Immunology basics

Why this matters to the anaesthetist

Primary expects innate vs adaptive, MHC/T and B cell roles, antibody classes, and Gell–Coombs hypersensitivity types with anaphylaxis mechanism. Final expects recognition, adrenaline, and culprit patterns (NMBAs, antibiotics, chlorhexidine, latex).[1]

One-liner: Innate is fast and non-specific; adaptive is specific with memory; Type I is IgE–mast cell–histamine minutes; anaphylaxis is airway + shock + rash/±GI — treat with IM adrenaline first. [1]

Innate immunity

• Barriers: skin, mucosa, cilia, acid, lysozyme.
• Cells: neutrophils, macrophages, dendritic cells, NK cells, eosinophils/basophils/mast cells.
• Molecules: complement, acute-phase proteins, cytokines, defensins.
• Pattern recognition: TLRs detect PAMPs/DAMPs → inflammation.
• Complement: classical (antibody), alternative, lectin pathways → C3 convertase → opsonisation (C3b), anaphylatoxins (C3a/C5a), MAC (C5–9). [1]

Anaesthetic link: surgical inflammation and SIRS are innate amplification; complement activation can cause non-IgE anaphylactoid reactions. [1]

Adaptive immunity

Cellular

• Antigen presentation: dendritic cells process antigen → MHC to T cells in lymph nodes.
• MHC I (all nucleated cells) → CD8 cytotoxic T (viral/intracellular).
• MHC II (APCs) → CD4 helper T → orchestrate B cells and macrophages (Th1/Th2/Th17 patterns — keep light).
• Memory T cells speed second response. [1]

Humoral

• B cells → plasma cells → antibodies.
• IgM: first response, pentamer, activates complement.
• IgG: major serum Ig, crosses placenta, opsonises, secondary response.
• IgA: mucosal/secretory.
• IgE: binds mast cells/basophils — allergy/parasites.
• IgD: B-cell receptor roles. [1]

Primary vs secondary response: lag then IgM→IgG first time; faster higher-affinity IgG on re-exposure (sensitisation for allergy). [1]

Hypersensitivity — Gell and Coombs

Anaphylaxis physiology (exam core)

Sensitisation: prior exposure → IgE on mast cells. Re-exposure: antigen cross-links IgE → degranulation. [1]

Mediators: histamine (vasodilation, capillary leak, bronchospasm, urticaria), tryptase (marker), leukotrienes/PGs (bronchospasm, leak), etc. [1]

Clinical triad domains: skin (urticaria, flush — may be absent), respiratory (bronchospasm, stridor, hypoxia), cardiovascular (hypotension, PEA), ± GI. [1]

Tryptase: rises after mast-cell events; timed samples support diagnosis; normal tryptase does not fully exclude. [1]

Anaphylaxis vs anaphylactoid (non-IgE): same final common mast-cell pathway clinically — treat the same. Difference is mechanism/testing (skin tests, specific IgE). [1]

Immediate management physiology logic

1. Stop trigger, call for help.
2. Adrenaline — α1 vascular tone/reduces leak; β1 cardiac support; β2 bronchodilation and mast-cell stabilisation. IM to anterolateral thigh early; IV carefully in monitored settings per protocol.
3. Airway/O2, crystalloid for leak-driven hypovolaemia.
4. Adjuncts: antihistamines, steroids (late modulation), bronchodilators — not substitutes for adrenaline.
5. Observe biphasic risk; investigate later (tryptase, allergy clinic). [1]

Transfusion immunology sketch

• ABO: preformed IgM isoagglutinins → acute intravascular haemolysis if incompatible.
• RhD: IgG after sensitisation → delayed haemolysis/HDFN.
• TRALI, TACO, allergic transfusion reactions — separate mechanisms (see transfusion leaves). [1]

Immunosuppression and anaesthesia

• Steroids, chemotherapy, transplant drugs, HIV, asplenia → infection risk, vaccination rules, stress-steroid cover if HPA suppressed.
• Live vaccines and timing are specialty details; know that cell-mediated immunity matters for opportunistic pathogens. [1]

Numbers / anchors

• Type I minutes; Type IV days.
• IgE mast-cell fixed; tryptase sampling timed (e.g. 1 h peak teaching, plus baseline later — follow local protocol).
• Complement MAC = C5–9. [1]

[1] [1] [1]

Viva scripts

List the four hypersensitivity types with one example each. [1]

Explain IgE anaphylaxis pathway from antigen to hypotension. [1]

Why give adrenaline before antihistamine? [1]

ABO mismatch mechanism in one minute. [1]

