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B cells and Antibodies
October 27 Lecture
59
Immunology
11/05/2011

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Term
B cells have on their membrane surface _______ embedded in plasma membrane of those cells, gives them their specificity for antigens
Definition
antibodies
Term
Lymphocytes
Definition
Cells of adaptive immune system that have very special receptors for antigens
Term
signal 1 for lymphocytes
Definition
form of antigen
Term
Signal 2 for lymphocytes
Definition
co-activation events
Term
Ag receptor in form of antibody immunoglobulin allows cells to bind to antigens (one way to bind to antigen). However, in majority of instances, b cells need _____________
Definition
t cell help

( so t cell help is the second signal)
Term
After signal 1 and 2, what happens?
Definition
terminal differentiation and the b cell becomes a plasma cell
Term
Antibodies are on surface of b cells and they are also secreted by _____
Definition
plasma cells
Term
how long do plasma cells live?
Definition
7 days
Term
function of plasma cells
Definition
to produce and secrete antibodies
Term
What is an antibody?
Definition
Protein chains that has 2 identical heavy chains and 2 identical light chains in shape of Y
Light chain is made up of 2 functional domains (end terminal is variable light domain found on both light chains and then there is also the C terminal domains)
Term
IgM and IgE have an additional ______
Definition
CH4 domain

AA’s that make up these domains determine how antibody will bind
Term
Specificity of antibody is determined by the ___________
Definition
variable domains
Term
variable domains
Definition
determines Specificity of antibody
Term
Each arm of variable domain
Definition
has capacity of binding an antigen

(will see the same exact antigen because both these chain components are identical)
Term
what type of bond makes up the chain interaction between variable light and constant light and variable heavy and constant heavy?
Definition
disulfide bonds
Term
2 main parts of antibody:
Definition
1) One part that binds to antigen and (FAB)
2) other part that serves role in effector function of antibodies (FC -fragment crystalline); what the antibody does when it is bound to an antigen is called its effector function
Term
one of the 2 main parts of an antibody that binds to antigen
Definition
FAB component
Term
Fc
Definition
one of the 2 main parts of antibody that serves role in effector function of antibodies
Term
effector function
Definition
what the antibody does when it is bound to an antigen
Term
Papain
Definition
this is an enzyme that cleaves an antibody above the disulfide bonds leaving the bottom portion (Fc) in tact
Term
Pepsin
Definition
enzyme that cleaves antibody so that the top portion stays in tact (disulfide bond stays with top portion of molecule
Term
when you use pepsin, what happens to the Fc portion of the antibody?
Definition
there are multiple recognition units in the Fc portion but when you use this particular enzyme, the Fc portion ends up digested in lots of little pieces
Term
Fabprime2
Definition
has two Fab’s held together covalently by being linked by disulfides

(combined antigen binding site still held together by disulfide bonds but lacks Fc (so doesn’t have effector condition so cant immediate an inflammatory immune response)
Term
all the types of constant domains
Definition
constant heavy 1
constant heavy 2
constant heavy 3 (for some of isotypes but not all isotypes of antibodies)
constant heavy 4 (only exist in IgM and IgE) (at the c terminal of the polypeptide chain molecules)
Term
Fc receptors
Definition
receptors for antibody on phagocytic cells that help mediate antibody neutralization and antigen elimination
Term
in the regions of variable diversity, how would you break it down even further?
Definition
regions of hyper-availability and regions of conservation
Term
what are all the different hyper-variable regions
Definition
1) Hyper-variable region 1 (HV1)
2) Hyper-variable region 2
3) Hyper-variable region 3
Term
Do amino acid sequences vary among different antibodies?
Definition
yes
Term
what is another name for hypervariable regions?
Definition
Complementary determining regions (CDR’s)
Term
for hyper-variable regions 1 and 2, where do gene segments encode?
Definition
in the germ line
Term
So how do we get the HV3 hyper-variable regions for each the heavy and the light chain then? (especially if only gene segments that encode for hyper variable regions 1 and 2 are in the germ line)
Definition
By genetic recombination! We can make tremendous changes in the sequence that will determine specificity of that particular antibody that can be recognized. This plays a role on how the structure folds and what its specificity is for things that it binds to.
Term
Does an antibody need all of its chains/regions in order to be fully functional?
Definition
YES
Term
______________ of heavy and light chains creates the specificity for the antibody.
Definition
Variability (rearrangement)
Term
which is made first in the antibody...
heavy or light chain?
Definition
heavy chain is made first

then light chain is made
Term
what are the 5 major isotypes of antibodies?

