Innate and Adaptive Immunity
Innate immunity provides rapid, non-specific defence, while adaptive immunity develops specific responses with immunological memory. Both systems are integrated and interdependent.
Key Facts
Innate immunity acts within minutes to hours — no memory, no specificity; includes neutrophils, macrophages, complement, NK cells Adaptive immunity takes days to weeks to develop but generates immunological memory for faster secondary responses Dendritic cells are the most potent antigen-presenting cells — bridge innate and adaptive immunity Toll-like receptors (TLRs) on innate cells recognise PAMPs (pathogen-associated molecular patterns) and DAMPs (damage-associated molecular patterns) Opsonisation (coating pathogens with IgG or C3b) enhances phagocytosis by neutrophils and macrophages NK cells kill virus-infected and tumour cells without prior sensitisation — recognise cells lacking MHC Class I ('missing self') T cell activation requires two signals: TCR-MHC interaction (signal 1) and co-stimulatory molecules B7-CD28 (signal 2) Clonal selection theory: Only lymphocytes with receptors specific to a given antigen proliferate upon exposure
Overview
Key Facts
The innate and adaptive immune systems are complementary defence mechanisms. Innate immunity provides the first line of defence and shapes the adaptive response, while adaptive immunity provides pathogen-specific, long-lasting protection.
Epidemiology
The clinical relevance of innate and adaptive immunity spans all medical specialties:
- Innate immune defects lead to recurrent pyogenic infections (e.g., chronic granulomatous disease, complement deficiencies)
- Adaptive immune defects lead to opportunistic infections (e.g., SCID, HIV/AIDS)
- Inappropriate immune activation causes autoimmune disease and chronic inflammation
Aetiology
Innate Immune Components:
- Barriers: Skin (keratinised epithelium), mucous membranes, cilia, gastric acid, lysozyme, defensins
- Cells: Neutrophils, monocytes/macrophages, dendritic cells, mast cells, basophils, eosinophils, NK cells
- Soluble factors: Complement system, acute phase proteins (CRP, ferritin), cytokines (TNF-α, IL-1, IL-6), interferons
Adaptive Immune Components:
- Cell-mediated: T lymphocytes (CD4+ helper, CD8+ cytotoxic, regulatory, γδ)
- Humoral: B lymphocytes → plasma cells → immunoglobulins
Pathophysiology
The innate immune response is triggered by PRR recognition of PAMPs:
- Bacterial: Lipopolysaccharide (LPS), peptidoglycan, flagellin
- Viral: Double-stranded RNA, single-stranded RNA, unmethylated CpG DNA
- Fungal: β-glucan, mannan
This triggers NF-κB signalling, cytokine release, and inflammation. Dendritic cells process antigens and migrate to lymph nodes to activate naïve T cells, initiating the adaptive response.
Clinical Presentation
Innate Immunity Disorders
- Chronic granulomatous disease: Recurrent catalase-positive organism infections (Staph. aureus, Aspergillus, Serratia)
- Leukocyte adhesion deficiency: Delayed umbilical cord separation, recurrent infections without pus
- Complement deficiencies: C3 — recurrent encapsulated bacteria; C5-C9 — recurrent Neisseria
- Hereditary angioedema: C1 esterase inhibitor deficiency — episodic swelling
Adaptive Immunity Disorders
- SCID: Severe infections from birth, failure to thrive, absent thymic shadow
- X-linked agammaglobulinaemia (Bruton's): Recurrent sinopulmonary infections from 6 months (maternal IgG wanes)
- DiGeorge syndrome (22q11.2 deletion): T cell deficiency, cardiac defects, hypocalcaemia, facial dysmorphism
Red Flags
- Life-threatening infections with common organisms in infancy → suspect SCID
- Recurrent Neisseria meningitidis → test complement pathway
- Granuloma formation with recurrent Staph aureus/Aspergillus → CGD
