Chapter 16: Interferons and Complement system Flashcards
What cells are involved with Type 1 Interferons?
(1) Leukocytes [alpha interferons] (2) Fibroblasts [Beta interferons] (3) Produces antiviral proteins in neighboring cells
Mechanisms of Interferons: Alpha and Beta
(1) Virus infects (2) Signal sent to host cell nucleus (3) Viral replication activates host cell gene for interferon (4) Interferon is synthesized and released (5) Interferon binds to surface of neighboring cell (6) Cell stimulates antiviral protein and they float around waiting for virus to enter (7) Antiviral protein block viral replication by attaching to virus
Interferons action plan
(1) Interferes with virion replication in other cells (2) Specific to kill uninfected cells NOT already infected (3) Implement production of Antiviral Proteins (AVPs)
Mechanisms of interferon: Gamma
(1) Lymphocytes and NK cells do not have to be infected with virus for synthesis of gamma (2) Helps macrophages rid themselves of viruses (3) Enhances the activity of lymphocytes, NK cells and macrophages
Anti viral proteins works best against what?
RNA
Phagocyte cells (removes debris and pathogens)
Fixed macrophage, Neutrophil, Free macrophage, Eosinophil, Monocyte
Extracellular killing cells (destroys abnormal cells)
NK cells break down abnormal cells and ends in lysis
Multiple effects on inflammation
(1) Blood flow increases (2) Phagocytes activated (3) Capillary permeability increased (4) Complement activated (5) Clotting reaction walls off region (6) Temp increased in region (7) Specific defenses activated
Fever is the rise above what temp?
37 degrees celcius
Interferons are released by what type of cell
Lymphocytes (gamma and do not need to be infected), NK cells macrophages and infected cell
Classical Pathway includes which 3 complements initially and what goes on?
C1, C4, C2 (Antibodies bind to antigens such as microbes)
Alternative Pathway includes which 3 Factors and what goes on?
(1) Properdin pathway: Factor B, Factor D, Factor P (2) Activated earlier than classical (3) Activated by the contact between complement proteins and polysaccharides at the pathogen surface
Which complement factors are involved in inflammation?
C4a, C3a, C5a
Which complement factors are involved in opsonization?
C3b
Which complement factors are involved in membrane attack complexes
C5b, C6, C7, C8, C9
What is the complement system?
(1) Series of reactions leading to death of pathogen (more than 20 regulatory pathogens involved)
Where is the complement system proteins produced?
Produced by the liver and circulate in plasma in an active form
General function of Complement system
(1) Enhance phagocytosis (2) Lyse microorganisms, bacteria and enveloped viruses directly (3) Generate peptide fragments that regulate inflammation and immune response (4) Fast
How does complement system work as a cascade
Works as a cascade because one protein amplifies another protein and stimulates a reaction
Deficiency of protein C3 can lead to what?
Problems with complement system and possibly autoimmune disease
Acute phase response
A response to acute illnesses that involves increased production of a specific blood protein called “acute phase proteins”
After both Classical and Alternative pathway finish what happens next?
(1) C3 and C9 are activated (2) C3 is key component that splits into C3a and C3b which participates in Opsonization, Inflammation and Membrane attack complexes
Opsonization
(1) Counteracts the bacteria that carry M protein which prevents them from phagocytosis (2) Sprinkling pathogen so that it is more recognizable to the macrophage
Opsonins
Bind to act and coat the surface of the infectious agent
Complement: Steps of Opsonization
(1) C1 binds to antibodies initiating cascade (2) C4 forms cleavage and branches into C4a and C4b (3) C4B leads to C2 split to C2a and C2b (4) C4bC2a complex forms (5) C2a splits C3 into C3a and C3b (6) C3b is what binds to surface of microbe
Complement: Steps of Inflammation
(1) C3a and C4a and C5a enhance acute inflammatory response stimulating chemotaxis and phagocytosis (2) Complement proteins [mainly C3a and C5a] adhere to membranes of basophils and mast cells which then release histamines
Complement: Steps of Membrane attack complex
(1) C3b leads to cell lysis through a process called “immune cytolysis” (2) C3b initiates C5 to split into C5a and C5b (3) C5b binds to C6 and C7 forming a complex C5bC6C7 which is hydrophobic and inserts into cell membrane (4) C8 binds to C5b in the membrane (5) C5bC6C7C8 complex is formed (6) This complex extends through cell membrane forming a pore constituting a MAC
Immune cytolysis
which is complement proteins producing lesions in cell membrane of organisms and other types of cells
Why don’t our cells get attacked my MAC?
Because MAC responsible for direct lysis of invading microorganisms and host plasma contains proteins that protect it against MAC lysis
C3a importance
Triggers inflammatory response
C3b importance
attaches itself randomly to pathogen and when its notices to be attached as organism, macrophage engulfs
Alternate route is used when?
When no antigen attaches to antibody leading to complement factors that attach themselves directly to a pathogen
What is a complement lesion?
A complex that lets a cell blow up and die
Steps of Phagocytosis by neutrophil
(1) Bacteria adheres to phagocyte (2) Pseudopodia grab bacteria and form cytoplasmic vacuole called a phagosome around (3) Lysosomes then attach to vacuole and phagolysosome forms to break down bacteria (4) Pieces of broken bacteria are then excreted out of cell
During complement cascade, what does C1 recognize?
Antigen on the constant region NOT variable region
What is the importance of C3b?
Macrophages have a C3b receptor so when organism presents C3b it flags it so the macrophage can identify it
What does C3a stimulate?
Mast cells releasing histamines
When is the alternate route used?
When there is not an antibody involved and you have never seen the antigen prior (with classical route you need to have antibodies already)
