Cell Mediated Immunity Flashcards
What do CD4+ cells do?
Secrete cytokines to help other immune cells gain functional ability.
What do CD8+ cells do?
CTL. Kill infected cells, tumor cells, and sometimes even healthy cells in an autoimmune response.
How are naive T cells activated?
Activated by pAPC (macrophages, DC, active B cells). DCs activate naive T cells most efficiently due to their high levels of costimulators.
What are the functions of cell adhesion molecules in immunity? What is an example of a cell adhesion molecule?
They glue t-cells and APC’s together so that TCRs can sample everything sufficiently. CD58 (on APC) and CD2 (on T cell).
What molecules give T cells signal 2?
B7 (on APC) and CD28 (on T cell). Also, CD40 (on APC), and CD40L (on T cell).
CTLA4
Can also bind to B7 on APCs with a higher affinity than CD28. Provides a suppressive signal to ensure proper T cell regulation. Gets upregulated when B7 binds to CD28.
Where does T Cell activation occur?
Lymphoid organs, then they migrate to the site of infection.
What happens if a T cell receives signal 1, but not signal 2?
Anergy, a state of partial paralysis, occurs.
CD40 and CD40L
Costimulatory molecules that activate APC’s to continue activating T Cells (through cytokine release, upregulation of B7, etc.)
What is signal 3?
Cytokines secreted following the delivery of signals 1 and 2 that determine the effector response.
Why are DC’s such powerful APCs?
Because they have a lot of costimulatory molecules.
TCR structure
Alpha and Beta chains, which, when bound, induce activation of the CD3 complex, a series of proteins that propagates the activation signals. CD3 complex also serves as a marker of mature T cells.
Marker of mature T cells?
CD3 complex
How do CD4 and CD8 participate in T Cell activation?
They stabilize the binding of the MHC to the TCR, and can stimulate ITAM phosphorylation which upregulates effector genes.
What happens when a CD4 cell is activated by signals 1 and 2?
It creates Th Cell that upregulates IL2R and releases IL-2, which causes clonal expansion of both CD4 and CD8 cells.
Th1 Cells
Secrete IL-2 and IFN-Gamma after signals 1 and 2 (MHC and CD40), promoting macrophage activation, T cell proliferation, antibody production.
IL-2
Induces T-cell proliferation. Released from Th1 cells.
IFN Gamma
Released from Th1 cells. Activates pAPCs by increasing expression of MHC and B7. This will activate both CTLs and Ths. Stimulates intra-APC destruction of pathogens. Also, helps B cells make antibodies, specifically IgG, which promote complement binding and opsonization.
Th2 Cells
Secrete IL4 and IL5. Involved in allergy and helminth attack.
IL-4
Induces production of IgE antibodies that mediate allergic responses.
IL-5
Activates eosinophils involved in allergy.
Th17 Cells
Secrete IL-17.
IL-17
Induce inflammatory response by activating neutrophils, promote secretion of defensins, and increase epithelial barriers.
Treg Cells
Suppress T cell responses by secreting TGF B and IL-10.
IL-10 and TGFß
Suppressive cytokines for T cells.
Immunological Tolerance
Unresponsiveness to an antigen induced by exposure of lymphocytes to that antigen.
Central Tolerance
Immature, self-reactive T cells undergo negative selection in the Thymus.
Peripheral Tolerance
Mature self-reactive T Cells that escape central tolerance and recognize self antigens can become anergic, can be killed, or suppressed. Occurs when signal 2 is absent.
IL-1, TNF
Pro-inflammatory cytokines released from macrophages after activation via IFN gamma from Th1 Cells.
How do Th1 and Th2 cells interact?
Their responses inhibit each other.
How do Th1 cells directly and indirectly stimulate CTL activation?
Directly by releasing pro-CTL cytokines. Indirectly by increasing costimulators on pAPCs, which will then be more effective at activating CTLs.
How do CTLs kill infected cells?
Activated CTLs can recognize any cell that expresses MHC class 1, even without costimulators like B7 and CD40. CTL will bind and release perforin and serine esterase granules. CTL detaches and target cell slowly dies.
After CTL attack, do target cells die immediately?
No serine esterase and perforin take some time to kill the cell.
How are CTLs deactivated?
By CTLA-4 on pAPCs.
