Module 32 - Adaptive Immunity Flashcards
Define “naive” cells.
Lymphocytes are said to be in a quiescent state or “naive” when they have not been exposed to any antigen yet.
Lymphocytes develop in the __________ and enter the __________.
primary lymphoid organs, blood circulation
Compare between the maturation process of B and T lymphocytes.
Both cells develop from the common lymphoid progenitor (itself differentiate from hematopoietic stem cell) in the bone marrow. B cells finish maturing in the marrow before transferring into the peripheral lymphoid organs, while T cells require maturing in the thymus (as thymocytes).
The maturation process of lymphocytes mainly involve ____________ expression.
antigen receptor
How do naive lymphocytes encounter antigens?
The lymphatic system allows antigen at peripheral lymphatic sites (lymph nodes) to interact with the naive lymphocytes
Describe lymphocytes.
Lymphocytes are the effector cells of the adaptive immune system. They display highly diverse receptors for antigen. Each cell has multiple copies of a receptor for a single antigen only, and thus responds to only one antigen.
How are the diversity of the antigen receptors of the lymphocytes achieved?
Receptors are generated by random somatic gene rearrangements that occur during B and T cell differentiation in the primary lymphoid tissues.
Define antigens.
Antigens are molecules which are recognised by receptors on lymphocytes and elicit a specific immune response to that antigen It can be proteins, CHO’s, lipids, nucleic acids
Explain the concept of clonal selection and expansion.
Clonal selection refers to the process in which an antigen is recognised by a specific lymphocyte in the peripheral lymphoid organ.
Clonal expansion refers to that particular lymphocyte type to be activated, divide, and differentiate.
Define immune effector and memory cells.
Immune effector cells are cells from the human body that have differentiated into a form capable of modulating or effecting an immune response.
Memory cells are responsible for the specific and rapid response to the secondary exposure to a previous antigen.
Explain the mechanism of activation of B and T cells.
It occurs in the secondary lymphoid organs. B cells activated when free antigens drain via the lymphatics to the lymph nodes.
Antigen-presenting cells (dendritic cells and macrophages) which possessed internalised antigens, migrate from the tissue to the lymph node and display the degraded antigen to the T cells.
Describe B cells antigens.
They can be simple or complex in structure. The site where the antibody binds is called the epitope or determinant. B cell receptors bind to conformational shape, where more than one epitope can be recognised in any given antigen.
Note: Protein determinants can be linear or discontinuous
Mention the 2 forms of B cells antibodies (immunoglobulin).
- *i). Surface Ig (IgM)** - embedded in the B cell membrane - acts as the B cell antigen receptor
- *ii). Secreted Ig** - secreted by activated B cells (plasma cells) - only when antigen binds to IgM
Describe the chemical structure of antibodies.
It consists of two identical heavy chains and two identical light chains. They have 2 distinct regions, the constant region (Fc) which can take one of 5 forms (isotypes) and the variable region (Fab) can take one of an almost infinite variety of forms
Connect between antibody affinity and antigen binding.
Antibody affinity is a measure of the strength of the bond between an antibodies binding site (F’ab region) and an antigen. Usually, the higher the affinity, the better the outcome of antigen-antibody binding
Mention the 5 isotypes (or classes) of antibodies.
IgA, IgD, IgE, IgG, IgM
Describe the antibody function and abundance related to their types.
IgA: high concentrations in mucosal secretions (dimer)
- preventing pathogen binding to mucosal surfaces (F’ab)
IgG: high conc. in plasma and tissue fluids
- binding with FcγR on phagocytes (opsonisation) - complement cascade
- binding with FcγR on NK cells (cytotoxic - lysis)
- neutralizing toxin (F’ab)
- Transplacental immunity
IgM: secreted into plasma as a pentamer/membrane-bound
- inducing the classical complement cascade (F’c)
- neutralizing of toxins (F’ab)
IgE: low levels in plasma, tissue fluids (bound to mast cells)
- binding with FcεR on eosinophils and mast cells leads to degranulation (release of immune mediators)
- usually in response to multicellular parasites
Describe the concept of antibody isotype switching.
