Flashcards in Immunology 6 (Kyle) Deck (71):
Where does activation of T cells take place?
Initiation of adaptive immune responses does not take place at the site of infection. Pathogen derived antigens are carried by the lymph to secondary lymph organs where the antigen is processed and presented.
How do niave T cells enter the lymph organ?
Niave T cells enter the secondary lymph organ by transversing the high epithelial venules (HEV) and is mediated by adhesion molecules.
What does L-Selectin do?
L-selectin is a cell surface adhesion molecule that binds to Glycam-1 and CD-34 to begin the process of diapedesis through the High Epithelial Venial
What are the first step for a leukocyte to cross the high epithelial venues ?
L selectin binds to ICAM-1 or CD-34
What is the second step (Step after Lymphocyte Function Associated Antigen-1 (LFA-1) has been activated)
LFA-1 then binds tightly to intracellular adhesion molecule-1 (ICAM-1) on the HEV
After binding of ICAM-1 to LFA-1 and ICAM- binds to CD-34 what happens to the leukocyte?
The tight interaction allows the T cell to squeeze between two endothelial cells and enter the 2degree lymphoid tissue.
What is the term for when a T cell squeezes between two endothelial cells and enters the 2degree lymph tissue?
What aspect of T cell circulation is curcial for the initiation of the adaptive immune response?
The sampling rate of T cells in the body, As T cells flow through the lymph circulation they come in contact with thousands of antigens every day which allows them to detect antigens derived from pathogens at any location in the body.
How is the interaction between the APC and the T cell mediated ?
Via adhesion molecules that are on the surface of the T cell as well as adhesion molecules on the surface of the APC.
What changes could be observed when a T cell encounters an antigen that it recognizes as foreign?
The adhesion molecule on the surface of the T cell will greatly increase its affinity for ICAMs which prolong the cell-cell contact
What are the three antigen presenting cells?
B Cells, Macrophages, and Dendritic Cells.
What is the feature of antigen presenting cells that distinguishes them from other cells in the body?
The Co-stimulator molecule or B-7.
What does B-7 do?
B-7 binds to the T cell surface receptor CD-28. This interaction is required for activation of a naive T cell.
Which cells can activate a niave T cell.
Only an antigen presenting cell.
What are the two signals that will activate a T cell?
1. Binding of a T cell to its cognate peptide in the context of MHC
2. Co stimulation signaling that results from interaction between B-7 and CD-28.
What are the two surface molecules involved in the second step of T cell activation
B7 on the APC
CD28 on the T cell
How many different functions do dendritic cells possess?
The only function of a dendritic cell is Antigen presentation.
What is the most potent APC in the body?
What surface proteins does this cell have?
Mature Dendritic Cells
MHC-1 and MHC-2
By what mechanism do immature dendritic cells take up an antigen?
What are interdigitating reticular cells?
Mature Dendritic Cells
What is DC-CK ?
DC-CK is a chemokine produced by mature dendritic cells that attracts niave T cells.
What is a macrophage?
Scavenger cells that can be induced by pathogens to present antigens to naive T cells. They are major players in the front line defense against micro organisms. They can phagocytose and destroy many microbes without the aid of the acquired immune response.
At rest do macrophages express high levels of MHC Class 2? What about B7
At rest macrophages express a very low level of MHC-2 and no B7.
What happens when a resting macrophage encounters an antigen in the absence of bacterial products?
They will upregulate MHC-2 slightly but no B7. This is an important form of peripheral tolerance because the macrophage will not sound the alarm.
What happens if the microbe persists?
The macrophage will get pissed off and express B7. Thus, will be an antigen presenting cell and activate the T cells.
In addition to humoral immunity what purpose do B cells serve?
Antigen presenting cells
how do B cells detect a foreign antigen?
What happens when a B cell internalizes an antigen?
Through their surface Ig molecules.
It processes the antigen and presents it on a MHC-2 molecule.
Do B cells normally express B7?
No, however it is upregulated in the presence of an infection or microbial invader.
What is the first signal to activate a T cell ?
An encounter with a specific peptide antigen bound to a MHC molecule on an APC
What is the second signal for T cell activation? (co-stimulation)
The interaction of CD28 with B7. As a result the upregulation of IL-2 is about 90-fold.
What happens if you have costimulation without the initial APC interaction.
What happens if you have interaction between the MHC-antigen complex without co-stimulation?
The T cell will become anergic (Peripheral Tolerance)
Who needs more co-stimulation and why?
CD8 because they are killas.
What APC most frequently activates CD8 ?
Dendritic cells because they are the most potent activators.
What happens if an APC other than a dendritic cell attempts to activate the cell?
The CD4 and CD8 will have to be activated simultaneously for there to be any increase in activity.
