Reviewing the 4 Types of Hypersensitivities: Videos & Practice Problems

Hypersensitivities are immune responses classified into four types: Type I (allergic reactions mediated by IgE antibodies causing immediate responses to soluble allergens), Type II (cytotoxic reactions involving IgG or IgM antibodies targeting cell-bound antigens, such as hemolytic transfusion reactions), Type III (immune complex-mediated with IgG/IgM antibodies forming small complexes that deposit in tissues causing inflammation, e.g., rheumatoid arthritis), and Type IV (delayed T cell-mediated responses causing tissue damage, like contact dermatitis). Understanding these mechanisms is crucial for grasping adaptive immunity, antigen-antibody interactions, and immune-mediated diseases.

Reviewing the 4 Types of Hypersensitivities

Hypersensitivities are immune responses that are exaggerated or inappropriate against antigens, classified into four distinct types often remembered by the acronym ACID. This mnemonic helps to recall the core characteristics of each hypersensitivity type: A for Allergic (Type I), C for Cytotoxic (Type II), I for Immune Complex-mediated (Type III), and D for Delayed T cell-mediated (Type IV).

Type I hypersensitivity involves immediate allergic reactions triggered by soluble allergens such as dust, pollen, and animal dander. This is the most common hypersensitivity and is mediated exclusively by IgE antibodies. Upon allergen exposure, IgE binds to mast cells and basophils, causing their degranulation and release of inflammatory mediators like histamine. These reactions occur rapidly, typically within 30 minutes, and can range from mild localized symptoms to severe systemic anaphylaxis.

Type II hypersensitivity is cytotoxic and involves IgG or IgM antibodies targeting cell-bound antigens or components of the extracellular matrix. Examples include hemolytic transfusion reactions and hemolytic disease of the newborn, where antibodies attack red blood cells. The response time varies from hours to days. Mechanistically, antibody binding can lead to cell destruction or alter receptor function by either inactivating or overstimulating them, highlighting that not all Type II reactions are cytotoxic.

Type III hypersensitivity is immune complex-mediated, involving IgG or IgM antibodies forming small soluble immune complexes with antigens. These complexes can deposit in tissues such as joints (rheumatoid arthritis) or kidneys (glomerulonephritis), activating the complement system and causing inflammation and tissue damage. The response time is variable, ranging from hours to days, and the antigen is typically soluble within these small immune complexes that evade clearance.

Type IV hypersensitivity is unique as it is not antibody-mediated but instead involves sensitized T cells. This delayed hypersensitivity manifests 24 to 72 hours after antigen exposure and can be triggered by soluble or cell-bound antigens. Examples include contact dermatitis from poison ivy, the tuberculin skin test for tuberculosis screening, type 1 diabetes as an autoimmune disorder, and transplant rejection. Sensitized T cells recognize antigens and promote inflammation, leading to tissue damage.

Understanding these hypersensitivity types is crucial for recognizing the mechanisms behind allergic reactions, autoimmune diseases, and transplant rejection. The immune reactants—IgE for Type I, IgG/IgM for Types II and III, and T cells for Type IV—along with the timing and antigen forms, define the clinical presentation and guide appropriate therapeutic interventions.

Reviewing the 4 Types of Hypersensitivities Example 1

Hypersensitivity reactions are classified into four main types, each with distinct immune mechanisms and clinical manifestations. Type IV hypersensitivity is characterized by a T cell-mediated delayed response, typically occurring hours to days after antigen exposure. This cell-mediated immunity distinguishes it from other types that involve antibodies. For example, allergic contact dermatitis, such as the rash caused by poison ivy, is a classic presentation of type IV hypersensitivity.

Type I hypersensitivity involves the rapid degranulation of mast cells and basophils, releasing pro-inflammatory mediators like histamine. When these mediators enter the bloodstream, they can trigger a severe systemic reaction known as systemic anaphylaxis. This immediate hypersensitivity reaction is responsible for common allergic responses such as hay fever, asthma, and anaphylactic shock.

Type II hypersensitivity, also called cytotoxic hypersensitivity, involves the formation of membrane attack complexes that lyse foreign or altered host cells. This antibody-mediated response leads to cell destruction and is implicated in conditions like hemolytic anemia and certain drug reactions.

Type III hypersensitivity is driven by the deposition of small immune complexes in tissues, which incite inflammation. These immune complexes activate complement pathways, leading to tissue damage seen in diseases such as systemic lupus erythematosus and rheumatoid arthritis.

Understanding these hypersensitivity types is crucial for diagnosing and managing immune-related disorders. The key distinctions lie in the immune components involved—T cells in type IV, antibodies and mast cells in types I, II, and III—and the timing and nature of the reactions, ranging from immediate to delayed responses.

