The Immune System: Components, Innate & Adaptive Immunity, Development

Introduction · Components of immune system · Innate immunity (barriers, phagocytes, complement, NK cells) · Adaptive immunity (B cells, T cells, MHC, antibodies) · Prenatal development · Neonatal immunity · Postnatal maturation
🧬 Key concepts: Hematopoiesis, primary vs secondary lymphoid organs. Innate (rapid, non-specific) vs adaptive (specific, memory). Neonatal immune immaturity (increased infection risk). Thymus development, B-cell maturation, maternal antibody transfer.

📖 Components, innate & adaptive immunity, development

🧬 Components of immune system
Primary lymphoid organs: bone marrow (B-cell development), thymus (T-cell maturation). Secondary: lymph nodes, spleen, MALT. Cells: lymphocytes, phagocytes (neutrophils, macrophages), dendritic cells, NK cells.
🛡️ Innate immunity (rapid, non-specific)
Barriers (skin, mucosa), complement (alternative/lectin pathways), phagocytes (neutrophils, macrophages), NK cells, pattern recognition receptors (TLRs). No memory.
🎯 Adaptive immunity (specific, memory)
Humoral (B cells → antibodies, class switching). Cellular (T cells → CD4+ helper, CD8+ cytotoxic). MHC presentation (MHC I: CD8, MHC II: CD4). Clonal selection, immunological memory.
👶 Development of immune system
Prenatal: yolk sac, fetal liver (3-6 months), then bone marrow. Thymus functional by 10-12 weeks. Newborn: low IgG (maternal), IgA/IgM low, complement lower, neutrophil storage pool limited. Postnatal: maturation with antigen exposure, vaccination schedule.
⚠️ Newborn immune vulnerability: Increased risk of encapsulated bacteria (lack of IgG to polysaccharides), intracellular pathogens (immature T cells), impaired neutrophil chemotaxis, low complement activity, delayed vaccine responses.

🩺 Approach to suspected immunodeficiency (based on immune system knowledge)

1
Clinical clues – Recurrent infections (sinopulmonary → antibody defect; opportunistic → T-cell defect; catalase-positive organisms → phagocyte defect). Family history, failure to thrive.
2
Initial evaluation – CBC with differential (lymphopenia, neutropenia), serum immunoglobulins (IgG, IgA, IgM), vaccine titers, lymphocyte subsets by flow cytometry.
3
Innate immunity testing – Complement CH50, AH50; DHR test for CGD; neutrophil adhesion markers (CD18).
4
Adaptive immunity testing – Lymphocyte proliferation to mitogens/antigens; specific antibody response to vaccines; TREC/KREC for newborn screening.
📌 Clinical pearl: A term newborn with recurrent infections, especially with opportunistic organisms or failure to thrive, should raise concern for a primary immunodeficiency such as SCID.

📋 General management principles based on immune system deficits

1
Antibody deficiency (B-cell/ humoral) – IVIG or subcutaneous immunoglobulin replacement (400-600 mg/kg every 3-4 weeks). Prophylactic antibiotics for select cases.
2
T-cell deficiency (cellular) – Protective isolation, avoid live vaccines, PCP prophylaxis (TMP-SMX), antifungal prophylaxis, IVIG. Definitive: HSCT or gene therapy.
3
Phagocyte disorders (e.g., CGD) – Prophylactic TMP-SMX, itraconazole, IFN-γ. HSCT for severe cases. Avoid exposure to mould.
4
Complement deficiencies – Meningococcal vaccination (all serogroups), pneumococcal, Hib vaccines; prophylactic antibiotics (penicillin).
5
General supportive care – Prompt antibiotics for infections, nutritional support, vaccination (inactivated only for T-cell defects), patient/family education.
🚨 Avoid live vaccines in: SCID, severe T-cell defects, DiGeorge (complete), patients on high-dose steroids, after HSCT until immune reconstitution.

🧠 Reflex prompts: immune system & development

🧬 Which immunoglobulin is primarily transferred from mother to fetus?
IgG (crosses placenta, provides passive immunity in first months of life).
🛡️ What is the first line of defense against pathogens?
Innate immunity: physical barriers (skin, mucous membranes), complement, phagocytes, NK cells.
🎯 Which cells mediate adaptive immunity?
B lymphocytes (humoral immunity → antibodies) and T lymphocytes (cellular immunity).
👶 Why are newborns more susceptible to infections?
Low IgG (maternal IgG declines), immature T-cell function, low complement activity, limited neutrophil storage pool.
🧬 Where do B cells mature?
Bone marrow.
🫀 Where do T cells mature?
Thymus.
🧪 What is the role of MHC class I?
Presents endogenous antigens (viruses) to CD8+ cytotoxic T cells.
🧪 What is the role of MHC class II?
Presents exogenous antigens to CD4+ helper T cells.
🩸 What is the most common primary immunodeficiency?
Selective IgA deficiency (1 in 500).
💊 Why is the newborn period vulnerable to encapsulated bacteria (e.g., GBS, E. coli)?
Lack of maternal IgG specific to polysaccharide antigens; inadequate antibody production.