Innate Immunity II Humoral Components

• 5. Which of the following statements about the alternative pathway is true?

  A. Antibodies can play part in activating this pathway

  B. It does not play any role in inducing inflammation

  C. A deficiency in C2 can inhibit the activation of this pathway

  D. It can be activated by bacterial cell wall components


  D. It can be activated by bacterial cell wall components
• 4. Which of the following is a potent component of anaphylatoxin?

  A. C1q

  B. MBL

  C. C9

  D. C5a

  D. C5a
• 3. Which of the following about C3b is true?

  A. C3b is an opsonin

  B. C3b can activate Mast cells

  C. C3b is an inactive fragment of C3

  D. C3b can activate T lymphocytes

  A. C3b is an opsonin
• 2. The C1q component of the classical complement pathway can interact with

  A. LPS

  B. IgM

  C. IgD

  D. Peptidoglycan on the bacterial cell wall

  B. IgM
• 1. A 18-year old female patient was confirmed to have a blood infection (septicemia) with the gramnegative bacteria E. Coli. Her early immune response to this pathogen will involve:

  A. Recognition of E.coli by B cell receptor

  B. Activation of the classical complement pathway.

  C. Secretion of E. coli specific IgG antibodies by B cells

  D. Recognition of mannose on E.coli by mannose binding lectin (MBL)

  D. Recognition of mannose on E.coli by mannose binding lectin (MBL)
• how do Homologues restriction factor (HRF) and CD59 regulate the complement system?

  Bind to C8 and prevents recruitment of C9 (inhibit MAN, the attack complex)
• how does Factor H regulate the complement system?

  Competes with Factor B on binding to mammalian surfaces. It can also inactivate C3b when it binds to it. (alternative pathway)
• how do Decay Accelerator Factor (DAF) and Membrane Cofactor Protein (MCP) regulate the complement system?

  Both are on many cell surfaces to protect them. They can inhibit C3 convertase (C3bBb or C4b2a) formation (all pathways).

  
• how does C1INH regulate the complement system?

  C1 inhibitor, inactivates C1 by dissociating the attached enzymes. It can also inhibit binding of MBL to its associated enzymes (for classical pathway)

  
• what are examples of Regulatory mechanisms of the complement system?

  C1INH, Decay Accelerator Factor (DAF) and Membrane Cofactor Protein (MCP), Factor H, Homologues restriction factor (HRF) and CD59
• Activation of the complement system have to be regulated to prevent severe damage to tissues. where are regulatory mechanisms present?

  Regulatory mechanisms are present as soluble and cell surface molecules.
• what are the outcomes of complement system?

  - Supporting phagocytosis - Inflammation, recruitment of leukocytes - Active lysis/clearance of a pathogen

  
• what happens to immune complexes in patients with SLE?

  inability to clear immune complexes and their accumulation. Uncleared circulating immune complexes can be deposited in glomerulus, blood vessels, synovium, lung, skin, eye, choroid plexus. Complement cascade activated by immune complexes can recruit and activate neutrophils, mast cells and macrophages causing tissue damage.

  
• what is deficient in patients with Systemic Lupus Erythematosus (SLE)?

  Patients with Systemic Lupus Erythematosus (SLE) have lower CR1 expression on their RBCs (i.e. defective immune complexes clearance).

  
• what do RBCs do to immune complexes?

  RBCs can trap immune complexes and drag them to the spleen where they are cleared from the blood circulation.

  
• what does C1q bind?

  C1q binds immune complexes (antigen and antibody) and bind its receptor (CR1) on RBCs.

  
• what happens when neutrophils degranulate?

  Degranulation of neutrophils releases proteases and toxic substances in their granules in the surrounding causing tissue damage.

  
• what activates macrophages and neutrophils in complement activation?

  C5a and C3a are (3) potent chemoattractant and (4) activators for neutrophils and monocytes).

  
• what binds and activated mast cells and macrophages in complement activation?

