Chp. 2 Chronic Inflammation B & T Lymphocytes Flashcards
What is chronic inflammation characterized by?
The presence of lymphocytes and plasma cells in tissue
What is the difference btwn chronic and acute inflammation as far as the type of reaction it is
Unlike acute, chronic is a delayed response and is more specific; chronic is an ex of adaptive immunity.
What is the stimuli for chronic inflammation?
Stimuli include:
Persistent infection (MOST COMMON CAUSE)
Infection with viruses, mycobacteria, fungi, and parasites
Autoimmune diseases
Foreign materials
Some cancers
Where are thymocytes produced?
They are produced in the bone marrow as progenitor T cells.
Where are thymocytes “educated”?
Thymocytes migrate from the bone marrow and enter the thymus as stem cells.
Once inside the thymus, the T cell receptor undergoes rearrangement. In addition, it either becomes a CD4+ or CD8+ T cell.
What is the TCR complex and what is it used for?
The TCR complex is made up of the TCR and CD3. This portion of the T cell is used for Ag surveillance and it is this that recognizes Ag bound to MHC
Obviously, CD8 and CD4 both have a TCR complex
CD4 - MHCII
CD8 - MHCI
What is required to activate a T cell?
It requires 2 things:
Binding of Ag/MHC to the TCR complex
An additional signal
So 2 signals are needed for T cell activation
How are CD4+ helper T cells activated?
What Ags are they used for (intra v extra cellular)
There are two signals needed:
First Signal:
EXTRACELLULAR Ag is phagocytosed, and presented on MHC II by an APC (macrophage or dendrite, i.e.) and presented to the CD4+ Helper T cell.
Second Signal:
B7 ON THE APC binds CD28 on the CD4+ T Helper cell.
The CD4+ T helper Cell is now activated and will secrete cytokines.
Once the CD4+ T helper has been activated, what will it do?
It will secrete cytokines to “help” inflammation and will become either a Th1 or a Th2 cell
If a CD4+ T cell becomes a Th1 cell, what two cytokines are released? What effect do these cytokines have?
Th1 cells secrete 2 cytokines:
- IFN-y; activates macrophages, promotes class switching from IgM—>IgG, promote Th1 phenotype while inhibiting the Th2 one
- IL-2 promotes the development of CD8+ T cells. This is the second signal necessary for CD8+ activation
Th1 supports killing intracellular pathogens.
If a CD4+ T cell becomes a Th2 cell, what two cytokines are released? What effect do these cytokines have?
Th2 cells secrete the following cytokines:
IL-4 & IL-13: Class switching to IgE and IgG
IL-5: Eosinophil activation and class switching to IgA, B cell maturation
IL-10: Inhibits the Th1 subtype
Th2 is for extracellular pathogen killing
How are CD8+ T cells activated? What is required for their activation?
CD8 cell activation requires 2 signals:
1st signal:
INTRACELLULAR Ag which came from proteins in the infected cell’s cytosol are presented on MHC I.
2nd signal:
IL-2 from Th1.
Now CD8+ is activated for killing.
What cells are MHC I located on? MHC II?
MHC I are located on all nucleated cells and platelets.
MHC II are on APCs (i.e. macrophages, dendritic cells)
When the CD8+ cell becomes activated what does it do? How does it do it?
IT KILLS!!!
This is how it kills (2 ways):
First way…It secretes perforin and granzyme. Perforin punches holes in the membrane of the infected cell. In these holes or pores, granzyme enters the cell.
Granzyme induces apoptosis by activating caspases.
Second way…The CD8+ cell will begin to express Fas Ligand on its surface and this ligand will bind to the FAS receptor on the target cell. Binding of FasL/Fas will induce apoptosis. (However, this is thought to be more important for getting rid of unwanted T lymphocytes)
How does granzyme secreted from activated CD8+ cells induce apoptosis?
It induces apoptosis by activating caspases. One way is to up regulate the Bax-Bak proteins that cleave cyto C out of the mitochondria. Cyto C activates Apaf-1 which activates caspases.
What are the caspases activated by?
Cyto C
FasL/Fas
Granzyme
Where are B lymphocytes made?
They are made in the bone marrow. While in the bone marrow they undergo Ig rearrangements to become NAIVE B CELLS THAT EXPRESS IgM and IgD.
How are B cells activated? How many signals are necessary and what are the cytokines/complexes necessary?
B cells are activated two ways:
First way: Direct activation by Ag. Ag binds to the surface of IgM or IgD. This binding leads to maturation of the naive B cell into a IgM or IgD secreting plasma cell.
Second way: This way requires 2 signals.
First Signal: THE B CELL ITSELF PRESENTS Ag TO THE CD4+ HELPER T CELL on MHC II
2nd Signal: CD40 on B cell binds CD40L on Th2 cell
Now the Th2 will secrete IL-4 & IL-5
After the B cell is activated by the Th2 cell, what does the Th2 cell secrete?
It secretes IL-4 & IL-5 which promotes B cell class switching, hypermutation, and maturation to plasma cells.
