Introduction to Hypersensitivites: Videos & Practice Problems

Immunological disorders arise from immune system dysfunctions, including hypersensitivities, autoimmune diseases, immunodeficiencies, and transplant rejections. Hypersensitivities are exaggerated immune responses following sensitization, classified into four types: Type I (allergic reactions mediated by IgE antibodies), Type II (cytotoxic antibody-mediated cell death), Type III (immune complex-mediated inflammation), and Type IV (delayed T cell-mediated responses). These disorders involve complex interactions of adaptive immunity, antibodies, T cells, and antigens, influenced by genetic and environmental factors. Understanding these mechanisms is crucial for grasping immune system pathologies and their clinical implications in diseases like rheumatoid arthritis and allergic reactions.

Introduction to Immunological Disorders

Immunological disorders arise from dysfunctions in the immune system, where it may become overactive, underactive, or misdirected. These disorders encompass hypersensitivities, autoimmune diseases, immunodeficiency disorders, and transplant rejections. Hypersensitivities occur when the immune system overreacts, leading to exaggerated responses that can damage tissues. There are four recognized types of hypersensitivities, each involving different immune mechanisms and triggers.

Autoimmune diseases develop when the immune system mistakenly targets the body's own cells and tissues instead of harmful pathogens. These diseases can be organ-specific, affecting particular tissues, or systemic, impacting multiple organs throughout the body. Immunodeficiency disorders represent conditions where the immune system is weakened or lacks essential components, reducing the body's ability to fight infections. These can be classified as primary immunodeficiencies, which are typically genetic, or secondary immunodeficiencies, which result from external factors such as infections or treatments.

Transplant rejection is another critical immunological disorder, where the immune system identifies transplanted organs or tissues as foreign and mounts an attack against them. It is important to understand that these categories are interconnected; for instance, many autoimmune diseases and transplant rejections are linked to hypersensitivity reactions, illustrating the complex interplay within immune system dysfunctions.

Understanding these immunological disorders provides insight into how the immune system's balance is crucial for maintaining health. Recognizing the mechanisms behind overactive, misdirected, or deficient immune responses is essential for diagnosing and developing treatments for these conditions.

Overview: Hypersensitivities & Sensitization

An appropriate immune response is carefully balanced to protect the body by eliminating pathogens or toxins without causing unnecessary damage. Hypersensitivities represent an exaggerated and harmful overreaction of the immune system, where the response is too strong and leads to collateral tissue damage. The term "hypersensitivity" itself highlights this excessive nature, with "hyper" meaning "too much."

Hypersensitivities only occur after a process called sensitization, which is the immune system's initial exposure to an antigen. During sensitization, the immune system prepares itself to react more vigorously upon subsequent exposures to the same antigen. Unlike a typical primary adaptive immune response, no hypersensitivity reaction occurs during the first encounter; the immune system is merely primed. This principle applies to all four types of hypersensitivities.

While much is understood about hypersensitivities, there remain gaps in knowledge, especially regarding why some individuals develop these exaggerated immune responses while others do not. Factors such as genetics and environmental influences contribute to this complexity, and hypotheses like the hygiene hypothesis offer partial explanations but do not provide a complete picture.

The four types of hypersensitivities are classified based on their mechanisms and mediators. Type I hypersensitivity, commonly known as classic allergic reactions, involves a rapid antibody-mediated response to allergens such as dust, pollen, animal dander, peanuts, and shellfish. This type is the most prevalent and is characterized by immediate symptoms following exposure.

Type II hypersensitivity, also called cytotoxic hypersensitivity, involves antibodies binding directly to antigens on cell surfaces or within the extracellular matrix, leading to cell destruction. A well-known example is hemolytic transfusion reactions caused by incompatible blood transfusions.

Type III hypersensitivity is immune complex-mediated. It arises from the formation of antigen-antibody complexes that deposit in tissues, triggering inflammation. Rheumatoid arthritis exemplifies this type, where immune complexes accumulate in joints, causing chronic inflammation and damage.