Extended viva dialogue

Examiner: What is the difference between innate and adaptive immunity? [1]

Candidate: Innate is immediate, uses barriers, phagocytes and complement without antigen specificity or classic memory. Adaptive uses T and B lymphocytes with specific receptors, MHC presentation, and memory for faster re-challenge responses. [1]

Examiner: A patient bronchospasms and crashes 3 minutes after rocuronium — mechanism? [1]

Candidate: Likely Type I hypersensitivity with mast-cell degranulation if previously sensitised, or non-IgE mast-cell activation; mediators cause vasodilation, leak and bronchospasm. Stop trigger, call help, give adrenaline, support airway and volume, sample tryptase later. [1]

Clinical synthesis: Immunology for anaesthesia collapses to host defence structure plus hypersensitivity timing — and anaphylaxis muscle memory. [1]

Complement pathways in 6 lines

Classical: antigen–antibody → C1. Lectin: mannose-binding lectin. Alternative: tick-over on surfaces. All form C3 convertase → C3a/C5a anaphylatoxins, C3b opsonin, C5–9 MAC. Hereditary angioedema is C1-inhibitor related — not IgE anaphylaxis, adrenaline less effective, need specific therapy pathways. [1]

Investigation after perioperative anaphylaxis

Timed tryptase (acute + baseline), referral for skin testing / specific IgE, document all exposures (including chlorhexidine, patent blue, gels), medic-alert, and future anaesthesia planning with tested alternatives. [1]

Worked SAQ

SAQ: Classify hypersensitivity with anaesthetic examples (8 marks)

Type I IgE immediate: anaphylaxis to neuromuscular blockers or antibiotics. Type II antibody against cells: ABO incompatible transfusion haemolysis. Type III immune complex: serum sickness-like reactions. Type IV T-cell delayed: contact dermatitis to rubber accelerators, some drug rashes. Timing and mechanism dictate acute treatment and later testing. [1]

MHC clinical hooks

MHC I presents cytosolic peptides to CD8 — viral immunity and transplant cytotoxicity. MHC II presents exogenous peptides to CD4 — helps B cells and macrophages. HLA matching matters for transplant; some HLA alleles associate with severe drug reactions (e.g. certain antiepileptics — specialty knowledge). [1]

Neutrophil life cycle

Marrow → circulating ↔ marginated pool → tissues. Steroids raise circulating neutrophils by demargination (not true new production acute). Neutropenia risk from chemo is infection physiology for lists. [1]

Extended viva add-on

Examiner: Why might tryptase be normal after a clinical anaphylaxis? [1]

Candidate: Timing may miss the peak, some reactions are basophil-predominant with less tryptase release, and clinical diagnosis can still stand. Always take correctly timed samples and baseline later, and refer for formal testing. [1]

Primary exam expansion — dense examiner pack

Innate versus adaptive immunity (framework first)

Cells and signals you must name

Neutrophils: acute bacterial phagocytosis; neutropenia → bacterial/fungal risk. Macrophages/monocytes: phagocytosis, antigen presentation, cytokine factories (IL-1, TNF, IL-6). Dendritic cells: bridge innate→adaptive. NK cells: virus/tumour without prior sensitisation. T helper CD4: orchestrate (Th1 cell-mediated, Th2 humoral/allergy teaching, Th17, Treg). Cytotoxic CD8: kill virus-infected cells. B cells → plasma cells → antibodies. [1]

Antibodies: IgM first acute; IgG memory/placental transfer; IgA mucosal; IgE allergy/parasites; IgD receptor roles. [1]

Complement pathways (short)

Classical (antibody-driven), alternative, lectin → C3 convertase centre → opsonisation (C3b), anaphylatoxins (C3a/C5a), MAC (C5–9). Deficiency → infection or immune complex disease patterns. Protamine–heparin and some extracorporeal circuits activate complement — inflammatory response teaching. [1]

Hypersensitivity types (Gell and Coombs) with anaesthesia examples

Anaphylaxis molecular steps

Sensitization → IgE on mast cells/basophils → re-exposure cross-links IgE → degranulation (histamine, tryptase, leukotrienes, prostaglandins) → vasodilation, ↑permeability, bronchospasm, urticaria. Under anaesthesia rash may be absent; cardiovascular collapse dominates. Tryptase supports diagnosis if timed correctly. Non-IgE anaphylactoid histamine release (vancomycin red-man, atracurium) can mimic — still treat life threats similarly first. [1]

