B-Cell Development & Clinical Applications of ABs Flashcards
DNA mechanism that creates many billions of BCRs (B-cell receptors) and TCRs (T-cell receptors) using relatively few Ig and TCR genes
V(D)J Recombination
V(D)J Recombination is mediated by two proteins:
RAG-1 and RAG-2
RAG-1 and RAG-2 are expressed only in ______ and ______
RAG-1 and RAG-2 are expressed only in developing B-cells (Bone marrow) and developing T-cells (thymus)
Recombination of light chains has a variable ____ region, a ____ regions and a constant ____ region
Recombination of light chains has a V region, a J regions and a CK region
4 methods of generation Ab diversity
- Germline
- Combinatorial
- Junctional
- Somatic Hypermutation
Germline diversity
multiple inherited V, D and j
Combinatorial diversity
V+D+J and H+L
Junctional
Imprecise joining and Tdt
Somatic Hypermutation
Point mutations in Ab variable regions
Affinity
strength of binding between an antibody’s Ag-binding site and its epitope.
A complete deficiency of either RAG1 or RAG2 results the _______and a _______
A complete deficiency of either RAG1 or RAG2 results the absence of both B cells and T cells and a complete loss of adaptive immunit
Abs on Mature (naive) B cell
IgD and IgM
Switching from Naive B cell from IgM/IgD to one of the other antigens to form memory B cell or secreting plasma cell
Class switch recombination (CSR)
Class switch recombination (CSR) and Somatic Hypermutation (SHM) occurs during ______ in ______ (location)
Class switch recombination (CSR) and Somatic Hypermutation (SHM) occurs during clonal expansion (after Ab stimulation) in Germinal centers of secondary lymphoid organs
Stages of B-cell development
Stem cell->Pre-B cell->Imature B cell-> Mature B cell
Stages of B-cell development
Stem cell->Pre-B cell->Immature B cell-> Mature B cell (naive B cell)
What does mature B cell expresses that immature B cell doesn’t?
IgD
What happens to self-reactive Immature B-cells
Get deleted by negative selection to prevent autoimmunity
First antibody that appears in immune response
IgM
____ and ____ are found in the surface of B-lineage cells and have clinical relvance
CD19 and CD20
Type of immunity: Maternal IgG passed through placenta
Passive (natural)
Type of immunity: Maternal IgA passed in milk
Passive (natural)
Type of immunity: injection of pre-formed immune globulin
Passive (artificial)
Type of immunity: infection with pathogen
Active (natural)
Type of immunity: Immunization (vaccination
Active (Arficial)
Immunity due to transfer of pre-formed antibody
Passive immunity
Immunity due to response to antigen
Active immunity
Intravenous immunoglobulin (IVIG)
Provides passive humoral immunity for the treatment of:
- Primary humoral immunodeficiency diseases
- Children with HIV
Ig preparations with high titers for specific pathogens
Prepared using serum from donors who are immune to a particular pathogen.
Example: Rabies imune globulin (RIG)
Convalescent plasma in the prevention or treatment of COVID-19
Transfer of Ab serum from an immune patient to a non immune patient
IVIG, RIG, and Convalescent plasma are:
- Examples of PASSIVE IMMUNITY
2. Consist of POLYCLONAL ANTIBODIES
Polyclonal Abs
recognize multiple epitopes in antigen
Monoclonal Ab
Recognize only one epitope in antigen
By B-cells from mouse immunized with specific antibody, and and mouse myeloma cells (plasma cell tumor cells), you can get
______
By B-cells from mouse immunized with specific antibody, and and mouse myeloma cells (plasma cell tumor cells), you can get
“immortal” hybrid cells
Enzyme-linked Immunosorbent Assay (ELISA)
If an antibody specific for an antigen is labeled with an enzyme, you can measure the presence and amount of that antigen by interacting the enzyme-labeled Ab with the antigen. The more antigen there is, the more Ab will bind. You add a substrate that gives color, and the more color the enzyme/antigen binds, the more of it is present
Example of ELISA test and what it detects:
Home pregnancy test, and detects hCG
Mouse monoclonal antibodies (mAbs) are not useful for therapeutic use because______
Mouse monoclonal antibodies (mAbs) are not useful for therapeutic use because humans will produce human anti-mouse antibodies (HAMA).
Chimeric Ab
Antibody with human constant region and mice variable region
Humanized Ab
Only uses CDRs (complimentary-determining regions) from mice and rest from humans
Fully human antibody
Ab genetically engineered that had no mice parts
Engineered Ab with lowest potential for immunogenicity
Fully Human Ab
-ximab
chimeric Abs
-zumad
humanized Abs
-umab
fully human Abs
