E 2.5: Hypersensitivity Allergy

Lecture 2.5: Hypersensitivity (Allergy)

Plan:

Type I (Anaphylactic) Reactions

Type II (Cytotoxic) Reactions

Type III (Immune Complex) Reactions

Type IV (Delayed Cell-Mediated) Reactions

The term hypersensitivity refers to an antigenic response beyond that which is considered normal; the term allergy is more familiar and is essentially synonymous. Hypersensitivity responses occur in individuals who have been sensitized by previous exposure to an antigen, which in this context is sometimes called an allergen. When an individual who was previously sensitized is exposed to that antigen again, his or her immune system reacts to it in a damaging manner. There are four principal types of hypersensitivity reactions: anaphylactic, cytotoxic, immune complex, and cell-mediated (or delayed-type) reactions (Table1).

Table 1

Types of Hypersensitivity

Type I (Anaphylactic) Reactions

The IgE antibodies produced in response to an antigen, such as insect venom or plant pollen, bind to the surfaces of cells such as mast cells and… Figure 1a The mechanism of anaphylaxis. IgE antibodies, produced in response to an antigen, coat mast cells and…

Systemic Anaphylaxis

Systemic anaphylaxis (or anaphylactic shock) can result when an individual sensitized to an antigen is exposed to it again. Injected antigens are…  

Localized Anaphylaxis

In allergies involving the upper respiratory system, such as hay fever, sensitization usually involves mast cells in the mucous membranes of the… Antigens that enter the body via the gastrointestinal tract can also sensitize… Gastrointestinal upset is a common symptom of food allergies, but it can also result from many other factors. Hives…

Type II (Cytotoxic) Reactions

Type II (cytotoxic) reactions generally involve the activation of complement by the combination of IgG or IgM antibodies with an antigenic cell. This activation stimulates complement to lyse the affected cell, which might be either a foreign cell or a host cell that carries a foreign antigenic determinant (such as a drug) on its surface. Additional cellular damage may be caused within 5 to 8 hours by the action of macrophages and other cells that attack antibody-coated cells.

The most familiar cytotoxic hypersensitivity reactions are transfusion reactions, in which red blood cells are destroyed as a result of reacting with circulating antibodies. These involve blood group systems that include the ABO and Rh antigens.

The ABO Blood Group System

In 1901, Karl Landsteiner discovered that human blood could be grouped into four principal types, which were designated A, B, AB, and O. This method of classification is called the ABO blood group system (Table 2).

Table 2

The ABO Blood Group System

A person's ABO blood type depends on the presence or absence of carbohydrate antigens located on the cell membranes of red blood cells (RBCs). Cells… When a transfusion is incompatible, as when type B blood is transfused into a…

The Rh Blood Group System

Blood Transfusions and Rh Incompatibility If blood from an Rh + donor is given to an Rh - recipient, the donor's RBCs stimulate the production of… Hemolytic Disease of the Newborn When an Rh - woman and an Rh + man produce a…

Figure 2 Hemolytic disease of the newborn.

 

HDNB is usually prevented today by passive immunization of the Rh - mother at the time of delivery of any Rh + infant with anti-Rh antibodies, which are available commercially. These anti-Rh antibodies combine with any fetal Rh+ RBCs that have entered the mother's circulation, so it is much less likely that she will become sensitized to the Rh antigen. If the disease is not prevented, the newborn's Rh + blood, contaminated with maternal antibodies, may have to be replaced by transfusion of uncontaminated blood.

Drug-Induced Cytotoxic Reactions

Blood platelets (thrombocytes) are minute cell-like bodies that are destroyed by drug-induced cytotoxic reactions in the disease called thrombocytopenic purpura. The drug molecules are usually haptens because they are too small to be antigenic by themselves; but when a platelet has become coated with molecules of a drug (quinine is a familiar example), and the combination is antigenic (Figure 3). Both antibody and complement are needed for lysis of the platelet. Because platelets are necessary for blood clotting, their loss results in hemorrhages that appear on the skin as purple spots (purpura).

Figure 3 Drug-induced thrombocytopenic purpura. Molecules of a drug such as quinine accumulate on the surface of a platelet and slImulate an immune response that destmys the platelet.

 

 

Type III (Immune Complex) Reactions

Figure 4 illustrates the consequences. These complexes circulate in the blood, pass between endothelial cells of the blood vessels, and become…

Type IV (Delayed Cell-Mediated) Reactions

Type IV reactions involve cell-mediated immune responses and are caused mainly by T cells. Instead of occurring within a few minutes or hours after a sensitized individual is again exposed to an antigen, these delayed cell-mediated reactions, (or delayed hypersensitivity) are not apparent for a day or more. A major factor in the delay is the time required for the participating T cells and macrophages to migrate to and accumulate near the foreign antigens. Transplant rejection is most commonly mediated by cytotoxic T lymphocytes, but other mechanisms are by antibody-dependent cell-mediated cytotoxicity or complement-mediated lysis.

Causes of Delayed Cell-Mediated Reactions

Sensitization for delayed hypersensitivity reactions occurs when certain foreign antigens, particularly those that bind to tissue cells, are phagocytized by macrophages and then presented to receptors on the T-cell surface. Contact between the antigenic determinant sites and the appropriate T cell causes the T cell to proliferate into mature differentiated T cells and memory cells.

When a person sensitized in this way is reexposed to the same antigen, a delayed hypersensitivity reaction might result. Memory cells from the initial exposure activate T cells, which release destructive cytokines in their interaction with the target antigen. In addition, some cytokines contribute to the inflammatory reaction to the foreign antigen by attracting macrophages to the site and activating them.

Delayed Cell-Mediated Hypersensitivity Reactions of the Skin

One delayed hypersensitivity reaction that involves the skin is the familiar skin test for tuberculosis. Because Mycobacterium tuberculosis is often located within macrophages, this organism can stimulate a delayed cell-mediated immune response. As a screening test, protein components of the bacteria are injected into the skin. If the recipient has (or has had) a previous infection by tuberculosis bacteria, an inflammatory reaction to the injection of these antigens will appear on the skin in 1 to 2 days.

Allergic contact dermatitis, another common manifestation of delayed cell-mediated hypersensitivity, is usually caused by haptens that combine with proteins (particularly the amino acid lysine) in the skin of some people to produce an immune response. Reactions to poison ivy (Figure 4), cosmetics, and the metals in jewelry (especially nickel) are familiar examples of these allergies.

Figure 4 Immune complex-mediated hypersensitivity.

Figure 5 The development of an allergy (allergic contact dennatitis) to catechols from the poison ivy plant. Pentadecacatechol is a mixture of…