Immuno Ch. 8: T-cell mediated immunity
What do CD4 T cells become?
CD4 T-cells become effector cells when activated that comprise 5 different functional subtypes *The different subtype are alike in the sense that they secrete cytokines that activate or suppress other immune system cells ***effector T cells help other cell types acquire and exert their effector fuctions, thus CD4 T cells are often called "HELPER T CELLS"
____ cells remain in, rather than leave, the secondary lymphoid organs in which they are differentiated
CD4 TFH cells---> remain in secondary lymphoid tissues unlike the other effector T-cells
What MHC class is associated with: 1) CD4 2) CD8
CD4---MHC class II molecules. CD4 T-cells express the CD4 co-receptor and recognizes peptide antigens presented by MHC class II molecules. CD8- MHC class I molecules. CD8 T-cells express the CD8 co-receptor and recognizes peptides presented by the MHC class I molecules.
What do CD8 T cells become?
CD8 T cells inevitably become cytotoxic T-cells that kill pathogen-infected target cells.
Describe the action of Dendritic cells in a skin infection:
Dendritic cells take up antigens at a site of wounding and infection in the skin and carry them to the draining lymph node for presentation to naïve T cells. Dendritic cells bearing antigen enter the draining lymph node, where they settle in T-cell areas. upon settling in T-cell area, they differentiate into mature dendritic celss that are specialized in activating naïve T cells immature dendritic cells of the skin aka :Langerhan cells Figure 8.1
Dendritic cells transport pathogens and their antigens from where to where?
Dendritic cells transport pathogens and their antigens from sites of infection to the T-cell areas of the draining lymph node
Why do dendritic cells, but not macrophages or B cells, contribute to the activation of naïve T-cells?
Dendritic cells upregulate B7 after engaging in innate immunity receptors at sites of infection
Dendritic cells carry TLRs except which one?
Except TLR9 They are highly sensitive to the presence of all manner of pathogens. The signals sent from the Toll-like receptors change the pattern of gene expression in a dendritic cell, leading to the cell's activation.
When an immature dendritic cell becomes an activated dendritic cell, all of the following changes occur except: a. confinement to T-cell regions of lymph node cortex b. development of elaborate finger-like projections c. upregulated expression of MHC class II (CD4 T-helper) at the cell surface d. loss of antigen-processing function e. Expression of Toll-like receptor TLR9
Expression of TLR9 does NOT occur (dendritic cells carry TLRs EXCEPT TLR9)
What is another name for CD4 T cells?
Helper T-cells
Homing of effector T cells to inflamed tissue is facilitated by the upregulation of ________ on the surface of the effector T cell
Homing is the process of naïve T cells leaving circulation (bloodstream) and entering a T cell zone of the lymph nodes (cortex). Homing guided by CCL21 and CCLR 19 **Upregulation of VLA-4 facilitates the homing VLA-4 integrin is present on the surface of T lymphocytes that binds to mucosal cell adhesion molecules.
What secretes IL-17? what does IL-17 activate and recruit?
IL-17 is secreted from TH17 cells (that's convenient, 17 for 17!) IL-17 activates and recruits neutrophils to the sites of infection with extracellular bacteria and fungi.
Identify which statement is INCORRECT a. naïve t cells have the capacity to survive for many years as nondividing circulating cells in the absence of specific antigen b. naïve t cells express LFA-1 molecules that change their conformation after encountering a specific peptide: MHC complex c. Naïve t-cells exit from lymph nodes using the same route as effector t cells d. naïve T cells express ICAM-3, which binds to DC-SIGN on dendritic cells with high affinity e. naïve T cells express high levels of S1P receptors on their surface
Incorrect: naïve T cells express high levels of S1P on their surface S1P= spingosine 1-phosphate is a chemotactic lipid that binds to a receptor on naïve T-cells. Not expressed on the surface. Naïve T cells that have not encountered specific antigen, are drawn back into peripheral circulation by a gradient of S1P
What complimentary function to dendritic cells are macrophages responsible for in the cortex and medulla of the lymph node?
Macrophages are responsible for removing pathogens and their breakdown products from the afferent lymph that arrives from the site of infection. -Macrophage-mediated- lymph filtration critical to prevent infectious agents from passing through the lymph node and gaining access to the blood via the efferent lymph (prevent infections from becoming systemic and life threatening) Remember: dendritic cells focus on activating naïve T-cells
What is the most numerous blood lymphocyte
Naïve T cells
Regulatory T cells (Treg)....
Suppress effector CD4 and CD8 T-cell function
Decreasing the projected immune response with effector T cells in action is conducted by which type of cells?
