Antibody, Lymphocytes and the generation of diversity Flashcards
What is SCID?
Also known as ‘bubble boy disease’, Severe Combined Immunodeficiency (SCID) is characterised by a complete lack of T lymphocytes and possible deficiencies in B cells and NK cells
Patients with SCID have a dysfuntional adaptive immune system and are highly vunerable to opportunistic and repeated infections.
Deficiency in RAG enzymes causes SCID
How does the adaptive immune system provide immunological memory and improved immune responses upon repeated exposure to the same antigen?
Diverse repertoire of TCRs and BCRs.
Production of memory B cells which produce the appropriate antibody upon exposure to the same antigen but faster and in more abundance than in the primary response.
B cells can undergo Somatic Hypermutation, which creates B cells with a BCR that has an increased affinity for the antigen.
How do T cells recognise a pathogen?
Helper T cell’s TCR recognises peptide fragments on MHC class II molecules expressed by APCs.
Cytotoxic T cell’s TCR recognises peptide fragments on MHC class I molecules expressed by host cells
How do B cells recognise pathogens?
The BCR is essentially a cell surface antibody, specific to an antigen.
The BCR therefore recognises whole antigen and upon activation, the B cells differentiate into plasma cells that secrete the receptor as antibody
What are the 4 functions of antibody?
Neutralisation - of toxins and viruses by binding to them and blocking their interaction with target cells
Opsonisation - Phagocyte FCRs can recognise Ab and bind to them
Complement Activation - Classical Pathway
Agglutination - of pathgen debris and viruses
What is the structure of an antibody?
The antibody molecule is a heterodimer with 2 copies of each Heavy chain and Light chain with disulphide bridges between the light and heavy variable regions and between the two constant chains.
Variable region with 2 binding sites - determines antigen specificity
Fc region - the constant region that determines the antibody’s isotype and therefore its function
What is the structure of the TCR?
The TCR is a heterodimer with one copy each of two different chains giving one binding site
Alpha-beta chain
Gamma-delta chain
True or False: BCR/IG and TCR undergo gene rearrangement?
True
This is how a diverse repertoire of highly specfic receptors is created.
Which type of lymphocyte can undergo Hypermutation and Class Switching?
B Lymphocytes
Describe the process of gene rearrangement in producing a great diversity of BCRs and TCRs.
Recombination Activating Genes - RAG1 and RAG2 combine different segments of genes.
There are 3 different segments:
48 V regions, 27 D regions and 6 J regions.
Each heavy chain utilses one of each type of region
(same for gamma-delta TCRs)
Each light chain utilises one V and one J region
(same for alpha-beta TCRs)
Diversity is further increased by the accidental removal of nucelotides at the end of each region and also by the random insertion of nucelotides between each region by the enzyme TdT.
What is Somatic Hypermutation?
It is the process that takes place in the germinal centres, within the follicles of secondary lymphoid tissues, by which activated B cells can further enhance the affinity of their BCR.
The Ig gene undergoes spontaneous mutation and the B cell which has the mutation that confers increased affinity for the antigen is postively selected by testing recognition of the original antigen by follicular Th cells and follicular dendritic cells.
How does class switching work?
Removal of the stop codons between the gene segments that precede the desired one.
Which immunoglobulin exists as a dimer?
IgA
What links immunoglobulins together in the case of IgA and IgM immunoglobulins?
J-chains
When is IgD expressed mostly?
On Naive B cells
