B & T cells, Macrophages

In the complex world of immunology, especially as it relates to blood banking, three key cell types form the backbone of the adaptive immune response: Macrophages, T lymphocytes (T cells), and B lymphocytes (B cells). Macrophages act as the initial responders and messengers, engulfing foreign materials and presenting antigens. T cells, particularly T helper cells, orchestrate the overall response and provide critical activation signals, while cytotoxic T cells can eliminate targeted cells. B cells are the antibody specialists, differentiating into plasma cells to produce the antibodies crucial for neutralizing threats and memory cells that ensure a rapid response upon future encounters. Understanding how these cells interact is fundamental to explaining processes like alloimmunization, transfusion reactions, and hemolytic disease of the fetus and newborn

Think of the immune system like a highly coordinated military operation against foreign invaders (antigens). Each of these cell types has a specialized job:

Macrophages: The Sentinels and Presenters

Macrophages are part of the innate immune system (the body’s first line of defense) but also play a crucial role in bridging the gap to the adaptive immune system (the specific, targeted response involving T and B cells)

• Role 1: Phagocytosis (The “Big Eaters”)
  • Macrophages patrol tissues, engulfing and digesting cellular debris, pathogens, and foreign materials – including potentially incompatible red blood cells, especially those coated with complement or antibodies (opsonized)
• Role 2: Antigen Processing and Presentation (The “Intelligence Officers”)
  • After engulfing a foreign entity (like a red blood cell with a foreign antigen), the macrophage breaks it down into smaller pieces (peptides)
  • It then displays these antigen fragments on its surface, attached to special molecules called Major Histocompatibility Complex (MHC) Class II molecules
  • This “display” acts like a signal flag, presenting the antigen to T helper cells. Macrophages, along with dendritic cells and B cells, are therefore known as Antigen-Presenting Cells (APCs)
• Role 3: Producing Cytokines
  • Activated macrophages release chemical messengers (cytokines like Interleukin-1, TNF-alpha) that help activate other immune cells and contribute to inflammation

Blood Bank Relevance

• Initiation: They are often the first cells to encounter foreign antigens from transfused blood
• Clearance: They are key players in extravascular hemolysis, removing antibody- or complement-coated red blood cells from circulation, primarily in the spleen and liver
• Activating T cells: Their antigen presentation function is essential for initiating the T-cell dependent immune response that leads to B cell antibody production

T Lymphocytes (T cells): The Conductors and Killers

T cells are central to the adaptive immune response. They don’t produce antibodies themselves, but they regulate the immune response and can directly kill infected or foreign cells. They mature in the Thymus (hence the name!)

• T Helper Cells (CD4+ T cells): The “Generals”
  • Recognition: They recognize antigens presented by APCs (like macrophages) on MHC Class II molecules. They can’t see the antigen unless it’s properly presented by an APC
  • Activation: Once activated, they orchestrate the immune response by:
    • Activating B cells: Providing essential signals (through cell-to-cell contact and cytokine release, like IL-4, IL-5) that stimulate B cells to proliferate, undergo class switching (e.g., from IgM to IgG), undergo affinity maturation, and differentiate into plasma cells and memory B cells. This T-cell help is crucial for producing high-affinity IgG antibodies – the kind most often implicated in significant blood bank reactions!
    • Activating Macrophages: Making them more effective killers
    • Activating Cytotoxic T cells: Helping them become fully functional killers
  • Cytokine Production: Release various cytokines that influence and direct the nature of the immune response
• Cytotoxic T Lymphocytes (CTLs or CD8+ T cells): The “Special Ops Soldiers”
  • Recognition: They recognize antigens presented on MHC Class I molecules. MHC Class I is found on almost all nucleated cells in the body and typically displays internal antigens (like viral proteins if the cell is infected, or abnormal proteins in cancer cells)
  • Function: Once activated (often with help from T helper cells), their main job is to kill targeted cells directly (e.g., virus-infected cells, tumor cells, or foreign cells in a graft). They release cytotoxic granules that induce apoptosis (programmed cell death) in the target cell
• Regulatory T cells (Tregs): The “Peacekeepers”
  • These T cells (often CD4+ and also expressing CD25) help to suppress the immune response. They are crucial for maintaining self-tolerance (preventing autoimmunity) and shutting down immune responses once an infection or antigen is cleared

Blood Bank Relevance

• Alloimmunization: T helper cells are absolutely essential for the development of most clinically significant IgG alloantibodies against red cell antigens. Without T cell help, the B cell response is often weaker, short-lived, and primarily IgM
• Transplantation: Both T helper and Cytotoxic T cells are major players in graft rejection (recognizing foreign MHC molecules on donor cells)
• Graft-versus-Host Disease (GVHD): In transfusion-associated GVHD (TA-GVHD), donor T lymphocytes (present in cellular blood components) engraft in an immunocompromised recipient and attack the recipient’s tissues as foreign. CTLs are the primary effectors here. This is why irradiation of blood components for susceptible patients is critical – it inactivates donor T lymphocytes

