The Ontogeny of Immune Cells
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Pluripotent stem cell
IL-3 - Myeloid pathway - erythrocytes, platelets, granulocytes and monocytes
IL-7 - Lymphoid pathway - innate and adaptive lymphocytes
Recombinant drugs available for therapy:
GM-CSF- Sargraostim or Molgramostin
G-CSF- Filgrastim or Lenograstim
CELLS OF MYELOID ORIGIN IN BLOOD:
1) Neutrophil, PMN - Pink cyto. granule
1800-7800/muL - abscess formation
2)Eosinophil - 0-450 muL, allergic and anti-helminth responses- kill IgE by release of MBP -> type 1 HS
3) Basophil - Purple cytoplasmic granules- release vasoactive chemicals
4) Monocyte - CD4+, CD 14+, CD16+ - 0-900/muL
CD14 - endotoxin
CD16- Tail of antibody
IN THE TISSUES
Macrophage - CD4+, CD14+, CD16+
Dendritic cell - Antigen transport and presentation
Mast cell - All barrier tissues- same function in tissue locations
CELLS OF LYMPHOID ORIGIN IN THE BLOOD
Lymphocyte - 1000-4000/muL
- B cells - 10% - more common in secondary lymphoid organs i.e. lymph nodes and spleen
- Th cells (CD4+) - 50% "general"
- CTLs (CD8+)
- NK cells (CD16 & 56)
IN THE TISSUES
Plasma cells - Lymph noes, bone marroe, spleen, MALT - secretion of monoclonal antibody for 2 week life span.
THE DEVELOPMENT OF ADAPTIVE LYMPHOCYTE ANTIGEN RECEPTORS
COOH- terminus of the protein chain through the cell membrane to assist in signal transduction.
* Figure 3 - understand well*
Mu - IgM
Alpha - IgA
Epsilon - IgE
COMPARISON OF THE BCR AND TCR
BCR - 2 copies each - any chem. composition - Idiotypes > 1/ cell variable, valence 2 - Isotypes> 1 or 2/ cell - Hinge- CD19, 21- Yes, Serum antibody
TCR- 1 copy each - peptides presented in HLA (MHC)- Rigid - CD3- Never
THE DEVELOPMENT OF LYMPHOCYTE ANTIGEN RECEPTOR DIVERSITY
V (variable), D ( diversity), J (joining)
RAG ( recombinant activating)
Terminal deoxyribonucleotidyl transferase (Tdt)
Undergo apoptosis, randomly arranged (chromosome), heavy chain genes are all on one chromosome , light chain genes are on 2 separate chromosomes.
RAG gene- SCID
SELECTION OF RECEPTORS FOR CENTRAL TOLERANCE
1 and 5% of all T cell precursors will emerge from the process alive.
MHC or the HLA ( human leukocyte antigens)
Class I MHC - Gene products A,B,C- all nucleated cells - expressed codominantly - long Alpha chain plus beta-2 microglobulin - CD8
Class II MHC - DP, DQ, DR - antigen presenting cells, expressed codominantly- Alpha and beta chains- CD4
Time of adolescence....
DN cells, they do not express either CD4 or CD8
TCR by VDJ recombination; they become DP cells interact with cTEC which express both MHC1 and MHC2 molecules. If DP thymocytes are not signaled, will die in the cortex from lack of cytokine support.
As cloning cells are pushed towards the inner thymic cortex - SP - MHC1 ( retaining CD8) or MHC2 ( retaining CD4) - move to thymic medulla, medullary thymic epithelial - evaluate the strength of MHC/ TCR binding.
Expression of tissue- restricted antigens in the thymic medulla is controlled by transcriptional regulator AIRE and transcription factor Fezf2 - necessary for strong development of central immune tolerance.
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