  The proteolytic fragments of complement proteins (C3 and C5), C5a and C3a can bind to and activate both(1) mast cells and macrophages (2).

  
• what can enhance the activation of B cell?

  Cross-linking of the BCR with the complex of complement receptor CR2/C3d by the pathogen can enhance the activation of B cell.

  
• when are B cells activated?

  when their cell receptor (BCR) binds its specific antigen

  
• what is Properdin (P)?

  a regulatory molecule acts on stabilizing C3 convertase (C3bBb) by increasing the half-life of the convertase by 5 to 10- folds.

  
• what is C3b? what is its role?

  C3b is an opsonin and binds to its receptor on neutrophils and macrophages.

  
• how is the alternative pathway for complement activation initiated?

  The pathway starts with spontaneous cleavage of C3 into C3a and C3b. This process is accelerated by two factors (factor D and Factor B). Factor D is a serine protease that cleaves a lysine-arginine bond in factor B .

  
• true or false: C1, C2 and C4 are involved in the alternative pathway

  false

  
• what is the difference between Mannose Binding Lectin Pathway and the classical pathway?

  The mannose-binding lectin (MBL) pathway and the classical pathway are identical, except for the involvement of MBL versus antibody and C1.

  
• how is the Mannose Binding Lectin Pathway initiated?

  Ficolins or mannose-binding lectin (MBL, a pattern recognition receptor) binds to mannose, glucose, or other sugars on the pathogen surface. MASP 1&2 (mannose-binding lectin-associated serine proteases) then activate the complement cascade, in a manner similar to C1r and C1s.

  
• are antibodies involved in the Mannose Binding Lectin Pathway?


  no
• what makes C5 convertase?

  C4bC2bC3b

  
• what are the steps of the Complement Activation Through the Classical Pathway?

  Opsonization (binding of antibodies to bacterial cell wall) → C1 binding to the antibodies → Initiating the proteolytic cascade where C4 and C2 and leaved and C4band and C2b make C3 convertase which cleaves and C3b joins to make C5 convertase which also cleaves to form C5b → Forming the 'membrane attack complexes' → Bursting the bacterium.

  
• In the classical pathway for Complement Activation, what is the function of C1 complement?

  (supports, finishes off) the antibacterial role of antibodies.
• In the classical pathway for Complement Activation, what does C1q bind to?

  C1q binds to the Fc regions of IgM and to the Fc regions of hexamers of IgG
• what is the difference between IgM and IgG?

  IgM is a pentamer complex, while IgG is a monomer.

  
• In the classical pathway for Complement Activation, C1 is involved. C1 consists of 3 components, what are they?

  C1q (main molecule) and the two serine proteases C1r and C1s.

  
• There are 3 pathways by which the complement system is activated, what are they?

  ➢ Classical pathway ➢ Mannose binding lectin pathway ➢ Alternative pathway they all lead to pathogen elimination and induction of inflammation.
• how are components activated in the complement system?

  The complement system consists of a group of proteins. Their activation involves a proteolytic cascade in which an inactive complement protein is cleaved to become activated. The activated component is involved in activating the next component by cleaving it.

  
• what is Ficolin3 deficiency?

  a rare form of immunodeficiency due to a complement cascade anomaly. Patients present with recurrent infections and autoimmunity
• what are MASP 1&2?

  mannosebinding lectin-associated serine proteases (enzymes), which activate complements.

  
• what do Ficolins recognize?

  Ficolins are proteins that recognize acetylated (esterification with acetic acid) polysaccharides on the cell surface of bacteria (e.g, N-acetylgalactosamine [GalNAc]) and fungi (eg, 1,3-β-Dglucan).

  
• what are the functions of the complement system?

  a group of proteins whos function is to eliminate pathogens, promote inflammation (eg, via C3a & C5a), and activate adaptive immune cells (via complement 1 [C1] binding to complement receptor 2 [CR2] on B cells).