Antigen receptor genes Flashcards
what is the issue of inheritance of DNA
most genes have a maternal and paternal form
the issue is that But B cells are clonal: one
B cell produce only 1 Ab
e.g. monoclonal Ab production
Issue 2. There is no limit to the number of
antigens that can be recognized by B cells
what is the solution to the monoclonal gene problem
So how can the immune system do this?
- have multiple genes
- ”re-use” the same genes
who performed the paradigm shifting experiment
hozumi and tonegawa
what are antibodies
Proteins made by B cells that bind antigen
what are the similarities and differences between secreted and membrane ig
they have the same Fab but a different C-terminus
Antibodies interact with Ag at
Complementarity-
determining regions (CDR)
what are CDRs
CDRs are the loops in the Fab region, the rest is called the framework regions
mithridatism
Protection against poisoning observed in response to small doses of
poisons
* Mithridatism – Mithradates VI, Greece, 135-63 BC
* Practice was thought to have saved Rasputin from being killed with poison
diptheria protection
1880-90s- Emil von Behring; protection against diptheria toxin is
found in the serum of animals if injected with non-lethal heat-treated
toxin (also tetanus)
what bacteria produce the diptheria and tetanus toxin
Toxins produced by bacteria: Corynebacterium diphtheriae and Clostridium
tetani, respectively
diptheria stats
Diptheria: Death rate: 5-10% (20% if <5 years or >40 years old), 1930’s – one
of top 3 causes of death in children
tetanus symptoms and antitoxin
- Tetanus: lockjaw, no natural immunity is acquired after natural exposure
- Antitoxin: inject non-lethal diptheria and tetanus toxin into horses and obtain
serum
what is the process for isolation and discovery of antibodies
- Serum is isolated from rabbits that have
been injected with Ovalbumin - Electrophoresis separates proteins by charge
and mass - Black line shows serum that has been pre-
incubated with Ovalbumin (the antigen) - Antibodies (Ab)= Immunoglobulin (Ig)
what do agglutination reactions do
demonstrate that Ab
are substances
Using
agglutination as
the read-out, it is
clear that the
“valency” of
antibodies and
antigens is
important
biological consequences of Ab binding
neutralization
opsonization
activation of complement
antibody depended cell mediated cytotoxicity (ADCC)
granule release
transcytosis
neutralization
Ab binding blocks binding of toxin or virus to cell
opsonization
promotes phagocytosis of Ag via interaction with Ab
activation of complement
directly destroys cells
Antibody-dependent cell-mediated cytotoxicity (ADCC)
killing
by NK cells
granule release
release of granules into the extracellular space
transcytosis
Moving Ab across epithelial layers (ie. placenta)
generation of Ab diversity occurs in
the bone marrow independent of Ag
Examining the DNA sequences of light chain reveals
the use of different ’V’ regions but the
same ‘C’ region
the same Ch or Cl region can be connected to
millions of different Vh or Vl regions
myeloma
plasma cell cancer
* secrete all of the same Ig or just IgL
(light chain)
* When just IgL called Bence Jones
proteins
2 types of light chain
Lambda
Kappa
X 2 parents
= 4 possible C gene alleles
