
- most common chemicals that cause ACD are:
- Nickel Preservatives, dyes, and fragrances
- Chemicals in rubber gloves
- Many are haptens
Poison Ivy
- ACD reaction
- component of plant penetrates skin and associated with proteins in keratinocytes
- Primary exposure: memory T cells
- Secondary exposure: Th1, macrophage, and CTL cells target skin
Chronic DTH reactions
- Cell types involved derived from macrophages
- Epithelioid cells
- Multinucleated giant cells
- Tissue damage due to size and location of granuloma
- Granulomas often form in diseases with persistent antigen
- Tuberculosis
- Leprosy
- Leishmaniasis
Type IV hypersensitivity reactions
Hashimoto thyroiditis Rheumatoid arthritis Type I Diabetes Celiac disease Crohn disease Multiple Sclerosis
