Immunology Chapter 4 Part 1

what are the different classes of isotypes

IgG IgA IgM IgE IgD

how do isotypes bind

high affinity and specificity

antibodies

secreted form of immunoglobulins

immunoglobulins

Mature B cells express them (B cell receptor or BCR) on their surface

BCR's

has a hydrophobic tail so it will stay attached to the membrane. Antibodies have a hydrophilic tail so it will be secreted. They are otherwise identical, and Antibodies are both referred to as Immunoglobulins

antigens

- anything a BCR (including antibodies) or TCR can bind to
- are bound by antibodies
- are biological macromolecules (usually proteins and carbs)

what do antigens bind to and are there covalent/noncovalent forces

- Antibodies binds to Antigens epitope (aka antigenic determinant)
- Peritope-epitope bond is noncovalent

linear epitope

primary AA sequence in a line

discontinuous epitope

different parts of Ag folded together (not in sequence)

multivalent in regards to epitopes

Ag that has more than one epitope

where is the fat of an antigen determined

- Fc fragment (constant region of heavy chain)
- aka fragment crystallizable/constant (constant domains of heavy chains)

neutralization of antibodies

the ability of antibodies to block the site(s) on bacteria or viruses that they use to enter their target cell.

opsonization of antibodies

the coating of pathogens with antibodies to increase their susceptibility to ingestion by phagocytes

activation of complement

Complimentary proteins bind to antigen antibody complex and trigger cascade of proteins that result in pore in foreign cell membrane

gold standard of vaccination

Neutralization; It prevents the pathogen from binding anywhere to cause harm

Fab region

where the antigen binds

Fc region

- Part responsible for effector functions
- Binds to Fc receptors on phagocytes, mast cells, basophils...
- Determines the fate of the antigen that is bound to theantibody.

heavy chain

constant regions define; 5 main Ab isotypes (GAMED), on 1 chromosome will have variable region genes and constant domain genes

light chain

2 isotypes are lambda and kappa, each Ab has either kappa or lambda chains, 2 individual light chain genes

v region

(great diversity), concentrated in N-terminal region, paired regions of H and L chain for Ag binding site (2 identical Ag binding sites)

c region

constant region, determines fate of Ag, less variation in AA sequence between Abs in the C region

Which confers the effector functions for antibodies?

heavy chain constants

Which comprises the antigen binding site?

V region

Do amino acid sequences differ greatly in both or just one?

AA differences are concentrated in the 3 HV loops of each chain (V heavy and V light) (specifically the loops furthest away from B cell surface)

affinity

the tightness of binding of an Ab binding site to an Ag; how strong peritope and epitope bind

avidity

the firmness of association between a multideterminant Ag and the Abs produced against it; energy to knock off several bonds

what antibody isotype has the highest avidity

IgM, it has 10 binding sites

what antibody isotype has the highest affinity

IgG

what is valence

- The maximum # of antigenic determinants (epitopes) with which an Ab can react
- Multiple binding sites on an Ab dramatically inc its binding (avidity) to Ags on pathogens

which isotype is mainly found in plasma

IgM

which isotype is commonly associated with mucosal secretions?

IgA

which isotype can cross the placenta and most abundant in the blood

IgG

What isotype mediates responses to allergic reactions and parasitic worm infections?

IgE

which isotypes are monomers in their membrane-bound form

all 5 isotypes

IgA is _____ when secreted outside the body

dimeric

IgM is ______ when secreted

pentameric

Where is the J-chain and secretory component?

In secreted IgA

how many subclasses are in IgG

4 subclasses

how many subclasses are in IgA

2 subc;asses

what isotypes are in the heavy chain

IgG IgA IgM IgE IgD

what isotypes are in the light chain

kappa and lambda

How many isotypes of the light chain and the heavy chain can a single BCR express

It will express only 1 heavy chain and 1 light chain, so each BCR on the surface of 1 B cell will be all the same sequence.

In each BCR, are the heavy chains the same? What about light chains?

- Each B cell will only express 1 heavy chain and 1 light chain
- Heavy chains are the same and light chains are the same

Explain how the antigen binding site is made up

- The pairing of the heavy and light chains brings together the hypervariable loops and createsa composite hypervariable surface that forms the antigen-binding site.
- Formed from the hypervariable regions of a heavy chain and a light chain V domain

Gene rearrangement in B cells will occur within what region of their structure? What gene segments must come together to make a functional gene in B cells for the heavy and light chains?

- Variable region
- VDJ

What laboratory technique that we discussed in class allows reactions to be measured using monoclonal antibodies as a source?

flow cytometer

What two cell populations did we specifically mention could be detected from flow cytometer?

can detect B and T cells

Monoclonal antibodies are highly efficient when utilized in certain clinical and research settings. Be able to understand what part of an antibody's structure provides monoclonal antibodies with such effectiveness

They are produced from a single specificity and therefore have identical Ag-binding sites and identical isotypes

what do CDR's stand for

complementarity determining regions

what does HV stand for

hypervariable regions

do HV's and CDR's do the same thing

yes

where are CDR's and HV's found in the BCR

In discrete loops at the end of the variable domains

How many CDR/HV's are in each V domain?

3 in light chain, 3 in heavy chain

How many CDR/HV's make up a single Fab region?

6 in total

What would the total amount of CDR/HV's be for one IgG molecule?

2 binding sites x 6 CDR = 12

What would the total amount of CDR/HV's be for one IgM molecule?

10 binding sites x 6 CDR = 60

Understand how specificity and diversity is achieved/determined

The pairing of the heavy and light chains brings together the hypervariable loops and create a composite hypervariable surface that forms the Ag-binding site--determines specificity and diversity