Development of Cells in the Adaptive Immune Response Flashcards
B-2 Cells
Develop after birth
Do not express CD5 glycoprotein
Replaced from bone marrow
Primary location is lymphoid organs
Produces only highly specific antibodies
Naive Cell Populations and their genotype
gamma delta T cells: CD3+gammadelta TCR+CD4-CD8- T cells
Helper T Cells: CD3+alphabeta TCR+CD4+CD8- T cells
Cytotoxic T Cells: CD3+alphabeta TCR+CD4-CD8+ T cells
What happens in Positive Selection?
- The Double positive cells bind to MHC I or MHC II on epithelial cells. Successful binding renders the cell MHC-restricted to self
- Binding to either MHC I or MHC II causes the other MHC molecule (CD4 OR CD8) to be eleminated and cells become single positive
- Self MHC-restricted cells move on to the medulla
T- Cell Maturation (Phase 1)
- T Cell precursors from the bone marrow enter the thymus
- T Cell lacks TCRs, CD3, CD4, CD8 surface and express early developmental antigens
- Beta chain rearranged by DN3 and pre-TCR expressed
- DN4 caused alpha chain rearrangement, with allows expression of a Double Positive aB TCR
MHC II pathway
- The antigen enters the macrophage
- It is ingested by lysosomes and then spit out
- Antigen then binds to the MHCII molecule
- The MHCII molecules goes to the surface of the cell, wheere it binds to the T- cell receptor of the Helper T cell
What components make up the surrogate light chain?
VpreB and gamma5
DN2 (Genotype, Location, Description)
Genotype: c-kit (CD117)++, CD44+, CD25+
Location: Subcapsular Cortex
Description: TCR gamma, delta, and Beta chain rearrangment; T- cell lineage commitment
Failure of light chain to rearrange leads to _________ or ____________
Apoptosis; light chain editing
Signals sent once Pre-TCR is formed by Beta chain rearrangement
Cell becomes permissive for TCR alpha-chain locus arrangement
Stimulates expression of CD4 and CD8 coreceptors
Stimulates proliferation
Stops additional TCR Beta-chain locus rearrangement
Other cells arising from Double Positive thymocytes
Natural Killer T cells- Innate Immunity, expresses TCR with invariant alpha chain. Binds to CD1, not classical MHC
Tregs- CD4 CD25
IELs (intraepithelial)- innate immunity, CD8, mucousal surfaces
TH17- Inflammation; protects againts fungal and bacterial infections
DiGeorge Syndrome results from delection in chromosome __________
22
Bruton’s Hypogammaglobulinemia
X-linked agammaglobulinemia (XLA)
Extremely low IgG levels and absence of other Ig classes
Babies are born with very few peripheral B cells and suffer recurrent bacterial infections
Defect in Bruton’s Tyrosine Kinase which is required for signal transduction through the pre-B/ B cells receptor; without functional Btk in developing B cells, cell development is arrested at pre-B stage
Heavy chain rearranged but light chains reamin in germline configuration
Disease manageable with antibiotics and passively administerd antibodies
What are the 10 Warning Signes of Primary Immunodeficiency
- Four or more new ear infections within 1 year
- Two or more serious sinus infections within 1 year
- Two or more months on antibiotics with little effect
- Two or more pneumonias within 1 year
- Failure of an infant to gain weight or grow normally
- Recurrent, deep skin or organ absesses
- Persistent thrush in mouth or fungal infection or skin
- Need for intravenous anitbiotics to clear infection
- Two or more deep-seated infections including septicemia
- A family history of Primary Immunodeficiency
The CD3 complex is composed of 4 distinct chains: __________,_________,____________, and ________
2 Episilon, delta, gamma,
Hyper IgE Syndrome (Job’s Syndrome)
Autosomal dominant mutation in the STAT3 gene
STAT3 gene is involved in intracellular signaling induced by IL-6 and TGF-Beta
Important in TH17 cell differentation
TH17 protects against fungal and bacterial infections; role in inflammation
Characterized by: Skin abscesses, recurrent pneumonia, eczema, elevated IgE, facial abnormalities, and bone fragility
What are the subsets of B cells?
B-1 cells (minor subset)
B-2 Cells (major subset)
Marginal Zone B cells
Which cells rearrange the Beta chain gene?
DN3
Functions of gamma- delta T cell
Lysis of infected or stressed cells
Cytokine and chemokine production
B cell help and IgE production
Priming of alphaBeta T cells via antigen presentation
Dendritc cell maturation
Regulation of stromal cell function via growth factor production
In the ________ stage, Double positive cells express a mature _______________
DN4; alphaBeta TCR
What happens in negative selection?
- Cells again bind to self MHC
- Medullary epithelial cells express AIRE transcription factor which facilitates the expression of tissue specific proteins to which thymocytes bind
- If those cells binds to avidly to MHC, self-peptide will undergo apoptosis and die
Checkpoints for B -Cell Receptor Development
- The early pro-B Cell commitss to the B-cell lineage
- Heavy chain rearrangement: Generates heavy chain gene diversity in pro- B cell population
- First checkpoint: Selects for functional heavy chain
- Light chain gene rearrangement: Generates light chain gene diversity in pre- B cell population
- Second check point: Selects for functional light chains
- Immature B cell: Makes functional IgM
Stages of B cell Development
- Lymphoid stem cell
- Pro B cell
- Pre B cell
- immature B cell
- Naive B cell
- Mature B cell
Positive selection occurs in the ___________
Cortex
Which immunoglobulins are present of Mature B cells?
IgM and IgD
