Immunology

This section explores how our body mounts an immune response when it encounters foreign antigens, focusing on the key cells like B cells, T cells, and macrophages, and the difference between a first-time (primary) and subsequent (secondary) encounter. We’ll then look closely at the specific weapons produced – the immunoglobulins (antibodies) – examining their different classes, structures, and unique properties. Understanding how these antibodies precisely bind to antigens (antigen-antibody interactions) and the principles governing this is crucial for our testing. Finally, we’ll unravel the powerful complement system, a cascade of proteins that amplifies the immune response, often working alongside antibodies to destroy target cells, a process vital to understanding transfusion reactions and compatibility

The Immune System’s Response to Foreign Antigens

1. The First Encounter & Recognition (Primary Immune Response)
   • When a foreign antigen (like a non-self red blood cell antigen from a transfusion or fetus) enters the body for the first time, Macrophages (acting as Antigen Presenting Cells - APCs) engulf it and show pieces of it to T Helper Cells. This recognition relies on the body’s ability to distinguish “self” from “non-self,” largely governed by the HLA system (genetically determined)
   • T helper cells activate specific B Cells whose surface receptors (thanks to V(D)J gene rearrangement providing immense diversity) happen to recognize the foreign antigen
   • There’s a lag phase, then the B cells differentiate into plasma cells
2. Producing the Weapons (Immunoglobulins - Primary Response)
   • The first antibody produced is mainly IgM. It’s a large pentameric molecule, excellent at activating complement and causing agglutination, but it generally doesn’t cross the placenta and has a shorter lifespan. Think ABO antibodies
   • Memory cells: (B and T) are also created, remembering this specific antigen
3. Antibodies Find Their Target (Antigen-Antibody Interactions)
   • Antibodies bind with high specificity to their corresponding antigen epitope (“lock and key”)
   • This binding uses weak non-covalent forces and is reversible. Strength is described by affinity (single site) and avidity (overall strength, high for multivalent IgM)
   • Testing: We detect these interactions using methods like:
     • Direct Agglutination: Works well for IgM
     • Antiglobulin Test (IAT/DAT): Essential for detecting non-agglutinating IgG or complement coating red cells, using Anti-Human Globulin (AHG)
     • Solid Phase & Gel: Modern, sensitive methods
4. Amplifying the Attack (Complement System)
   • The binding of IgM or certain IgG subclasses (IgG3>IgG1) to antigens on a cell surface can trigger the Classical Complement Pathway
   • The Alternative Pathway can be activated spontaneously or amplify the classical pathway
   • Both pathways lead to:
     • Opsonization: Coating the cell with C3b, marking it for destruction by macrophages (Extravascular Hemolysis). Detected as C3d on DAT
     • Inflammation: Release of Anaphylatoxins (C3a, C5a), causing inflammatory symptoms
     • Lysis: Formation of the Membrane Attack Complex (MAC, C5b-9), punching holes in the cell -> Intravascular Hemolysis
5. The Second Encounter (Secondary Immune Response)
   • If the same antigen is encountered again, the memory cells respond much faster and more strongly
   • The predominant antibody produced is IgG. It’s a monomer, generally crosses the placenta, is a key opsonin, and some subclasses activate complement (less efficiently than IgM). IgG often requires the Antiglobulin Test for detection
   • This rapid, high-titer IgG response is responsible for Delayed Hemolytic Transfusion Reactions (DHTR) and Hemolytic Disease of the Fetus and Newborn (HDFN)

Why This Matters in Blood Banking

Understanding this sequence – from initial antigen recognition and the types of antibodies produced (IgM vs. IgG with their distinct properties), to how they interact with antigens and activate complement, leading to different types of red cell destruction – is fundamental to:

• Performing accurate blood typing and compatibility testing
• Detecting and identifying: clinically significant antibodies
• Understanding the mechanisms behind transfusion reactions and HDFN
• Selecting appropriate blood components for patients