Adaptive Antigen Recognition in the Immune System Flashcards
Describe the structure of a B-cell receptor.
Composed of a surface immunoglobulin and 2 invariant chains (IgAlpha and IgBeta)
IgAlpha and IgBeta function in signal transduction via the use of ITAMs they are attached to in the cytoplasmic side
ITAM=Immunoreceptor Tyrosine based Activation Motif
Describe the structure of a T-0cell receptor.
Alpha:Beta Heterodimer
Associated proteins form the CD3 complex, which is involved in signal transduction (CD3Zeta)
What is meant by the term Immune Repertoire?
One person makes more different forms of antibodies than all other proteins put together.
Gene rearrangement events occur in the absence of antigen explains what process?
Describe this process.
Clonal Selection
Lymphocyte forms clones with a diverse set of receptors
Clones of mature lymphocytes become specific for many antigens
Antigen-specific clones are “selected” by antigens (Note that this shows that the lymphocytes gain diversity and specificity before ever meeting the antigen)
Antigen-specific immune response occurs after clonal expansion
What are the 3 mechanisms by which lymphocytes gain receptor diversity? Describe each.
Combinatorial Diversity- Multiple germline genes. V-J or V-D-J somatic recombinations.
Junctional Diversity- Addition fo nucleotides during the process of D-J or V to DJ joining.
Somatic Hypermutation- point mutations occuring in fully assembled V-J and V-D-J regions during an immune response. Provides significant source of Ab diversity.
How are the mechanisms of diversity for B cells/antibodies IDENTICAL to T cell receptors?
Production of heavy chain B cells= production of beta chain T cell
Production of light chain B cell= production of alpha chain T cell
Somatic hypermutation does not occur in ______
TCRs
Describe the process of Combinatorial Diversity.
V(D)J Recombinase is responsible to recombining V, D, and J segments.
Recombination activating genes (RAG1 and RAG2), only made by lymphocytes, encode for these 2 necessary components of recombinase.
Describe the process of Junctional Diversity.
At the junction between D and J there is an insertion of Terminal Deoxyribonucleotidyl Transferase (TdT), which catalyzes the random polymerization of nucleotides into DNA.
P nucleotides are added to hairpins in a template manner
N nucleotides are added in a non-template manner
This leads to further diversity in the third hypervariable region (idiotype)
The diversity generated by junctional diversity occurs in the ______ region
Hypervariable region
For combinatorial diversity, what kind of cells make RAG1 and RAG2?
RAG- Recombination activating genes
Lymphocytes only
What cell surface marker is CD19 specific for?
B cells
What is the primary site of lymphocyte maturation?
Bone marrow
Thymus
Primary means antigen presentation does not occur here
What are the 3 secondary sites of lymphocyte maturation?
Lymph nodes
Spleen
Peyers patches in the intestines
What are signals from the pre-BCR responsible for?
Inhibit rearrangement of the Ig heavy chain on the other chromosome so an individual B cell can express one heavy chain that is encoded by only one of the two inherited alleles. This ensures that every B cell will express a single receptor, thus maintaining clonal specificity,
This is called Allelic Exclusion
_______ deletes or inactivates cells that display antigen receptors that are self-reactive
Selection
________ is acquired by immature B cells that do NOT become activated when challenged with self antigen.
Tolerance
What kind of cells can undergo receptor editing to fix tolerance?
B cells only
T cell DO NOT undergo receptor editing
What are are the 2 regions of the thymus?
Thymic cortex- outer cortical region
Medulla-inner cortical region
In humans, thymic activity peaks during _____ and declines thereafter
Puberty
This is why older people get sick more often
Where are thymocytes (immature T cells) found in the thymus?
Within the thymic stroma (outer cortex)
When T cells obtain the ability to be CD4+ and CD8+ (double positive) where are they found within the thymus?
Medulla
Describe the route of T cells within the body as they go from stem cells to mature T cells.
Stem cells within the bone marrow
Pro-T cells within the outer cortex of the thymus
Double Positive T cells within the medulla of the thymus
Mature Naive T cell in the periphery
What is the difference between positive selection and negative selection of double positive T cells?
Positive selection- Recognizes self MHC/HLA and is able to mature into either CD4+ or CD8+ T cells.
Negative Selection- T lymphocytes do not become activated by self antigen. Establishment of central tolerance. Failure of positive selection leads to apoptosis.
What is the function of Treg cells? How are they formed?
Function is to inhibit self-reactive helper 1 T cells in the periphery.
These are a small population of self-reactive CD4+ T cells that undergo differentiation to become Treg cells.
What 2 surface markers do Treg cells express?
CD4 and CD25** on the surface
What unique transcription factor do Treg cells express?
FoxP3
Does clonal selection depend on antigens?
NO, clonal selection is independent of antigen
For BCRs, describe the recombination process for both heavy and light chains.
Heavy (u) chain: D-J joining V-D-J joining Transcription Splicing of RNA to get Constant region next to VDJ
Light (kappa) chain:
V-J joining
Transcription
Splicing of RNA to get Constant region next to V(D)J
*Note that light chains do not have a diversity segment
For TCRs, describe the recombination process for both chains.
Beta chain: D-J joining V-D-J joining Transcription Splicing of RNA to get Constant region next to VDJ
Alpha chain:
V-J joining
Transcription
Splicing of RNA to get Constant region next to V(D)J
Compare BCR and TCR recombination.
Heavy chains from BCRs and Beta chains from TCRs have the same process
Light chains from BCRs and Alpha chains from TCRs have the same process
Which cell, B or T, can undergo receptor editing if negatively selected?
B cells only
This gives the B cell another chance to fix its response to the antigen before it is deleted/apopstosed
For B and T cells, which chains do not have Diversity segment?
B cells- Light Kappa or Lambda chains
T cells- alpha chains
For B cells and T cells, which chains HAVE the Diversity segment?
B cells- Heavy chain
T cells- Beta chains
