How are progenitor cells activated to early B-cell stage?
CAMs act as adhesion between progenitor and bone marrow cell.
What causes progenitor to enter early pro-B-cell stage?
VLA-4 on progenitor binding VCAM-1 on stromal bone marrow cell.
What converts Early Pro-B-cell to Late Pro-B-cell?
Binding of kit on Early pro-B-cell to SCF on stromal cell.
What is required for development from Late Pro-B-cell to Pre-B-cell?
IL-7 released from stromal cell binding to surface of pro-b-cell.
What is required for maturation from Pre-B-cell to Immature B-cell?
More IL-7 from the stromal cell binding the pre-B-cell.
What are stromal cells?
Non-lymphoid cells located in the bone marrow that provide a microenvironment for B-cell maturation.
What is the major secretion of stromal cells?
What is another term for immunoglobulin?
When does heavy-chain Dh to Jh gene rearrangement occur?
Early pro-B-cell stage
When does a Vh to DhJh rearrangement occur?
Late pro-B-cell stage
When is heavy-chain rearrangement completed?
At pre-B-cell stage.
When is u chain expressed?
At pre-B-cell stage
What does the u chain associate with?
A surrogate for the light chain of the Ig polypeptides.
What is the function of the surrogate light chain?
To signal the completion of the heavy chain, thus trapping the heavy chain in the ER, ending heavy chain rearrangement and initiating light chain rearrangement.
What is X-linked agammaglobulinemia?
Lack of B-cells and circulating antibodies due to B-cell being arrested at pre-B-cell stage.
When does light chain rearrangement occur?
In pre-B-cell stages.
What are the two light chain isotypes?
kappa and lambda
What do immature B-cells express on their surface?
How many chances does the heavy chain get for a V-DJ rearrangement?
How many chances does the light chain get for rearrangement?
4: two for lambda and two for kappa
What happens if either heavy chain or light chain rearrangement is unsuccessful?
What is Burkitt's Lymphoma?
Ig gene joins gene involved in cellular growth due to translocation.
How do immature B-cells become mature/naive B-cells?
Expression of IgD which causes them to be exported to lymphoid organs.
What percentage of B-cells make it to circulation?
~10% due to negative selection
What has recent research indicated regarding self recognizing light chains?
Some can be saved and rearranged into non-self reactive. Prevents apoptosis.
What is multiple myeloma?
Malignancy of plasma cells causing tumors in bone marrow. Excess production of light chains (Bence Jones proteins) which appear in urine.
What are Bence Jones Proteins?
Light chains seen in urine that indicate multiple myeloma
What is humoral immunity?
Host defense mediated by secretion of antibodies.
How does humoral defense prevent infection?
1. Ab neutralization of pathogens 2. Opsonization facilitating phagocytosis 3. Antibody-dependent cellular cytotoxicity (ADCC) 4. Complement activation
What is complement's roll in humoral immunity?
1. Lysis of microbes 2. Inflammation 3. Assisting phagocytosis
What determines an antibody's class?
The heavy chain
What are the five antibody classes?
IgG, IgA, IgM, IgD, IgE
Where does the proteolytic enzyme papain cleave an antibody?
Between Fab and Fc creating two Fab and one Fc.
How are B-cells activated?
By cross-linking of IgM's on surface with an antigen. Also requires signal from coreceptors or Helper T-cells. This causes ab release.
What are thymus-independent antigens?
Complex polysaccharides on bacterial cell surfaces that are so distinct from self cells that a Helper T-cell is not required for activation.
What are thymus-dependent antigens?
Antigens that are processed by APC and require a Helper T-cell initiation of B-cell.
What receptor is on a Helper T-cell?
What are thymus-dependent antigens presented on?
What type of B-cell does vaccination create?
Memory B-cell is the goal
What are the two types of neutralization?
Ab's bind a pathogen and can either block its ability to bind host cells or block uptake of pathogens which are harmful if internalized.
What does a phagosome recognize in opsonization?
The phagosome has receptors that recognize the Fc portion of ab's.
What is opsonization?
Ab's coat a pathogen and facilitate a recognition site for phagosomes to ingest the complex.
How does Antibody dependent cell-mediated cytotoxicity (ADCC) occur?
Antibodies bind and act as recognition site for NK cells which release cytotoxic chemicals to lyse the target cell.
What does the NK cell recognize in ADCC?
The Fc portion of the antibody complexed with a target cell.
How does complement bind a target cell?
Antigen-antibody complex is bound by C1s. C4 binds and cleaves and binds C4b to the surface. C2 also recognizes and cleaves. C2a binds C4b and C2b leaves. C3 comes, recognizes the C4b and C2a complex, cleaves. C3a leaves and C3b bind the surface alone.
How does C3 further activate the complement cascade?
C5 recognizes C3b, cleaves, and C5b binds. C5 is recognized by C6, C7, C8, and C9 which recruit multiple C9's to form pore. Pore induces cell lysis.
Which complement pieces lead to inflammation?
C3a and C5a
If C3b doesn't lead to complement cascade, what other function does it promote?
What is the membrane attack complex (MAC)?
C5b, C6, C7, and C8 which polymerizes C9 to create a pore causing lysis in target cell.
What complement actually forms the pore in complement mediated lysis?
Which is the first antibody produced in an immune response?
What structure does IgM usually form as a complex?
What is the second antibody produced in immune response?
What is the dominant antibody in blood that is able to cross placental barrier?
Which antibodies prevent septicemia by attack microbes that enter the blood?
IgG and IgM
What are the two forms IgA takes?
Monomer for tissue and fluid protection and dimer for epithelial surfaces.
Where is the IgA dimer located?
In epithelial cells and made in Mucosal-associated lymphoid tissue (MALT). They are secreted on one side of epithelial layer and migrate to the other side where antigens are.
What is the main function of IgE?
To assist in phagocytosis of pathogens by binding and having their Fc recognized by phagocytes so pathogen/antibody complex is ingested and destroyed.
What cells have Fc receptors for IgE?
Mast cells, basophils, and activated eosinophils.
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