Complement System- Exam III Flashcards
Component of the immune system in animals that is genetically determined and nonspecific
Innate immune system
Elements of the system include mucous secretions, complement proteins, certain WBCs (especially neutrophils, macrophages, & dendritic cells)
Innate immune system
Component of the vertebrate immune system involving lymphocytes (B cells and T cells), containing a small number of genetically encoded proteins that combine to produce an enormous variety of proteins capable of recognizing and deactivating specific antigens.
Adaptive immune system
What immune system are you born with? What immune system do you acquire?
Innate ; adaptive
The first function of the complement system:
Alter membrane pathogens and cellular debris
The first function of the complement system is to alter membrane pathogens and cellular debris via:
Opsonization
What promotes removal of particles via complement receptors on host cells via a coating?
Opsonization
Opsonization also leads to the assembly of ______ on pathogen and subsequent _____.
MAC ; Lysis
MAC
Membrane Attack Complex
The second function of the complement system is to:
Enhance the inflammatory response
The complement system enhances the inflammatory response via:
Release of anaphpylatoxins that promote cell activation or migration to inflammatory site
Migration to inflammatory site
Chemotaxis
The complement system becomes activated in innate immunity when it sense:
Apoptotic cells, tissue debris, or pathogens
What level does the innate immune system function at?
Very low
The body has mechanisms in place to prevent the innate immune system from:
Destroying all the cells in our body
The complement system can be activated in 3 ways:
- C3 turnover
- Natural antibodies
- Lectins
Activation of the complement system by C3 turnover engages what pathway?
Alternative pathway
Activation of the complement system thought natural antibodies engages what pathway:
Classical pathway
Activation of the complement system by binding of lectins engages what pathway?
Lectin Pathway
In adaptive immunity, natural antibodies are replaced by:
Specific antibodies
Complement system triggers the following immune functions (3)
- Phagocytosis
- Inflammation
- Membrane attack
Phagocytosis in the complement system occurs by:
Opsonizing antigens
_____ has most important opsonizing activity
C3b
______ occurs by chemotactically attracting macrophages and neutrophils
Inflammation
What anaphylatoxins are involved in inflammation?
C3a & C5a
What process ruptures the cell wall of bacteria (punching holes in it)
Membrane attack
A local response to cellular injury that is marked by capillary dilatation, leukocytes infiltration, redness, head, and pain
Inflammation
What serves as a mechanism initiating the elimination of noxious agents and of damaged tissue?
Inflammation
Wheal and flare response is characteristic of:
Type 1 allergic reaction
Swelling produced by the release of serum into the tissues
Wheal
Redness of the skin resulting from the dilation of blood vessels
Flare
The classic pathway is triggered by:
The C1-complex
The mannose binding (lectin) pathway is homologous to the classical pathways but uses the opsonins ______ and ______ instead of C1q
Mannose-binding lectin (MBL) & Ficolin
What opsonin is used in the classical pathway
C1q
The alternative pathway is continuous activated at a _____ level.
Low level
The alternative pathway is continuously activated at a low level as a result of:
Spontaneous C3 hydrolysis
In the alternative pathway spontaneous C3 hydrolysis occurs as a result of:
Breakdown of the internal thioester bond
The breakdown of the internal thioester bond is due to C3 being mildy unstable in:
Aqueous environment
Pathway that does not rely on pathogen-binding antibodies like other pathways
Alternative pathways
Which pathway responds when you have antigen:antibody complexes (on pathogen surfaces)
Classical pathway
The classical pathway involves what type of molecules? (3)
C1, C4, C2
The C1 molecule in the classical pathway breaks down into:
C1q, C1r, C1s
Pathway involving mannose binding lectin or ficolin binding carbohydrates on pathogen surfaces
Lectin Pathway
Lectin pathway involves mannose-binding lectin or ficolin binding to _____ on pathogen surfaces
Carbohydrates
What molecules does the election pathway involve?
MBL/ficolin, C4 and C2
The enzymatic activity of the MBL/ficolin complex in the lectin pathway:
MASP-2
What molecules do the lectin and classical pathway have in common?
C2 & C4
The alternative pathway occurs on:
Pathogen surfaces
The molecules involved in the alternative pathway include:
C3, B and D
All 3 pathways converge at the production of:
C3 convertase
What two pathways are pretty much identical except for what triggers them?
