OVERVIEW OF THE CLINICAL PATHWAY Flashcards
coined the term “complement”
Paul Ehrlich
Described how the nature of the complement
system and how it works
Jules Bordet
Main role of complement
Lysis of cells, bacteria and viruses
Enhance phagocytosis
Opsonization
The contents of the granules of certain
cells are being released
Cellular degranulation
What do you call the cleaved complement protein?
Anaphylatoxins
removal of immune complexes
and deposition in the spleen and liver
Immune clearance
Proteins and glycoproteins synthesized mainly by?
Liver hepatocytes
Proteins and glycoproteins mostly circulate in the serum functionally inactive forms
as?
Proenzymes or zymogens
Proteins and glycoproteins are heat labile, therefore it is destroyed when heated at what temperature?
56°C for 30 minutes
•
They bind to receptors on mast cells and basophils
•
Induce degranulation and release of influx mediators including
histamine
•
small peptide that causes increased vascular permeability, contraction of
smooth muscle, and release of histamine from basophils and mast cells
•
In order to initiate anaphylactic or allergic reaction
Anaphylatoxins
• Can lead to edema if complement is not controlled
•
Enhance some cases of immune processes
Increased capillary permeability
• Attract cells and play important role in recruitment of cells to an influx site
•
Attract phagocytic cells toward the site where this is
Chemotaxis
Enhances neutralization of viruses by homologous antibodies
Virus neutralization
C3b on particles such as bacteria or an Ab-Ab complex promotes the
attachment and ultimate ingestion of the particles
Opsonization
C1q, C1r, C1s are called?
C1 complex
Recognizing molecule for the initiation of classical complement cascade
C1q
proteins that recognize and bind to certain carbohydrates?
Lectin
What is the main complement involved in anaphylatoxins?
C3a, C4a, C5a
What is the main complement component involved in increased capillary permeability?
Role of C2b fragment
What is the main complement component involved in chemotaxis?
C5a
What is the main complement component involved in neutralization?
C4
What is the main complement component involved in opsonization?
C3b
1
st to be studied
Antibody dependent
Classical pathway
Classical pathway is initiated by?
Ag-Ab complex
C-reactive Protein
Some Viruses
Mycoplasma
Some protozoans
Select Gram-negative bacteria
Most potent activator
among the IgG subclasses
IgG3
Alternate pathway is initiated by?
- Aggregates of IgA
- Yeast cell or zymogen
- CVF
- Lipopolysaccharide
What initiates the MBL?
Mannose and other similar sugars in
the cell wall (Ab independent)
What recognizes MBL?
-
Lectins
-
Ficolins
-
CL-K1
Recognition event which will initiate complement cascade
Initiation phase
•
This is where the 3 pathway meets in order to create a C3 convertase which
activates C3 complement protein (most important step)
•
Approximately 200 C3 molecules can be activated in a single C3 convertase
•
Activation of early components culminate in activation of C3 which is the critical
component
Amplification activation phase
•
Culminates in target cell lysis
•
Classical and alternate pathway is the same at this phase
•
The formation of this will form in the surface of
the pathogen that induces cell lysis
Membrane attack phase
What pathway begins with the formation of soluble antigen-antibody
complexes or with binding of antibody to antigen on a
suitable target such as a bacterial cell
Classical pathway
o
present in the plasma in the largest quantities
o
fixation of this is the major quantitative
reaction of the complement cascade
C3
• It is not dependent on immune
complexes
• Does not require antibody for it to initiate
Innate immunity
The starting point of the alternative pathway would be
the?
Hydrolysis of C3 protein
This pathway serves to amplify the activation of the cascade and is initiated by cell-surface constituents.
Alternate pathway
Will act upon the C5 complement protein
C5 CONVERTASE COMPLEX
stabilize the structure of C5 convertase
Properdin
Composition of STABLE C5 convertase?
C3bBbPC3b
recognizing the molecule mannose starts
this pathway
Collectins
proteins that recognize and bind to specific
carbohydrate targets
Lectins
Lectin pathway will not serve its purpose if calcium
concentration is?
low in the blood
initiates the final steps to form MAC
C5b
initiates the final steps to form MAC
C5b
Forms a large channel through the membrane of the
target cell enabling ions and small molecules to diffuse
freely across the membrane
MEMBRANE ATTACK COMPLEX
(initiates the final steps to form MAC)
C5b
all pathways will meet at the?
C3b
