Acquired (Adaptive) Immunity – Lecture Review

Overview of the Immune System

• Two functional divisions
  • Innate (non-specific) immunity
  • Immediate, broad response to anything foreign.
  • Acquired (adaptive/specific) immunity
  • Tailors response to a particular pathogen (e.g., chickenpox, rabies, COVID-19).
• Important caveat
  • All body systems interlock; separating them is a reductionist teaching tool.
  • Analogy: Cardiovascular system is meaningless without respiratory or renal support—likewise, innate and acquired arms overlap.
• Shared goal: preserve homeostasis by neutralizing pathogens, toxins, or abnormal cells.

Fundamental Concepts of Acquired Immunity

• Two major branches
  • Humoral immunity (B-lymphocytes → antibodies in blood “humors”).
  • Cell-mediated immunity (T-lymphocytes → direct cellular actions).
• Key cellular players
  • Lymphocytes: subtype of WBCs devoted to adaptive immunity.
• Antigens ("antibody generators")
  • Large proteins or polysaccharides on pathogen surface; act as ID tags.
  • Allow immune system to "zero-in" on a unique invader.
  • Mostly foreign, yet term is also used for self-markers (e.g., blood group antigens).
• Immunological memory
  • After first exposure, memory B & T cells persist.
  • Subsequent exposures → faster, stronger, longer response (months vs. days/weeks).
  • Can tolerate infectious doses \sim 10^5 times the normal lethal level.

Antibodies (Immunoglobulins)

• General features
  • Plasma proteins secreted by activated B-cells (plasma cells).
  • Structure: Y-shaped
  • Constant (C) region: vertical stems; uniform.
  • Variable (V) region: tips; antigen-specific.
  • Each Ig binds ≥2 antigenic determinants → forms antigen–antibody complex.
• Major classes
  • IgG – predominant, long-term immunity.
  • IgM – first produced; later class-switches to IgG.
  • IgE – allergic responses.
• Functional consequences of Ag–Ab complex
  • Agglutination – clumping pathogens for easier phagocytosis.
  • Precipitation – renders soluble antigens insoluble, aids clearance.
  • Neutralization – blocks toxin release or binding sites.
  • Lysis – direct or complement-mediated cell rupture.
  • Complement activation – most critical downstream effect.

Complement System (Bridge Between Innate & Adaptive)

• ~20 inactive plasma proteins circulate (analogous to fibrinogen \rightarrow fibrin concept).
• Activation sequence
  1. Constant region of bound antibody engages C1.
  2. Cascade amplifies through sequential proteolytic cleavage.
• Resulting actions
  • Additional agglutination & opsonization.
  • Release of cytokines (broad) & chemokines (attract WBCs → chemotaxis).
  • Activation of basophils/mast cells → histamine → vasodilation & ↑capillary permeability → inflammation.
  • Recruitment/activation of phagocytes (macrophages, dendritic cells, neutrophils).
  • Lytic pathway forms membrane-attack complex → pathogen explosion.

B-Lymphocytes (Humoral Arm)

• Origin & maturation
  • Synthesized in bone marrow ("B = Bone").
  • Serve as antigen-presenting cells (APCs).
• Surface receptors = membrane-bound antibodies (B-cell receptors, BCRs).
• Activation sequence
  1. Specific antigen binds matching BCR.
  2. B-cell undergoes clonal expansion → two daughter populations:
  • Plasma (effector) cells – secrete soluble antibodies.
  • Memory B cells – long-lived sentinels for rapid future response.
• Lifespan note: Effector cells are short-lived; memory cells persist.

T-Lymphocytes (Cell-Mediated Arm)

• Origin & maturation
  • Synthesized in thymus (mediastinal gland above heart).
  • Migrate to lymph nodes, spleen, MALT, etc.
• Surface receptors = T-cell receptors (TCRs) – antigen-specific.
• Subtypes & roles
  • Helper T (T_H)
  • Orchestrate immune responses; activate B cells & other T cells.
  • Depletion (e.g., HIV/AIDS) cripples acquired immunity.
  • Cytotoxic T (T_C)
  • Killer cells for virus-infected cells, cancer cells.
  • Release perforins → pore formation; osmotic lysis.
  • Secrete toxins to induce apoptosis.
  • Repressor/Suppressor T (T_R)
  • Dampen excessive T_H and T_C activity; maintain balance.
• Upon activation → clonal division into
  • Effector T cells (subtype-specific functions).
  • Memory T cells – reservoir for quicker future action.

Immunocompetency & Self-Tolerance

• During early development, millions of naive B & T cells generated with random receptors.
• Negative selection
  • Any lymphocyte whose receptor binds a self-cell is destroyed.
  • Ensures “self vs. non-self” discrimination; failure → autoimmunity.

Herd Immunity Concept

• Population dynamics
  • Light blue = immunocompromised (IC) individual(s).
  • Red = currently infected.
  • Dark blue = healthy, non-immune.
• If nobody has prior immunity → rapid spread, IC at highest risk.
• If majority possess adaptive immunity (through infection or vaccination)
  • Pathogen’s transmission chain is interrupted.
  • IC individuals “shielded” by the immune majority – communal altruism.
• Vaccines provide safe antigenic exposure so recipients gain memory without disease.
  • Some IC persons cannot even receive vaccines, relying on herd effect.

Vaccine Effectiveness & Controversies

• U.S. epidemiological data (2016) shows near-eradication of several diseases after vaccination programs:
  • Smallpox: 100\% reduction.
  • Rubella: 100\%.
  • Measles: 99.98\%.
  • Mumps: 98.9\%.
  • Tetanus: just below 100\%.
• 1998 Lancet article linked thimerosal to autism
  • Subsequent decades of research found no causal link.
  • 10/13 original authors retracted; lead author lost medical license.
• Safety profile
  • Vaccines extremely safe for general population; rare adverse events occur.
  • Risk–benefit heavily favors vaccination, especially for herd immunity.
• Barriers
  • Political, social, religious objections persist; education crucial.

Integrative & Ethical Notes

• Complement system exemplifies cross-talk: adaptive antigen specificity triggers innate effector cascades.
• Cancer surveillance: Cytotoxic T cells routinely eliminate emerging malignancies.
• Reductionist teaching aids clarity but true physiology is synergistic.
• Herd immunity illustrates societal ethics—community action to safeguard vulnerable members.