1 Immune System Disorders and Immune Dysfunction

How immune defenses work

The immune system detects and helps eliminate infectious agents and other threats while limiting damage to the body’s own tissues. Its defenses include physical barriers, immune cells, and soluble proteins such as antibodies and complement.

Innate and adaptive defenses work together. Innate responses can act quickly and help activate adaptive responses, while adaptive responses can enhance innate mechanisms.

Rapid innate defenses

Innate immunity is the rapid, broadly acting first response. Skin and mucosal surfaces help block entry. If these barriers are breached, neutrophils and macrophages can engulf microbes, natural killer cells can destroy some infected cells, and inflammatory signals can recruit or activate other defenses. Complement proteins can mark microbes for removal or contribute to their destruction.

Innate recognition responds to common patterns associated with microbes or tissue damage rather than to one uniquely identified antigen.

Antigen-specific adaptive defenses

Adaptive immunity is more antigen-specific and develops after exposure. B cells can become plasma cells that secrete antibodies. Antibodies bind particular antigens and can neutralize them or help other immune defenses remove them. T cells coordinate immune activity or kill infected cells, and antigen-presenting cells, including dendritic cells, help initiate many T-cell responses.

After an infection or vaccination, some B and T cells persist as memory cells. During an initial encounter with a new virus, innate defenses respond first while adaptive cells are activated; later, memory cells can recognize the virus and mount a more rapid, targeted response.

When immune responses cause harm

Hypersensitivity describes an inappropriate or exaggerated immune response that can injure tissues. The traditional Gell–Coombs classification groups reactions into four mechanisms, and a single condition can involve more than one.

• Type I — immediate: IgE and activated mast cells release inflammatory mediators. Examples include hives or anaphylaxis after exposure to an allergen.

• Type II — antibody-mediated: Antibodies bind antigens on cells or tissues and can activate complement or other destructive mechanisms. Some immune-mediated hemolytic anemias are examples.

• Type III — immune-complex: Antigen–antibody complexes deposit in tissues and provoke inflammation. Serum sickness is an example.

• Type IV — delayed, T-cell-mediated: Sensitized T cells cause tissue injury, often over hours to days. Allergic contact dermatitis, such as a reaction to poison ivy, is an example.

These categories describe mechanisms, not severity. Type I reactions range from localized symptoms to life-threatening anaphylaxis, and the other types can also cause significant tissue injury.

Inadequate immune protection

Immunodeficiency is a defect in immune-system development or function that increases vulnerability to infection and may also be associated with other complications. Defects can affect antibody-producing B cells, T cells, both cell types, phagocytes, or complement.

Primary immunodeficiencies, also called inborn errors of immunity, arise from genetic defects. Depending on the affected component, a person may have repeated or unusually severe infections, infections with opportunistic organisms, or other immune-related problems. An antibody-production defect can impair defense against certain bacteria, whereas a T-cell defect can increase susceptibility to some viral, fungal, and opportunistic infections. These are broad patterns, not rules for diagnosing an individual.

Secondary immunodeficiencies develop because of an external condition or exposure and are more common than primary forms. Causes include HIV infection, undernutrition, some systemic illnesses, prolonged serious illness, and immunosuppressive treatments such as chemotherapy or radiation. Their impact depends on the cause and the immune functions affected; some secondary impairments may improve if the underlying cause is addressed.

Recognizing and evaluating possible deficiency

Recurrent infections alone do not prove immunodeficiency: common exposures and other medical conditions can also explain them. Concern rises when infections are unusually severe, persistent, difficult to treat, caused by uncommon organisms, or accompanied by a suggestive family history.

Clinical assessment combines a person’s history and examination with tests selected to evaluate likely immune components. Examples include blood-cell counts, immunoglobulin levels, vaccine-antibody responses, and specialized immune-cell or complement tests. Infection patterns can offer clues about which defenses are impaired, but no single pattern establishes a diagnosis.