10 - Lymphoid Cells: Adaptive Immunity Flashcards
What are lymphoid cells categorised as?
- Lymphoid cells all originally categorized as adaptive, except for NK cell
- Changed with recent (ca. 6-7 years) characterization into innate lymphoid cells and lymphocytes
Morphology of lymphocytes
- Morphologically indistinct, characterized by cell surface markers
- Responsible for specificity and memory
B cells and T cells
B CELLS:
- Primarily responsible for antibody mediated immunity, T cell dependent
T CELLS:
- Main divisions: Helper (Th) and Cytotoxic (Tc)
CD molecules
CD molecules: markers on cell surface, recognized by specific sets of monoclonal antibodies, used to identify cell type, stage of differentiation and cell activity
- E.g.: CD40: signals B cell activation, CD4; specific to Th cells, binding to MHC Class II. CD8; marker for Tc cells
B cell development
- lymphoid stem cell - bone marrow
- pre B cell - gene rearrangement, heavy chain V-J-D
- pre B cell - gene rearrangement, light chain V-J
- immature B cell
- apoptosis (END) or IgM or IgD
B cell receptor
B cell receptor: antibody (IgM and IgD), Igα and Igβ polypeptides, involved in assembly of complex with membrane
Antibody structure
- Heavy (H) chains: μ, γ, α, δ, ε, defines class of Ab
- Light (L) chains: κ, λ
- Each chain comprised by immunoglobulin (Ig) domains
- Heavy: 4 Ig domains; Light: 2
- Ig domain: distinct sequence, ca 110 a-a long
- Each Ab - only one L or H type
- Fab: antigen-binding fragment
- Fc: crystallizable fragment; Mediates effector functions e.g. receptor binding
Pentameric IgM
IgM: 1st Ab produced by B cell, and expressed on its surface.
- Also present as soluble molecule in blood
Dimeric IgA
- Main Ig in saliva, milk, respiratory/GI/genito-urinary secretions
- Synthesized by submuscosal plasma cells, crosses epithelial layer
- Monomeric: IgA1, dimeric, IgA2
IgG
IgG: major Ig in serum (70-75%)
- Single, 4-chain molecule
- Maternal IgG provides immunity in human neonates
- Heavy chain: γ
- 4 subclasses (IgG1 - 4) based on a-a sequence
IgD & IgE: monomeric forms
Generation of diversity
- DNA encoding the variable H & L chains of antibody are composed of segments, namely variable, joining and diversity (V, J, D)
- From germline ‘database’ random combinations of V, J, D segments form the DNA of each cell
- There is then random recombination and gene shuffling within each cell by recombination activating gene (RAG) enzymes
- This creates lymphocytes able to express a very diverse array of genes able to encode ‘receptors’
- These undergo random somatic mutation to further increase the
diversity of potential proteins that these cells express - Overall, this creates massive receptor diversity (1014 +) on lots of
effector cells
What can B cells modify
- During the course of an infection, B cells can further modify antibody specificity
- Activation-induced cytidine deaminase (AID) makes random mutations
in the antibody variable region genes
Antibody functions
- Recognize and bind foreign material (antigen)
- Binding of antibody-coated foreign material to effector molecules to trigger elimination mechanisms:
including complement activation, phagocytosis,
antibody-dependent cellular cytotoxicity
Monoclonal antibody (MAb) production
- [immunisatio with antigen: e.g., protein, pathogen etc., mouse produces Ab to antigen, Ab producing cells isolation] OR [tumour cells (myelomas) grown in culture]
- Ab forming cells fused with myeloma cells to form hydribomas = hybridoma combines myeloma immortality with specific Ab-producing property
- hydridomas screened for Ab production
- useful hybridomas cloned
- continuous supply of identical Ab
How is Ab diversity generated?
Ab diversity generated by gene rearrangement of heavy and light chains, as well as somatic diversification, directed by enzyme AID
How many Ab classes
Five Ab classes: M, G, A, D & E. Class switching inhibited or induced by
cytokines
Ab production
- Ab production varies by time, location, quantities in serum and function
- Ab production can be manipulated for production of monoclonal antibodies
