Complement System (Exam III) Flashcards
Component of the immune system that is genetically determines and nonspecific
Innate immune system
Elements of this system include mucous secretions, complement proteins, certain WBCs (especially neutrophils, macrophages, and dendritic cells)
Innate immune system
Component of the 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
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 leads to the assembly of _____ on pathogens and subsequent _____
MAC; lysis
MAC
Membrane attack complex
Second function of the complement system
Enhance the inflammatory response
The complement system enhances the inflammatory response via
Release of anaphylatoxins that promote cell activation or migration to inflammatory site
Migration to inflammatory site
Chemotaxis
The complement system becomes activated in innate immunity when it senses:
Apoptotic cells, tissue debris or pathogens
Innate immune system is always functioning at:
A very low level
The body has mechanisms in place to prevent the innate immune system from:
Destroying all cells in our body
The complement system can be activated in three ways:
- C3 turnover
- Natural antibodies
- Lectins
Activation of the complement system by C3 turnover engages what pathway
The alternative pathway
Activation of the complement system through natural antibodies engages what pathway
Classical pathway
Activation of the complement system by binding of lectins engages what pathway
The lectin pathway
In adaptive immunity naturally antibodies are replace by:
Specific antibodies
The complement system triggers the following immune functions (3):
- Phagocytosis
- Inflammation
- Membrane attack
phagocytosis in the complement system occurs by:
Opsonizing antigens
has the 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 cells wall of bacteria (punching hole in it)
Membrane attack
A local response to cellular injury that is marked by capillary dilatation, leukocytic infiltration, redness, heart, and pain
Inflammation
Serves as a mechanism initiating the elimination of noxious agents and of damaged tissue
Inflammation
Wheel and flare response is characteristic of:
Type I 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 activation of:
C1-complex
The mannose-binding (lectin) pathway is homologous to the classical pathway, but uses the opsonins:
Mannose-binding lectin (MBL) and ficolin
What opsonins does the classical pathway use
C1q
The alternative pathway is continuously activated at a ______ level
Low
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 the internal thioester bond in C3 is due to C3 being mildly unstable in:
Aqueous environment
Pathway that does not rely on pathogen-binding antibodies like other pathways
Alternative pathway
Pathway that responds when you have antigen:antibody complexes (on pathogen surfaces)
Classical pathway
The classical pathway involve what 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
The lectin pathway involves mannose-binding lectin or ficolin binding to _____ on pathogen surfaces
Carbohydrates
What molecules does the lectin pathway involve
MBL/ficolin,C4, C2
Enzymatic activity of the MBL/ficolin complex in the lectin pathway
MASP-2
What molecules do the lectin pathway and classical pathway have in common
C4 and C2
The alternative pathway occurs on
Pathogen surfaces
The molecules involves in the alternative pathway include
C3, B, D
All three pathways converge at the production of
C3 convertase
What two pathways are pretty much identical excepting for what triggers them
Classical and lectin pathways
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 bind
C3 convertase
When C3b combines with C3 convertase bind together, this leads to the cleavage of
C5 into C5a and C5b
What molecules are peptide mediators of inflamantion and phagocyte recruitment
C3a and c5b
What molecule binds to complement receptors on phagocytes and leads to the opsonization of pathogens and removal of immune complexes
C3b
What molecule triggers MAC formation along with lysis of certain pathogens and cells
C5b
- Molecule important in opsonization
- Molecule important in MAC formation
- Molecules important in inflammation
1- C3b
2- c5b
3- C3a & C5a
In addition to the C3 being broken down into C3a and C3b during activation of the complement system our bodies also:
Constitutively 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 fixation of the complement system what molecule recruits phagocytes and functions in inflammation
C3a
Cleavage of c3 exposes a:
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 to the surface and the ____ molecule is going to bind to that
C1 molecule (made of C1q, C1r, C1s)
What subunit of the C1 molecule will cleave C4 into C4a and C4b
C1s
The cleavage of c4 into c4a and c4b will induce the celaveage of:
C2 into C2a and C2b
C4b and C2a together will cleave C3 into
C3a and C3b
C4b + C2a together form
C3 convertase
C1 is a complex of c1q, c1r and c1s. The c1q portion is composed of:
Six identical subunits with globular heads and long collagen-like tails
The headlight structure of c1q function to:
Sit down and bind pathogen surfaces
Once the c1q globular heads are bound to the pathogen surface, the c1r portion undergoes conformational change which results in:
Cleaving and activating the c1s zymogen
C1s will bind the:
Receptors on the pathogen surface
What cleaves C4 into C4a and C4b
Activated c1s
When the C4b binds to C2, the C2 undergoes cleavage by ____ to form C2a and C2b
C1s
After the c2 is cleaved into c2a and C2b, ___ combine with the c4b to create _____
C2b; c3 complement (c4bc2a)
Because c4b2a is an activate c3 convertase it functions to cleave
