Herlihy anaphylaxis Flashcards
Describe the sequence of events that occurs in the early and late phase of type 1 hypersensitivity that culminates in anaphylaxis
1.Immediate Phase (~Minutes)
a. Following initial antigen exposure, Th2 cells secrete IL-4 and IL-13, promoting B cell class switching to produce IgE. This IgE binds to FcεRI receptors on mast cells, sensitizing them.
b. Upon re-exposure, allergen cross-links mast cell-bound IgE, triggering mast cell degranulation. This releases preformed mediators (e.g., histamine, tryptase, chymase) and newly synthesized lipid mediators (e.g., prostaglandin D2, leukotriene C4, platelet-activating factor).
c. These mediators cause bronchoconstriction, vasodilation, increased vascular permeability, and smooth muscle contraction, leading to hypotension, airway obstruction, gastrointestinal symptoms, and urticaria in systemic anaphylaxis.
2.Late Phase (~2-6+ Hours)
a. The late-phase reaction occurs due to cytokine and lipid mediator recruitment of inflammatory cells (primarily eosinophils, basophils, and T cells).
b. Endothelial activation increases vascular permeability and facilitates leukocyte infiltration to sites of allergen exposure.
c. Eosinophils release toxic granules (major basic protein, eosinophil peroxidase, cationic proteins), causing tissue damage and amplifying the inflammatory response, leading to prolonged bronchoconstriction and tissue edema.
Define hypersensitivity and anaphylaxis
Hypersensitivity is a group of disorders characterized by abnormal immune responses, excessive or uncontrolled, against a self or foreign antigen.
Anaphylaxis is a systemic immediate type 1 hypersensitivity reaction characterized by tissue edema and hypotension secondary to vasodilation and vascular leak
Describe the 3 steps in naive T cell activation by antigen-presenting cell in the lymph node
In the lymph node, the DC interacts with a naïve CD4+ T cell via:
a. MHC-II + Allergen Peptide → T Cell Receptor (TCR) binding (antigen recognition).
b. CD80/CD86 → CD28 on the T cell (costimulatory signal for activation).
c. Cytokine signaling (determines T cell fate)
IL-4, IL-25, IL-33 –> Th2
IL-12 –> TH1
Name 3 criteria that suggest anaphylaxis
(1) Sudden onset and rapid progression of symptoms
(2) Life threatening airway, breathing, circulatory problems
(3) Skin and/or mucosal changes e.g. urticaria, angioedema, flushing
Describe the sequence of molecular events that occurs within the mast cell to cause degranulation via IgE-mediated degranulation
*IgE cross-linking of antigen causes activation of Lyn and Syk tyrosine kinases which phosphorylate tyrosine components of beta and gamma chains of the IgE receptor.
*Downstream activation of phospholipase C-gamma results in increase in IP3 and Diacylglycerol causing release of calcium from endoplasmic reticulum and protein kinase C activation.
*Calcium allows for fusion of mast cell granules with its plasma membrane triggering degranulation/exocytosis
Name 4 things that can cause non-IgE mediated mast cell degranulation
Complement proteins (C3a, C5a) – Bind to C3aR and C5aR on mast cells, triggering degranulation.
Certain venoms & toxins – e.g., bee venom (mellitin), wasp venom (mastoparan), snake venom can directly activate mast cells.
Drugs – e.g., opioids (morphine, codeine), radiocontrast agents, vancomycin, NSAIDs, neuromuscular blockers (rocuronium, succinylcholine) via MRGPRX2 receptor activation.
Bacterial toxins or physical stimuli – e.g., Staphylococcus aureus enterotoxins, lipopolysaccharides (LPS), heat, cold, mechanical pressure
MOA of sabutamol
-Binds to Beta 2 receptors of bronchial smooth muscle (GPCR)
-The alpha subunit dissociates and increases adenyl cyclase activity.
-Adenyl cyclase increases cAMP levels which subsequently activate protein kinase A.
-PKA phosphorylates mediators of calcium availability and myosin light chain kinase (inactivating it)
-There is therefore less calcium influx, reduced calcium release of SR and increases calcium storage.
-This causes bronchial smooth muscle relaxation.
-Salbutamol can also cause hyperpolarisation of smooth muscle cells by coupling with calcium-activated K+ channels.
Define atopy and sensitization
Atopy refers to the genetic predisposition to produce allergen-specific IgE thereby increases the chance of developing atopic conditions including eczema, allergic rhinitis and asthma.
Sensitization refers to the presence of allergen-specific IgE in the absence of clinical disease i.e. not allergic to the allergen.
What type of bacteria is Campylobacter jejuni? Explain its pathogenesis in causing symptoms when ingested.
gram-negative, curved, rod with flagella.
- Uses adhesins and its flagella to penetrate the intestinal mucus layer and interact with enterocytes.
- It is internalized by M cells in Peyer’s patches and enters intestinal epithelial cells via a Type IV secretion system.
- Infected epithelial cells release IL-8, recruiting neutrophils, which cause mucosal inflammation and destruction. Dendritic cells and macrophages also function to increase the inflammatory response.
- Cytolethal Distending Toxin (CDT) induces DNA damage, leading to epithelial apoptosis and further mucosal injury.
- The inflammatory response leads to crypt abscesses, mucosal ulceration, and increased vascular permeability.
- The resulting loss of absorptive surface and inflammation contribute to diarrhea, which is often bloody due to neutrophilic tissue damage and capillary leakage
