Hematopoetic Stem Cells Rare: 1 in 10-50,000 cells in marrow; 1 in 100,000 in blood Relatively-rich in umbilical cord blood. Useful for stem cell transplants Join the National Marrow Donor registry!!

How are HSCs identified? Functionally Colony formation assays Restoration of immune system Specific antigens on cell surface. Negative selection Positive selection

Panning negative selection Lineage specific marker negative cells

C-Kit = CD 117

Aging marrow repleaced with fat (10% per year)

Eosinophils attacking a schistosome larva in the presence of serum from an infected patient.

(blood)

(tissue)

Common lymphocyte progenitor

CD markers identified by 2 or more monoclonal antibodies (clusters of differentiation) Appendix 1.

PART 2

Flow Cytometry and Fluorescence Activated Cell Sorting (FACS)

CD14 LPS receptor CD1a Lipid presentation to T cells

Primary Lymphoid Organs fetal yolk sac fetal liver and spleen bone marrow thymus Secondary Lymphoid Organs lymph nodes spleen Peyer’s patches (M.A.L.T.)

CD4 CD8

nu/nu +/+ or +/nu

antibody formation that requires CD4+ helper T cellsCD4helper T cells cell-mediated immune responses, which require CD4+ and/or CD8+ T cells cell-mediated immune responses delayed-type hypersensitivity responses (require CD4+ T cells)hypersensitivity killing of virus-infected or malignant cells (requires CD8+ cytotoxic T cells)malignantCD8cytotoxic T cells graft rejection (requires both CD4+ and CD8+ T cells) graft rejection and are furlesss Spontaneous deletion of FOXN1 gene (forkhead box protein N1) transcription factor Wikipedia hyperlinks Phenotype: nude mice are deficient in

Secondary Lymphoid Organs Deployed in strategic locations to encounter infectious agents Location of adaptive immune response Clonal selection and expansion Differentiation into effector cells

Photomicrograph of Lymphatic vessel with valve 100x. Note the one way valve center of slide within the lymph vessel. Keeps flow of lymph going in one direction. There is a blood vessel running parallel to the lymph vessel.

Soluble, particulate or processed antigen enters pass through HEV

periarterial lymphatic sheaths

Something happens

Downstream effects 1. Conformational change in receptor 2. Tyrosine kinase activation 3. Assembly of adaptor scaffold 4. Enzyme activation 5. Production of second messengers 6. Activation of transcription factor

“Cyclosporin binds to the cytosolic protein cyclophilin (immunophilin) of lymphocytes, especially T cells. This complex of cyclosporin and cyclophilin inhibits calcineurin, which, under normal circumstances, is responsible for activating the transcription of interleukin 2. In T-cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to activate calcineurin. Calcineurin then dephosphorylates the transcription factor nuclear factor of activated T-cells (NFATc), which moves to the nucleus of the T-cell and increases the activity of genes coding for IL-2 and related cytokines. Cyclosporin prevents the dephosphorylation of NFAT by binding to cyclophilin”.cyclophilinlymphocytesT cellscyclophilin calcineurininterleukin 2calmodulinNFATc Approved Use RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% helps increase your eyes’ natural ability to produce tears, which may be reduced by inflammation due to Chronic Dry Eye.

metalloproteinases