Innate and Acquired (Adaptive) Immunity

Fig. 5.1 — Innate immunity acts within hours; adaptive immunity unfolds over days. (Robbins & Kumar Basic Pathology)

Overview

I. Innate Immunity

Key Features

• Responds within minutes to hours
• Uses a limited repertoire of pattern recognition receptors (PRRs) — approximately 100 types recognizing a few thousand conserved molecular patterns
• Does not improve with repeat exposure — each encounter produces a virtually identical response
• Acts both independently and as a launcher for adaptive immunity

Components

Pattern Recognition: PAMPs and DAMPs

• PAMPs (Pathogen-Associated Molecular Patterns): conserved microbial structures (e.g., LPS, viral RNA, bacterial peptidoglycans). These are essential for microbial survival, so pathogens cannot easily mutate away from them.
• DAMPs (Damage-Associated Molecular Patterns): signals released by necrotic or injured host cells (e.g., uric acid, released ATP).

PRR Classes

• Toll-Like Receptors (TLRs) — the best-characterized. Plasma-membrane TLRs detect extracellular bacterial products (e.g., LPS). Endosomal TLRs detect phagocytosed viral/bacterial nucleic acids. Activation triggers cytokine production, interferons (IFNs), and costimulators for lymphocyte activation.
• NOD-Like Receptors (NLRs) — cytosolic sensors; detect cell damage products (uric acid, K⁺ efflux) and microbial products. Form the inflammasome, which activates caspase-1 to produce IL-1β.
• RIG-like receptors — cytosolic RNA sensors; induce type I IFNs during viral replication.
• C-type lectin receptors — on macrophages/DCs; detect fungal and bacterial polysaccharides; promote phagocytosis.

Effector Reactions

1. Inflammation — cytokines, complement activation, and other mediators recruit leukocytes that phagocytose and destroy pathogens, and clear damaged cells.
2. Antiviral defense — Type I interferons (IFN-α, IFN-β) inhibit viral replication in infected and neighboring uninfected cells.

II. Acquired (Adaptive) Immunity

Key Features

• Slower onset — days to weeks for the primary response
• Highly specific — can distinguish minute structural differences between antigens (epitopes)
• Improves with exposure — secondary responses are faster, stronger, and qualitatively different (immunological memory)
• Clonally distributed — each lymphocyte clone bears a unique receptor for one antigen

Types

Lymphocyte Development

• T lymphocytes migrate to and mature in the thymus. There they acquire antigen-specific T-cell receptors (TCRs) and undergo thymic selection — up to 90% of developing T cells are destroyed because they either fail to recognize self-MHC or react against self-antigens (preventing autoimmunity).
• B lymphocytes are preprocessed in the fetal liver (mid-fetal life) and bone marrow (late fetal life and after birth). In birds, this occurs in the bursa of Fabricius — hence "B" cells.

Clonal Selection

T Lymphocytes

• CD4⁺ Helper T cells (~60–70% of circulating T cells): secrete cytokines (e.g., IFN-γ, IL-4) that stimulate B cells to produce antibodies and activate macrophages to kill phagocytosed microbes. HIV destroys these cells, causing the profound immune failure of AIDS.
• CD8⁺ Cytotoxic T lymphocytes (CTLs) (~30–40%): directly kill virus-infected cells and tumor cells.
• Regulatory T cells (Tregs): suppress immune responses; maintain self-tolerance.

B Lymphocytes and Antibodies

• Neutralize pathogens and toxins
• Opsonize microbes for phagocytosis
• Activate complement
• Provide protection against doses of toxin up to 100,000 times the lethal dose in unimmunized individuals (Guyton & Hall)

Immunological Memory

• More rapid (memory cells are more abundant and have lower activation thresholds)
• Greater in magnitude
• Often qualitatively different (e.g., antibody class switching from IgM to IgG)

Comparing the Two Systems

How They Work Together

Viruses vs. Bacteria — and General Properties of Viruses

Part I: Viruses vs. Bacteria — Key Differences

Structural Comparison

Fig. 12.1 — Major features of prokaryotic vs. eukaryotic cells (Medical Microbiology 9e)

Part II: General Properties of Viruses

1. Size and Basic Nature

"Viruses are parasites at the genetic level, replicating only in living cells and are inert in the extracellular environment." — Jawetz, Melnick & Adelberg's Medical Microbiology

2. Structural Components

FIGURE 29-1 — Schematic diagram of complete virion structure. A: Enveloped icosahedral virus. B: Enveloped helical virus. (Jawetz, Melnick & Adelberg's Medical Microbiology)

3. Capsid Symmetry

• Icosahedral symmetry — 20 triangular faces; roughly spherical appearance (e.g., poliovirus, adenovirus, herpesvirus)
• Helical symmetry — rod-shaped or filamentous; capsomeres arranged in a helix around the nucleic acid (e.g., influenza, rabies)
• Complex symmetry — neither icosahedral nor helical (e.g., poxviruses, bacteriophages)

4. Enveloped vs. Non-enveloped (Naked)

5. Classification Criteria

1. Type of nucleic acid — DNA or RNA
2. Strandedness — single-stranded (ss) or double-stranded (ds)
3. Polarity — positive-sense (+), negative-sense (−), or ambisense
4. Segmentation — number and size of genome segments
5. Capsid symmetry — icosahedral, helical, complex
6. Envelope — present or absent
7. Size of virion — 20–300 nm
8. Physicochemical properties — thermal/pH stability, buoyant density
9. Antigenic properties — reactions to antisera
10. Biologic properties — host range, tissue tropism, mode of transmission, pathogenicity

6. Replication Strategy

1. Attachment (Adsorption) — viral surface proteins bind specific host cell receptors
2. Penetration/Entry — fusion with membrane or receptor-mediated endocytosis
3. Uncoating — nucleic acid is released from capsid within the cell
4. Early gene expression — virus encodes enzymes needed for genome replication (DNA-binding proteins, polymerases)
5. Genome replication — viral nucleic acid is copied many times
6. Late gene expression — structural proteins (capsid proteins, glycoproteins) are synthesized
7. Assembly — new nucleocapsids are assembled
8. Release — naked viruses lyse the cell; enveloped viruses bud through the host membrane, acquiring their envelope

7. Host Range and Tropism

8. Effects on the Host Cell

• No apparent effect — subclinical infection
• Cytopathic effect (CPE) — cell swelling, rounding, fusion, inclusion bodies, death
• Cell transformation — oncogenic viruses integrate into the host genome, driving uncontrolled cell proliferation (e.g., HPV, EBV)
• Latency — viral genome persists silently in the host, reactivating later (e.g., HSV, VZV)

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