Term
when can switch site activation occur?
and what enzyme is used in class switch recombination? |
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Definition
After VDJ recombination,
-the cell can then make its isotype (switch sites are affected by AID enzyme in such a way to create mutations and adds a number of mutations which destabilizes the DNA and opens up the chromatin and allows for homologous recombination) |
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Term
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Definition
| the name for a specific type of sequence that allow for DNA from one strand to invade another to anneal to as a new double stranded element to potentiate the process of recombination through AID |
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Term
12,23 spacer rule
aka 1 turn, 2 turn rule |
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Definition
this rule gives insight to DNA contribution to gene rearrangement.one turn takes about 12 gene segments and 2 turns takes about 23 gene segments ;
recombination only works with this rule in mind |
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Term
| Why don’t all the V gene segments rearrange with each other |
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Definition
| It doesn’t satisfy the 12-23 spacer rule! |
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Term
| Why does V(l) rearrange with J(k)? |
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Definition
| bc it does fit 12-23 spacer rule |
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Term
| Are the kappa and lambda genes on separate chromosomes? |
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Definition
Yes!
And the orientation of DNA on separate chromosomes also has additional constraints. Spacers get excised out. (Everything between the signal joints eventually gets removed from the transcript) |
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Term
| Humoral effector mechanisms |
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Definition
| effector mechanisms that are mediated by soluble substances |
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Term
| 3 major pathways of activation of complement system: |
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Definition
1) Classical (adaptive immune system)
2) Mannose-binding lectin pathway (terminal mannose in innate immunity is considered a PamP)
3) Alternative Pathway |
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Term
| Complement system is highly _______ |
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Definition
pro-inflammatory
(it’s a way for body to respond to antigen in either innate or adaptive way) to give rise to antigen elimination |
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Term
| the 3 major pathways of activation of the complement system all converge together to the cleavage of what molecule? |
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Definition
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Term
| what molecule is found in the highest serum concentration of all the complement components? |
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Definition
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Term
| When C3 gets activated (activate the terminal components of complement), then you can activate what complex? |
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Definition
| Membrane Attack Complex MAC |
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Term
| What are the 3 major components of classical pathway? |
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Definition
C1, C4, C2
C1 cleaves C4 and then cleaves C2 |
|
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Term
| how do c1, c4, and c2 work together? |
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Definition
| C1 cleaves C4 and then cleaves C2 |
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Term
| what does the c1 molecule look like? |
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Definition
| C1 is very interesting molecule ; it looks like a bouquet of flowers (6 globular head groups each associated with a collagen-like stalk). (made up of hydroxylated amino acids). |
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Term
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Definition
(6 globular head groups each associated with a collagen-like stalk). (made up of hydroxylated amino acids).
made up of 3 elements
1) C1q (the 6 globular domains)
2) C1r (stalks)
3) C1s (stalks) |
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Term
| what is C1q activated by? |
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Definition
|
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Term
| what are the complement activators through the classical pathway? |
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Definition
| IgM (only as secreted pentamer) and IgG |
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Term
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Definition
it associates with C1r and C1s
-bind to antibodies such as IgM and IgG once those antibodies are bound to an antigen
-does not bind to IgG or IgM unless those antibodies are first bound to antigen. (you do not want complement activated against normally circulating IgM and IgG antibodies)
- it is very aggressively activated when IgM or IgG is bound to an antigen surface (ex. Bacteria) |
|
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Term
| how does the C1q molecule work? |
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Definition
| this molecule comes along with its 6 globular head groups and if at least 2 of the globular head groups binds to the Fc portion of the IgG molecule that itself is bound to bacteria, that will be sufficient to activate the classical pathway of the complement system; at least 2 of the six globular head groups must be bound to the Fc of the IgG or IgM for classical pathway to undergo activation. |
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Term
| When C1qR when senses the changes in the collagen-like stalks, it undergoes an auto-catalytic event where it does what? |
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Definition
| it cleaves itself (C1R is a serine protease that can cleave itself) (goes from pro-enzyme form/zymogen form to an active form which is a serine protease looking for serine in the active site that will then allow it to cleave itself in autocatalytic process, simply by sensing changes in collagen-like stalk) |
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Term
| Once C1qr cleaves itself, what does it then cleave? |
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Definition
| it then cleaves C1qs (and it also then becomes a serine protease enzyme) |
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Term
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Definition
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Term
| when c1s cleaves c4, what 2 molecules are generated? |
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Definition
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Term
| when c4 is cleaved by C1s to make 2 products, describe the size of both products and what are they both called? |
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Definition
| this generates a large MW product C4b and a small MW product C4a |
|
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Term
| what type of molecular bond does C4b make? |
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Definition
| it will form a covalent bond with the surface of the bacteria through a labile thioester bond. (it is looking for an available hydroxyl group or available amino group) |
|
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Term
| how does the binding of C4b regulate the complement system? |
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Definition
| If C4b doesn’t bind immediately to the surface at which its been activated, then it will by hydrolyzed and the thioester bond will no longer be in tact and it will no longer be able to bind to pathogen surface. |
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Term
| When C4b sticks to pathogen surface, what does it create? |
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Definition
| it creates a binding site for C2 (c2 sticks to C4b to generate c4b2) |