Unlike the first three types, which are antibody-mediated, Type IV hypersensitivity is mediated by T cells and is often referred to as delayed cell-mediated hypersensitivity. The response typically occurs several hours to days after exposure. An example is the skin rash caused by contact with poison ivy, where T cells orchestrate the immune reaction.

A useful mnemonic to remember these types is "ACID": A for Allergic (Type I), C for Cytotoxic (Type II), I for Immune complex-mediated (Type III), and D for Delayed cell-mediated (Type IV).

Of the four types of hypersensitivity reactions, which type is characterized by a delayed immune response triggered by antigen-specific T cells?

• A. Type I - Allergic reaction hypersensitivity.
• B. Type II - Cytotoxic hypersensitivity.
• C. Type III - Immune-complex mediated hypersensitivity.
• D. Type IV - Cell-mediated hypersensitivity.

Answer: (D)

Hannah is allergic to wasp venom. During a picnic with friends, she is stung by a wasp and has an immediate, rapid, life-threatening response. Which type of hypersensitivity is this?

• A. Type I.
• B. Type II.
• C. Type III.
• D. Type IV.

Answer: (A)

Here’s what students ask on this topic:

What are the four types of hypersensitivities and how do they differ?

Hypersensitivities are exaggerated immune responses that cause tissue damage. There are four types: Type I is an allergic reaction mediated by IgE antibodies, causing rapid responses to allergens like pollen or peanuts. Type II is cytotoxic, where antibodies bind to antigens on cell surfaces, leading to cell death, such as in hemolytic transfusion reactions. Type III involves immune complex-mediated inflammation, where antibody-antigen complexes accumulate and cause damage, exemplified by rheumatoid arthritis. Type IV is delayed and mediated by T cells rather than antibodies, with responses occurring hours to days later, like the rash from poison ivy. Remembering the acronym ACID helps: Allergic (Type I), Cytotoxic (Type II), Immune complex (Type III), and Delayed (Type IV).

What is sensitization in the context of hypersensitivities?

Sensitization is the immune system's first exposure to an antigen, which does not cause an immediate hypersensitivity reaction but prepares the immune system to respond more strongly upon subsequent exposures. During this initial phase, the immune system recognizes the antigen and produces specific antibodies or T cells, setting the stage for an exaggerated response later. Hypersensitivity reactions only occur after sensitization, meaning the first exposure primes the immune system, and later exposures trigger the harmful overreaction. This concept is crucial for understanding why allergic reactions or other hypersensitivities do not happen immediately upon first contact with an allergen.

How do Type I hypersensitivity reactions occur and what are common examples?

Type I hypersensitivity reactions are rapid allergic responses mediated by IgE antibodies. Upon first exposure to an allergen, sensitization occurs, leading to IgE production that binds to mast cells and basophils. On subsequent exposures, the allergen cross-links these IgE antibodies, triggering the release of histamine and other inflammatory mediators. This causes symptoms like itching, swelling, and bronchoconstriction. Common examples include allergic reactions to dust, pollen, animal dander, peanuts, and shellfish. These reactions can range from mild hay fever to severe anaphylaxis, highlighting the importance of understanding Type I hypersensitivity in clinical and everyday contexts.

What distinguishes Type IV hypersensitivity from the other types?

Type IV hypersensitivity is unique because it is mediated by T cells rather than antibodies, unlike Types I, II, and III. It is also called delayed-type hypersensitivity because the immune response takes several hours to days to develop after antigen exposure. In this reaction, sensitized T cells recognize the antigen and release cytokines that recruit and activate macrophages and other immune cells, leading to tissue inflammation and damage. A classic example is the skin rash caused by poison ivy. This delayed response contrasts with the rapid antibody-mediated reactions seen in the other hypersensitivity types.

How are autoimmune diseases related to hypersensitivities?

Autoimmune diseases occur when the immune system mistakenly targets the body's own cells and tissues. Many autoimmune diseases are linked to hypersensitivities because they involve an overactive or misdirected immune response. For example, some autoimmune disorders result from hypersensitivity reactions where antibodies or T cells attack self-antigens, causing tissue damage. This connection shows how hypersensitivities can contribute to the pathogenesis of autoimmune diseases, highlighting the delicate balance the immune system must maintain between defense and self-tolerance.