T regulatory cells Treg interacts with other populations of effector T cells to prevent too excessive an immune response and to shut it down when the pathogen has been eliminated
Describe the process of T-cell activation (T-cell priming)
T-cell activation or priming, is the first stage of a primary adaptive immune response.
Antigen recognition by T-cells in the absence of co-stimulation results in
T-cell anergy (state of non-responsiveness to an antigen_
Where do TFH cells remain and what do they activate?
TFH cells (unlike other types of effector T-cells) remain in the secondary lymphoid tissue, where they activate naïve pathogen-specific B cells to differentiate into antibody-producing cells.
What is the cytokine secreted by TH 1 cells and what does this cytokine do?
TH1 cells secrete IFN-gamma. This cytokine is instrumental in activating macrophages
What does TH2 secrete (cytokine and what does this cytokine do?)
TH2 secretes IL-4 to act on basophils, mast cells, and eosinophils to respond to parasitic infections
Which of the following statements are True in reference to T-cell priming, and which are False? a. it occurs in the Primary lymphoid organs b. it transforms naïve T-cells into differentiated effector T-cells c. it is the first stage of a primary adaptive immune response d. it requires interaction between naïve T-cells and antigen-presenting cells e. it takes place in many locations including, but not limited to, lymph nodes, Peyer's patches, and the tonsils
TRUE STATEMENTS about T-cell priming: -It is the first stage of a primary adaptive immune response -it transforms naïve T-cells into differentiated effector T-cells -it requires interaction between naïve t-cells and antigen-presenting cells -it takes place in many locations including lymph nodes, peyer's patches, and the tonsils FALSE STATEMENT:( T-cell priming does NOT occur in primary lymphoid organs, but rather T-cell priming occurs in SECONDARY lymphoid tissues (spleen, lymph nodes, and mucosa-associated lymphoid tissues
Which of the following statements regarding naïve T-cells is/are True and which is/are false? -naïve T cells enter lymph nodes in two different ways, from the blood and from the lymph -naïve T cells can only be activated in secondary lymphoid tissues -naïve t-cells differentiate into effector T-cells after T-cell priming has occurred -naïve t cells occupy both the cortex and the medulla of lymph nodes -naïve T-cells are only activated by dendritic cells, not by macrophages or B cells
TRUE about naïve T cells: -naïve T cells enter lymph nodes in two different ways, from the blood and from the lymph -naïve T cells can only be activated in secondary lymphoid tissues -naïve tcells differentiate into effector T cells after T-cell priming has occurred (the 1st stage in primary adaptive response to activate the T-cells) -naïve t cells are only activated by dendritic cells, not by macrophages or B cells FALSE: Naïve T cells occupy both the cortex and the medulla of the lymph node (naïve T cells live in circulation in absence of specific antigen, move through lymph (secondary) where they could be activated into effector T cells through the draining lymph node. The naïve T cells enter the lymph node cortex (Where activation could occur) and then activated and unactivated (remain naïve) leave the lymph through the efferent lymphatic vessel; thus they do not reside or enter the medulla (Figure 8.4)
Describe the complimentary roles and the formation of a cognate pair of the effector T-cells with a target cell that presents a pathogen derived peptide that is recognized by the effector T-cell antigen receptor:
The T cell delivers effector molecules that induce changes in the target cell -the cytotoxins delivered by a cytotoxic CD8 T cell kills the target cell whereas helper CD4 T cells deliver cytokines that inform the target cell to increase or decrease its immune response against the pathogen.
What are the secondary lymphoid tissues?
the lymph nodes, spleen, and mucosa-associated lymphoid tissues. These are the tissues in which the immune responses are initiated. AKA the "peripheral lymphoid tissue"
T-cells that encounter their antigen presented by antigen-presenting cells in the lymph do what?
They are activated to proliferate and differentiate into effector cells. These effector cells can then also leave the lymph via the efferent lymph and enter circulation.
Which the expression of CTLA4, is T-cell proliferation enhanced or limited?
