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Questions and Answers
What is the primary function of antibodies?
What is the primary function of antibodies?
Where are antibodies primarily produced?
Where are antibodies primarily produced?
Which regions of immunoglobulin molecules mediate the effector functions of antibodies?
Which regions of immunoglobulin molecules mediate the effector functions of antibodies?
How do antibodies neutralize the infectivity of microbes?
How do antibodies neutralize the infectivity of microbes?
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What role do Fc receptors play in antibody-mediated phagocytosis?
What role do Fc receptors play in antibody-mediated phagocytosis?
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Which statement about humoral immunity is correct?
Which statement about humoral immunity is correct?
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What is the function of opsonization in the immune response?
What is the function of opsonization in the immune response?
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Which of the following describes antibody-dependent cell-mediated cytotoxicity (ADCC)?
Which of the following describes antibody-dependent cell-mediated cytotoxicity (ADCC)?
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What is the main reason complement activation needs to be regulated?
What is the main reason complement activation needs to be regulated?
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Which regulatory mechanism inhibits the formation of C3 convertases?
Which regulatory mechanism inhibits the formation of C3 convertases?
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Which condition is characterized by the absence of both DAF and CD59?
Which condition is characterized by the absence of both DAF and CD59?
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What is a common treatment to accelerate erythropoiesis in individuals with PNH?
What is a common treatment to accelerate erythropoiesis in individuals with PNH?
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What consequence results from the deficiency of CD59 in PNH?
What consequence results from the deficiency of CD59 in PNH?
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Hereditary angioedema is primarily caused by a deficiency in which protein?
Hereditary angioedema is primarily caused by a deficiency in which protein?
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What is one of the functions of complement in the immune response?
What is one of the functions of complement in the immune response?
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How does eculizumab contribute to the management of PNH?
How does eculizumab contribute to the management of PNH?
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What is the main difference between inherited and acquired forms of Hereditary Angioedema (HANE)?
What is the main difference between inherited and acquired forms of Hereditary Angioedema (HANE)?
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During a clinical episode of HANE, which symptoms are primarily observed?
During a clinical episode of HANE, which symptoms are primarily observed?
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What treatments are commonly used for HANE?
What treatments are commonly used for HANE?
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Which complement deficiency is most commonly identified and increases the risk for neisserial infections?
Which complement deficiency is most commonly identified and increases the risk for neisserial infections?
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What do individuals with C3 deficiency typically experience?
What do individuals with C3 deficiency typically experience?
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What clinical condition is associated with deficiencies in properdin, factor H, factor I, and the complement MAC?
What clinical condition is associated with deficiencies in properdin, factor H, factor I, and the complement MAC?
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What is the primary function of the complement system?
What is the primary function of the complement system?
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How do the three major pathways of complement activation converge?
How do the three major pathways of complement activation converge?
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Study Notes
Complement Activation
- Classical Pathway: Activated by antigen-antibody complexes.
- Alternative Pathway: Activated on microbial surfaces independently of antibody.
- Lectin Pathway: Initiated by circulating lectins binding to carbohydrates on pathogens.
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Regulatory Mechanisms:
- Inhibit formation of C3 and C5 convertases in early steps.
- Break down and inactivate C3 and C5 convertases.
- Inhibit formation of the Membrane Attack Complex (MAC) in the late steps.
Molecules and Receptors that Inhibit Complement Activation
Functions of Complement
- Lysis of Microbes: The Membrane Attack Complex (MAC) forms a pore in the microbial membrane leading to lysis.
- Opsonization: Complement proteins (C3b) bind to microbial surfaces and facilitate phagocytosis by phagocytes.
- Inflammation: Fragments of cleaved complement proteins activate mast cells and other cells to release inflammatory mediators.
Complement Deficiencies
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Paroxysmal Nocturnal Hemoglobinuria (PNH): Individuals lack DAF and CD59 leading to complement lysis and hemolysis.
- Symptoms: Intravascular red cell hemolysis, hemoglobinuria (loss of iron), recurrent thrombosis.
- Treatment: Transfusion of packed red blood cells, androgens, recombinant erythropoietin, heparin, standard anticoagulants, supplemental iron, eculizumab.
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Hereditary Angioedema (HANE): Caused by C1 INH deficiency.
- Symptoms: Well-circumscribed edema localized to the face, tongue, and larynx.
- Treatment: Oral androgens, anabolic steroids, antifibrinolytic agents, glucocorticosteroids.
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Other Deficiencies:
- C2 deficiency: Increased risk of neisserial infections.
- C3 deficiency: Recurrent infections of the respiratory tract, gut, and skin.
- Deficiencies in properdin, factor H, factor I, and MAC: Life-threatening meningitis.
- Meningococcal vaccination is recommended for those with certain deficiencies.
Humoral Immunity
- Antibodies neutralize and eliminate infectious microbes and microbial toxins.
- Antibodies are produced by plasma cells.
- Antibody effector functions are mediated by Fc regions of immunoglobulin (Ig) molecules.
- Different Ig heavy chain isotypes serve distinct effector functions.
- Effector functions of antibodies are triggered by binding of antigens to variable regions.
Vaccine-Induced Humoral Immunity
- Vaccines stimulate the production of antibodies specific for the vaccine antigen.
- Vaccination is a safe and effective way to prevent infectious diseases.
Functions of Antibody Isotypes
- IgG: Most abundant antibody isotype. Can cross the placenta and provide passive immunity to the fetus.
- IgM: First antibody isotype produced during an immune response. Involved in complement activation and neutralization.
- IgA: Found in mucosal secretions (e.g., breast milk, saliva). Protects against mucosal infections.
- IgE: Involved in allergic reactions and parasitic infections.
- IgD: Present on B cell surfaces. Role in B cell activation is not fully understood.
Neutralization of Microbes and Toxins by Antibodies
- Antibodies bind to microbes and toxins, preventing their attachment to host cells.
- Neutralization prevents the spread of pathogens to other cells.
Subunit Composition of Fcγ Receptors
- FcγRs are found on various immune cells, including phagocytes, NK cells, and mast cells.
- Different FcγRs bind different subclasses of IgG with varying affinities.
Antibody-Mediated Opsonization and Phagocytosis of Microbes
- Antibodies bind to microbes and facilitate phagocytosis.
- Phagocytosis involves engulfment of microbes by phagocytes.
- Fcγ receptors on phagocytes bind to the Fc regions of antibodies.
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)
- The process by which NK cells destroy antibody-coated target cells.
- Fcγ receptors on NK cells bind to the Fc regions of antibodies on target cells.
Summary
- Humoral immunity relies on antibodies to defend against extracellular microbes and toxins.
- Antibodies neutralize pathogens and toxins by binding to their critical sites, inhibiting their activity.
- Antibodies enhance phagocytosis by opsonizing (coating) microbes.
- Antibodies participate in cell-mediated cytotoxicity, enabling NK cells to kill infected or cancerous cells.
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