The complement system

a cat is diagnosed with a viral infection; what is the initial trigger for the classical component pathway in this cat's immune response to the viral pathogen?

antibody-antigen complexes

3 multiple choice options

what is the complement system?

a set of plasma proteins produced by hepatocytes that act together in a proteolytic cascade as a defense against pathogens in extracellular spaces

the complement system is part of what within the innate immune system?

humoral part of innate immune system

what pathogens typically remain outside the cell?

bacteria

what pathogens typically remain inside the cell?

viruses

what are the characteristics of the complement system?

a cascade of proteases activating other proteases by cleavage

what are the two pathways of the complement system?

1. classical pathway

2. alternative pathway

what triggers the classical pathway?

antibodies binding to antigens of pathogen surface

what triggers the alternative pathway?

complement protein binding to surface of pathogens

what complex is only part of the classical pathway?

C1 complex

what is the specificity of the classical pathway?

highly specific

what is the immune response time for the classical pathway?

require 7-10 days due to antigen/antibody binding requirement

what is the C1 complex of the classical pathway?

recognizes binding of antigen to antibody then binds to specific antigen-antibody complex at the surface of the antigen

what is the C3 complex of the complement system?

binds mainly to microbial surfaces through interactions with sugars and lipids

what is the C5 complex of the complement system?

formation of MAC leading to cell death

how does C5 kill the cell?

continuously pokes holes in newly formed membrane causing the cell to swell and explode

MAC

membrane attacking complex

why does the alternative pathway have a faster immune response compared to the classical pathway?

does not require antigen/antibody binding to initiate reaction, can bind directly to C3 complex

what are the different reactions that can occur after C3 binds to C3b in the complement cascade?

1. terminal pathway

2. opsonization of pathogen surface by C3b

3. cleavage of products in complement cascade

what happens if cleavage of products in complement cascade occurs in the complement cascade?

anaphylatoxins and chemolactic factors will be created leading to inflammation

what happens if opsonization of pathogen surface by C3b occurs in the complement cascade?

enhanced phagocytosis will result in antigen presentation to cells of adaptive immune system

in the classical component pathway _________ bind to _______ on ____________ surfaces, including bacteria and viruses

1. antibodies

2. antigens

3. pathogen

what specific complement protein triggers the alternative pathway of complement activation?

C3b

which pathway is not specific?

alternative pathway

which immune cell is the first responder to extracellular material?

neutrophil

3 multiple choice options

a dog is being treated for an autoimmune disorder, and the veterinarian is explaining how the complement system may be involved in the disease's progression. What function of C3b perform within the complement system that could influence the pathology of this autoimmune disorder in the dog?

enhances phagocytosis as an osponin

3 multiple choice options

according to bordet's findings, what are the two components of serum?

1. heat-sensitive component

2. heat-stable component

what happens to bacterial killing properties upon heating of the heat-sensitive component of serum?

loses its bacterial killing effect

what happens to bacterial killing properties upon heating of heat-stable component of serum?

maintains bacterial killing effect

what component of immunity does the heat-sensitive component provide?

provides non-specific antimicrobial activity

what component of immunity does the heat-stable component provide?

contributes to immunity against specific pathogens

what are the different effects from complement proteins coating pathogens in the host?

1. Kill certain pathogens directly via the alternative pathway of complement activation

2. Facilitate phagocytosis by opsonization

what is another function of the complement system besides coating pathogens with complement proteins?

production of signaling molecules

what happens if the complement system produced chemotaxis signaling molecules?

phagocytes will be recruited towards the site of infection

what happens if the complement system produces cytokines?

stimulation of basophils and mast cells triggers the production of histamine leading to a pro-inflammatory response

what is the difference between chemotaxis and cytokines in reference to the complement system?

cytokines do not attract cells towards the site of infection like with chemotaxis; cytokines stimulate the PRODUCTION of cells

what molecules in the complement system can perform opsonization?

1. complement proteins

2. antibodies

what is the benefit to directly killing pathogens via the alternative pathway of complement activation?

does not require help of immune cells or antibodies (can kill certain pathogens directly!)

what is the issue with directly killing pathogens via the alternative pathway of complement activation?

since process is facilitated by MAC, it can only be utilized on gram-negative bacteria since gram-positive bacteria are resistant

which bacteria are resistant to MAC?

positive-gram bacteria

what are MAC most effective against?

gram-negative bacteria, nucleated cells (parasites and enveloped viruses)

what is the process for directly killing pathogens via the alternative pathway?

1. Invading microbe crosses physical barrier of host

2. Microbe coated by C3b complement protein

3. C3b protein amplified on surface of microbe

4. Formation of MAC (triggered by C5b formation) as cytolytic pore in microbe's plasma membrane leading to lysis of microbe

what are the responding cells for facilitating phagocytosis via opsonization?

1. neutrophils

2. macrophages

what process must occur for the pathogen to be labelled for phagocytosis (specific step)?

binding to complement receptor on phagocytic cell labels pathogen for phagocytosis

what portion of the serum component in Erlich's experiment became known as "complement"?

heat-sensitive component

amboceptors

now known as antibodies

what did erlich suggest about complement and antibodies?

they work together in immune system

if specific antibodies bind to ______ that initates the _________ of complement system activation

1. antigen

2. classical pathway

direct binding of complement protein _____ initiates the _____ of complement system activation

1. C3b

2. alternative