Altered Immunity, Hypersensitivity, and Autoimmunity

1. Normal function first

Innate immunity is the fast, nonspecific first line of defense — physical barriers (skin, mucous membranes), cells such as neutrophils and macrophages that engulf microbes, and chemical defenses. It responds immediately but has no memory. Adaptive immunity is slower to start but highly specific and long-lasting, built on lymphocytes: B cells produce antibodies (humoral immunity), and T cells coordinate responses and kill infected cells (cell-mediated immunity). Central to healthy function is tolerance — the process by which the immune system learns not to attack the body's own tissues, established partly by deleting or silencing self-reactive lymphocytes during development.

2. What changes in disease

Disease results when this balance fails in one of several directions:

• Hypersensitivity — an exaggerated or misdirected immune response. Type I is immediate, antibody (IgE)-mediated, with mast cells releasing histamine (allergy, anaphylaxis). Type II involves antibodies attacking cells or tissues (some hemolytic anemias). Type III involves immune complexes lodging in tissues and triggering inflammation (some forms of vasculitis or serum sickness). Type IV is delayed and T-cell–mediated, with no antibody involvement (contact dermatitis, the tuberculosis skin test).
• Autoimmunity — a loss of tolerance in which the immune system attacks the body's own tissues, producing organ- or system-specific damage (as in thyroiditis, or systemic processes such as systemic lupus erythematosus). Autoimmunity is a distinct failure of self-tolerance, not simply a reaction to an outside trigger.
• Immunodeficiency — an underperforming immune system. Primary immunodeficiency is present from birth (often genetic); acquired (secondary) immunodeficiency develops later from causes such as infection (for example, HIV), malnutrition, certain medications, or other illnesses. The shared result is increased susceptibility to infection.
• Immune dysregulation — a broader term for an immune response that is excessive, misdirected, or poorly controlled, which can overlap with hypersensitivity and autoimmunity.

3. Why the changes matter

Each category produces a recognizable clinical pattern: allergy produces immediate or delayed reactions to usually harmless substances; autoimmunity produces chronic, tissue-specific or widespread inflammation and organ damage; immunodeficiency produces recurrent or unusual infections. Transplant rejection applies the same recognition logic — the recipient's immune system identifies the donor organ as non-self and mounts an attack, which is why immunosuppression (reducing immune activity) is a central concept in transplantation. Understanding these patterns supports recognizing when an immune response is protective versus harmful.

How it works

The four hypersensitivity types, by mechanism:

1. Type I (immediate): First exposure produces IgE that binds to mast cells; re-exposure cross-links that IgE, and mast cells release histamine within minutes — causing allergy and, in severe cases, anaphylaxis.
2. Type II (antibody-mediated): Antibodies bind to antigens on cell surfaces or tissues, marking them for destruction or interfering with their function.
3. Type III (immune complex): Antigen–antibody complexes deposit in tissues and trigger inflammation at those sites.
4. Type IV (delayed, cell-mediated): Sensitized T cells react to the antigen hours to days later, with no antibody involvement — as in contact dermatitis.

Common confusions

Memory aids

Use "ACID" for the four hypersensitivity types — Anaphylactic (Type I, immediate), Cytotoxic (Type II, antibody against cells), Immune-complex (Type III), Delayed (Type IV, T-cell). For the immune balance, remember "too much, too wrong, too little": hypersensitivity is too much response to a harmless trigger, autoimmunity is too wrong (aimed at self), and immunodeficiency is too little response.

Quick review

Topic Recap

• Innate immunity is fast and nonspecific; adaptive immunity is specific and memory-forming, using B cells (antibodies) and T cells.
• Tolerance is the ability to ignore self; its loss underlies autoimmunity.
• Hypersensitivity has four types — immediate (I), cytotoxic (II), immune-complex (III), and delayed (IV).
• Immunodeficiency may be primary (from birth) or acquired (secondary) and increases infection risk.
• Transplant rejection is immune recognition of non-self, and immunosuppression is the resulting therapeutic trade-off.

Knowledge Check

1. What is the key functional difference between innate and adaptive immunity?
2. Which hypersensitivity type is immediate and mediated by IgE and mast cells?
3. What is the difference between allergy and autoimmunity?
4. Give one cause of acquired (secondary) immunodeficiency.
5. Why does the immune system reject a transplanted organ?

Answers and Rationales

1. Answer: Innate immunity is fast and nonspecific with no memory; adaptive immunity is specific, slower to develop, and forms lasting memory. Why: These two arms together provide immediate defense plus long-term, targeted protection.
2. Answer: Type I hypersensitivity. Why: Pre-formed IgE on mast cells triggers rapid histamine release on re-exposure to the antigen.
3. Answer: Allergy is a hypersensitivity reaction to an outside, usually harmless substance; autoimmunity is a loss of tolerance in which the immune system attacks the body's own tissues. Why: The target — external antigen versus self-tissue — is the defining difference.
4. Answer: Any of: HIV infection, malnutrition, certain medications, or other illnesses. Why: These can reduce immune-cell number or function after birth.
5. Answer: The recipient's immune system recognizes the donor organ's antigens as non-self and attacks it. Why: Immune recognition of self versus non-self is the same mechanism that normally targets microbes.