Immunology Notes: T Cells and B Cells

T Cell Markers and MHC Presentation

  • Identify CD markers on T cells:
    • Helper T cells express CD4+CD4^+.
    • Cytotoxic T cells express CD8+CD8^+.
  • Identify which MHC presents to different T cell types:
    • MHC I presents peptides to CD8+CD8^+ cytotoxic T cells.
    • MHC II presents peptides to CD4+CD4^+ helper T cells.
  • Why this matters:
    • Determines which T cell subset can recognize which antigen-presenting cell.
    • Drives the division of labor in adaptive immunity (cell-mediated vs humoral responses).

Major T Cell Types and Their Functions

  • Naive T cells differentiate into several effector and memory subsets:
      • Th1 cells: promote cell-mediated immunity; activate macrophages; secrete IFN-γ; important against intracellular pathogens.
    • Transcription factor: T-bet.
      • Th2 cells: support humoral immunity and B cell activation; promote class switching to certain antibody isotypes; secrete IL-4, IL-5, IL-13; important for defense against helminths and involved in allergic responses.
    • Transcription factor: GATA-3.
      • Th17 cells: recruit neutrophils and are important for defense against extracellular bacteria and fungi; secrete IL-17 family cytokines; implicated in autoimmunity when dysregulated.
    • Transcription factor: RORγt.
      • Tfh (T follicular helper) cells: provide help to B cells in germinal centers; promote affinity maturation and class switching; secrete IL-21.
    • Transcription factor: Bcl-6.
      • Treg (Regulatory T cells): maintain self-tolerance and limit immune responses; suppress autoimmunity.
    • Markers and function: expression of FoxP3, CD25; mechanisms include CTLA-4 and anti-inflammatory cytokines (e.g., IL-10, TGF-β).
    • Cytotoxic T cells (CTLs, CD8^+): kill infected or abnormal cells via perforin/granzyme pathways; recognize peptide–MHC I complexes; crucial for eliminating intracellular pathogens and tumor cells; can form memory CTLs.
  • Memory T cells:
    • Central memory (Tcm): reside in lymph nodes; rapid proliferation upon antigen re-encounter.
    • Effector memory (Tem): circulate in blood/tissues; ready to exert immediate effector functions.
  • Activation and differentiation cues (two-signal model):
    • Signal 1: TCR recognition of peptide–MHC complex (via the CD3 complex).
    • Signal 2: Co-stimulation (e.g., CD28CD28 on T cells binding to CD80/CD86CD80/CD86 on APCs).
    • Cytokine milieu guiding differentiation into specific helper or cytotoxic subsets.
  • Key signaling and transcription landscape:
    • Th1: transcription factor T-bet; IFN-γ production.
    • Th2: transcription factor GATA3; IL-4, IL-5, IL-13 production.
    • Th17: transcription factor RORγt; IL-17 family cytokines.
    • Tfh: transcription factor Bcl-6; IL-21 production.
    • Treg: transcription factor FoxP3; CTLA-4; regulatory cytokines.
  • Interplay and coordination:
    • Th cells coordinate B cell help and cytotoxic responses depending on the pathogen.
    • Regulatory cells help prevent collateral tissue damage and autoimmunity.
  • Connections to foundational principles:
    • Adaptive immunity relies on specificity, clonal expansion, and memory.
    • APCs bridge innate sensing to tailored T cell responses via antigen processing and presentation.
    • The two-signal requirement minimizes accidental activation and autoimmunity.
  • Real-world relevance:
    • Vaccines aim to elicit robust Th and B cell responses for durable protection.
    • Immunotherapies target T cell subsets (e.g., enhancing CD8^+ responses in cancer, modulating Treg activity in autoimmunity).
  • Numerical references, formulas, and key values:
    • Peptide lengths commonly presented:
    • MHC I: 8−108-10 amino acids.
    • MHC II: 13−2513-25 amino acids.
    • Activation signals: typically at least two signals (Signal 1 + Signal 2), plus cytokine cues for differentiation.

B Cell Activation and Differentiation into Plasma Cells

  • Overview of B cell activation:

    • Antigen binding to B cell receptor (BCR) triggers receptor cross-linking and internalization for processing.
    • B cells present processed peptides on MHC II to helper T cells and receive help via CD40–CD40L interactions and cytokines (e.g., IL-4, IL-5).

  • TD (T-dependent) vs TI (T-independent) activation:

    • TD antigens: proteins; require T cell help; typical outcome includes germinal center formation and long-lasting humoral immunity.
    • TI antigens: polysaccharides or repetitive structures; can activate B cells without T cell help (TI-1, TI-2); responses are often weaker and less class-switched.

  • Germinal center reactions (TD pathway):

    • B cells proliferate in germinal centers of lymph nodes/spleen.
    • Somatic hypermutation: introduces mutations in variable regions to increase antibody affinity.
    • Class switch recombination: changes antibody isotype (e.g., IgM to IgG, IgA, or IgE) depending on cytokines and CD40 signaling.
    • Selection for higher-affinity BCRs ensures more effective antibodies.

  • Differentiation outcomes:

    • Plasma cells: antibody-secreting cells produced from B cells; secrete antibodies of various isotypes with different effector functions (neutralization, opsonization, complement activation).
    • Memory B cells: long-lived cells that provide rapid and robust antibody responses upon re-exposure.

  • Isotype switching cues (cytokine influence):

    • IL-4 promotes switching to IgG1 and IgE in humans (context-dependent isotype patterns).
    • IFN-γ promotes switching to IgG2.

  • Antibody functions (brief):

    • Neutralization of pathogens/toxins.
    • Opsonization for phagocytosis.
    • Complement activation via classical pathway.
    • Fc receptor-mediated effector functions.

  • Clinical relevance:

    • Vaccines rely on eliciting high-affinity antibodies and memory B cell formation for lasting protection.
    • Immunodeficiencies affecting B cells or T-B collaboration can lead to poor vaccine responses.

  • Notable metaphors/examples:

    • BCR–antigen interaction as a lock-and-key mechanism; germinal center reactions as a training ground to fine-tune antibody quality.

  • Connections to foundational principles:

    • Humoral immunity is generated through B cell receptor–antigen recognition and T cell help, enabling targeted antibody responses.
    • The interplay between B cells and T helper cells shapes affinity maturation and isotype distribution.

  • Ethical, philosophical, and practical implications:

    • Designing vaccines and immunotherapies requires understanding how to steer T helper responses and B cell maturation without triggering autoimmunity.
    • Personalized vaccines may consider individual HLA/MHC makeup and T cell repertoire to optimize responses.