Complement Flashcards
What is the definition of the complement system?
A complex network of proteins that enhance the ability of phagocytes and antibodies in clearing microbes and damaged cells
What makes up the complement system?
Over 30 proteins, including serum proteins, cell membrane receptors and regulatory proteins
What are the main roles of the complement system?
- Chemotaxis- attracting immune cells to infection site
- Opsonisation- marking pathogens for phagocytosis
- Cell lysis- direct destruction of pathogens
- Immune clearance- Removal of immune complexes and apoptotic cells
What are the different complement pathways?
Classical pathway
Lectin (mannose) binding pathway
Alternative pathway
What triggers the classical pathway?
Formation of antigen-antibody complexes (IgM or IgG)
What is the main difference between each complement pathway?
All complement pathways perform the same functions, but they are activated by different mechanisms
What triggers the lectin mannose-binding pathway?
Mannose-binding lectin (MBL) binds to carbohydrate patterns on the pathogen surfaces
What triggers the alternative pathway?
Activated spontaneously on pathogen surfaces (e.g. bacteria or fungal cell walls) without the need for antibodies or lectins.
What are the different functional pathways of the complement pathway?
- Cell lysis - Membrane attack complex (MAC)
- Chemotaxis - Anaphylatoxins
- Opsonisation - Opsonins
How does the complement pathway causes cell lysis?
- Once activated, a cascade of reactions occurs, an a complex of complement proteins is formed, known as the membrane attack complex
- This complex inserts into the pathogen membrane and forms a pore
- This pore disrupts the integrity of the cell, leading to uncontrolled flow of water and ions
- Cell lyses
How does the complement pathway cause opsonisation?
- Activation leads to formation of C3b (an opsonin)
- C3b binds to pathogen cell surface, marking it for phagocytosis
- Phagocytes have receptors that specifically recognize and bind to C3b
- Faciliatates easier engulfment and phagocytosis
How does the complement pathway cause chemotaxis?
- Activation leads to formation of anaphylatoxins (C3a, C4b, C5a)
- Anaphylatoxin acts as a chemoattractant. It diffuses away from the site of activation and creates a gradient that immune cells can detect.
- Neutrophils and macrophages move towards the higher concentration of anaphylatoxin, guiding them to the site of infection
What complement proteins make up the membrane attack complex?
- C5b, C6, C7 first complex
- C8, C9 binds once inserted, leading to pore formation
What is the consequence of C1, C2 and C4 deficiencies?
- Impaired classical pathway activation (as these proteins are involved in the activation)
- Reduced immune clearance
- Increases susceptibility to infections, and autoimmune diseases
What is the consequence of C3 deficiency?
- Impaired opsonisation- reduced phagocytosis
- Severe recurrent invasive bacterial infections - especially encapsulated bacteria
What is the consequence of C5-C9 deficiency?
- Inability to form MAC - reduced cell lysis
- Increased risk of Neisseria infections (e.g. meningitis)
What are 3 different ways in which microbes can evade complement?
- Inhibition of complement activation
- Degradation of complement proteins
- Mimicking host cells
Example of microbe inhibiting complement activation
S. aureus produces protein A, which binds to IgG and prevents complement activation
Example of microbe degrading complement proteins
Streptococcus pyogenes secretes C5a peptidase, which inactivates C5a
Example of microbe mimicking host cells to avoid complement
T. cruzi expresses complement regulatory proteins, mimicking host cells to avoid detection