Which of the following statements about the four types of hypersensitivity is true?

• A. They all involve activation of the complement system.
• B. In most cases they occur upon second exposure to an antigen (after sensitization upon first exposure).
• C. They are all caused by foreign antigens only.
• D. Hypersensitivities increase in severity from type I up to type IV.

Answer: (B)

Which type of hypersensitivity involves the production of naturally forming, M class antibodies that trigger immune reactions to foreign cells?

• A. Type I only.
• B. Type II only.
• C. Types I & II.
• D. Type III only.
• E. Type I & III only.
• F. Type II & III only.

Answer: (A)

Here’s what students ask on this topic:

What are the four types of hypersensitivities and their key characteristics?

The four types of hypersensitivities are classified based on the immune mechanisms involved. Type I hypersensitivity is an allergic reaction mediated by IgE antibodies, causing immediate responses to soluble allergens like pollen or food. Type II hypersensitivity is cytotoxic, involving IgG or IgM antibodies targeting cell-bound antigens, such as in hemolytic transfusion reactions. Type III hypersensitivity is immune complex-mediated, where IgG or IgM antibodies form small complexes that deposit in tissues, causing inflammation, as seen in rheumatoid arthritis. Type IV hypersensitivity is delayed and T cell-mediated, not involving antibodies, leading to tissue damage, examples include contact dermatitis and transplant rejection. Each type differs in immune reactants, antigen forms, and response timing, highlighting diverse immunopathological mechanisms.

How does Type I hypersensitivity differ from the other types in terms of immune reactants and response time?

Type I hypersensitivity is unique because it is mediated by IgE antibodies, unlike Types II and III, which involve IgG or IgM antibodies, and Type IV, which is T cell-mediated without antibody involvement. The response time for Type I is immediate or very rapid, typically occurring within 30 minutes after exposure to the allergen. This rapid response is due to IgE antibodies binding to mast cells and basophils, triggering degranulation and release of inflammatory mediators like histamine. In contrast, Types II and III have variable response times ranging from hours to days, and Type IV hypersensitivity is delayed, occurring 24 to 72 hours after antigen exposure.

What are common examples of Type II cytotoxic hypersensitivity reactions?

Type II cytotoxic hypersensitivity involves IgG or IgM antibodies targeting cell-bound antigens, leading to cell destruction or receptor dysfunction. Common examples include hemolytic transfusion reactions (HTRs), which occur when incompatible blood is transfused, causing destruction of red blood cells. Another example is hemolytic disease of the newborn (HDNB), where an Rh-negative mother produces antibodies against Rh-positive fetal red blood cells, leading to fetal anemia. These reactions can vary in onset from a few hours to several days and involve antibody binding that activates complement or recruits immune cells to destroy targeted cells.

How do immune complexes contribute to tissue damage in Type III hypersensitivity?

In Type III hypersensitivity, immune complexes are formed when IgG or IgM antibodies bind to soluble antigens, creating small complexes. These small immune complexes can evade clearance by the immune system and deposit in tissues such as joints or kidneys. Once deposited, they activate the complement system, which attracts inflammatory cells to the site. This inflammation leads to tissue damage, as seen in diseases like rheumatoid arthritis (joint inflammation) and glomerulonephritis (kidney inflammation). The immune complex deposition and subsequent inflammation are central to the pathology of Type III hypersensitivity.

Why is Type IV hypersensitivity called delayed, and what immune cells mediate it?

Type IV hypersensitivity is called delayed because the immune response typically occurs 24 to 72 hours after exposure to the antigen, unlike the immediate responses seen in Types I, II, and III. This delay is due to the involvement of sensitized T cells rather than antibodies. Specifically, T helper cells recognize the antigen and release cytokines that recruit and activate macrophages and other immune cells, leading to inflammation and tissue damage. Examples include contact dermatitis from poison ivy and the tuberculin skin test. This T cell-mediated mechanism distinguishes Type IV from the antibody-mediated hypersensitivities.

What role do mast cells and basophils play in Type I hypersensitivity reactions?

In Type I hypersensitivity, mast cells and basophils play a crucial role by serving as effector cells. IgE antibodies bind to their surface receptors on these cells. When an allergen cross-links the bound IgE, it triggers degranulation, releasing pro-inflammatory mediators such as histamine, leukotrienes, and prostaglandins. These mediators cause symptoms like vasodilation, increased vascular permeability, smooth muscle contraction, and mucus secretion, leading to allergic reactions ranging from mild localized symptoms to severe systemic anaphylaxis. Thus, mast cells and basophils are central to the rapid onset and severity of Type I hypersensitivity responses.