8-T Cell Mediated Immunity Flashcards
Which cells carry bacterial Ag’s from the tissues to the secondary lymphatic tissues?
Dendritic cells
When do dendritic cells turn from immature to mature cells?
When they have degraded a bacteria and presented the Ag’s on their MHC-I and MHC-II molecules
Why do dendritic cells have both MHC-I and MHC-II molecules?
Because they are both a professional antigen-presenting cell (which have MHC-II) and nucleated (all nucleated cells in the body (every cell except RBC’s) have MHC-I)
What happens to the dendrites of dendritic cells when they mature?
They become super awesome
Where do dendritic cells carry Ag’s to from infections on the skin?
lymph nodes
Where do dendritic cells carry Ag’s to from infections in the blood?
spleen
Where do dendritic cells carry Ag’s to from infections in the lungs?
tonsils or BALT
Where do dendritic cells carry Ag’s to from infections in the gut?
GALT
How do naive T cells get to the lymph node from the blood? (generally)
They bind to the vessels endothelial cells of the high endothelial venules (HEV) and squeeze through to the lymph node
What is another way a naive T cell can get to a lymph node? (other than through the blood)
Through the lymph from passing through a prior lymph node
What are the 2 things that could happen to a naive T cells once it enters a lymph node?
- It could find the Ag:MHC match to its TCR and begin to proliferate or 2. not find a match and be sad.
What chemokines attract a naive T cell in the blood to the HEV?
CCL21 and CCL19
What does the L-selectin on the naive T cell bind to on the HEV?
CD34 and GlyCAM-1
Binding of the L-selectin of the T cell to the CD34 and GlyCAM-1 causes what?
The slowing down of the T cell in the blood.
What additional interaction occurs between the T cell and the HEV to add to the strength of the interaction?
The LFA-1 receptors on the T cell bind to the ICAM-1 and 2 on the HEV
How does the dendritic cells in the lymph node enhance the strength of the bond of between the naive T cell?
They express LFA-3 which binds to the CD2 on the T cell
What does the TCR bind to on the dendritic cell?
The Ag that is being presented by the MHC
What are the 2 proteins involved in the costimulatory complex between the T cell and the dendritic cell?
CD28 of the naive T cell and B7 of the dendritic cell
What is the point of the costimulatory signal?
Just the binding of the TCR to the Ag and the CD4 to the MHC-II isn’t enough to activate the T cell, therefore we need a second costimulus to activate the naive T cell.
What is the function of CTLA-4?
It’s secreted by the T cell and it inhibits the CD28 by binding to the B7 receptor. This inhibits the costimulatory signal and dampens down the activation and limits cell proliforation.
What are functions of Langerhans cells?
They will uptake and process antigens just like regular dendritic cells?
What makes Langerhans cells different than dendritic cells in the lymph node?
Theyre called interdigitating cells- in addition to having B7 and MHC, they increase the expression of adhesion molecules, which attracts naive T cells towards them.
Where in the lymph node are the dendritic cells?
T cell areas
Where in the lymph node are the macrophages?
Eeerywhere
What is the function of dendritic cells?
activate T cells
What are the functions of macrophages?
There are lots- eat stuff, be an APC, kill lymphocytes that are gonna die, and have TLR’s for innate immunity
Why is Listeria so super goofy?
Because it escapes the phagosome of macrophages and can grow in the cytoplasm of the macropahge
How does the body kill Listeria?
Its growth in the cytoplasm triggers CD8 Tc cells to come and kill it.
What is the purpose of the CD4 molecule?
It checks that the Ag that is being presented to the TCR is from a MHC-II
Which proteins on the TCR transmit the signal to the intracellular portion upon binding of the Ag?
CD3
What do the cytoplasmic tails of the CD3 proteins contain?
ITAMs
What do the ITAMs associate with?
Protein tyrosine kinases
What do the protein tyrosine kinases do on the ITAMs?
They phosphorylate them so that enzymes and other molecules can bind and then alter gene expression.
What do the cytoplasmic portions of the CD4 molecules associate with?
A protein tyrosine kinase called Lck
What does Lck do?