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Term
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Definition
| the genes that make up the episome; they will not be expressed |
|
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Term
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Definition
| are those exposed on JVD segments that allow for coding to take place. |
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Term
| signal joints versus coding joints |
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Definition
Signal joints are the genes that make up the episome; they will not be expressed
The coding joints are those exposed on JVD segments that allow for coding to take place. |
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Term
| Humoral effector mechanisms |
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Definition
| effector mechanisms that are mediated by soluble substances |
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Term
| How many of the globular head groups of the C1q molecule must be bound to the Fc portion of the IgG or IgM molecules bound to bacteria in order to activate the classical pathway of the complement system? |
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Definition
| at least 2 of the six globular head groups must be bound |
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Term
| when c1qr senses that c1q (looks like a bouquet with stalks that have now at least 2 Fc portions bound) is bound to an antibody, what then happens? |
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Definition
once it senses the changes in its collagen-like stalks, it undergoes auto-catalytic event where it cleaves itself (it acts as a serine protease and cleaves itself)
) (goes from pro-enzyme form/zymogen form to an active form which is a serine protease looking for serine in the active site that will then allow it to cleave itself in autocatalytic process, simply by sensing changes in collagen-like stalk) |
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Term
| Once c1qr cleaves itself, then what does it do? |
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Definition
|
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Term
| once c1qr cleaves c1qs, then what happens? |
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Definition
| c1qs can also act as a serine protease enzyme |
|
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Term
| explain the cascade from c1q until you generate C4b and C4a... |
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Definition
-C1q activated by IgM or IgG
-activated C1q binds C1qr
-C1qr cleaves itself to generate an active serine protease
-active c1qr then cleaves C1qs to generate C1qs serine protease
-C4 comes along and is cleaved by C1qs to generate 2 molecules (C4b and C4a). |
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Term
| What is C1q activated by? |
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Definition
| IgM and IgG (part of classical pathway) |
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Term
| cleavage of C4 becomes what? |
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Definition
it creates multiple chains
(one is cleaved by C1s to generate large MW product C4b and a small MW product C4a) |
|
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Term
| when you cleave C4, what two structures are made? |
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Definition
-large MW C4b
-small MW C4a |
|
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Term
| what type of bond does C4b generate? |
|
Definition
a labile thioester bond
-(it is looking for an available hydroxyl group or available amino group)
-However, if the protein doesn’t bind immediately to the surface at which its been activated, then it will be hydrolyzed; the thioester bond will no longer be in tact and it will no longer be able to bind to pathogen surface. This is one of the very important control mechanisms of the complement system. |
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Term
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Definition
| it binds to the pathogen surface and creates a binding site for C2. Then then protein will bind to c4b on the pathogen surface to generate c4b2 |
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Term
| When c2 binds to c4b, what does c1s decide to do? |
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Definition
| C1s changes its mind and decides it doesn’t want to cleave C4 anymore because it generated some c4b and now its going to cleave c2 (thus the same serine esterase that cleaved c4 will now cleave c2 to generate large produce called C2b and small product C2a) |
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Term
| when c2 binds to c4b, what happens? |
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Definition
| C1s changes its mind and decides it doesn’t want to cleave C4 anymore because it generated some c4b and now its going to cleave c2 (thus the same serine esterase that cleaved c4 will now cleave c2 to generate large produce called C2b and small product C2a) |
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Term
| what is the large MW complement written as? |
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Definition
|
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Term
| what is called the C3 convertase of the classical pathway? |
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Definition
|
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Term
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Definition
| it can cleave c3 to generate breakdown products of c3 (C3b large product and C3a small product) |
|
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Term
| what is special about C3b? |
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Definition
| it is an opsonin. it coats bacteria for phagocytosis |
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Term
what are the 2 opsonins in host defense mechanisms mediated by humoral responses?
(opsonins coat bacteria for phagocytosis) |
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Definition
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Term
| Mannose-binding lectin pathway (aka MBL pathway)-3 has components |
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Definition
1) MBL (mannose binding lectin) and
2) MASP-1 (mannose binding lectin associated protease 1)
3) MASP-2 (mannose binding lectin associated protease 2) |
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Term
| convertase of the classical pathway is called what? |
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Definition
|
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Term
| Mannose-binding lectin pathway (aka MBL pathway)-has 3 components |
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Definition
1) MBL (mannose binding lectin); circulates as a molecule that can bind to terminal mannose sugars on carbohydrates expressed by certain bacteria (has overall homology with C1q)
2) MASP-1 (mannose binding lectin associated serine protease 1)
3) MASP-2 (mannose binding lectin associated serine protease 2) |
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Term
| MBL (mannose binding lectin) |
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Definition
| circulates as a molecule that can bind to terminal mannose sugars on carbohydrates expressed by certain bacteria (has overall homology with C1q) in MBL pathway |
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Term
MASP-1 (mannose binding lectin associated serine protease 1) and
MASP-2 (mannose binding lectin associated serine protease 2) |
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Definition
these are in the MBL pathway but are highly homologous to C1qr and C1qs;
-these two proteins cause cleavage of themselves and then ultimately they borrow molecules from the classical pathway which are c4 and c2 to generate that same enzyme c4b2b called the c3 convertase that can now cleave c3. |
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Term
| what is one way that the MBL pathway is different from the classical pathway? |
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Definition
| MBL pathway is antibody-independent and the classical pathway is antibody-dependent |
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