Immunopathology -- The Hypersensitivities

Review Chapter 14 - Type I Reactions

Read over the introduction to this chapter.  It gives a very good overview of the 4 types of hypersensitivity reactions. 

Type I - IgE mediated.  Allergic reactions.

Type II - IgG or IgM mediated cyotoxic reactions

Type III - IgG or IgM mediated immune complex reactions

Type IV -T_Hcell mediated, delayed hypersensitivity reactions

Type I Hypersensitivity - Anaphylaxis  (Local and Systemic) - Allergy (or Atopy) - Immediate Hypersensitivity.

The important aspects describing how an allergic response is triggered are shown in figure 14.2. 

If the response is localized it can be called local anaphylaxis if generalized throughout the body it is called systemic anaphylaxis.

First the individual needs to be sensitized to an allergen (antigen).  Sensitization  involves two things:  1.) an IgE response to an antigen and, 2.) the attachment of the IgE to high affinity Fc_eRI receptors on mast cells and basophils.

The mast cell/basophil is the effector cell in this response.

See the electron micrograph of this cell in Fig 14.1 and note the large granules filled with various inflammatory mediators and the fact that they are discharging in the second picture.

Once mast cells or basophils are coated with IgE , they become reactive with the allergen that caused the IgE to be made. 

The antigen cross-links the IgE on the surface of the cell and causes the cell to release and make mediators of inflammation.  (Note that mast cells can be activated by alternative mechanisms including C3a, C5a, some drugs, temperature and pressure, and lectins in certain foods.)

The preformed mediators of inflammation released by mast cells include:

Histamine – which causes smooth muscle contraction and increased vascular permeability and vasodilation – in systemic reactions this results  in bronchoconstriction and loss of fluids from blood vessels (edema).

Cytokines and Chemokines – GM-CSF, IL-5, TNFa, IL-8, eosinophil chemotactic factor (ECF ) work together to mobilize a variety of WBC’s and attract them to the area. Inflammation increases.

Newly synthesized mediators include:

Leukotrienes – also previously known as SRS-A, which cause prolonged slow contraction of smooth muscle.  Especially important in asthma.

Thromboxanes and Prostaglandins – increased vascular permeability, bronchoconstriction and chemotaxis

Platelet activating factor – small amounts of this can cause shock – it is both bronchoconstricting and vasodilating.

This initial process is summarized in Figures 14.4:

In many individuals this is as far as it goes.  However in some patients, particularly those with asthma, a late-phase reaction may occur.

In these individuals, the accumulated polys and eosinophils become activated and release more inflammatory mediators leading to airway hyperreactivity and tissue damage.  These events are summarized in Fig. 14.5.

Please read about Clinical tests and interventions.  Also about the “real” role for IgE in the immune response.