This only occurs after B cells have bound to antigens and IgM made, such as secondary exposures or after vaccination (involving irreversible DNA recombination events).
The process is determined by external signals (from T cells and pathogen) on which isotype is being produced.
Note: this may lead to an increase in the affinity of the newly-produced isotypes to the antigen.
Describe the mechanism of production of a diverse range of antibodies.
The immunoglobulin gene locus encodes for multiple genes for the variable and constant regions of both chains.
The variable region of the H chains is encoded by 3 separate segments (V, D, J), while for the L chain it is encoded by 2 segments (V, J). Each variable domain is a result of the recombination of the option from each segment.
Ig diversity comes partly from having:
- Multiple gene segments
- 2 light chain genes (κ and λ) to choose from, and
- Multiple VDJ (heavy) and VJ (light) genes
Describe the mechanism of immunoglobulin gene rearrangement.
It occurs during the development of B cells in the bone marrow. It is antigen-independent, with the heavy chain rearranging first before the light chain. It is then followed by rapid cell division.
The rearrangement process itself involves the joining of regions of DNA (separate segments of the variable region) through somatic recombination and RNA splicing (after transcription).
It is facilitated by recombinase enzymes - recombinase-activating genes (RAG’s), terminal deoxynucleotide transferase(TdT), and exonucleases and controlled by genes.
In mature B cells, ___ genes are turn off to prevent further recombination of the immunoglobuloin gene.
Rag
Describe the mechanism of isotype switching.
It involves DNA deletion by cutting and rejoining of the switch sequences (during the transcription/translation process). The VDJ (variable) gene is unchanged but switches to a new CH gene.
Describe the structure of T cell receptors.
It is a heterodimer made up of α and β chain (resembling the F’ab tegion of an antibody), with a transmembrane domain (membrane-bound)
It consists of a diverse variable domain and a constant domain for each chain.
Describe the mechanism of rearrangement of the T cell receptor gene.
Encoded by rearranging TCRα and TCRβ genes (similar to Ig):
- TCRα V, J and C region gene segments
- TCRβ V(20), D, J and C region gene segments
Only one TCR specificity per T cell (allelic exclusion). Rapid division accompanies rearrangement.
Mention a difference between PRRs and antigen receptors.
PRRs of the innate immune system are inherited, while antigen receptors of the adaptive immune system are entirely generated by random gene rearrangements and joinings.
T cell receptors can only recognise antigen derived from ______.
proteins
as only proteins can be degraded to peptide, which is the only molecule to be presented in the MHC.
Differ between MHC I and MHC II.
MHC I: expressed on all nucleated cells
MHC II: expressed on antigen-presenting cells (dendritic, macrophages, B cell)
Explain the concept of gene polymorphism in MHC.
There are hundreds of different MHC (HLA) alleles in the human population (gene polymorphism)
These alleles are not generated by gene rearrangements, as for TCR and BCR, but inherited. A particular allele can bind a restricted range of diverse peptides.
Explain the mechanism of antigen processing.
Antigen processing involves the intracellular proteolytic generation of MHC-binding peptides Protein antigens may be processed (degraded into peptides) either in endosomes or in the cytosol
- Cytosolic processing (endogenous antigens) results in “presentation” on Class I MHC molecules
- peptide antigen transported to ER from cytosol
- Endosomal processing (exogenous antigens) results in “presentation” on Class II MHC molecules
- the antigen in vesicle merges with vesicle containing the MHC II
Describe the two types of T lymphocytes.
CD4 and CD8 acts as __________ for MHC I and II respectively.
co-receptors
Mention what is required for the effective activation of naive T cells.
The antigen-presenting cell must:
- acquire and process antigen in compartments which gain access to MHC Class I and Class II pathways
- Interact with naïve T cells to induce effector T cells
- Locate appropriate T cells (in the secondary lymphoid tissue)
- Adhere to T cells
- Present MHC associated peptides to T cells (Signal 1)
- Provide “co-stimulation” (Signal 2) for T cell expansion
- Induce T cell differentiation (Signal 3)
APC is activated by binding to _______. When activated, APC migrates to local ________ to present the antigen to T cells.
PAMP, lymph nodes (secondary lymphatic organs)
