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30 Cards in this Set

  • Front
  • Back

is a malignant transformation of a singleB-cell




clone of Ig secreting cells


may cause immunogenic amyloidosis

Myeloma

When sufficient antibody is secreted, Ag-Abcomplexes form




B-cells constitutively express surface FCgR.BCR and FCgR cross-linked by immune complexes deliverssignals which block further B-cell activation

Regulation of humoral response

activationand proliferation of T and B cells takes 4-7 days, creating the lag period between antigen exposure andthe appearance of Ig in plasma

first exposure

1) short lagperiod


2) IgG (long 1/2-life) prod inpreference to IgM


3) more antibody produced


4)secreted antibody binds antigen more tightly

secondary response

mediates hypermutation

Activation induceddeaminase (AID)

membrane vs secreted antibodyoccurs by...

...alternative splicing of the primary RNA transcript of the heavy chain in antigenactivated B cells.

IgM Þ IgG, IgE or IgA production. Occurs when heavy chainconstant domain DNA is eliminated.

Isotype switching

“Antigens participate in their own demise bypicking the best executioner.”

Clonal selection

stimulated to proliferate and differentiate into antibody secreting cells. All ofthe progeny of the initially activated ________ will be identical (clonal)

B cells

important laboratory reagents and therapeutic agents

monoclonal antibodies

caninizedmonoclonal antibody targeting IL-31, for use in dogs to reduce pruritis.

canine atopic dermatitis immunotherapeutic (Zoetis)

infiltration of tissues withdeposition of partially degraded proteins as insolubleb-pleatedsheets leading to loss of organ function.

immunogenicamyloidosis

Basic antibody structure

Two heavychains (m, d, g, e, a)


Two light chains (l, k).


Chains are joined by disulfide bonds.


Antigen binding site grooves - 2 per complex

light chain disulfide bonded to heavy chainvariable plus1st constant domain

FAB domain (Fragment of Antigen Binding)

heavy chain 2nd and 3rd constant domains held byhinge region disulfide bonds

F c domain (Fragment Crystallizable)

two F ab held together by hinge region disulfide bonds

F (ab)2

differencesdefined by the use of different heavychains

Isotypes,also called classes

inherited variations that distinguish Ig's of oneindividual within a species from those of another. Individual differences in constant domains.

Allotypes

monomer


Crosses placenta


largest component of colostrum


T1/2=20-25days.

IgG

pentamer ofthe basic design


10 antigen binding sites.


join Fc portions


Efficient intravascularcomplement fixation andagglutination


Produced 1st inimmune response


T1/2=3-5 days

IgM

Dimer


Crosses mucous membranes in defense of body surfaces


Does not fix complement nor opsonize well, but agglutinates well


Major component of most non ruminant milk


T1/2=5-6 days

IgA

Monomer


Mostly bound to Fc(epsilon)R on mast cells and basophils.


Acts primarily as a signal-transducing molecule that signals degranulation


Does not fix complement, opsonizes poorly


T1/2=2.5 days

IgE

found only on the surface of naïve B-cells as a BCR in primates and rodents.

IgD

mediatecomplement activation and opsonization for phagocytosis.

FC domains

Important part of structure because it can do 2 things- immune complexes & agglutination

Divalency

Antibodies directed against the microbial attachment structure...

...prevent attachment and subsequent infection

What's happening in Fc domains

Complement activation by C3b opsonization


Antibody Opsonization


ADCC

CTL effectorresponse

cell killing by induction of apoptosis

2 types of cell killing by apoptosis

1. Fas-ligand (Fas-L) expression on CTL engages Fason target cell




2. Directed secretion of pore-forming perforins andintracytoplasmic delivery of granzymes. "Lethal hit."

A Tcell response that generates CTLs in the presence of activated T helper cells also produces...

...memory CD 8+ T cells