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Innate immune defect | Pyogenic infections, fungal infections, poor pus formation | NBT/DHR test (CGD), complement levels, neutrophil count |
| T cell deficiency | Viral, fungal, opportunistic infections | Lymphocyte subsets, HIV test |
| B cell/antibody deficiency | Encapsulated bacterial infections (after 6 months age) | Immunoglobulins, vaccine responses |
| Combined immunodeficiency | Features of both T and B cell deficiency | Lymphocyte subsets, immunoglobulins, genetic testing |
| Secondary immunodeficiency | Drug history, HIV, malnutrition | Identify underlying cause |
| Autoinflammatory syndrome | Recurrent fevers, sterile inflammation | Genetic testing, SAA, CRP |
Diagnosis / Investigation
Bedside
- Clinical assessment: Growth parameters, lymph node assessment, tonsil presence
- Vaccination history: Poor responses suggest antibody deficiency
Bloods
- FBC with differential: Neutrophil count, lymphocyte count
- Lymphocyte subsets: CD3 (total T), CD4 (helper T), CD8 (cytotoxic T), CD19/CD20 (B cells), CD56 (NK cells)
- Immunoglobulins: IgG, IgA, IgM levels
- Complement: C3, C4, CH50 (classical pathway), AP50 (alternative pathway)
- CRP, ESR: Acute phase response assessment
Imaging
- CXR: Thymic shadow (absent in SCID, DiGeorge)
- CT chest/abdomen: Lymphadenopathy, splenomegaly
Special Tests
- NBT/DHR flow cytometry: CGD (oxidative burst assessment)
- Vaccine responses: Pre/post-immunisation antibody levels
- Lymphocyte proliferation assays: T cell functional assessment
- Genetic testing: For specific immunodeficiency syndromes
- Mannose-binding lectin (MBL): Lectin pathway deficiency
Management
Non-pharmacological
- Infection prevention (hand hygiene, food safety, environmental precautions)
- Avoid live vaccines in T cell deficiency
- Family screening and genetic counselling
Pharmacological
- Immunoglobulin replacement: For antibody deficiencies (IV or SC)
- Antibiotic prophylaxis: Co-trimoxazole (PCP), itraconazole (fungal) in severe deficiencies
- G-CSF: Neutropenia
- Interferon-gamma: CGD prophylaxis
- C1 esterase inhibitor concentrate: Hereditary angioedema (acute and prophylactic)
Surgical/Interventional
- HSCT: Curative for SCID, CGD, WAS, and other severe primary immunodeficiencies
- Gene therapy: ADA-SCID, X-linked SCID (emerging)
- Thymic transplantation: Complete DiGeorge syndrome
Referral Criteria
- Any suspected primary immunodeficiency → specialist immunology
- SCID is a medical emergency — refer immediately for HSCT evaluation
- Recurrent serious or unusual infections → infection/immunology team
Prognosis
- SCID: >90% survival with early HSCT (within first 3.5 months of life); fatal within 1 year if untreated
- CGD: Median survival >40 years with prophylaxis; cure possible with HSCT
- XLA (Bruton's): Near-normal life expectancy with immunoglobulin replacement
- C5-C9 deficiency: Generally good prognosis with awareness and vaccination against Neisseria
- CVID: Increased risk of autoimmunity (20%), lymphoma (5-10%); life expectancy reduced if granulomatous disease develops
Other Relevant Information
Innate vs Adaptive Immunity Comparison
| Feature | Innate | Adaptive |
|---|---|---|
| Speed | Immediate (minutes-hours) | Delayed (days-weeks) |
| Specificity | Non-specific (PAMPs) | Highly specific (antigens) |
| Memory | No | Yes |
| Key cells | Neutrophils, macrophages, NK cells | T cells, B cells |
| Key molecules | Complement, cytokines, CRP | Immunoglobulins, cytokines |
| Receptors | PRRs (TLRs, NOD-like receptors) | TCR, BCR (highly diverse) |
CD Markers — Key for Exams
| Marker | Cell Type |
|---|---|
| CD3 | All T cells |
| CD4 | Helper T cells |
| CD8 | Cytotoxic T cells |
| CD19/CD20 | B cells |
| CD56 | NK cells |
| CD14 | Monocytes |
| CD25 + FoxP3 | Regulatory T cells |
| CD34 | Haematopoietic stem cells |