B Lymphocytes (B cells): The Antibody Factories

B cells are the stars of humoral immunity (immunity mediated by molecules in body fluids, i.e., antibodies). They mature in the Bone marrow

• Recognition: Unlike T cells, B cells can recognize intact, whole antigens directly using their B Cell Receptor (BCR), which is essentially a membrane-bound antibody molecule on the B cell surface. Each B cell has BCRs specific for only one particular antigenic shape (epitope)
• Activation
  • T-dependent: For most protein antigens (like many blood group antigens), B cell activation requires two signals: 1) Binding of the antigen to the BCR, and 2) Co-stimulation from an activated T helper cell that recognizes antigen presented by the B cell (acting as an APC) on its MHC Class II molecules. This leads to robust activation, proliferation, class switching (IgM -> IgG), affinity maturation, and the formation of plasma cells and long-lived memory B cells
  • T-independent: Some antigens (often large molecules with repeating units, like bacterial polysaccharides) can directly activate B cells without T cell help. This response is generally faster but weaker, produces mainly IgM, and generates little immunological memory
• Differentiation: Upon successful activation (usually T-dependent), B cells proliferate and differentiate into:
  • Plasma Cells: These are terminally differentiated B cells – essentially antibody-producing factories. They have extensive endoplasmic reticulum geared towards synthesizing and secreting large quantities of specific antibodies into the blood and tissues. They are relatively short-lived
  • Memory B Cells: These are long-lived B cells that persist after the antigen is cleared. They retain the “memory” of the antigen and are primed to respond quickly and strongly upon subsequent exposure (secondary/anamnestic response), rapidly differentiating into plasma cells producing high-affinity IgG

Blood Bank Relevance

• Antibody Production: B cells (specifically, plasma cells derived from them) are the source of all the antibodies we deal with in the blood bank – ABO antibodies, Rh antibodies (like anti-D), antibodies to other blood group systems (Kell, Duffy, Kidd, etc.), and antibodies involved in autoimmune hemolytic anemia
• Primary vs. Secondary Response: The differentiation into plasma cells (producing IgM then IgG) and memory B cells underlies the differences between the primary and secondary immune responses. Memory B cells are why a previously sensitized patient can rapidly produce high levels of IgG upon re-exposure to an antigen, leading to delayed hemolytic transfusion reactions or HDFN
• HDFN: Maternal B cells produce the IgG antibodies (like anti-D) that cross the placenta and attack fetal red blood cells

Key Terms

• Macrophage: A large phagocytic cell type that acts as an Antigen Presenting Cell (APC) by engulfing pathogens or foreign cells (like transfused RBCs) and displaying processed antigens on its surface to T helper cells; also involved in removing antibody-coated cells (extravascular hemolysis)
• T Lymphocyte (T cell): A type of lymphocyte maturing in the thymus, central to cell-mediated immunity and regulating humoral immunity. Includes T helper (CD4+) and Cytotoxic T (CD8+) subsets
• B Lymphocyte (B cell): A type of lymphocyte maturing in the bone marrow, responsible for humoral immunity. Upon activation, differentiates into plasma cells (antibody production) and memory cells
• Antigen Presenting Cell (APC): A cell (like a macrophage, dendritic cell, or B cell) that processes and presents antigens on its surface via MHC molecules to T lymphocytes, initiating an adaptive immune response
• MHC Class II Molecules: Surface proteins found primarily on APCs used to present processed exogenous antigens (those originating outside the cell) to T helper (CD4+) cells
• T Helper Cell (CD4+ T cell): A subset of T lymphocytes that recognizes antigens presented on MHC Class II molecules and provides essential activation signals (cytokines, co-stimulation) to B cells and other immune cells, orchestrating the adaptive response. Crucial for IgG antibody production
• Cytotoxic T Lymphocyte (CTL or CD8+ T cell): A subset of T lymphocytes that recognizes antigens presented on MHC Class I molecules (found on most nucleated cells) and kills target cells (e.g., virus-infected cells, tumor cells, foreign graft cells)
• Plasma Cell: A terminally differentiated B lymphocyte that is specialized for mass production and secretion of a specific antibody isotype (like IgG or IgM)
• Memory Cell (B or T): Long-lived B or T lymphocytes generated during a primary immune response that remain dormant but are quickly activated upon re-exposure to the same antigen, mediating a faster and stronger secondary response
• B Cell Receptor (BCR): A membrane-bound antibody molecule on the surface of a B cell that allows it to recognize and bind specifically to an intact antigen, initiating the B cell activation process