Q.103 A patient comes with symptoms of autonomic hemolysis. The diagnostic tests reveal that he has
auto-antibodies to red blood cells (RBCs). Which one of the following mechanisms is the cause of
this condition?
(A) Neutrophils release granzymes which lyse RBCs
(B) Complement is activated and membrane attack complex lyse RBCs
(C) Cytotoxic T-cells lyse RBCs
(D) Interleukin-2 binds to the receptor on RBCs
Autoimmune hemolytic anemia (AIHA) with autoantibodies to RBCs causes intravascular hemolysis primarily through complement activation forming the membrane attack complex (MAC), which directly lyses RBCs. This matches the “autonomic hemolysis” description (likely meaning autologous or autoimmune). The correct answer is (B).
Correct Answer
(B) Complement is activated and membrane attack complex lyse RBCs
Mechanism of AIHA Hemolysis
Autoantibodies (typically IgG in warm AIHA, IgM in cold agglutinin disease) bind RBCs, activating the classical complement pathway. C1q initiates the cascade, leading to C3 convertase, C5 convertase, and terminal MAC (C5b-9) pore formation on RBC membranes. This causes rapid intravascular lysis with hemoglobinuria—hallmark of the condition. Extravascular phagocytosis occurs too, but MAC explains acute hemolytic crises.
Option Analysis
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(A) Neutrophils release granzymes which lyse RBCs: Wrong. Granzymes are cytotoxic T-cell/NK cell serine proteases delivered via perforin pores to induce apoptosis in nucleated target cells. RBCs lack nuclei; neutrophils use phagocytosis/ROS, not granzymes.
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(B) Complement is activated and membrane attack complex lyse RBCs: Correct. Primary mechanism in intravascular AIHA (especially cold types with IgM); IgG can also fix complement efficiently.
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(C) Cytotoxic T-cells lyse RBCs: Incorrect. CD8+ CTLs target MHC-I on nucleated cells via perforin/granzyme or FasL. RBCs lack MHC and nuclei—CTLs don’t mediate AIHA.
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(D) Interleukin-2 binds to the receptor on RBCs: Wrong. IL-2 acts on T-cell/NK cell IL-2R (CD25/CD122/CD132) for proliferation/activation. Mature RBCs lack cytokine receptors.
Introduction to Autoimmune Hemolysis Mechanisms
Autoimmune hemolysis autoantibodies RBC complement MAC is critical for GATE Life Sciences immunology, where Q.103 tests AIHA destruction pathways. Patient symptoms with anti-RBC antibodies point to complement-mediated lysis via MAC, distinguishing from cellular cytotoxicity absent on anucleate RBCs.
AIHA Pathophysiology Breakdown
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Autoantibody binding → Classical complement activation (C1q-C4-C2 → C3 → C5).
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MAC (C5b-9) forms transmembrane pores → Colloid osmotic lysis.
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Intravascular hemolysis releases free hemoglobin, haptoglobin depletion.
Q.103 Detailed Solution
“Autonomic hemolysis” = autoimmune RBC lysis. Complement cascade is definitive; granzymes/CTLs irrelevant for enucleate RBCs; IL-2 doesn’t bind erythrocytes. Answer: (B) confirmed by AIHA literature.
Why Complement Dominates AIHA Options
| Option | Target Cells | Mechanism | RBC Valid? |
|---|---|---|---|
| (A) Neutrophils/granzymes | Nucleated | Apoptosis | ❌ No nucleus |
| (B) Complement MAC | Any w/Ab | Pore lysis | ✅ Correct |
| (C) Cytotoxic T-cells | MHC-I+ | Perforin/granzyme | ❌ No MHC |
| (D) IL-2 | Lymphocytes | Proliferation | ❌ No receptors |
Complement pathway is high-yield for hemolysis questions.
GATE Immunology Exam Tips
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Mnemonic: “MAC Attacks Anucleates” (Complement lyses RBCs).
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Compare: Warm AIHA (IgG, extravascular ± complement) vs. Cold AIHA (IgM, intravascular MAC).
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Key diagnostic: Positive DAT + low haptoglobin + hemoglobinemia.
Master autoimmune hemolysis autoantibodies RBC complement MAC for perfect immunology scores in competitive exams.
