Allergic asthma

Principles to understand

• T_H2 cells help B cells make IgE (this is mediated by IL-4). recall that IgE is much more potent that IgG

• IgE + antigen makes mast cells degranulate

• mechanism of action of histamine, leukotrienes

• range of reactions mediated by IgE depends on dose and route of antigen

• mechanism of action of “allergy shots”

• general concepts of Type I, II, III, IV reactions

Rhinitis

• first exposure to pollen

• if lots of T_H2 cells are around, IL-4 is produced, leading to IgE production. if lots of T_H1 cells are around, IL-2 is produced, and lots of complement-fixing IgG is produced

• in the absence of antigen, IgE, produced by B cells in response to IL-4, binds to Fc receptors of mast cells

• in a couple of weeks, the second exposure to pollen leads to activation of mast cells coated with anti-pollen IgE

• crosslinking of IgE causes mast cells to degranulate

Mast cells

• you need your mast cells, so you can’t just get rid of mast cells with the intent of curing asthma

• the signal that makes the mast cells degranulate is the clustering of surface IgE bound to antigen

• similarly, crosslinking of immunoglobulins, or, more specifically, clustering of surface IgG, is the mechanism by which B cells are stimulated to turn on when they see a big polysaccharide antigen

Acute responses and chronic responses in asthma

• acute responses

  • more mucus is produced in bronchi lumen; smooth muscle contracts; overall, your airways narrow

  • inflammatory mediators also act on blood vessel cells in the same ways we’ve been talking about

• chronic responses

  • if you are a T_H2 type person, any antigen processed will be processed in a T_H2 environment and you will be predisposed to allergic responses

  • T­_H2 cells make all interleukins they normally make, including IL-5, which stimulates eosinophils

  • all the eosinophil products cause permanent hypertrophy of your smooth muscle, permanent increase in mucus secretion, and scarring

  • remember, “mast cells degranulate when you even just say something mean to it”

  • when you have this kind of airway, you are susceptible to anything

Mast cell contents

• enzymes

  • tryptase, chymase, cathepsin G, carboxypeptidase

  • important for remodeling connective tissue matrix

  • however, it also destroys the basement membrane, causing scarring

• toxic mediators

  • histamine, heparin

  • these are toxic to parasites

  • increase vascular permeability

  • cause SM contraction

• cytokines

  • appropriate for starting your response up

  • IL-13, IL-4: T_H2 cells

  • IL-3, IL-5, GM-CSF: eosinophils

  • TNFα: inflammation, activation of endothelium

• chemokine: CCL3

• lipid mediators

  • leukotrienes: SM contraction, ↑vascular permeability, mucus secretion; this is a more delayed response because leukotrienes are not preformed

  • PAF attracts leukocytes, amplifies production of lipids, activates neutrophils, eosinophils, platelets

• so, mast cells are good at turning on the entire immune response as well as mediating allergies

Category: Pathology Notes