Sepsis immune sketch

Pathogen-associated molecular patterns (LPS etc.) → TLR → cytokine storm → endothelial dysfunction, capillary leak, coagulopathy (DIC), myocardial depression, vasoplegia. Later immunoparalysis concept in ICU. Anaesthetist: source control, antibiotics, fluids, vasopressors, organ support — immunology explains why not just “low BP.” [1]

Transfusion immunology

ABO IgM isoagglutinins → acute haemolytic reaction if incompatible. RhD IgG → delayed haemolytic / HDFN. TRALI: immune/non-immune neutrophil lung injury. Allergic transfusion reactions: donor plasma proteins. Irradiation prevents TA-GVHD in at-risk hosts. [1]

Immunosuppression perioperative notes

Chronic steroids, transplant drugs (tacrolimus, ciclosporin, mycophenolate), biologics, chemotherapy — infection risk, wound healing, adrenal suppression, drug interactions (CYP3A calcineurin inhibitors). Avoid live vaccines context. Asepsis and antibiotic timing matter more, not less. [1]

Wound healing phases (brief)

Haemostasis → inflammation → proliferation → remodelling. Factors impairing: hypoxia, steroids, malnutrition, diabetes, smoking, infection, radiation. [1]

SAQ: classify hypersensitivity with anaesthetic examples (8 marks)

Four types with mechanisms (4). One detailed Type I perioperative anaphylaxis recognition and immediate management outline (3). Non-IgE contrast (1). [1]

Viva

Q: Why measure tryptase? A: Mast-cell activation marker supporting anaphylaxis diagnosis when timed (peak 1–2 h, baseline later). Q: Difference Type I vs non-immune histamine release? A: IgE-specific vs direct mast-cell displacement; history/testing differ, emergency Rx overlaps. Q: Why is complement relevant on CPB? A: Circuit activation drives systemic inflammatory response. [1]

High-yield viva battery and numbers lock-in

Anaphylaxis under anaesthesia — recognition clusters

Sudden hypotension ± tachycardia or bradycardia; increased airway pressures/bronchospasm; desaturation; urticaria/flushing/angioedema (may be hidden under drapes); cardiovascular collapse alone. Differential: PE, air embolism, MH, scombroid, high spinal, haemorrhage, vaso-vagal, primary cardiac. Treat as anaphylaxis if probable — do not wait for rash. [1]

Antibody classes one-liners

IgM: primary response, pentamer, ABO. IgG: secondary, crosses placenta, opsonises. IgA: mucosal secretions. IgE: mast-cell allergy. IgD: B-cell receptor co-role. [1]

Transfusion reaction rapid sort

Full viva dialogue (additional)

Examiner: Walk through Type I hypersensitivity mechanism. [1]

Candidate: After sensitisation, antigen-specific IgE coats mast cells and basophils. Re-exposure cross-links IgE, causing degranulation of histamine, tryptase and lipid mediators. The result is vasodilation, capillary leak, bronchospasm and urticaria — clinically anaphylaxis when systemic. [1]

Examiner: Why is chlorhexidine a modern anaphylaxis culprit? [1]

Candidate: It is ubiquitous in skin prep and impregnated lines; repeated exposures sensitise; reactions can be severe. Prevention includes history of prior reactions to prep or central lines and using alternatives when allergy confirmed. [1]

Exam traps

• Waiting for rash before treating anaphylaxis.
• Confusing TACO and TRALI.
• Saying all vancomycin red-man is IgE anaphylaxis.
• Forgetting tryptase timing for later diagnosis. [1]

References

1. [1]Trujillo-Ocampo A, et al. Human NKT10 cells are enriched in cord-derived invariant natural killer T cells and mediate immune-regulation in a xenogeneic graft-versus-host disease model Front Immunol, 2026.PMID 42358969
2. [2]Shende S, et al. Vitamin D as an Immuno-Endocrine Modulator: Discovering Its Role in Autoimmune Disorders and Host Defense Mechanisms J Clin Med, 2026.PMID 42355910
3. [3]Takazawa T, et al. Perioperative anaphylaxis in Japan: Epidemiology, diagnosis, and challenges Allergol Int, 2026.PMID 41455630
4. [4]Jo Y, et al. Remimazolam-Induced Anaphylaxis After Spinal Anesthesia: A Case Report and Literature Review J Clin Med, 2026.PMID 42278971
5. [5]Habib R, et al. Sugammadex-Associated Delayed Laryngeal and Upper Airway Edema: A Novel Adverse Effect J Investig Med High Impact Case Rep, 2026.PMID 42113672
6. [6]Tanei R. Revisiting Atopy: The IgE-Dependent Amplification Loop as a Forgotten Driver of Atopic Dermatitis Pathophysiology, 2026.PMID 42347026