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Blood Bank

Immune response

The interaction between macrophages, T cells, and B cells, the distinct nature of primary vs. secondary responses, and the underlying genetic control of receptors (V(D)J), antigen presentation (HLA), and the antigens themselves (blood group genes) are all interconnected pieces explaining how and why immune events happen in transfusion and transplantation medicine!

Overview: The Adaptive Immune Response in Blood Banking

Think of the adaptive immune response as your body’s highly specific, targeted defense system that learns from experience. It involves key cells, distinct phases upon encountering an antigen, and is all built upon a genetic blueprint

  1. The Spark: Antigen Encounter & Presentation
    • It often starts when Macrophages (or other Antigen Presenting Cells - APCs) encounter something foreign – like a transfused red blood cell carrying an antigen the patient lacks (e.g., the K antigen)
    • The macrophage engulfs and processes this antigen. Crucially, it then displays fragments of the antigen on its surface using special molecules coded by HLA genes (specifically MHC Class II). This presentation is like waving a flag to alert the immune system’s commanders
  2. The Commanders & Soldiers: T Cells and B Cells
    • T Helper Cells (CD4+): These cells are the orchestrators. They recognize the antigen presented by macrophages (on MHC Class II). Once activated, they provide essential help signals (cytokines and direct contact)
    • B Cells: These are the potential antibody factories. Each B cell has a unique B Cell Receptor (BCR) on its surface (thanks to V(D)J gene rearrangement: during its development, creating vast receptor diversity). A B cell whose BCR happens to match the foreign antigen binds to it
    • Cytotoxic T Cells (CD8+): While less directly involved in typical red cell antibody production, they are critical in recognizing antigens presented on MHC Class I (found on most cells) and killing cells seen as foreign or infected (vital in graft rejection/GVHD)
  3. The First Fight: Primary Immune Response
    • For the B cell to become fully activated (especially to make high-quality IgG), it usually needs that help from the activated T helper cell
    • There’s a lag phase (days/weeks) as B cells multiply and differentiate
    • The first antibody produced is mainly IgM. It’s a decent first responder but usually doesn’t cross the placenta and might not persist long
    • Importantly, Memory B cells and Memory T cells specific for that antigen are generated and stored away
  4. The Rematch: Secondary (Anamnestic) Immune Response
    • If the same antigen enters the body again (e.g., another transfusion with K-positive blood), those memory cells swing into action
    • The response is faster (shorter lag phase), stronger (much higher antibody levels), and the dominant antibody produced is IgG (due to class switching)
    • These IgG antibodies often have higher affinity (bind better) due to refinement processes (somatic hypermutation) that occurred earlier. IgG can cross the placenta and is often more efficient at causing red cell destruction
  5. The Genetic Blueprint
    • Diversity: V(D)J recombination generates the vast repertoire of B and T cell receptors before antigen encounter, ensuring we have cells ready to recognize almost anything
    • Recognition & Compatibility: The HLA genes code for the MHC molecules essential for antigen presentation and distinguishing self from non-self. Their high polymorphism (many variations) is key to immune defense but also the major hurdle in transplantation and can cause issues like platelet refractoriness or TRALI
    • Antigens: The specific blood group genes inherited by an individual determine which antigens (like ABO, Rh, Kell, Duffy, etc.) are present on their red blood cells. Differences in these genes between donor/fetus and recipient/mother are the basis for alloimmunization

Why This Matters in Blood Bank

  • Alloimmunization: The primary response explains how a patient first develops an antibody after transfusion/pregnancy
  • Delayed Hemolytic Transfusion Reactions (DHTR): The secondary response explains why a patient with a previously made antibody (even if undetectable now) can have a rapid, potent IgG response upon re-exposure, destroying transfused cells days later
  • Hemolytic Disease of the Fetus and Newborn (HDFN): The secondary response in a sensitized mother produces high levels of IgG (like anti-D) that cross the placenta
  • Compatibility: Understanding HLA genetics is vital for platelet matching and preventing TRALI/GVHD. Knowing blood group genetics is the foundation of red cell compatibility testing