Adaptive Immune System Flashcards
Discuss recognition of antigens by immune system
PRRs- cell surface, cytoplasmic, secreted
MHC-cell surface
T cell receptor(TCR)- cell surface
Antibody (BCR)- cell surface, secreted
Where does B cell develop and what are it’s stages?
In the bone marrow
Stem cell —> Pro-B —> Pre-B —> Immature B —> Mature B
What are the types of B cells and their features?
B1 and B2
B1
- derives from fetal liver
- self renewing
- in peritoneal and pleural cavities
- T independent response
- low affinity for IgM
B2
- conventional B cells
- replenished from bone marrow
- present in secondary lymphoid tissues
- T dependent
- high affinity for IgG, IgA, IgE
At which stage of B cell maturation does VDJ recombination finish?
Pre-B
What does recombination allow B cells to do?
Create antigen receptors that can recognize each individual antigen in a specific way (only 1 antigen specificity expressed per B cell)
What is ITAM? What is it required for?
Immunoreceptor Tyrosine based Activation Motif
Required for B cell to send signal to nucleus that an antigen has been detected.
What is the variable region that is expressed as a protein after recombination contains CDR segments referred to as?
Hypervariable regions
What is an antibody?
Also known as immunoglobulin.
A fragment, antigen binding, Y shaped protein consisting of light and heavy chains that recognize antigens
What are two different forms of light chain immunoglobulins?
Kappa and lambda
What is the main difference between the gene segments of the immunoglobulin light chain and heavy chain?
The light chain gene segment does not have a diversity segment
Genetic recombination of the immunoglobulin heavy and light chains occur in a specific sequence? What is the sequence?
2 attempts at recombination of the heavy chain
2 attempts at recombination of the kappa light chain
2 attempts at recombination of the lambda light chain
If allelic exclusion were to malfunction during an immunoglobulin recombination, what may occur?
a B cell that expresses different light and heavy chains on it IgM and IgD
What causes the generation of antibody diversity? (Antigen independent)
- random recombinations of VJ and VDJ genes
- random addition of nucleotides to DNA during recombination by TdT
- random combination of heavy chains with light chains
What causes the generation of antibody diversity? (Antigen dependent)
- somatic hypermutation and affinity maturation (variable region)
- isotype switching (constant region)
How are heavy chain and light chain recombination mediated?
Recombinase enzymes RAG-1 and RAG-2 (recombination activating gene) that recognize recombination signal sequence (RSS) nucleotides flanking V, D and J gene segments
What are the types of T cells?
Th: helper T cell
Tc/CTL: cytotoxic T cell/cytotoxic T lymphocyte
Treg: naturally occurring regulatory T cell
Where do T cells develop?
They travel from the bone marrow as T cell precursor and enter and develop in the thymus and later enter the secondary lymphoid tissues
What occurs in the thymus?
Thymic education. T cells learn to recognize “self” and where any reactivity again self antigens are eliminated
Where do T cells pass through and what do they interact with?
Within the thymus:
The cortex: interact with thymic epithelial cells
The medulla: interact with dendritic cells and macrophages
What is positive selection and where does it occur?
T cells expressing TCRs (T cell Receptors) capable of binding self-MHC on cortical epithelial cells survive. Occurs in the thymic cortex
What is negative selection and where does it occur?
T cells expressing TCRs with high affinity for self undergo apoptosis or become Treg. Occurs in the medulla
What does the B cell costimulation complex consist of?
Leu13, CR2, CD19 with ITAM attached and CD81
Why is the co stimulatory complex needed?
Along with the transmembrane version of the antibody and the Ig-alpha and Ig-beta molecules are needed for B cell activation
What do CD4+ T cells recognize? What do CD8+ T cells recognize?
CD4+ T cells recognize MHC class 2 molecules
CD8+ T cells recognize MHC class 1 molecules
What are the two pathways a B cell could differentiate into?
Naive B cell —> Activated B cell —> proliferation —> 1 of 2 pathways
- Plasma cells —> antibody
Antibody secreting version of B cell - Memory B cell
Important in developing secondary immune response
What does clonal selection allow the immune system to do?
Recognize a wide variety of antigens and produce a tailored response to that antigen
What does the activation of Naive T cells require?
Dendritic cells are a requirement.
What occurs during T cell differentiation?
Naive T cell —> Activated T cell —> proliferation —> effector T cell or Memory T cell
Which molecules are unregulated on the surface of a dendritic cell to convert it from phagocytic to antigen presenting?
MHC Class 2, B7 (CD80, CD86)
How many signals does lymphocyte activation require?
2 signals.
Signal 1- from specific interaction of TCR with peptide-MHC complex on an APC
Signal 2- binding of costimulator receptor such as CD28with its ligand (CD80)