Immunology: How the Immune System Defends the Body

Innate Immunity

First line of defense: physical barriers (skin, mucosa), chemical barriers (lysozyme, defensins, stomach acid pH 1.5-3.5). Pattern recognition receptors (PRRs): Toll-like receptors (TLR4 recognizes LPS), NOD-like receptors, RIG-I (viral RNA). PAMPs (Pathogen-Associated Molecular Patterns): conserved microbial molecules. DAMPs (Danger-Associated Molecular Patterns): released by damaged host cells. Inflammatory response: vasodilation, increased permeability, recruitment of neutrophils and macrophages. Complement system: ~30 proteins, three pathways (classical, lectin, alternative) → MAC (membrane attack complex). NK cells: kill virus-infected and tumor cells by detecting missing MHC-I ("missing self"). Response time: minutes to hours, no memory.

Adaptive Immunity

Adaptive/acquired immunity: specificity + memory. T cells: mature in thymus, express TCR (T-cell receptor). CD4+ T helper cells: Th1 (intracellular pathogens, activate macrophages), Th2 (helminths, activate eosinophils/B cells), Th17 (extracellular bacteria/fungi), Treg (suppress immune response, maintain tolerance). CD8+ cytotoxic T cells: kill infected cells via perforin/granzyme pathway. MHC restriction: CD8+ recognizes peptide-MHC-I (all nucleated cells), CD4+ recognizes peptide-MHC-II (APCs). Clonal selection: antigen-specific lymphocyte activated → clonal expansion → effector + memory cells. B cells: produce antibodies (immunoglobulins). V(D)J recombination: generates >10¹¹ unique antigen receptors from limited gene segments.

Antibodies

Immunoglobulin structure: two heavy chains + two light chains, Y-shaped. Variable region (Fab): antigen binding, constant region (Fc): effector functions. Isotypes: IgM (pentamer, first response), IgG (most abundant, crosses placenta), IgA (mucosal immunity, dimer), IgE (allergy and parasites), IgD (B cell receptor). Effector functions: neutralization, opsonization (enhance phagocytosis), complement activation, ADCC (antibody-dependent cellular cytotoxicity). Affinity maturation: somatic hypermutation in germinal centers → selection for higher affinity. Class switch recombination: IgM → IgG/IgA/IgE based on cytokine signals. Monoclonal antibodies: hybridoma technology (Köhler & Milstein, 1975, Nobel 1984) — therapeutic applications.

Vaccines

Principle: prime adaptive immunity without disease → memory cells ready for real infection. Types: live attenuated (MMR, yellow fever), inactivated (polio-Salk, flu), subunit/protein (HBV, HPV), conjugate (pneumococcal), toxoid (tetanus, diphtheria). Modern platforms: mRNA (Pfizer/BioNTech, Moderna — COVID-19), viral vector (AstraZeneca, J&J), DNA vaccines. mRNA vaccines: encode antigen (spike protein) → translated by host cells → immune response. Advantages of mRNA: rapid development (days to design), no live pathogen, strong cellular + humoral response. Adjuvants: enhance immune response (alum, MF59, AS01). Herd immunity threshold: depends on R₀ (measles R₀ = 12-18: need ~92-94% immunity). Vaccine development: Phase I (safety), Phase II (immunogenicity), Phase III (efficacy) — typically 10-15 years, compressed to 11 months for COVID-19.

Immunotherapy

Cancer immunotherapy: harnessing immune system to fight cancer. Checkpoint inhibitors: anti-PD-1 (pembrolizumab, nivolumab), anti-PD-L1 (atezolizumab), anti-CTLA-4 (ipilimumab). Mechanism: release "brakes" on T cells → enhanced anti-tumor response. CAR-T cell therapy: patient's T cells engineered with chimeric antigen receptor → expanded → infused. Approved: Kymriah (CD19, B-cell lymphoma/ALL), Yescarta. BiTE antibodies: bispecific T-cell engagers connecting T cells to tumor cells (blinatumomab). Cancer vaccines: personalized neoantigen vaccines (mRNA-4157 + pembrolizumab for melanoma). Autoimmune therapy: biologics (anti-TNF: infliximab, adalimumab), anti-IL-6 (tocilizumab), B cell depletion (rituximab). Nobel Prizes: 2018 (Allison, Honjo — checkpoint therapy), 2024 (miRNA, foundation for understanding immune regulation).

Frequently Asked Questions

What is the difference between innate and adaptive immunity?

Innate immunity provides immediate, non-specific defense using barriers and pattern recognition. Adaptive immunity is specific to particular pathogens, takes days to develop, and creates immunological memory.

How do vaccines work?

Vaccines expose the immune system to a harmless form of a pathogen or its components, triggering adaptive immune responses that create memory cells, enabling rapid protection upon actual infection.

What are checkpoint inhibitors?

Checkpoint inhibitors are immunotherapy drugs that block inhibitory receptors (PD-1, CTLA-4) on T cells, releasing the "brakes" on anti-tumor immune responses, enabling the immune system to attack cancer.

What is CAR-T therapy?

CAR-T therapy involves engineering a patient's own T cells to express a chimeric antigen receptor targeting cancer cells, then expanding and infusing them back to fight the cancer.

What are antibodies?

Antibodies are Y-shaped proteins produced by B cells that bind specific antigens, neutralizing pathogens, marking them for destruction, and activating the complement system.

Try it live

Everything above runs in your browser — open Cardiac Action Potential and change the parameters while it is running. Nothing is installed, nothing is uploaded, the whole model lives in one tab.