Humoral immunity Flashcards
What is the humoral immune system?
A component of the immune system that involves antibodies produced by B cells to fight infections
What are acute-phase proteins?
Plasma proteins produced by the liver during inflammation that mimic antibodies and aid in immune responses
What are some examples of acute-phase proteins?
C-reactive protein for opsonization and complement activation and haptoglobin for binding hemoglobin
What is the role of complement proteins?
They enhance immune responses by opsonizing pathogens promoting inflammation and forming the membrane attack complex MAC
What are the three pathways of complement activation?
The classical pathway the alternative pathway and the lectin-binding pathway
What triggers the classical pathway?
Binding of antibodies such as IgM or two IgG molecules to antigens on the pathogen surface
What triggers the alternative pathway?
Direct activation by microbial surfaces such as lipopolysaccharides LPS or aggregated IgA
What triggers the lectin-binding pathway?
Binding of mannose-binding lectin MBL to carbohydrate structures on the surface of pathogens
What are the main steps in the classical complement pathway?
C1 binds to antibodies followed by activation of C4 and C2 forming C3 convertase which cleaves C3 into C3a and C3b
What is the role of C3 convertase?
It cleaves C3 into C3a and C3b initiating amplification of the complement cascade
What happens to C3b after it is formed?
C3b binds to pathogen surfaces aiding in opsonization and forming C5 convertase
What is the role of C5 convertase?
It cleaves C5 into C5a a chemoattractant and C5b which initiates the formation of the membrane attack complex MAC
What is the membrane attack complex MAC?
A structure formed by C5b C6 C7 C8 and multiple C9 molecules that creates pores in the membrane of pathogens causing osmotic lysis
What is the role of C3a and C5a in the complement pathway?
They act as chemoattractants recruiting immune cells to the site of infection and enhancing inflammation
What is the difference between opsonization and lysis in the complement system?
Opsonization involves coating pathogens with C3b to enhance phagocytosis while lysis involves the destruction of pathogens via the MAC
What is the role of mannose-binding lectin MBL in the lectin pathway?
It binds to mannose residues on pathogen surfaces activating a cascade similar to the classical pathway
What is the role of C4 and C2 in the classical and lectin pathways?
C4 and C2 are cleaved to form C3 convertase which is central to complement activation
What is the role of factor B in the alternative pathway?
Factor B binds to C3b on pathogen surfaces and is cleaved by factor D to form an alternative C3 convertase
What is the role of factor D in the alternative pathway?
Factor D cleaves factor B when it is bound to C3b forming the C3 convertase in the alternative pathway
What is the importance of complement regulation?
To prevent excessive activation and damage to host tissues
What are some key complement regulators?
Complement inhibitors such as C1 inhibitor decay-accelerating factor DAF and CD59 protect host cells
What is the role of C3b in opsonization?
C3b coats the pathogen surface making it easier for phagocytes to recognize and engulf the pathogen
What is the role of complement in inflammation?
Complement components like C3a and C5a recruit immune cells and increase vascular permeability to enhance the immune response
What is the role of C5b in the complement cascade?
C5b binds to C6 and C7 initiating the assembly of the MAC
What are the terminal steps of the complement cascade?
C5b recruits C6 C7 C8 and multiple C9 molecules to form the MAC which creates pores in the pathogen membrane
What is the significance of the complement system in humoral immunity?
It enhances the effectiveness of antibodies by promoting pathogen destruction opsonization and immune cell recruitment
How does complement activation link the innate and adaptive immune systems?
Complement bridges innate and adaptive immunity by amplifying antibody responses and directly targeting pathogens for destruction
What is the primary role of IgM in humoral immunity?
It is the first antibody produced in infections and is efficient at activating the complement system
What is the primary role of IgG in humoral immunity?
It provides long-term immunity neutralizes pathogens and enhances phagocytosis
What is the primary role of IgA in humoral immunity?
It protects mucosal surfaces by neutralizing pathogens and preventing their attachment
What is the primary role of IgE in humoral immunity?
It mediates allergic responses and provides defense against parasites
What are the outcomes of complement activation?
Pathogen lysis immune cell recruitment and enhanced phagocytosis
What is antibody-dependent cellular cytotoxicity ADCC?
A process where antibodies recruit natural killer cells to destroy target cells
How do IgM and IgG differ in complement activation?
IgM is more efficient in activating the complement system while IgG subclasses vary in their efficiency
What is the importance of acute-phase proteins during infections?
They act as diagnostic markers of inflammation and enhance immune responses
What is the role of antibodies in neutralization?
They block pathogens from binding to host cells and neutralize toxins
What are the differences between the three complement pathways?
The classical pathway is antibody-dependent the alternative pathway is triggered by microbial surfaces and the lectin pathway is triggered by MBL binding
What are the effector functions of antibodies in humoral immunity?
Neutralization opsonization complement activation and recruiting immune cells
What is the order of the classical complement pathway?
1- Initiation: C1q binds to antigen-antibody complexes (e.g., IgM or IgG bound to antigens).
2- Activation of C1 Complex: C1r and C1s are activated, leading to cleavage of C4 into C4a and C4b.
3- Formation of C3 Convertase: C4b binds to the pathogen surface and combines with C2a, forming the C4b2a complex (C3 convertase).
4- C3 Activation: C3 convertase cleaves C3 into C3a (inflammatory mediator) and C3b (opsonin).
5- Formation of C5 Convertase: C3b joins C4b2a to form C5 convertase.
6- MAC Formation: C5 convertase cleaves C5 into C5a (chemoattractant) and C5b, initiating the assembly of the membrane attack complex (MAC).
What is the order of the alternative complement pathway?
1- Spontaneous Hydrolysis of C3: C3 undergoes spontaneous hydrolysis to C3(H2O).
2- Formation of C3 Convertase: C3(H2O) binds factor B, which is cleaved by factor D to form the alternative C3 convertase (C3bBb).
3- Amplification Loop: C3 convertase generates additional C3b, which can further amplify complement activation.
4- Formation of C5 Convertase: Additional C3b binds to C3 convertase, forming the alternative C5 convertase.
5- MAC Formation: Similar to the classical pathway, C5b initiates the assembly of the MAC.
What is the order of the lectin binding pathway?
1- Initiation: Mannose-binding lectin (MBL) binds to mannose residues on pathogens.
2- Activation of MASPs: MBL-associated serine proteases (MASPs) cleave C4 and C2, forming C3 convertase (C4b2a).
3- C3 Activation: Similar to the classical pathway, C3 convertase cleaves C3 into C3a and C3b.
4- Formation of C5 Convertase: C3b binds to C3 convertase, forming C5 convertase.
5- MAC Formation: C5b initiates the assembly of the MAC.