Lecture 9- antibodies and B cells Flashcards
how do B-cells develop in the bone marrow?
-multipotent progenitor cell
-common lymphoid progenitor
-early pro-B cell
-pre B cell
-immature B cell
what is an antibody?
-a blood protein produced in response to and counteracting a specific antigen.
-Present in serum and other body fluids.
-Anti-serum = serum containing Abs against more than one antigen.
what is an antigen?
-Any molecule that can be bound by an antibody.
-It can be foreign or self.
what are the biological effects of antibodies?
Protection from infectious disease
Neutralize bacterial toxins
Immobilization - flagellae of motile bacteria
Opsonization - phagocytosis via Fc receptors
Cytolysis - complement fixation
how are antibodies produced?
by B cells but not all B cells are the same
what is the Humoral immune response and Clonal Selection Theory?
To generate a heterogenous antibody response to defend the host from attack
what is Burnet’s Clonal Selection Theory?
-Each B-cell has different Antigen receptor (BCR).
-Antigen binds to the cognate BCR.
-Activation resulting in cell division
Activation resulting in cell division and differentiation
The plasma cells (antibody Factories) secrete Ab of the same specificity
Predictions:-
Each B-cell has BCR of only 1 specificity
Specificity of Ab = BCR
1 cell → 1 Ab
Ag binding –> clonal proliferation –> Ab secreting plasma cells
what is antibody structure?
the antigen binding area is the variable region and the effector function area is th constant region
what is the antigen binding site/
the area responsible for variability
what are complementarity determining regions (CDR)?
Kabat & Wu plot of amino acid variability along the length of Ig heavy & light chain variable regions, showing positions of complementarity determining regions (CDR). Amino acids at these positions are often in contact with antigen. The framework regions (FR) provide the supporting structure.
Heavy chains folding is approximately the same
how does the body generate such variability?
V (D) J recombination
what is the effector function site?
Responsible for specific activation of the immune system
what are Fc receptors?
Fc receptors (FcRs) are key immune regulatory receptors connecting the antibody mediated (humoral) immune response to cellular effector functions
Surface molecules expressed on different cell types and bind with Fragment Constant (Fc) region of immunoglobulin
FcRs are antibody class specific and isotype selective
Dysregulation of Fc receptors leads to several diseases
Fc = crystallizable fragment.
what are the classes of antibodies?
an important part of the humoral immune response and form an essential link between innate and adaptive immunity
what is the antibody response in an infection?
At different points of the immune response there are different classes antibodies being produced
All have the selected variable region but different Fc
This is called:
CLASS SWITCHING
how are antibody classes and their functions distinguished?
by the type of heavy chain they contain
what is an IgM?
- heavy chain constant region
-expressed on naive B cells
-Secreted as a pentameric molecule
-1st immune response
what is the J-train?
IgM & polymeric IgA have J-chains added
Required for polymerization
Can be removed (experimentally) post polymerization without disrupting structure
what are IgM functions?
Ag binding - toxin and virus neutralization
Agglutination
Fc complement activation
Fc phagocytosis / opsonization
does not cross placenta via FcRn
what is an IgD?
Membrane bound
Trace in serum
Long hinge region
What are IgD functions?
B Cell Receptor (BCR):
On the surface of mature, naive B cells as a B cell receptor.
initiates B cell activation when an antigen binds to it.
Antigen Recognition:
B cells recognize and bind to specific antigens.
triggers the B cells to proliferate and differentiate into plasma cells and memory B cells.
Regulation:
controls the activation threshold of B cells, ensuring that they are not activated inappropriately by self-antigens or weak antigens.
Immune Surveillance:
found in the upper respiratory tract and other mucosal surfaces, where they play a role in immune surveillance and protection against respiratory pathogens.
what are IgGs? and their functions
Human IgG1, 2, 3, 4
Mouse IgG1, 2a, 2b, 3
monomers
Hinge regions are flexible
Functions:
Ag binding - toxin and virus neutralisation
Agglutination
Fc complement activation
Fc phagocytosis / opsonization
cross placenta via FcRn
what are IgAs?
IgA1 & 2
monomers, dimers and tetramers
Serum mainly monomers, external secretions - dimers and tetramers
Heavy chain ε
what is IgA secretion?
Secretory piece (Sp) not produced by plasma cell
Added during secretion into exocrine fluid eg Saliva or bile “exocrine secretion”
polymeric IgA (IgA)2 or small amounts of (IgA)3 in extracellular fluids of Lamina propria in the gut
Epithelial cells in gut have S-piece precursor in abluminal membranes
Sp acts as membrane receptor of pIgA
pIgA internalized - transported to luminal side released following proteolytic cleavage of Sp into 2 fragments
what are IgAs functions?
Mucosal immunity: Protection at external surface
Oral transition to infant
Agglutination
what are IgEs?
Trace in serum
Increased in atopies
Extra C_4 domain
Heavy chain _
Th2 driven Ab response
what are IgEs functions?
interact with FcεR on mast cells
addition of Ag = allergic response
Expulsion of parasites at mucosal surface via inflammatory response - eosinophils
how are B cells generated?
-in bone marrow
-negative selection in bone marrow
-migration of b cells to peripheral lymphoid organs and activation
-antibody secretion and memory cells in bone marrow and lymphoid tissue
what are Naïve B cells in the periphery (spleen or lymph node) B cells in the spleen?
-antigen recognition induces expression of effect molecules by the T cell which activates the b cell
- b cell proliferation
- differentiation to resting memory cells and antibody secreting plasma cells