Why is there a need for simultaneous activation for CD8's ?
When they are activated together there will be a large upregulation of B7 which will make the APC (Other than a dendritic cell) a much more potent activator.
What is the first order of business for a newly activated T cell?
The newly activated T cell must re-enter the cell cycle to make large numbers of progeny that will differentiate into armed effector T cells.
What autocrine growth factor drives proliferation and differentiation of of activated T cells?
Interlukin-2 or (IL2) which is produced by activated T cells
Who produces IL-2
Activated T cells
Describe the affinity of IL2 receptors for IL2 before activation and after activation.
Before Activation T cells have a low affinity for IL2. After activation the affinity for IL2 greatly increases.
What does IL2 actually do?
After activation and binding to IL-2 the T cell is able to divide two to three times a day until there are thousands of mature T cells.
What is the structure of the IL2 receptor? ( activated State)
The activated ( high Affinity ) IL2 receptor is a heterodimer consisting of alpha beta and gamma chains that all transverse the cell membrane.
The unactivated IL2 receptor consists of what?
Beta and gamma chains of the IL2 receptor. upon activation The Beta and Gamma subunits interact with the alpha subunit to form the high affinity version of the receptor.
What is an armed effector T cell?
A T cell that can produce all of the proteins that are required for its specialized function.
Do armed effector T cells require costimulation?
No, They can perform their function with stimulation from the antigen alone.
Describe the concentration of adhesion molecules on the armed T cell.
They have higher concentrations of LFA-1 and CD2 but lose cell-surface L-Selectin
What is a CD8 cell? what does it do?
Cytotoxic killer cell. Recognizes peptide antigens bound to MHC class 1 molecules presented on the surface of infected cells. Could be any nucleated cell in the body that is infected with a virus or intracellular parasite.
What is a Th1 CD4 cell?
Involved in the development of cell mediated immune responses.
What antigens to Th1-CD4 cells recognize?
Recognize peptide antigens bound to MHC-2 molecules presented on the surface of macrophages or B cells.
Do Th1-CD4 cells modulate APC's ?
Yes, TH1-CD4 cells producecytokines that modulate the function of the APC that is presenting the antigen to the CD4 T cell.
Th1-CD4 provide helper signals to what innate cell?
Macrophages making them more bactericidal and phagocytic.
How do TH1-CD4 cells help B cells?
TH1-CD4 cells, through cytokines, serve as the second signal for B cell activation inducing them to produce antibodies that are efficent for opsination.
What are Th2-CD4 cells?
They are primarily involved in the development of the humoral immune system
Are Th2 cells involved in cell-mediated or humoral immune responses?
Th2-CD4 cells are involved in the humoral immune response which focuses on the Production of antibodies.
TH1-CD4 cells are involved in which type of immunity?
TH1-CD4 cells are involved primarily in Cell Mediated Immunity.
Which cells differentiate in the thymus?
CD8 cells fully differentiate in the thymus. CD4's leave the tymus and then decide if they want to by Type 1 or Type 2
What type of Ab's to Th2-CD4 cells produce?
All isotypes except for Opsonization which are produced by TH1 CD4
What will a TH0 CD4 differentiate into in the presence of IL-12 and IFN-y ?
TH1 effector cells.
Where does IFN-y come from and what does it do?
NK cells and IFN-y cells produce IFN-y and it inhibits the proliferation of TH-2 cells.
Where is IL-12 produced and what does it do?
IL-12 is produced by macrophages and dendritic cells in response to viral and some intracellular bacterial infections.
In the presence of IL-4 and IL-6 what will a TH0 CD4 cell differentiate into?
TH2 CD4 cell.
What do TH2 CD$ cells produce that inhibits the activation of Th1 CD4 cells?
IL-10 and TGF-B
What do IL-4 and IL-10 do?
Inhibit the generation of TH-1 cells.
What other than surface molecules can induce differentiation of T cells?
The nature and amount of antigen presented to the TH0 cell.
In low conc of antigen that weakly binds to TCR what will the cell differentiate into?
In high concentrations of antigen that bind tightly to the T cell what will the TH0 cell differentiate into?
What do regulatory T cells do?
1. Have Self Antigen specific TCR's
2. Express CD25 on their surface
3. Express the transcriptional repressor FoxP3
What do Treg cells do when they recognize their cognate Self antigen?
They produce mediators that supress proliferation of niave T cells that are responding to self antigens presented on the same APC. Important for peripheral tolerance mechanism
What will a deficiency of FoxP3 produce?
Fatal autoimmune disease. IPEX
What does TH17 do?
Promote neutrophil influx into inflammatory sites. If deficient the host will be vulnerable to opportunistic pathogens.