Allergic and Immune Hypersensitivity Reactions: Types I & II

Type I Hypersensitivity Reactions: Immediate Allergic Responses

These are the most common type of allergic reactions. They are mediated by Immunoglobulin E (IgE) antibodies, which are primarily located on mast cells found in various tissues throughout the body. The reaction between an antibody (Ab) and an antigen (Ag), also known as an allergen in this context, triggers a cascade of responses that can sometimes lead to tissue damage.

Phases of Type I Hypersensitivity

Type I hypersensitivity reactions occur in two distinct phases:

• Immediate Phase: Mediated primarily by histamine, leading to rapid symptoms.
• Late-Phase Reaction: Mediated by other compounds such as Leukotriene C₄ (LTC₄) and Prostaglandin D₂ (PGD₂), which have similar inflammatory effects and develop hours after exposure.

Type II Hypersensitivity Reactions: Antibody-Mediated Cytotoxicity

Type II reactions are primarily mediated by Immunoglobulin G (IgG) antibodies. In this case, the binding of an antibody to an antigen on a cell surface can activate the complement system, or the antibody-antigen complex can be recognized by inflammatory cells (e.g., macrophages, NK cells) via their IgG Fc receptors. When these cells are activated, they release substances that ultimately cause cellular or tissue damage.

Examples of Type II Hypersensitivity Reactions

• Post-transfusion reactions (due to incompatible blood transfusions)
• Autoimmune hemolytic anemia
• Goodpasture's disease (involving antibodies against glomerular basement membrane)
• Pemphigus (involving antibodies against desmosomes)
• Myasthenia gravis

Key Antibody Classes in Immune Responses

Immunoglobulin G (IgG)

IgG antibodies, such as maternal Rh-specific antibodies, are actively transported across the placenta. They opsonize fetal RhD+ red blood cells, marking them for phagocytosis by liver cells, which can lead to a dangerous or fatal drop in fetal hematocrit levels.

Immunoglobulin E (IgE)

The binding of an antigen to IgE antibodies on mast cells induces the release of histamine, heparin, and other pharmacological agents involved in the inflammatory response.

Immunoglobulin A (IgA)

IgA is secreted in large quantities in various bodily fluids, including breast milk, saliva, tears, nasal secretions, sweat, and secretions of the genitourinary and gastrointestinal tracts, providing mucosal immunity.

Antibody Structure: Fab and Fc Fragments

Proteases like papain or fractionated pepsin can cleave the hinge region of an antibody, producing two distinct fragments: Fab and Fc.

Fab Fragment (Fragment Antigen-Binding)

The Fab fragment is the region responsible for binding to a variety of antigens, specifically through its variable regions. This is where the antibody's specificity for a particular antigen is determined.

Fc Fragment (Fragment Crystallizable)

The Fc fragment is formed by the constant regions of the heavy chains. It plays a crucial role in mediating various biological functions by binding to a limited number of effector molecules and cells, thereby linking antigen recognition to downstream immune responses.

Dual Role of Antibodies

An antibody's structure allows it to perform a dual role in the immune system:

• Antigen Recognition: The Fab portion can specifically recognize and bind to an extracellular antigen, for example, on a tumor cell.
• Effector Function: The Fc portion then mediates the effector function, such as recruiting immune cells or activating complement, which can lead to the elimination of the target cell (e.g., by joining with a toxin to specifically kill a tumor cell).