Immunoglobulins Flashcards
What are immunoglobulins
Proteins that react to a specific antigen (that stimulated their production)
Part of the specific immune response
What produces immunoglobulin?
B cells that have differentiated into Ig producing plasma cells
Where are antibodies present?
Plasma/serum (20% of blood plasma protein)
Secretions (milk, saliva, tears, interstitial fluid)
On surface of cells (B cells, via receptors on NK cells, macropahges, phagocytic cells, granulocytes- basophil/eosinophil)
Describe immunoglobulin structure
2x heavy chains, 2x light chains
Light has 1 variable, 1 constant region
Heavy has 1 variable, 3-4 constant regions
2 types of light chains (lambda, kappa)
5 types of heavy chains (determines class of Ig)
2x identical Fab (antigen binding fragments)
1x Fc (crystallisible fragment)
Regions of hypervariability within the V regions account for the wide diversity of Ags that can be recognised by different Abs
Differences in C regions account for Ab “flexibility” and recognition by enzymes
Which immunoglobulins are expressed by Naive B cells as surface receptors?
IgM (as monomer)- lower affinity for Ag than as pentamer
IgD
IgM Features:
- heavy chain
- half life
- % of Ig in serum
- ? complement activation
- Interaction with cells
- ? transplacental transfer
- forms
- affinity for antigen
- role in immune system
IgM Features:
- heavy chain: Mu
- half life: 5-10 days (GMADE)
- % of Ig in serum: 10
- ? complement activation: ++++ classical pathyway
- Interaction with cells: phagocytes via C3b receptors, epithelial cells via polymeric Ig receptor
- ? transplacental transfer: No
- forms: monomeric surface of B cells, pentamers/hexamers increases affinity
- affinity for antigen: Monomeric IgM low affinity, Pentameric IgM high avidity
- role in the immune system: produced by primary immune response, fixes complement, defense against bacteria and viruses
IgD Features:
- heavy chain
- half life
- % of Ig in serum
- ? complement activation
- Interaction with cells
- ? transplacental transfer
- forms
- role in immune system
IgD Features:
- heavy chain: Delta
- half life: 2-8 days
- % of Ig in serum: 0.2
- ? complement activation: No
- Interaction with cells: T cells via lectin like IgD receptor
- ? transplacental transfer: No
- forms: Monomer only
- role in immune system: co-expressed on naive B cells with IgM, component of BcR
IgG Features:
- heavy chain
- half life
- % of Ig in serum
- ? complement activation
- Interaction with cells
- ? transplacental transfer
- forms
- role in immune system
- functional differences between the subclasses
IgG Features
- heavy chain: Gamma 1-4
- half life: Gamma 1, 2, 4 21-24 days, Gamma 3 7-8 days
- % of Ig in serum appprox 60% total (major Ig in serum)
- ? complement activation Gamma 1 +++, Gamma 2 +, Gamma 3 ++++, Gamma 4 No
- Interaction with cells: All via IgG receptors on macrophages and phagocytes (Fc gamma receptors). mostly IgG1 and IgG3
- ? transplacental transfer: YES (only 1)
- forms: Monomer
- role in immune system: predominant Ig in secondary immune response, defence against bacteria and viruses, responsible for opsonisation (enhance phagocytosis), activate complement,
- functioanl differences between the subclasses: complement activation IgG1, IgG3
antiprotein antibodies IgG1 and IgG3, antipolysaccharide antibodies IgG1 and IgG2
predominant against viruses IgG3
IgA Features:
- heavy chain
- half life
- % of Ig in serum
- ? complement activation
- Interaction with cells
- ? transplacental transfer
- forms
- role in immune system
IgA Features:
- heavy chain: Alpha 1 or Alpha 2
- half life: IgA1 5-7 days, IgA2 4-6 days
- % of Ig in serum: approx 15%
- ? complement activation: IgA1 by alternate/lectin pathway, IgA2 No
- Interaction with cells: Epithelial cells by pIgR, phagocytes by IgA receptor
- ? transplacental transfer: No
- forms: serum IgA as a monomer, Secretory IgA as a dimer
- role in immune system: major Ab in secretions (colostrum, saliva, tears) and at mucosal surfaces (intestinal, genital), IgA1 mostly serum, IgA2 mostly secreted
IgE Features:
- heavy chain
- half life
- % of Ig in serum
- ? complement activation
- Interaction with cells
- ? transplacental transfer
- forms
- role in immune system
IgE Features:
- heavy chain: Epsilon
- half life: 1-5 days
- % of Ig in serum: 0.004
- ? complement activation: No
- Interaction with cells: Via high affinity for IgE receptor (FcepsilonR) expressed by mast cells, basophils, eosinophils, langerhans cells, via low affinity IgE receptor on B cells and monocytes
- ? transplacental transfer: No
- forms: Monomer
- role in immune system: mediates immediate hypersensitivity (anaphylaxis) by degranulation/histamine release, predominant Ig mediating host defence against paracytic infections, elevated in allergy
Describe the pathogenic mechanism of IgE in allergy
Allergen detected by B cell
Presented (via MHCII) to Th2 cell which secretes IL-4
Development of Memory B cells and IgE secreting Plasma cells
Allergen specific IgE binds to Fc receptor on mast cell–>mast cell sensitised
Mast cell encounters allergen (via IgE on receptor) and degranulates
What is Ig class switching?
Process of a naive B cell (expressed surface IgD and IgM) altering the type of Ig that is expressed and secreted
Mediated by signals provided by T cells
Which cytokines specifically influence class switching (for each Ig class)?
IgG1, IgG3–> IL-10 and IL-21
IgG4, IgE–> IL-4, IL-13
IgA1, IgA2–> TGFbeta/IL-10
IgG2–> unknown
List the functions of immunoglobulins
1) B cell activation- expressed as surface receptor, activated by Ag, B cell then divides and differentiates into Ab secreting cell (with T cell help), Ab produced by the clone have the same specificity as the original
2) Ab dependent cell mediated toxicity- Ig binds to target pathogen, Cells with FcgammaR bind and lyse target coated in Ab, also results in release of cytokines to direct other leukocytes
3) Fab fragments bind to Ag, block site of toxin/pathogen assoc molecules
Fc region responsible for activating- inflamm/effector function of immune cells or complement (by acting as a receptor), traficking Ag to appropriate pathway, placental transfer
What is the pattern of immunoglobulin transplacental transfer, by gestational week?
Placental transfer selective for IgG
IgG1=IgG3>IgG4>IgG2
Occurs by receptor mediated active transport
Begins at 17 weeks
By 33 weeks foetal Ig= maternal Ig levels
By term foeal Ig>maternal Ig levels