(Ig- immunoglobin and the upper case letter after shows the isotype name)
Definition
1) IgM -
2) IgD
3) IgG- 4 subtypes
a. IgG1,
b. IgG2
c. IgG3
d. IgG4
4) IgA has 2 subtypes
a. IgA1
b. IgA2
5) IgE
Term
what are the 4 IgG subtypes?
Definition
a. IgG1,
b. IgG2
c. IgG3
d. IgG4
Term
what are the subtypes of IgA?
Definition
a. IgA1
b. IgA2
Term
First membrane receptors that b cells produce is _________
Definition
IgM (found on immature b cells)
Term
what form of IgM is found on immature b cells?
Definition
monomeric form
Term
2 major forms of receptors of b cells
Definition
IgM and IgD
Term
what isotype is only a membrane associated form of the antibody?
Definition
IgD
Term
can IgM be secreted?
Definition
Yes! Typically in multimeric form (in pentameric form that looks like a snowflake)
Term
J chain
Definition
holds the pentameric form of IgM together ; the ‘glue’ that holds the pentamer together, actually reacts with the Fc portion of the molecules to hold them together
Term
When IgM is on b cell, it is in _________form, but if it is secreted by plasma cell, this is only in __________form
Definition
monomeric

pentameric
Term
IgM as a pentamer if secreted by cell and held together serves as an antibody. Why is this important?
Definition
It is a very potent activator of complement system
(made every day in fluids, made by hepatocytes) in terms of inflammatory response and cell mediation
Term
IgD membrane receptor
Definition
membrane receptor for antigens on mature b cell surface
Term
IgG-
Definition
very important isotype; found in high ester concentrations , not necessarily synthesized in greater amounts, but it has a much larger half life than any of the other isotypes, which allows it to accumulate; has multiple properties; a complement activator
Term
There are 2 complement isotypes that can activate complement system :
Definition
(IgM and IgG)

IgM is a lot more effective complement activator than IgG is; this has to do with its pentameric structure
Term
3 major pathways of complement system
Definition
1) Classical (depends on IgM or IgG for its activation) (thus it is part of adaptive immune system); these are products of b cells and b cells are part of adaptive immune system
2) Mannose binding lectin (innate immune system)
3) Alternative (innate immune system)
Term
Is IgG an opsonin?
Definition
Yes! opsonin (forms a small, thin coat on the antigen) antigen binding portion is stuck on bacteria and the Fc portion is available and exposed and then a phagocytic cell comes along with an Fc receptor, binds to antibody through Fc portion and that makes up the first phase of phagocytosis ; promotes attachment (phagocytic cell attaches to pathogen and initiates internalization.
Term
opsonin
Definition
(forms a small, thin coat on the antigen)
Term
what must you do before ingesting an antigen by phagocytosis?
Definition
it must be opsonized first!
Term
2 types of opsonins
Definition
1) IgG
2) One that does complement activation
Term
IgM-monomer
Definition
a membrane receptor
Term
IgM Pentamer
Definition
a complement activator
Term
IgD
Definition
a membrane receptor
Term
what are the 5 things IgG does/serve as?
Definition
1) complement activator,
2) opsonin,
3) placental transfer(as fetus develops it needs protection from infections; IgG crosses placenta to provide protection from fetus),
4) Feedback inhibition
5) antibody dependent cell mediated cytotoxicity (AL-dependent cell mediated cytotoxicity) this means that ; can also be a feedback inhibitor of b cell activation (b cells can sense amount of antibody in environment and if theres enough of a particular antibody they the b cell gets inhibitory signal and that’s based upon amount of IgG that’s present within the system (feedback inhibition)
Term
IgE
Definition
-found in vanishingly small amounts -synthesized and is cytotropic to mast cells, (binds devoid of antigen, to mast cells); also to basophils or eosinophils,
-cytotropic because it has Fc epsilon receptors) receptors for this are called Fc epsilon receptors; involved in hypersensitivity (allergic) reactions, binds to Fc epsilon receptor on mast cells and antigen/allergen will bind to Fab portion of the molecules and a nut has multiple epitopes; engranulate to produce histamines and prostaglandins, etc. ,
-there is IgE cross-linking on receptors on mast cells and this creates robust allergic response and release of nasty things; sneezing, coughing, diarrhea are all results associated with allergies ;
-is in vanishing small amounts;
-this is a protective mechanism against parasites (helps eliminate parasites by robust reactions).
Term
IgA
Definition
-exhibits mucosal immunity,
-principal antibody in intestinal tract, involved in host defense,immunologic defense in mucosa (ex. If you have an inflammatory bowel disorder) ;
-secreted as dimer, held together by J chain; purpose is to bind to antigen and then allow body to remove the antigen in the form of bacteria by normal peristalsic reaction of the gut,
-binds to bacteria/toxins and prevents them from colonizing in the gut. Allowing normal reaction of GI tract to eliminate those pathogens