Detail of Lymph Node:
-T cells can only leave lymph node when they have differentiated into effector cells and start to proliferate.
Details of Changes in Dendritic Cells During Journey:
-DCs are in peripheral tissues traveling to site of infection once pathogen is endocytosed.
-As DCs move into lymphatic circulation they bein combining phagosomes (containing peptide) with lysosomes (containing MHC II molecule with clip place holder).
-As DC moves into the lymph tissues it begins presenting MHC on its surface.
B Cells and Small Soluble Antigens:
-When a B cell antibody binds to its antigen it may also bind other proteins.
-These proteins are endocytosed and presented at high density on surface.
The 3 APC Signals:
1) CD4/CD8 which stabilizes interaction between MHC and TCR --> this is the specificity feature.
2) CD28/B7 interaction is the safety feature.
3) Various cytokines are released that induce activation, proliferation, and differentiation.
>IL-12 tends to promote Th1.
>IL-4 tends to promote Th2.
-Activated T cells produce IL-2 and its receptor.
-IL-2 stimulates proliferation and differentiation.
-Naive T cells have weaker affinity for IL-2 but activated T cells have strong affinity allowing it to expand and differentiate the activated T cell.
-A resting T cell expressed only a moderate affinity IL-2 receptor.
-When T cell is activated it expresses a high affinity IL-2 receptor which turns on IL-2 and IL-2R genes ultimately secreting IL-2.
-The binding back of IL-2 then signals T cell to expand and proliferate.
-This cytokine is a competitive inhibitor for CD28.
-It sends signals inside the T cell to downregulate the production of IL-2 and therefore downregulates activation.
-This prevents dangerous over activation of T cells.
Ways Cytotoxic T Cells Kill:
1) A naive cytotoxic T cell can be stimulated by a virus infected DC.
-The Tc cell then recognizes same antigen from DC
on an infected epithelial cell.
-The Tc cell is activated and kills epithelial cell by
injecting perforin into the cell which allows toxins
within its walls to cross the membrane into the
-The granzyme toxin then releases mitochondrial
DNase which breaks down the DNA within the cell
and triggers apoptosis.
2) Cytotoxic T cells can also secrete FasL which is a cytokine signal that will bind to Fas receptors on the target and signal apoptosis.
3) Cytotoxic T cells can also secrete IFN-y which is an antiviral cytokine.
Th1 Cells Activate Macros:
-When Th1 cell contacts an infected macro, the T cell is induced to secrete the macro-activating IFN-y and to express CD40.
-Together these newly synthesized Th1 proteins activate the macros.
-Macros can keep themselves activated by continually secreting TNF-a as well as upregulating the B7 and MHC II in the cell.
Th2 Cells Secrete:
-They secrete IL-4 which stimulates B ells to produce antibodies (IgG and IgE) and IL-4 stimulates IgA.
Th1 Cells Secrete:
-These cells have GM-CSF on their surface that causes bone marrow cells to differentiate to granulocytes and macros.
-They secrete IFN-y and TNF-a which activate macros.
-They help to recruit neutrophils to sites of infection early in the adaptive immune response.
-They also aim their responses mainly at extracellular pathogens and are said to be pro-flammatory.
-They secrete IL-17 which can make them pro or anti-inflammatory.
-They tend to suppress the adaptive immune response.
-They are important in preventing immune responses from becoming uncontrolled as well as preventing autoimmunity.
-They are said to be anti-inflammatory.
-They secrete TGF-b and IL-10 which suppresses macros.
-TGF-b also inhibits T and B cells from clonally expanding.
-Th1 Response: macros suppress bacteria.
-Th2 Response: unactivated macros done kill bacteria but protect them from antibodies.