It phosphorylates a protein kinase called ZAP-70
What does ZAP-70 do?
binds to the tails of the CD3 receptors and initates the intracellular pathway
Question: patient presents with immunodeficiency symptoms. There are normal serum levels of T cells, but it found that the signaling mechanism is defective when an Ag is presented by an MHC-II molecule. What key enzyme must be missing in the T cell?
ZAP-70
How does activation of ZAP-70 lead to cell division, proliferation and differentiation of effector T cells (generally)?
IT initiates a series of reactions that leads to the PLC pathway (kinda like the Gq pathway) which activates transcription factors
When is IL-2 released from the T cells?
when the T cell becomes activated from binding of an Ag to the TCR
What is the function of IL-2?
It binds to the IL-2R’s on the SAME cell and drives colonal expansion of the activated cell
What subunit gets added to the IL-2R on the T cell surface to activate it?
The α subunit is added to the γ and β dimer, thus activating the cell.
When is the IL-2R α subunit synthesized?
The same time IL-2 is synthesized- when the T cell is activated
What happens when an Ag:MHC binds to a TCR but there is NOT any binding of CD28 to B7?
Lack of costimulation leads to anergy of the cell
What happens during T cell anergy?
They are unable to make IL-2 and become indefinitely nonresponsive to Ag stimulation.
What are the 2 main cytokines of TH1?
IL-2 and interferon (IFN)-γ
What do IL-2 and interferon (IFN)-γ do?
macrophage activation, inflammation, and the production of opsonizing antibodies
TH1 is said to activate what type of immunity?
Innate (cell-mediated) immunity
What are the 2 main cytokines of TH2?
IL-4 and IL-5
What are the main functions of IL-4 and IL-5?
They lead to B cell activation and differentiation
What type of immunity does TH2 lead to?
Adaptive (humoral) immunity
What is the main determining factor as far as which type of leprosy an indiviudal might suffer from?
Whether the immune response to M. leprae is strongly biased towards a TH1 or TH2 response
What are the clinical manifestations of a TH1-biased response to leprosy?
it enables the macrophages to supress the bacterial growth- disease progresses slowly and the pts usually survive.
What is TH1-biased leprosy called?
Tuberculoid leprosy
What are the clinical manifestations of a Th2-biased response to leprosy?
Since there can’t be Ab’s made to the intracellular pathogen, there can’t be an immune response- massive tissue destruction and soon death.
What is Th2-biased leprosy called?
Lepromatous leprosy
What are the 3 ways CD8 cells can be activated?
(1) High levels of B7 expresison fo dendritic cells. (2) CD4 activates the APC which activates the CD8. (3) APC makes CD4 make IL-2 which activates neighboring CD8
Why is activation of effector T cells different than naive T cells?
Cuz they can respond to their specific Ag w/o the need for co-stimulatory signals.
What type of cells do CD8 cells kill?
Cells that have become overwhelmed by intracellular infection.
What are the 2 things that the CD8 cells secrete?
Lytic Granules (they have a lot of bad stuff in them) and IFN-γ for macrophage recruitment
What are the proteins in the CD8 cytotoxic granules that punch holes in the membrane of cells, inducing apoptosis?
Perforin and Granulysin
What is expressed on the surface of CD8 cells that signals the target cell to undergo apoptosis?
Fas ligand
What are the 2 things released from the TH1 cell that activate macrophages?
CD40 and TNF-α
Why is TH2 cells anatonists to Th1?
They act like a safety mechanism to make sure there isn’t an extreme cell-mediated immune response
What is the main cytokines released from TH2 cells that inhibit TH1 cells?
IL-10 and IL-4
What is the fxn of IL-3 from Th1?
induces macrophage differentiation in the bone marrow
Why do granulomas form?
They form when microbes resist macrophage eating, so they wall off and form a big mass of gross pathogens.
What does the CD40 ligand get released from TH2 cells?
When they are activated from B cells when B cells present an Ag that the TCR can bind to
What does the CD40 ligand from TH2 do to B cells?
The B cells have a CD40R which drives teh resing B cell into the cycle of cell division.
What is the function of regulatory CD4 T cells?
They suppress the activation of naïve autoreactive CD4 and CD8 cells that have the potential to attack the body’s tissues
