Allergy (Lec 10) Flashcards
allergies
hypersensitivity responses to allergens
Allergens
Environmental antigens
Allergy epidemic
every generation has more allergies than the previous
Allergies and parasites
- allergies are more frequent where parasites are eradicated
- Immune systems developing in areas with improved sanitation and healthcare, lack contact and context with our “old friends.”
- Old friends = certain mutualistic microorganisms and pathogens, especially helminth parasites
Atopy or Atopic individuals
predisposition to allergies due to genetics and environment
Basophils in TH2 response to parasites
- Basophils are recruited early on to produce key cytokines for TH2 responses.
- IgE secreted by plasma cells binds to receptor on basophils
- activated basophils induce class switching in B cells to stimulate IgE production
- IgE activates basophils to degranulate
IgE in mediating allergies
- B cells with a specific BCR get
activated and become plasma
cells that produce IgE - B cells have an IgE
receptor (FcεRII), lower affinity - Soluble FcεRII cross-links the B cell receptor (BCR) and B cell co-receptor
- Activates B cells to become plasma cells and produce IgE antibodies
Sensitization
allergies only occur after the first exposure to the antigen
Urticaria (Hives) or Angioedema
- type 1 allergic reaction in the skin
- localized allergic response mediated by mast cells
- antigen under the skin, low dose activates mast cell
- leads to increase vascular permeability which results in localized swelling
atopic dermatitis or eczema
Prolonged allergy response in skin (chronic and relapsing
Allergic conjunctivitis
- Type I Allergic Reaction in the Respiratory System
- itching, tears and inflammation of eyes
Allergic rhinitis or Hay fever
- Type I Allergic Reaction in the Respiratory System
- sneezing and runny nose in
response to inhaled antigen
Allergic asthma
- mucosal mast cell captures antigens
- inflammatory mediators contract smooth muscle, increase mucus secretion and increase blood vessel permeability
- chronic response mediated by cytokines and eosinophil products
Type 1 allergic reactions in the digestive system
- Food allergens induce intense smooth muscle contractions = vomiting and diarrhea
- ingestion of antigen activates mucosal mast cells
- activated mast cells release histamine, which acts on epithelium, blood vessels, and smooth muscle
Routes of allergen entry
- impacts severity of allergic response
- intravenous
- subcutaneous
- inhalation
- ingestion
Antigens entering through the bloodstream
- can result in systemic anaphylaxis
- antigen in bloodstream enters tissues and activates connective tissue mast cells throughout the body
- leads to mast-cell degranulation and release of inflammatory mediators
- Epi-pen (epinephrine) is the only way to improve symptoms
Type II Hypersensitivity Reaction
caused by an antigen binding to our cells and creating new epitopes for antibody recogntion
Mechanism of Type II Allergy: Penicillin
- penicillin modifies proteins on human erythrocytes (RBCs) to create foreign epitopes
- they are phagocytosed by macrophages
- macrophages present peptides from the penicillin protein conjugate and activate CD4 T cells to become TH2 cells
- B cells activated by antigen and activated TH2 cells
- plasma cells secrete penicillin-specific IgE which arms mast cells
- penicillin-modified erythrocytes activated armed mast cells, causes anaphylaxis
Type III Hypersensitivity Reactions
- mediated by immune complex formation (antigen:antibody complexes) that activate complement
- Fast and strong IgG reaction to large amount of antigen that is typically injected can result in Serum Sickness (transient/short-lived immune complex disease)
Therapeutic anti-IgE for Allergies
- only binds to soluble IgEs to prevent allergic reactions
- prevents mast cell from acquiring cell-surface IgE
- blocks binding site on IgE for FcεRI, mast cell cannot be activated
Type IV Hypersensitivity Reactions
- delayed allergic responses
- mediated by T cells, not mast cells
Stages of Delayed-Type Hypersensitivities (Type IV)
- little inflammation and low numbers of antigen-specific T cells result in delayed response (1-3 days post-exposure)
- contact-sensitizing agent = agents that modify proteins
and change their epitopes to
induce type IV hypersensitivity responses
Celiac Disease
- type IV hypersensitivity response caused by immune response to gluten, results in autoimmune features
- peptides naturally produced from gluten do not bind to MHC class 2 molecules
- an enzyme modifies them so they can bind
- when bound, it activates gluten-specific CD4 T cells
- activated T cells can kill mucosal epithelial cells, secrete IFN-y to produce cytokines and chemokines that recruit other inflammatory cells
