CH. 13-15: Hypersensitivity Flashcards
Describe sensitization, activation, and effector phases of hypersensitivity I.
- upon 1st exposure, IgE is produced and binds to Fc-epsilon-RI receptors on mast cells and basophils
- on re-exposure, allergen cross-links IgE on mast cells, leading to degranulation and release of histamine, leukotrienes, and prostaglandins
Effector phase of hypersensitivity I: What are performed mediators?
- stored in granules
- cytokines released by mast cells undergoing degranulation plays a role in attracting and activating inflammatory cells locally
Effector phase of hypersensitivity I: What are newly synthesized mast cell mediators?
- consists of substances synthesized from membrane lipids
- extends duration and severity of allergic responses, results in tissue damage and recruitment of other immune cells
Effector phase of hypersensitivity I: Describe the late-phase reaction.
- early phase release of chemokines and cytokines during mast cell activation; attracts inflammatory cells to site of allergen exposure
- mostly eosinophils and neutrophils
- generates a 2nd, milder wave of smooth muscle contraction and sustained edema (swelling)
Describe environmental, pharmacological, immunologic intervention of hypersensitivity I.
environmental:
- avoid exposure to known allergens
- use of masks and air filters
pharmacological:
- bronchodilators: allows expansion of air passages of lungs
immunologic:
- desensitization = increases synthesis of IgG specific for allergen, in which, IgG binds and removes allergen before it has a change to react with IgE; eventually leads to prolonged decrease of IgE
- use of humanized IgE monoclonal antibody and miRNA
Describe the (3) different destruction mechanisms of hypersensitivity II.
- complement activation —> formation of MAC and cell lysis
- opsonization and phagocytosis by macrophages
- antibody-dependent cellular cytotoxicity (ADCC) by NK cells
Describe antibody-mediated cellular dysfunctions in hypersensitivity II.
- when autoantibodies bind to cell-surface receptors, they impair cell function without causing cell injury or inflammation
Describe the major phases of hypersensitivity IV.
- upon initial exposure, antigen is present to naive CD4+ T cells by APCs, leading to generation of memory Th1 or Th17 cells
- upon re-exposure, memory T cells release cytokines that recruit macrophages and cytokines CD8+ T cells to site, causing inflammation and tissue destruction
What is the general mechanism of hypersensitivity I? What cells and antibodies are involved? What is the timing? Name an example.
- caused by allergens
- mast cells, basophils, eosinophils
- IgE
- seconds to minutes
- ex. allergic rhinitis, asthma, anaphylaxis
What is the general mechanism of hypersensitivity II? What cells and antibodies are involved? What is the timing? Name an example.
- antibodies (IgG or IgM) bind to antigens on surfaces of host cells, marking them for destruction (3 different ways)
- macrophages, neutrophils, NK cells
- IgG or IgM
- hours to days
- ex. hemolytic anemia, Goodpasture syndrome, Rh incompatibility
What is the general mechanism of hypersensitivity III? What cells and antibodies are involved? What is the timing? Name an example.
- immune complexes (antigen-antibody complexes, mainly with IgG) form in excess and deposit in tissues
- these complexes activate complement system, leading to recruitment of neutrophils and inflammation; tissue damage
- neutrophils, macrophages
- IgG or IgM
- hours to days
- ex. systemic lupus erythematosus (SLE), serum sickness
What is the general mechanism of hypersensitivity IV? What cells and antibodies are involved? What is the timing? Name an example.
- does not involve antibodies; mediated by T cells
- CD4+ T cells (Th1, Th17), CD8+ T cells, macrophages
- 48 to 72 hours
- ex. contact dermatitis, TB skin test, graft rejection
