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Adaptive Immunity – T & B Cell Activation, Cytokines, Antibodies, and HIV Case Study

Helper T Cells (CD4⁺)

  • Also called “helpertcells.com” in lecture – emphasized that they ‘help’ several branches of immunity.
  • Functions
    • Serve as central coordinators: amplify the activity of other T cells (especially cytotoxic CD8⁺) and B cells.
    • Release cytokines (chiefly \text{IL-2}) that act as chemical ‘broadcast signals’ to surrounding leukocytes.
  • Presence indicated in lab by the surface glycoprotein CD4.
  • Do not directly kill infected cells; instead, they orchestrate responses.

Major Histocompatibility Complex (MHC)

  • Nicknamed the immune system’s “ID badge”.
  • Two classes discussed:
    • MHC I — found on all nucleated cells (i.e., every cell except mature RBCs). Signals “self.”
    • MHC II — restricted to antigen-presenting cells (APCs).
  • Recognition principle: Foreign invaders generally lack host MHC; absence or alteration triggers immune attack.

Antigen-Presenting Cells (APCs)

  • Primary professional APCs highlighted:
    • Dendritic cells (most potent T-cell activators)
    • Macrophages
  • Role: Capture, process, and “display” antigenic peptides in MHC II grooves for inspection by CD4⁺ T cells.
  • Metaphor used: “Cops arresting people, putting them in the squad car, and delivering them to court (T cell).”

Two-Signal Model for T-Cell Activation

  1. Signal 1 (Contact)
    • Physical binding of the T-cell receptor (TCR) to the peptide–MHC complex on the APC.
    • Stabilized by CD4 (for MHC II) or CD8 (for MHC I).
  2. Signal 2 (Co-stimulation/Cytokine release)
    • Delivery of additional co-stimulatory molecules + cytokines, especially IL-2 secreted by activated helper T cells.
    • If Signal 1 occurs without Signal 2 → T cell becomes anergic or disengages (“fails to recognize” → no attack).

CD4 vs CD8: Quick Mnemonic

  • “Always equal 8.”
    • 1\times8 = 8 → MHC I pairs with CD8 (cytotoxic T cells).
    • 2\times4 = 8 → MHC II pairs with CD4 (helper T cells).

Cytotoxic T Cells (CD8⁺)

  • Described as the immune system’s “hit-men.”
  • Activation requires help from IL-2 (produced by CD4⁺ cells) plus direct antigen recognition on MHC I.
  • Effector mechanism:
    1. Perforin – forms transmembrane pores in target.
    2. Granzyme – serine protease enters via pores → triggers apoptosis.
  • Overall result: Programmed cell death (apoptosis) of infected or malignant cells while sparing bystanders.

Interleukins & Cytokine Highlights

  • IL-2
    • Key growth factor for both helper and cytotoxic T cells.
    • Acts as an autocrine & paracrine signal to expand activated clones.
  • Mention that “hundreds of interleukins exist, each with specific jobs.”

B-Lymphocyte Activation & Antibody Generation

  • Steps
    • Proliferation (divide) & differentiation (change function).
    • Differentiation yields:
    – Plasma cells → secrete antibodies (Immunoglobulins: IgM, IgG, IgA, IgE, IgD).
    – Memory B cells → long-lived sentinels for rapid re-exposure response (can persist lifetime but may wane ≈6 months post-infection without stimulation).
  • T-cell-independent activation can occur, but robust memory and high-affinity antibodies require CD4⁺ help.

Antibody Titers

  • Definition: Concentration of antibodies in serum; determined by serial dilution.
  • Interpretation
    • Higher dilution still yielding detectable antibody = high titer (good protection).
    • Low or undetectable after minimal dilution → booster or vaccination indicated.

Apoptosis & Self-Defense Logic

  • Apoptosis = programmed cell death; “self-sacrifice” of irreparably damaged cells to protect the organism.
  • Ensures minimal collateral damage vs. necrosis.

HIV Case Discussion & Immune Phases

  • Clinical vignette: Patient contracted HIV via blood transfusion in Haiti; illustrates global disparities in blood screening.
  • Primary (acute) infection
    • Flu-like illness; often IgM appears first.
    • Viral load high; standard antibody tests may still be negative (window period).
  • Latent phase
    • May last up to 10 \text{ years}; patient feels well.
    • Virus replicates at low level; antibodies (IgG) present and detectable.
  • Progression to AIDS when CD4⁺ count drops & opportunistic infections emerge.
  • Drugs
    • Modern antiretroviral therapy (ART) lowers viral load → reduces transmission risk.
    • Requires lifelong adherence.
  • Ethical / public-health angle: Unequal access to testing & treatment versus high-income countries.

Vaccine Principles

  • Provide artificial active immunity by exposing immune system to weakened, inactivated, or subunit antigen.
  • Some vaccines confer lifelong protection; others require periodic boosters (\approx5{-}10\text{ yr} cycles) or COVID-19 style 6-month boosters mentioned.

Herd Immunity

  • Collective protection achieved when ≈90\% of population immune.
  • Immune individuals form a “wall” blocking transmission to those who cannot be vaccinated.

Active vs Passive Immunity

  • Active (body makes its own antibodies)
    • Natural: infection & recovery.
    • Artificial: vaccination.
  • Passive (antibodies supplied from outside)
    • Natural: maternal IgG across placenta, IgA in breast milk (vertical transmission).
    • Artificial: lab-made immunoglobulin preparations, antivenoms (e.g., IVIG, anti-snake venom).
  • Passive offers immediate but temporary protection – no memory cells generated.

Useful Analogies & Mnemonics

  • APC :dendritic cell/macrophage = “cop” arresting criminals (antigens) & delivering to court (T cell).
  • CD4 helper T cell = “dispatcher” sending instructions; CD8 cytotoxic T cell = “SWAT officer.”
  • “Always equals 8” math trick to pair MHC class with appropriate CD marker.

Key Terms & Quick Definitions

  • TCR – T-cell receptor detecting specific peptide + MHC.
  • Cytokine – small proteins (e.g., IL-2) for cell–cell signaling.
  • Perforin – pore-forming protein from CTLs.
  • Granzyme – protease inducing apoptosis.
  • Plasma cell – differentiated B cell producing antibodies.
  • Titer – quantitative measurement of antibody concentration.
  • Anergy – unresponsiveness of lymphocyte when co-stimulation absent.
  • Attenuated vaccine – live pathogen weakened so it cannot cause disease yet provokes immunity.

Ethical & Practical Take-Home Points

  • Importance of rigorous blood screening standards; disparities can lead to preventable infections.
  • Cost vs. quality paradox: high U.S. healthcare costs but cutting-edge therapies when accessible.
  • ART availability programs dramatically lower community viral load and transmission (public-health success story).
  • Herd immunity relies on community participation; vaccine hesitancy undermines protection for vulnerable groups.