Classical and lectin pathway
A molecule that cleaves different members of the complement pathways
C3 convertase
C3 convertase cleaves C3 into:
C3a and C3b
After C3 convertase cleaves C3 into C3a and C3b, the C3b will then bind:
C3 convertase
When the C3 convertase and C3b bind together, this leads to the cleavage of:
C5 into C5a and C5b
What molecules are peptide mediators inflammation and phagocyte recruitment?
C3a & C5b
What molecule binds to the complement receptors on phagocytes and leads to the opsonization of pathogens and removal of immune complexes
C3b
What molecule triggers MAC being formed along with lysis of certain pathogens and cells
C5b
- Molecule important in opsonization:
- Molecule important in MAC formation:
- Molecules important in inflammation:
- C3b
- C5b
- C3a & C5a
In addition to the C3 being broken down into C3a and C3b during activation of complement system, our bodies also
Constituitively hydrolyze C3 into C3a and C3b but at a very low level
The central component of the complement system:
Complement fixation
In fixation of complement what molecule tags the bacterium for destruction?
C3b
In the fixation of the complement system, what molecule recruits phagocytes & functions in inflammation
C3a
The cleavage of C3 exposes:
Thioester bond
When the thioester bond is exposed on C3, this allows ____ to strongly covalently bind
Nucleophiles
In the classical pathway of complement, you have antibodies coating the antigen surface and the _____ molecule is going to bind to that
C1 molecule made of C1q+r+s
What component of the C1 molecule will cleave C4 into C4a and C4b?
C1s
The cleavage of C4 into C4a and C4b will induce the cleavage of _____ into _____.
C2 into C2a and C2b
C4b and C2a together will cleave C3 into:
C3a and C3b
C4b+C2a =
C3 convertase
C1 is a complex of C1q, C1r, and C1s. The C1q portion is composed of:
6 identical subunits with globular heads and long collagen-like tails
The head-like structures of C1q function to:
Sit down and bind pathogen surface
Once the C1q globular heads are bound to the pathogen surface, the C1r portion undergoes a conformational change which:
Cleaves and activates C1s zymogen
C1s will bind to the
Receptors on the pathogen surface
What cleaves C4 into C4a and C4b?
Activated C1s
When the C4b binds to C2, the C2 will be cleaved by ____ to form C2a and C2b
C1s
After the C2 is cleaved into C2a and C2b, _____ combines with theC4b to create ____.
C2b to create C3 complement (C4bC2a)
Because the C4bC2a is an active C3 convertase, it functions to cleave:
C3 into C3a and C3b
After C3 is cleaved by the C3 convertase into C3a and C3b, it will bind either:
Microbial surface or the convertase itslef
One molecule of C4b2a can cleave up to _____ molecules of C3 into C3b.
1000
The whole process starting with the C1s binidng to the microbial surface and ending with the cleavage of C3 and all the in between steps are part of the :
Opsonization process
When molecules get coated with _____ they are said to be opsonized.
C3b
In the mannose lectin binding pathway, instead of the antibody binding event, it uses:
Lectin binding proteins
Mannan-binding lectin forms a complex with ______ that resembles the complement C1 complex.
Serine proteases
MLB forms cluster of two to six _______ heads around a central _____ like stalk.
Carbohydrate binding heads; collagen-like
What are the 2 associated enzyme activities of the two serine proteases in mannan-binding lectin?
MASP1 and MASP2
The function of the MASP1 & 2 enzymes associated with Mannan-binding lectin allows for the cleavage of:
C4 and C2
Mannan-binding lectin and ficolin both are associated with:
MASP-1 and MASP-2
in the mannose-binding lectin pathway, the C4b2a is a C3 convertase; it will cleave the C3 into C3a and C3b and the C3b will bind the the C4b2a complex generating:
C5 convertase
In the alternative pathway: The C3b is deposited by the classical pathway or lectin pathway’s:
C3 convertase
In the alternative pathway: The C3b binds to _____.
Factor B
In the alternative pathway: The bound factor B is cleaved by _____ into Ba and Bb
Plasma protease factor D
The C3bBb complex is a:
C3 convertase
The alternative pathway of complement involves creating a C5 convertase that ultimately leads to the deposition of:
MAC complexes
In addition to the alternative pathway, the C5 convertase can also be generated by other pathways, the key is that you need to generate a _____ in order to create a convertase that will cleave C5 into C5a and C5b
C3b complex
The alternative pathway is triggered by the:
Covalent binding of C3b to pathogen or cell surface
In the alternative pathway, what forms the pore on the membrane surface?
C9
The MAC complex is composed of molecules:
C5b, C6, C7, C8, and a bunch of C9
All three pathways lead up to:
MAC complex
What is the most direct path leading to the MAC complex?
