Immunoglobulin Flashcards
In what two situations would you see a gamma -globulin band on electrophoresis?
- Hyper-immunized
2. Multiple mylenoma (plasma cell tumor)
Papain digestion of the Ig results in what?
- 2 Fab fragments- antigen binding components
2. 1 Fc fragment- effector portion of the Ig
What is an isotype?
a distinct form the Ig heavy chain (mu, alpha, gamma, delta, epsilon) or the light chain (lamda or kappa) present in all members of a species
Which isotypes can be readily found in normal sera?
All of them (but E and D in trace amounts)
What is an allotype?
Genetic variants in the constant regions of Ig that are inherited in an allelic manner. This varies by member of a species.
____________is the same for all members of a species while ______________differs amongst members of the same species.
Isotype; allotype
What is an idiotype of an Ig?
a unique antigenic specificity conferred in the variable region of the Ig which distinguishes it from all other antibodies.
What antibodies will have the same idiotype?
those that arise from the same B-cell founder clones
_______________can be detected in serum, while ________ cannot be detected in serum due to their extremely low frequencies.
Isotype; idiotype
In what people are you actually able to detect idiotypes in serum?
Patients with B-cell clonal expansion
What is the level of IgG in serum?
12-14 microg/ml
What percent of serum is IgG?
80%
What are the major sites for IgG?
intravascular and extravascular (tissue)
What is the half life of IgG?
23 days (IgG3 is only 7)
Where are IgA found?
Intravascularly and In secretions
Which Ig contains J and S chains?
Which Ig only contains J chains?
J+S = IgA J= IgM
Why is the molecular weight of IgM significantly more than the other Ig?
It exists as a pentamer which is why it is also mainly intravascular (too big to get into tissue)
Where are IgD found?
on mature B-cells (with IgM)
Where are IgE found?
on mast cells and basophils
What antibody is best at binding FcR? What does this allow it to do?
IgG-> recycles the antibodies to maintain constant serum levels
What antibodies can induce ADCC?
IgG
What antibodies are best at neutralizing toxins?
IgG
What antibodies can be found in breast milk?
IgG and IgA although IgG can also cross the placenta
Which antibodies have antiviral functions?
IgG and IgA
Which antibodies are antibacterial?
IgG and IgA (with the assistance of lysozyme)
Which antibodies are agglutinators?
IgM is the best (then IgA, and a tiny bit IgG)
Which antibodies are best at fixing complement?
IgM
Which antibodies can degranulate mast cells?
IgE
What is agglutination?
Organized clumping of antigen
What test uses hemoagglutination to do blood typing tests?
Coomb’s test where there is agglutination of anti-RBC coated RBCs
IgM coated antigens can readily be __________________ by phagocytes if they are coated with __________________.
opsonized; complement C3b
What are the three major reasons why IgG are the best at neutralizing toxins and small pathogens like viruses?
- high affinity
- high serum levels (and high tissue levels)
- long half life
What is the main strategy of IgG to keep viruses from infecting cells?
block their cell attachment site
Once a target is coated with _________ or _________ macrophages can readily engulf the “opsonized target” because they have _____ and _____ receptors.
IgG or C3b because they have Fc and complement (CR1) receptors
The complement receptor on the macrophage is _______ whereas the complement receptor on the B-cell is __________.
CR1; CR2 (CD21)
What is ADCC?
What antibody is best at inducing it? Why?
antibody-dependent cell mediated cytotoxicity.
IgG is best at inducing it because it can bind to FcR.
What four cell types have FcR that can engage IgG-target complexes?
Which 2 release perforins?
Which 2 release TNF?
- macrophages- TNF
- basophils
- NK cells- perforin
- eosinophils- perforin
Monoclonal Abs are being used in clinic to target and destroy tumor cells in the body. They do so via_____________________.
Antigen-dependent cell-mediated cytotoxicity
By what age do IgG and IgA become dominant over IgM?
4 years of age
Maternal ______ crosses the placenta but the serum levels in the baby drop by __________.
IgG; 6 months
The first Ig the baby will make is ______ which plateaus at________ years of age.
IgM, 1-2 years old
Which cell produces IgA heavy and light chains?
Which cell produces J-chains?
Which cell produces Poly-IgR?
Plasma cells produces IgA heavy and light chains and the Jchain
Epithelial cells produce the Poly-IgR chain
What feature of IgA increases its avidity?
its dimerization
What is the major role of IgA?
to neutralize toxins (can’t bind complement or do ADCC)
What is the most common immunodeficiency disease (freq 1:500)?
Selective IgA deficiency- GI, respiratory, ear infections (because IgA is the antibody in secretions
What is passive immunization?
Xenogenic anti-pathogen or anti-toxin is transferred from 1 species to another (ex. horse or sheep anti-venom)
What is the only real use for passive immunization anymore?
anti-venom to snake or spider bites (infect horse or sheep with venom, collect their antibodies and inject into the human)
What are three advantages of passive immunization?
What is the major disadvantage?
Advantages: 1. pre-made and fast 2. inexpensive 3. usually pretty effective Disadvantage: It can lead to serum sickness because the immune system will make antibodies to the horse antibodies
What type of hypersensitivity is frequently caused by passive immunization?
Type III- immune complex hypersensitivity because the immune system makes antibodies to the immunizations antibodies –> serum sickness
What is given as a plasma protein replacement therapy for immunodeficient patients?
Polyclonal IVIG (usually for IgG)
What if IVIG used for?
What type of immunity does it confer?
it is given to maintain adequate antibody levels to prevent infection.
It confers passive immunity and is transferred human to human so there is less chance of serum sickness
How frequently does treatment of IVIG need to be given? Why?
every 3-4 weeks because the half-life of IgG is 23 days.
What diseases are treated by IVIG?
- Immunodificiencies
- pediatric HIV
- lymphoprolifative disease
- Kawasaki’s diseas
- Guillian-Barre
Why can IVIG be used to treat autoimmune disorders?
IgG is used to overload the immune system because it used FcRN to keep serum levels equal. By adding IgG, more of the “bad” antibodies (autoreactive) will be gotten rid of and the “good” will be recycled
What are four way by which IVIG may work?
- binding inhibitory Fc regions
- binding FcR on macrophages to recycle to pathogentic Ab can bind
- Complement consumption
- engagement of anti-idiotypic networks
What are monoclonal antibodies and how can they be produced?
They are antibodies specific for one antigen. They can be produced by:
- by immortalized plasma cells in the bone marrow
- recombinant engineering
Why may monoclonal antibodies be more safe than IGIV passive therapy?
IVIG uses Ab from a donor, whereas the Ab of monoclonal therapy are genetically engineered in a lab. There is less likelihood of transferring donor infections
What is the difference between a chimeric Ab and humanized Ab when engineering Ab via monoclonal Ab therapy?
Chimeric- The Fab fragments belong to mice but the Fc belongs to humans to reduce chance of serum sickness
Humanized- HV regions are mice, the rest of the Ab is human
