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
- Constant region of bound antibody engages C1.
- 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
- Specific antigen binds matching BCR.
- 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.
- 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.