With CLTA4, T-cell proliferation is limited
Review: Define a NK cell (glossary terms)
a large, granular, cytotoxic lymphocyte that circulates in the blood and is important in innate immunity to intracellular pathogens such as viruses. NK cells do not have variable receptors for antigen but have numerous other receptors by which they can recognize and kill virus-infected cells
Define a naïve B cell
a mature B cell that has left the bone marrow, but has not yet encountered its specific antigen
T-cells that do not encounter their specific antigen in the lymph node go where?
they leave the lymph node in the efferent lymph and eventually rejoin in the bloodstream
Which cell types are unable to interact with naïve T cells and induce their activation?
cells that are unable to induce T cell activation in naïve T-cells: -macrophages resident in infected tissues (outside of sencondary lymphoid tissues where activation occurs, because note, macrophages in secondary lymphoid tissue do in fact activate naïve T-cells) -immature dendritic cells (these are still resident in the bone marrow)
Linked recognition is best described as....
cooperation between T-follicular helper (TFH) and naïve B cells bearing specificity for different epitopes of the same antigen and where the B cell serves as the antigen-presenting cell
CD4 TH1 cells....
differentiate under the influence of IL-12 and IFN-gamma
CD4 TH17 cells.....
facilitate neutrophil response to fungal and extracellular bacterial infections
CD4 TH2 cells....
help basophils, mast cells, eosinophils, and B cells respond to parasitic infections
How does the activation occur for a naïve T-cell once it passes through the T-cell area or T-cell zone?
in this crowded tissue of the T-cell zone, the naïve -cells encounter mature dendritic cells, and their T-cell receptors examine the peptide: MHC complexes on the dendritic cell surface. When a T-cell receptor binds to a peptide: MHC complex, the Tcell is selected for activation and is retained in the lymph node by the dendritic cell
Which of the following statements regarding T-cell activated by specific antigen is incorrect? -they receive co-stimulatory signals through CD8 -they suppress expression of S1P -they take several days b4 differentiating into effector T-cells -they cease to secrete and respond to IL2 -they begin o express CTLA4 which serves to limit T-cell proliferation
incorrect: they cease to secrete and respond to IL2 (they need IL2...in the absence of IL2, t-cell proliferation and differentiation does not occur)
CD8 T cells....
induce apoptosis of target cells after targeted delivery of cytotoxins
What are the two immunoglobulin components of the light chain?
lambda and kappa
outline the process of homing of circulation of naïve T cells to the lymph node draining the infection
1) Cirulationg naïve T cell enters the high endothelial venule in the lymph node 2) Binding of L-selectin to GlyCAM-1 and CD34 allows rolling action 3) LFA-1 is activated by chemokines bound to extracellular matrix 4) Activated LFA-1 binds tightly to ICAM-1 5) Diapedesis- lymphocyte leaves blood and enters lymph node
What are the two routes in which Naïve T cells can enter draining lymph nodes?
1) In the blood 2) Afferent lymph coming from an upstream lymph node (moving from one lymph node to another via the lymphatics that connect them
list all of the effector T-cells and what they primarily interact with:
1) TH1- macrophages 2) TH2-basophils, mast cells, and eosinophils 3) TH17-neutrophils 4) TFH-B cells
What are the 6 type of effector T-cells?
1) cytotoxic CD8 cells 2) Helper CD4 TH1 3)Helper CD4 TH2 4) Helper CD4 TH17 5) Helper CD4 TFH 6) T regulatory cells *All of these cells have complementary roles in the immune response to infection.
Outline how dendritic cells use several pathways to process and present protein synthesis:
1)uptake of antigens by phagocytosis or macropinocytosis (nonspecific ingestion of larger volumes of extracellular fluid to capture pathogens not recognized by any endocytic receptor) delivers antigens to endocytic vesicles for presentation by MHC class II molecules of CD4 T cells. 2)Viral particles taken up by Class II pathways of phagocytosis and macropinocytosis can be delivered to the cytosol for processing and presentation to CD8 T cells by MHC class I. Mechanism of cross-penetration not understood. 3) Lastly, antigens taken up by one dendritic cell can be delivered to a second dendritic cell for presentation by MHC class I molecules to CD8 T cells
If CD4 or CD8 co-receptors are absent, then approximately ____specific peptide: MHC complexes are needed to activate a T-cell
100 times the number of specific peptide:MHC
What is a B7 molecule?
B cell molecule (as defined in glossary) -either of the B7.1 and B7.2 proteins, which are co-stimulatory molecules present on the surface of professional antigen-presenting cells such as dendritic cells. With other related proteins they form the B7 family of co-stimulatory molecules.
why is the immune response suppressed in the absence of IL-2?
Background: in an immune response, binding of IL-2 to a high-affinity IL-2 receptor of alpha, beta, and gamma chains drives the proliferation and differentiation of T cells that occur after encountered antigen. IN ABSENCE of IL-2: T-cells will not be fully activated, will not differentiate, and will not undergo clonal expansion. Thus, preventing IL-2 and it's receptor prevents clonal expansion of T cells specific for the foreign antigens on the graft and their differentiation into effector T-cells, and thus suppresses the immune response directed against the graft.