An Attack on Self Tissues

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An Attack on Self Tissues

W hen the immune system mistakes self tissues for nonself and mounts an inappropriate attack, the result is an autoimmune disease.

There are many different autoimmune diseases. Some examples are Wegener's granulomatosis, multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis.

Autoimmune diseases can each affect the body in different ways. For instance, the autoimmune reaction is directed against the brain in multiple sclerosis and the gut in Crohn's disease. In other diseases, such as systemic lupus erythematosus (lupus), affected tissues and organs may vary among individuals with the same disease.

Many autoimmune diseases are rare. As a group, however, they afflict millions of Americans. Most autoimmune diseases strike women more often than men, particularly affecting women of working age and during their childbearing years.

FIGURE 1. Cells of the immune system potentially involved in demyelination. APCs can take up Antigen or Ag from a foreign source (such as an invading pathogen) or from self-tissue (myelin or oligodendrocyte proteins)

(no. 1). Ag is processed into peptides, which are loaded onto MHCs and presented to T cells via the TCR

(no. 2). Activated cytolytic T cells (Tc, activated by MHC class I on APCs) cause damage by direct lysis of the target
(no. 3). Th cells (activated by MHC class II) release inflammatory cytokines that are directly damaging to tissue and also activate monocytes/macrophages (Mϕ)

(no. 4). T cells may be specific for self-tissue (direct damage), specific for a tissue-resident pathogen (bystander damage), or cross-reactive with pathogen and self-epitopes (molecular mimicry). Surface Ag (foreign or self) is recognized by B cells via the BCR

(no. 5). Upon receiving T cell help (no. 6), the B cell secretes Abs specific for self or dual specific for foreign and self-epitopes (molecular mimicry)

(no. 7). The binding of Ab to tissue may interfere with biological function

(no. 8). Abs can also simultaneously bind to and activate Mϕ via its FcR (Fc), which mediate tissue damage

(no. 9). Damaged tissue releases self-Ag, including new Ags not involved in the initial activation

(no. 10), which are taken up by APCs (epitope spread)

(no. 11). This further propagates the self-reactive immune response and leads to additional tissue damage. The immune system is a complex network of specialized cells and organs. When it malfunctions, it can cause a wide array of problems. Scientists are making great strides in detecting, treating, and preventing disorders of the immune system.

Inappropriate Immune Responses

In some people, a usually harmless substance such as a food, pollen or animal dander provokes the inappropriate immune response known as allergy.

In 1967 a husband and wife team of NIAID-supported scientists discovered the IgE antibody that causes most allergic reactions.

Nonallergic people produce small amounts of this antibody, but allergy sufferers produce vast quantities as a reaction to allergens.

The IgE antibodies bind to two types of cells, basophils (circulating in blood) and mast cells, that are plentiful in the lungs, skin, tongue, and linings of the nose and intestinal tract. These cells then release histamines and other chemicals that cause allergic symptoms.

When the susceptible person encounters the same allergen again, it attaches to the IgE antibodies already bound to basophils and mast cells, starting the same chain reaction.

Anatomy of an allergic reaction

Inner-City Asthma Study

In 1997, a large NIAID-supported study documented that a combination of cockroach allergy and exposure to insects is a major cause of asthma-related illness and hospitalizations among inner-city children.

Scientists with NIAID's National Cooperative Inner-City Asthma Study looked at 476 children living in the New York City area. Most were either African American (78%) or Hispanic (16%). The researchers measured levels of cockroach, dust mite, and cat allergens in the children's homes. They also tested the children for allergies to these substances and assessed the severity of the children's asthma over the previous 12 months.

Risk factors

Their discovery: children who were both allergic to cockroaches and exposed to high levels of cockroach allergens were hospitalized for asthma 3.3 times more often than children who had only one of these two risk factors. In contrast, neither dust mite nor cat allergens was so closely associated with more severe asthma.

Little boy with "spacer" bag

As part of the Inner City Asthma Project, this little boy is using a "spacer," a device that can be added on to an inhaler.

A spacer allows for greater dispersion of the aerosol medication that's expelled from the inhaler.

The study's findings will aid efforts to prevent and treat asthma in high-risk populations. That is an important public health goal--asthma-related deaths rose 118% from 1980 to 1993 among Americans younger than age 25.

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