Term
| What are five functions of antibodies (immunoglobulins)? |
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Definition
1) Opsonization (bind to foreign molecules and encourage phagocytes to eat it)
2) Activation of complement system
3) Antibody-dependent cell-mediated cytotoxicity or ADCC (bind to cell and mediate its death)
4) Cross through epithelium or placenta
5) Activation of mast cells, eosinophils and basophiles by IgE |
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Term
| Each individual may possess how many structurally different antibody molecules? |
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Definition
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Term
| In terms of antibodies, what is the complementary defining region (CDR)? |
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Definition
| A hypervariable region on both heavy and light chains. There are three CDRs on each chain, each ~ 10 amino acids long. |
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Term
| In general, what does the Fc portion of secreted antibodies bind to? |
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Definition
1) cell surface Fc receptors
2) complement molecules |
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Term
| What is the difference between a secreted and a membrane-bound forms of antibody molecules (if they were both from the same B cell) |
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Definition
On the heavy chain carboxyl terminus:
- Membrane-bound: has transmembrane helix, present only on unstimulated B cell
- Secreted: hydrophilic sequence |
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Term
| What is the structure of the constant and variable domains of immunoglobulins? |
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Definition
Both have: two antiparallel beta sheets held together by disulfide bond.
They also have variable loops between the beta sheets which point out into the solution and contain CDR (where the antigen binds). |
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Term
| Where is "the hinge" and what is its purpose? |
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Definition
Location: between first and second constant domains of heavy chains
Purpose: provides flexibility to bind two antigenic determinants that are separated by varying distances
NOTE: proteases also target this hinge region. Therefore, a longer hinge = more flexibility, but also more likely to be targeted by proteases. |
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Term
| How many variable and constant regions are in heavy and light chains on an IgG antibody? |
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Definition
Heavy: 1 Variable + 3 Constant
Light: 1 Variable + 1 Constant |
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Term
| What is so important about the second constant region of an IgG heavy chain? |
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Definition
1) Site of carbohydrate attachment
- aids in solubility and protects it from proteases
2) Region of interaction with Fc receptors and complement components |
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Term
| True or False: The IgA is secreted submucosal plasma cells, traverse the epithelium and is secreted as the same structure into the lumen. |
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Definition
False.
Dimeric IgA2 mjust bing to polyIg receptors to traverse epithelial cells. These receptors get cleaved and a secretory component remains with the IgA2 molecule. |
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Term
| What are some unique characteristics of IgM structure? |
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Definition
1) consists of mu heavy chains
- 1 Variable + 4 constant regions
- Glycosylated
- cysteine-rich tail piece (involved in pentamer formation)
2) cystein-rich J (joining) peptide - helps pentamer formation |
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Term
| According to the lecture, what would be a normal serum level of IgM? What would be considered immunodeficiency? Immune response? Cancer/Myeloma? |
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Definition
Normal: ~1.25 mg/mL
Immunodeficiency or monoclonal gammopathy of Ig A or IgG: <~0.4 mg/mL
Infection, polycythemia vera, heroin addiction/infection, Waldenstrom's macroglobulinemia, etc: >~3mg/mL
Myeloma, Monoclonal gammopathy: >~10 mg/mL
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Term
| What is Berger's Disease? |
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Definition
IgA nephropathy --> high circulating levels of IgA complexes deposit in mesangial region of kidney, activate complement. Eventually leads to renal failure. (50% of transplant pts) |
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Term
| Which antibody can cross the placenta and protect the fetus? |
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Definition
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Term
| According to the lecture, what would be a normal serum level of IgA? What would be considered immunodeficiency? Immune response? Cancer/Myeloma? |
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Definition
Normal: ~2.1 mg/mL
Immunodeficiency or monoclonal gammopathy of Ig G or IgM: <~0.4 mg/ml
Infection, Liver dz, IgA neuropathy or Berger's dz, etc: >~4.5 mg/mL
Myeloma, Monoclonal gammopathy: >~10 mg/mL |
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Term
| Which immunoglobulin is rarest? And where is it usually seen? |
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Definition
IgD. Seen on at various stages of B lymphocyte development.
NOTE: associated with chornic idiopathic thrombocytopenia. |
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Term
| What percentage of total circulating immunoglobulin does IgG comprise? |
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Definition
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Term
| In addition to hypersensitivity reactions, what else is IgE good for? |
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Definition
| IgE is primary antiparasitic antibody- sensitizes worms and other parasites for destruction by eosinophils (IL-5) |
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Term
| What is the difference between IgA1 and IgA2? Which one is found in mucosal secretions? Which is glycosylated? Which has a J chain? |
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Definition
IgA1 - Circulating monomer
IgA2 - Secreted
Glycoslyated - both
J-chain - IgA2 |
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Term
| What immunoglobulin contains 5 domains on its heavy chain and is monomeric? |
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Definition
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Term
| True or False: IgG is the principal antibody mediator of a primary immune response. |
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Definition
| False. IgG is the principal mediator of a secondary response. |
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Term
| What is the normal serum level for IgE? What does decreased and increased IgE levels mean? |
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Definition
Normal - 0.0003 mg/mL
Decreased - immunodeficiency, hypo/agammaglobulinemia
Increased - allergic disorders, hypersensitivity disorders, parasitic infections, immunologic disorders, infectious mononucleosis, IgE myeloma |
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Term
| What are the main differences between the subclasses of IgG? Rank them in order of their concentration in the serum. |
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Definition
Differences:
- Size of hinge region
- Number and postion of disulfide bonds
- 90-95% homologous in DNA sequences
Serum Concentration
IgG1 > IgG2 > IgG3 > IgG4 |
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Term
| True or False: IgM is the principal antibody mediator of a primary immune response. |
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Definition
| True. IgMs are good at agglutinating antigens (increases antigen visibility) and fixing complement. |
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Term
| What percentage of total circulating immunoglobulin does IgM comprise? |
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Definition
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Term
| According to the lecture, what would be a normal serum level of IgG? What would be considered immunodeficiency? Immune response? Cancer/Myeloma? |
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Definition
Normal: ~12 mg/mL
Immunodeficiency or monoclonal gammopathy of Ig A or IgM: <~0.6
Infection, Liver dz, autoimmune dz, cystic fibrosis, etc: ~17
Myeloma, Monoclonal gammopathy: >~50 |
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Term
| Which is takes more effort - immunogenicity or antigenicity? |
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Definition
Immunogenicity - ability to evoke immune response
Antigenicity - ability to bind antibody (small molecules can bind antibody, but not activate B cells) |
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Term
| What factors contribute to immunogenicity? |
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Definition
1) Foreigness
2) Molecular size - usually >6000 Da
- small molecule/hapten + large carrier can make it immunogenic
- Chemical complexity (2-3 units)
- Easily degraded (by APCs)
Other factors
- method of antigen administration
- Genetic constitution of immunized animal
- Amount of antigen
- Presence of adjuvant (irritant/stimulant) to promote response |
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Term
| True or false. Proteins, nucleic acids and lipids are immunogenic antigens. |
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Definition
False.
While carbohydrates and proteins are immunogenic, nucleic acids, metal ions, and small organic compounds are only immunogenic as haptens. Lipids are not immunogenic. |
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Term
| What are some examples of cross-reactivity causing diseases? Name the antigen and the self |
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Definition
Chlamydia - myocarditis (cardiac muscle)
Hepatitis B - Multiple Sclerosis (myelin)
Herpesvirus - Myasthenia gravis (nAChR)
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