Immuno Lecture 1....5 Flashcards
antibodies functions
immunomodulation reduced damage to host from inflammatory response organized T cell response opsonization activation of complement toxin neutralization direct antibacterail acitvity
Where are most abs found?
the thrid fastest migrating group of globulins, named gamma globulins for the thrid letter of the Greek alphabet (count alpha 1 and alpha 2 as one)
Abs have a basic unit of?
four polypetide chains
What are the chains of abs?
two light chains and heavy chains, bound together by covalent disulfide bridges as ewll as by noncovalent interactions
What can abs be proteolytically cleaved to yield?
Fab fragments(fragment Ag binding Fab) and an Fc fragment (fragment crystallized, Fc) responsible for effector functions
What are both H and L chains dividied into?
V and C regions
the V region
containg the Ag binding site
C region
determining the fate of the Ag
What are the five different kinds of H chains?
epsilon, alpha, gamma, u, ga…
What do the H chains determine?
the class of antibody…. M, D, E, A
What are the two different kinds of L chains?
k and lambda, each with a MW of 23kDa
Each Ab unit can have only k and lambda
L chain, but not both
What do both H and L chains have?
intrachain disulfide bridges every 90 amino acid residues, which creates polypetpteide loops, domains, of 110 amino acids
What are the domains refered to?
Vh, Vl, Ch1, Ch2, etc
Know what parts are responseibl efor
on basic structure of Abs
Abs have lots of flexibility, bc?
hinges
What is the Ag binding sites formed by? Secreted IgG
the juxtaposition of Vl and Vh domains
Where does the heavy chain C regions end? Secreted IgG
tail pieces
Whaat is the location of complement and Fc receptor biding sites/ Secreted IgG
within the heaby chain constant regions are approximations
membrane-bound IgM on B cell… has …… thant IgG
one more Ch domain
membrane bound IgM on B cells
has C terminal trnasmembran and cytoplamsic protions that anchor the molecule in the plasma membrane
Igm is for?
activation of phagocytosis
What is IgG cleaved by?
The enzymes papain at the hinges
What does papain diegestion in IgG allow?
the separation of two Fab fargments and complemetn and Fc receptors biding the Fc fragment
what generates a single bivalent antigen bidning fragment F(ab’)2…
pesin….. makes fragments of IgG
What are the two roles of hinges?
widely spaced cell surface determeinatn closely spaced cell sufrace determinatns
What is teh flexibiilty due to..
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What are a large group of cell sufrace and solubel proteins involved in?
Recognition, binding, or adhesion process of cells belogs to the imunoglobulin super family
What are Ig superfamily proteins? list 6
IgG, TCR, Class I MHC, CD4, CD28, ICAM1
Ig ag binding site
three CDrs in Vh and three CDRs in Vl domains
T cell receptor Ag binding site
three CDRs in Valpha and three CDRs in Vbeta domains
Ig Ag that may be bound
proteins, lipids, polyscaccarides and small chemicals
T cell receptors Ag that may be bound
peptide MHC complexes
Ig antigenic determinatns recognized
linear and conformational determinats of various macromolecules and chemicals
T cell receptor antigenic determinants recognized
linear determinants; only 2 or 3 aa residues of a petide boudn to an MHC molecule
Ig affinity of Ag binindg
Kd 10^-7-10^-11 M
Ig on-rate/ off rate
rapid on rate, variable off rate
T cell recetor affinity of Ag binding
Kd 10^-5-10^-7M
Ig Onrate/off rate
slow on rate slow off rate
CDR
complementarity determining region
Kd
disociation constant
Vh
variable domain of heavy chaing Ig
Vl
vairable domain of light chain ig
from the H and L chain are loops that protrude from the surface of the two Ig V domains and in combination creat an Ag binding region
complementarity- determining regions (CDRs)
What is each domain of the Ag binding site composed of?
two anitparallel beta strands, colored yellow and red, to form two beta pleated sheets held together by a disulfide bond
Confamitonal determinatn—> denaturation
determinant lost by denaturation
linear determinant nenaturation of
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neoantigenic determinant (created by proteolysis)
determinatnnear site of proteolysis
the tighness of Ag-Ab binding
affinity
Abs ??? in their affinity to the same Ag determinant
vary
The higher the….. the less liekly the Ab is to …… from the Ag
binding contstnt, dissociate
Abs formed in the primary response?
soon after the injection of an Ag are gnereally of lower affinity
Abs produced by memory response?
have higher affinity thatn those in a primary repsosne ( association constats 1000 times higher)
What is critical in Ab when the Ag is a toxin or virus and must be neutralized rapidly?
affinity
What is the maximum numnber of antigenic determinatns with which an Ab will react?
the valence of an Ab
What contains two Fab regions and can bind two moleucles of Ag or two identical sites on the same particles and thus of have valance of???
IgG, two
What is the valence improtnat for?
binding affinity, as having two or more binding sites for an Ag can dramatically increase the tighness of binding of the Ab to Ags
What is avidity?
comvined effect that results from synergy of the binding strngths of each binding site
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Stem cell
no Ig expression
Pre B cell
Cytoplasmic u heavy chaing and pre B receptor
immature B cell
membrane IgM
mature B cell
membran IgM, IgD
Activated B cell
low rate Ig secretion; heavy chain isotype swithcing; affinity maturation
antibody secreteing cell
high rate Ig secretion; reduced membrane Ig
most common Ab in mucosal secretions
IgA
mainly found in the plama
Igm
absorbed on the surface of mast cells
IgE
penetrates deeper into the tissue
IgG
Different microbes have different/
biological properties
Microbes can enter the body through ?
different routes skin, gi, respiratory tract, genitourinary
The five different Ab classes such as IgM, IgD, IgG, IgE, and IgA, and their subclasses have evolved
to facilitate protection agianist microbes entering at the different sites
What classes have a J chain?
A and M
all Ig have
heavy chain and light chain
what have seretory ocmpononet?
IgA
What is the most abudnant immunoglobulin in the blood?
IgG
What is the IgG class MW?
150 kDa
Where are IgG found
both in vacular and extravascular spaces as well as in secretion
What provides the bulk of immunity to most blood borne pathogens?
IgG
What is the only Ig to cross the placenta?
IgG, it provides
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What is present in the placenta?
The epithelial cell surface receptor for Fc regions (FCRn) of maternal IgG
What does FCRn do? .
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What is teh major Ig present in extermal secreitons such as colostrum, milk, and saliva?
IgA where it exists as a 420 kDa dimer
What does the IgA contian?
lambda chian, H alpha chain, two more polypeptide chians secretory component J chaing… joining chain
What is part of the poly Ig receptor involbed in transepithelial transport of eoxcirn
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