Allergy & Hypersensitivity Overview

Allergy & Hypersensitivity

• Immune responses can be triggered by environmental agents, foods, or drugs not inherently harmful.

Type I Hypersensitivity

• Immediate allergic responses classified as IgE mediated, leading to release of histamine, leukotrienes, and prostaglandins from mast cells and basophils.
• Characterized by familial associations; examples include acute anaphylaxis, hay fever, and food allergies.

Type II Hypersensitivity

• Cytotoxic reactions mediated by IgG or IgM and involve complement, affecting cells contacting circulating plasma.
• Results in opsonization, inflammation, and antibody-mediated dysfunction.
• Examples include hemolytic anemia, transfusion reactions, and Graves’ disease.

Type III Hypersensitivity

• Immune complex reactions that are also mediated by IgG or IgM and depend on complement, causing tissue damage through immune complex formation.
• Notable examples: serum sickness from horse or bovine serum, and the Arthus reaction—a dermal inflammatory response.

Type IV Hypersensitivity

• Delayed or cell-mediated reactions primarily involving T-cells sensitized to local antigens, mediated by lymphokines and direct cellular toxicity.
• Contact sensitivity reactions, such as those caused by poison ivy, exemplify this type.

Autoimmunity

• Occurs when the immune system mistakenly recognizes self-antigens as foreign, leading to diseases like Crohn’s disease.

Major Histocompatibility Complex (MHC)

• Found on chromosome 6 in humans, MHC is crucial for immune function, distinguishing self from non-self.
• Class I MHC interacts with T cytotoxic cells, while Class II MHC interacts with T helper cells. Class III MHC is involved in complement activation.

Autoimmune Disease Mechanisms

• Pathogenesis may be triggered by drug-induced or virus-induced cell surface changes, genetic predispositions (like HLA-DR2 in systemic lupus erythematosus), and abnormal immune regulation.
• Dysregulation can stem from B cell overactivity or the presence of spontaneously activated immune cells.

Types of Autoimmune Diseases

• MHC Class II-associated diseases may be organ-specific or systemic. Systemic lupus erythematosus is representative of systemic diseases.
• MHC Class I-linked diseases include ankylosing spondylitis and psoriasis.

T Cell Mediated Autoimmune Diseases

• Examples include multiple sclerosis (specific to myelin) and insulin-dependent diabetes mellitus (involves pancreatic islet cells).

Systemic Lupus Erythematosus (SLE)

• Characterized by the production of autoantibodies against nucleic acids, red blood cells, and phospholipids, causing tissue damage from immune complex deposition.
• Diagnosed through specific patterns in anti-nuclear antigen tests.

Alloimmunity

• Immune response against the antigens of other individuals of the same species, potentially leading to neonatal diseases (e.g., Graves’ disease).
• Transplant rejection can occur in various phases: hyperacute, accelerated, acute, and chronic.

Immunodeficiency Diseases

• Classified as primary (hereditary) or secondary (acquired). Over 50 known primary immunodeficiency diseases exist.
• Deficiency types include B cell, T cell, complement, and phagocytosis deficiencies.

B Cell Deficiencies

• Primary deficiencies include transient hypogammaglobulinemia, X-linked hypogammaglobulinemia (Bruton’s disease), and selective IgA deficiency (most common).
• Secondary deficiencies may arise from lymphomas or nephrotic syndrome.

T Cell Deficiencies

• DiGeorge Syndrome involves a deletion on chromosome 22, affecting thymus development and T cell maturation.
• Chronic mucocutaneous candidiasis leads to persistent Candida infections and impaired cytokine production.

Combined Immunodeficiencies

• Primary combined deficiencies affect approximately 1 in 58,000 newborns, and can involve both antibody and cellular immune responses.