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Immunology Ch 9 b objs
Terms in this set (18)
What guides T cell to find their target cells and to interact with them (9-20).
changes in adhesion molecules expressed on the endothelium of the local blood vessels as a result of infection and by local chemotactic factors
What is a SMAC and describe the events surrounding T cell polarization (9-21).
supramolecular activation complex, or immunological synapse. contains important signaling proteins for T cell activation.
3 steps: binding, polarization (reorientation of cortical actin cytoskeleton at contact site; reorientation of microtubule-organizing center and Golgi apparatus), and synthesis and release of molecules.
Broadly describe the 2 classes of effector molecules released from T cells and their target cells (9-22).
CD8 T cells- cytotoxins; any cell they contact
CD4 T cells- cytokines, membrane associated proteins; cells bearing MHC II and proper cytokine receptors
Know the main cytokines released by CD8 effector T Cells. What is its function? (9-23).
IFN gamma- block viral replication or lead to elimination of virus from infected cell without killing them. Increases MHC I molecules.
What cytokines have distant effects and what are the effects (9-23)?
IL3 and GM-CSF-- act on bone marrow cells to stimulate production of macrophages and granulocytes. stimulate production of dendritic cells.
IL5-- stimulates production of eosinophils
Understand the role of Fas ligand, TNF-alpha, LT-alpha and their receptors role in apoptosis (pg 372).
Fas ligand contains death domain and binding induces death by apoptosis.
TNFa and LTa can induce apoptosis by binding to TNFRI.
What is the importance of CD40 (pg. 372)?
activates B cells and macrophages.
Ligation of CD40 on B cells promotes growth and isotype switching
Ligation of macrophages induces them to secrete TNFa and become receptive to much lower concentrations of IFN gamma.
Deficiency linked to immunodeficiency.
Differentiate necrosis and apoptosis and understand why one in used by CTLs (9-25).
necrosis- cells disintegrate and degraded by phagocytic cells. chemically injured or oxygen deprived or complement lysed cells.
apoptosis- cell destroys itself from within.
CTLs use apoptosis because it is clean and confined and fast.
What are Fas and Fas ligand and their use (9-25)?
used mainly to regulate lymphocyte numbers. induces apoptosis by death signal. ALPS is mutations in genes coding Fas and Fas ligand.
Describe the content and functions of cytotoxic granules (9-26).
modified lysosomes that contain at least three distinct classes of cytotoxic effector proteins-- perforin, granzymes, granulysin.
perforin-- aids in delivering contents of granules into the cytoplasm of target cell.
granzymes-- serine proteases which activate apoptosis once in cytoplasm of target cell
granulysin-- has antimicrobial actions and can induce apoptosis
What happens inside the cell when granule content affects cells? What molecules are involved (9-26).
granzymes trigger apoptosis in target cell by activating caspases. Caspase cascade, CAS degrades DNA. Other pathway: BID cleaved mitochondrial intermembrane disrupted and leaks apoptotic molecules like cyt c.
Phagocytosis activated by changing cell membrane contents. PS replaces PC.
What cytokines are released by cytotoxic T cells and why (9-28).
-IFN gamma inhibits viral replication directly and induces the increased expression of MHC I. Increases chance that infected cells recognized as target cells. Also activates macrophages.
-TNFa and LTa can synergize with IFN gamma in macrophage activation and in killing thru TNFRI, which induces apoptosis.
What is a granuloma (pg. 380).
a central area of macrophages surrounded by activated lymphocytes.
serves to wall off pathogens that resist destruction. TH2 and TH1 cells participate in granulomas by regulating their activity and preventing widespread tissue damage.
What is macrophage activation and when/why does it happen (pg 377).
the boost to antimicrobial mechanisms of intracellular pathogens. This occurs because the intracellular pathogens grow in phagosomes of macrophages and are shielded from the effects of both antibodies and cytotoxic T cells.
What roles do various cells and molecules play in macrophage activation and maintenance (9-29).
TH1 cells synthesize membrane associated proteins and soluble cytokines which stimulates the macrophage and enables it to eliminate the pathogen. CD8 T cells too; produce IFN gamma and use MHC I. LPS can make macrophages IFNgamma sensitive
IFN gamma and CD40 to sensitize to IFN gamma--activates macrophage.
LTa, can substitute CD40 ligand, TNFalpha stimulates macrophages thru TNFR1 & maintains viability of macrophage.
What happens to activated macrophages and how are they regulated or shut down (9-30; 9-31).
activation converts the macrophage into a potent antimicrobial effector cell. Phagosomes fuse with lysosomes, microbicidal reactive oxygen and nitrogen species generated to increase intracellular killing. Also B7, CD40, MHC II and TNF R on surface increase making more effective at antigen presentation and more responsive to CD40 ligand and TNFa.
regulated because toxic to host cells especially with large extracellular pathogens. activation is inhibited by cytokines like TGF-B and IL10 (produced by TH2 cells and reg cells)
List and understand the functions of T helper 1 cells in responding to intracellular bacteria (9-31; fig 9.42).
1. IFN gamma and CD40 ligand-- activates macrophage to destroy engulfed bacteria
2. Fas ligand or LT-beta-- kills chronically infected cells, releasing bacteria to be destroyed by fresh macrophages
3. IL2- Induces T cell proliferation, increasing numbers of effector cells
4. IL3, GM-CSF-- induces macrophage diff in the bone marrow
5.TNF a and LTa-- activates endothelium to induce macrophage binding and exit from blood vessel at site of infection
6.CXCL2-- causes macrophages to accumulate at sites of infection
What macrophage cleared pathogens persist when Th-1 cells are deficient (9-31)?
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