Alternative pathway
During the process of opsonization and phagocytosis, the phagocytic cell expresses a specific receptor for the ___________ that are on the surface
Complement molecules
If the Phagocytic cells don’t have the complement receptor receptor specific to the complement molecules coating the pathogen they:
Will not be able to phagocytose the molecule
You can opsonize and coat the bacteria with C3b, bind them to the complement receptor on the phagocytic cell, but if ____ is not present, the bacteria will not be internalized by the phagocytic cell
C5a
All of the cells in our body contain different proteins on their surfaces in aims to prevent the complement pathway:
From attacking self-cells
Membrane protein that displaces Bb from C3b and C3b from C4b:
Decay-accelerating factor (DAF)
Membrane proteins that promotes C3b and C4b in activation by I
Membrane cofactor protein (MCP)
DAF and MCP are both:
Control proteins
We have spontaneous production of ____ at low levels.
C3b
If we C3b binding to autologous host membranes it will interact with _____ which blocks the association of factor B with C3b thereby preventing the formation of _____.
DAF; C3 convertase
On the cell membrane, DAF causes the C3 convertase to ______ .
Dissociate
MCP binding to the C3bBb complex causes the release of the _____ portion, and following, a ______ molecule will come in and bind to the C3b cleaving it into an inactive form.
Bb portion; factor I molecule
MCP and DAF both involve the dissociation of the Bb portion, but MCP additionally makes the C3b susceptible to:
Cleavage by facto I
Factor I works to:
Cleave C3b
Diseases that are involved in the complement pathway boil down to: (2)
- Inappropriate activation of the complement pathway
- Destruction of self cells
Acquired disorder that results in premature death and impaired production of blood cells.
Paroxysmal nocturnal hemogloburinuria
What cells does PNH affect?
RBC, Leukocytes, and platelets
Who does PNH effect and when does diagnosis typically occur?
Both sexes equally, and young adulthood
Paroxysmal nocturnal hemoglobinurina results from:
Deficiency in the DAF protein
PNH is named based on:
It occurring at night
In PNH, the deficiency of DAF protein:
Results in destruction of self cells
Results from chronic uncontrolled activation of the complement system
Atypical hemolytic uremic syndrome
Disease in which multiple blood clots form throughout the body in small blood vessels which can lead to stroke, heart attack, kidney failure, and death
Atypical hemolytic uremic syndrome
Atypical hemolytic uremic syndrome is due to:
Mutations in factor H, Factor I, or membrane cofactor protein
The most common functional defect in atypical hemolytic uremic syndrome in age-related macular degeneration syndrome:
Reduced cofactor activity (MCP or Factor H) for C3b
Atypical hemolytic uremic syndrome is a very ______ disease in terms of which proteins are affected, which also determines the _____ of the disease.
Heterogenous; severity
In atypical hemolytic uremic syndrome, the most commonly affected factor causing the disease is:
Factor H
In normal conditions you have MCP or factor H that will bind to the C3b when C3b is created, and this is where factor I comes in and cleaves C3b into an inactive form. If you don’t have this factor H or MCP molecule, then you wont be able to bind _____.
Factor I
If there is spontaneous creation of the C3b from the C3 convertase or from hydrolysis that occurs naturally, these molecules that are our defense mechanism are there to:
Prevent initiation of the complement cascade
Disease characterized by recurrent attacks of severe swelling
Hereditary angioedema
Angioedema caused by mutations in the gene that makes the C1 inhibitor
Type 1 and Type 2 angioedema
Hereditary angioedema where there is a deficiency of C1
Type 1
Hereditary angioedema characterized by an atypical C1 proteins that is less capable of suppressing activation of the complement system
Type 2 HA
Hereditary angioedema characterized by mutations in the Factor XII gene
Type 3 HA
Factor XII is present in the:
Clotting cascade
Factor XII gets cleaved into Factor XIIa also known as:
Plasmin
Factor XIIa (Plasmin) functions to cleave prekalikrein into:
Kalikrein
Factor XIIa also function in the conversion of the _____ pathway in the clotting cascade
Common
Kalikrein converts a high-molecular-weight Kinninogen into Bradykinin and the bradykinin plays a role in: (3)
- Vasodilation
- Smooth muscle contraction
- Edema
The classic pathway works through what type of complexes?
Antigen-antibody complexes
The lectin pathway and alternative pathway function within the _______ immune system, whereas the classical pathway functions with ______ immune system.
Innate immune system
Both innate and adaptive