C3 into c3a and C3B
After c3 is cleaved by the c3 convertase it will bind either:
Microbial surface or the convertase itself
One molecule of c4b2a can cleave up to _____ molecules of c3 into C3b
1000
The whole process starting with the c1s binding to the microbial surface and ending with the cleavage of c3 and all the in between steps are part of the:
Opsonizaiton process
When molecules get coated with _____ they are said to be opsonized
C3b
In the mannose-binding lectin pathway, instead of the antibody binding event it uses:
Lectin binding proteins
The Mannen-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
Collagen-like
What are the two associated enzyme activities of the two serine proteases in mannan-binding lectin
MASP-1
MASP-2
The function of the MASP-1 and MASP-2 enzymes associated with Mannan-binding lectin allows for the cleavage of:
C4 and C2
Mannan-binding lectin and Ficolin both 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 c4b2a complex generating:
C5 convertase
In the alternative pathway:
C3b is deposited by the classical pathway or lectin pathway’s:
C3 convertase
In the alternative pathway:
C3b binds:
Factor B
In the alternative pathway:
Bound factor B is cleaved by ________ into Ba and Bb
Plasma protease factor D
In the alternative pathway:
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 in other pathways, the key is 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:
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 of the pathway ultimately lead up to
MAC complex
What is the most direct pathway leading the the MAC complex
Alternative pathway
In order for phagocytosis to follow opsonization - the phagocytic cells must contain
A specific receptor for the complement molecules on their surface
If the phagocytic cells do not contain the receptors specific to the complement molecules coating the pathogen:
Phagocytosis will not occur
For phagocytosis to occur what specific molecules must be present and why?
C5a and has to internalize it
You can opsonize and coat the bacteria with C3b, bind them to the complement receptor on the phagocytic cell, but if _____ is not present then the bacteria will not be internalized by the phagocytic cell
C5a
All of the cells in our body carry different proteins on their surfaces designed to prevent the complement pathway:
From attacking self cells
Membrane protein that displaces Bb from C3b and C2b from C4b
Decay-accelerating factor (DAF)
Membrane protein that promotes C3b and C4b inactivation by I
Membrane cofactor protein (MCP)
DAF and MCP are both
Control proteins
We have spontaneous production of ____ at low levels
C3b
If you get 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 C3b Bb complex causes the release of the ____ portion and allows _____ to come in and bind to the C3b and cleaving it into an inactive form
Bb
Factor I molecule
DAF and MCP both involve the dissociation of the Bb portion, but MCP additionally makes the C3b susceptible to:
Cleavage by factor I
Factor I functions to:
Cleave C3b molecule into an inactive form
Innapropriate activation of the complement pathway leads to: (2)
Diseased state and destroying of self cells
Acquired disorder that results in premature death and impaired production of blood cells
Paroxysmal Nocturnal Hemoglobiuria
What cells does PNH affect
RBCs, leukocytes and platelets
Who does PNH affect and when does diagnosis typically occur
Both sexes equally
Diagnosed in young adulthood
Paroxysmal Nocturnal Hemoglobinuria results from
Deficiency of the DAF protein
Paroxysmal nocturnal hemoglobinuria gets its named based on it occuring mainly 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 clothes 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 and age-related macular degeneration is:
Reduced cofactor activity (MCP or factor H) for C3b
Atypical hemolytic uremic syndrome is a very _____ disease in terms of which protein is affected which also determines:
Heterogeneous
The severity of the disease
In Atypical hemolytic uremic syndrome, the post commonly affected factor causing the disease is
Factor H
In normal conditions MCP or factor H will bind to C3b when C3b is created, this is when factor I comes in and cleaves C3b into an inactive form. If you don’t have a functional MCP or factor H:
Factor I will be unable to bind
If there is any spontaneous creation of C3b from C3 convertase or the hydrolysis that occurs naturally the molecules of our defense mechanism are there to prevent:
Initiation of the complement cascade which leads to cell death
Disease characterized by recurrent attacks of severe swelling
Hereditary angioedema
Angioedema caused by mutations in the gene that makes the C1 inhibitor
Type I & Type II
Hereditary angioedema caused by deficiency of C1
Type I
Hereditary angioedema caused by atypical C1 protein that is less capable of suppressing acitvation of complement system
Type II
Hereditary angioedema associated with mutations in Factor XIII gene
Type III
Factor-XII gets cleaved into Factor-XIIa also known as
Plasmin
Factor-XIIa (Plasmin) function to cleave:
Prekallikrein into Kallikrein
Factor-XIIa also functions in the conversion of the _____ pathway of the clotting cascade
Common
Kallekrein convertes a high-molecular-weight Kininogen into
Bradykinin
Bradykinin plays a role in (3)
1- vasodilation
2- smooth muscle contraction
3- edema
The classic pathways works through:
Antigen-antibody complexes and C1
The lectin pathway and alternative pathway function within the ____ immune system, whereas the classical pathway functions with _____ immune system
Lectin & alternative = innate immune system
Classical = both innate and adaptive immune system
