Hypersensitivity reactions are exaggerated or inappropriate immune responses to benign antigens. It is the immune response, not the antigens that are harmful to the host. Generally speaking, hypersensitivity reactions occur in response to external stimuli (antigens), whereas autoimmune reactions (see Chapter 66) occur in response to internal stimuli (antigens). The term allergy is often equated with hypersensitivity but more accurately should be limited to the immunoglobulin (Ig) E-mediated reactions discussed later in the section “Type I: Immediate (Anaphylactic) Hypersensitivity.” Note that many autoimmune diseases have pathologic features of one or more hypersensitivity reactions. This chapter will cover the patterns of hypersensitivity reactions using examples of diseases in which there are known external triggers. Chapter 66 will cover autoimmune diseases in which the immune reactions are largely against are self antigen(s).
These reactions are antigen-specific, meaning that the first contact with the antigen sensitizes the immune system (i.e., primes the adaptive immune system), and subsequent contacts elicit the hypersensitive (allergic) response. Within an individual, these subsequent antigen exposures elicit similar clinical manifestations, although the severity of the hypersensitivity reactions may increase with time.
Hypersensitivity reactions can be subdivided into four main types. Types I, II, and III are antibody-mediated, whereas type IV is cell–mediated (Table 65–1). Type I reactions are mediated by IgE, whereas types II and III are mediated by IgG. The immunologic reactions are summarized in Table 65–1. The clinical manifestations of the hypersensitivity reactions are described in Table 65–2.
Table 65–1Immunologic Aspects of Hypersensitivity Reactions |Favorite Table|Download (.pdf) Table 65–1 Immunologic Aspects of Hypersensitivity Reactions
|Type ||Sensitization ||Immunologic Reaction |
I (Immediate, anaphylactic)
|Antigen (allergen) induces IgE antibody that binds to mast cells and basophils. ||When exposed to the allergen again, the allergen cross-links the bound IgE on those cells. This causes degranulation and release of mediators (e.g., histamine). |
|Antigens on a cell surface elicit Tfh and B-cell activation. ||Antibody binding to cell membrane antigens leads to complement-mediated lysis of the cells (e.g., transfusion or Rh reactions) or autoimmune hemolytic anemia. |
III (Immune complex)
Multiple types of antibodies
|Soluble antigens elicit Tfh and B-cell activation. ||Antigen–antibody immune complexes are deposited in tissues, complement is activated, and polymorphonuclear cells are attracted to the site. They release lysosomal enzymes, causing tissue damage. |
|CD4 and/or CD8 T cells sensitized by protein antigens. ||Memory T cells release cytokines upon second contact with the same antigen. The lymphokines induce inflammation and activate macrophages, which, in turn, release various inflammatory mediators. |
Table 65–2Clinical Manifestations of Hypersensitivity Reactions |Favorite Table|Download (.pdf) Table 65–2 Clinical Manifestations of Hypersensitivity Reactions
|Type ||Typical Time of Onset ||Clinical Manifestation or Disease |
|I (Immediate, anaphylactic) ||Minutes ||Systemic anaphylaxis, urticaria (hives), asthma, hay fever, allergic ...|