Complement, MHC, And Antigens Flashcards
What are the three complement pathways?
Classical
Lectin
Alternative
What are the main outcomes of the complement system?
Recruitment of inflammatory cell
Opsonization of pathogens
Killing via pores in membrane
What are the three ways the classical pathway is activated?
Bind directly to surface of bacterial components
Binds C-reactive proteins that binds to phosphocholine residues on bacterial polysaccharides
Binds to antigen-antibody couples on pathogen surface
How is the lectin pathway initiated??
Binding of carbohydrate-binding protein (mannone-binding lectin or Ficolins) on surface of pathogen
How is the alternative pathway initiated?
Spontaneously derived plasma C3b to pathogen surfaces
Activation of C1 in the classical pathway is caused by?
C1 binding to Fc region of the antibody
C1- cleaves C4 to C4a and C4b
What are the steps of classical complement cascade?
- C1 cleaves C4 to C4a and C4b
- C1 cleaves C2 to C2a and C2b
- C4b and C2a bind and form C3 convertase
- C3 convertase cleaves C3 to C3a and C3b
- C3b binds to C3 convertase to make C5 convertase (C4b2a3b)
- C5 convertase cleaves C5 to C5a and C5b
- C5b recruits C6 and C7 to form C5b67 compelx
- C8 joins complex with hydrophobic tail that is inserted into membrane
- C9 recruited (9-10copies) to form pore in membrane (MAC)
How is C3 convertase formed in the lectin pathway?
Mannose binding lectin binds to surface of pathogen, becomes activated, and cleaves both C4 and C2.
C4b and C2a bind to form C3 convertase
Describe the alternative pathway of the complement system.
- C3b spontaneously hydrolyzes
- C3b binds to Factor B on microbe surface -> C3bB complex
- Factor D cleaves C3bB to C3bBb (C3 convertase)
- C3 convertase cleaves C3 to C3b and C3a
- C3b combines with C3 convertase (C3bBb) to form C5 convertase (C3bBb3b)
- C5 cleaved
- C5b recruits C6, C7, C8, and C9 to form MAC
If a C3b (spontaneously lysed) binds to a host cell, what is the outcome?
Sailic acid promotes binding of C3b to Factor H
Factor H and I degrades C3b
Prevent lysis of host cells
How does C1 inhibitors prevent the complement cascade?
Inactivates C1r, C1s, and MASPs (classical and lectin pathways)
How does decay-accelerating factor control the complement pathway?
Accelerates the decay of C3 convertase (alternative)
How does Protectin contro the complement pathway?
Binds to C5b678 and prevents C9 recruitment and MAC formation
What are the possible outcomes of the complement pathway?
Direct target lysis Tissue inflammation Endothelial activation Chemotaxis Opsonization Immune complex clearance
The genes responsible for survival or rejection of a graft are called ______________________
Tissue or histo-compatibility genes
Each MCH cluster of genes has at least _____ classs of gene loci
3
Class I MHC are expressed on ?
All nucleated cells
Class II MHC are expressed on?
Professional antigen presenting cells
B cell
Macrophage
Dendritic cells
MHC class III genes encode proteins which function as?
Complement proteins
Not antigen presenting molecules
MHC genes are ____________ expressed, therefore each individual will have ______ MHC I genes
Co-dominantly
Six
What is the main role of MHC I and II in adaptive immunity?
Antigen presenting
MHC I present antigens to __________ T lymphocytes
CD8+
MHC II presents antigens to ________ T lymphocytes
CD4+
What is the structure of MCHi
Heterodimer - a (a1, a2, and a3) and B2-microglobulin
Extracellular domain makes up antigen binding groove
Transmembrane domain
Cytoplasmic domain