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53 Cards in this Set
- Front
- Back
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What happens at secondary lymphoid organs?
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B and T cells recognize foreign antigens presented by macrophages and dendritic cells
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What do you need to have an effective immune response?
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T cell activation
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What enables T cells to migrate from thymus to lymph nodes?
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chemokine/chemokine receptor interactions and adhesion molecules
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What 3 signals must a naive T cell receive once in the lymph node?
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1. TCR signaling after it reacts w/ peptide/HLA
2. CD28 interactions w/ B7-1 and B7-2 (costimulatory molecules) 3. Cytokine receptor signaling after binding w/ IL-2 growth factor released by activated T cells |
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What are two types of effector T cells?
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Helper - secrete cytokines
- help B cells become plasma cells to produce Ab - help cytotoxic T cells become effector cells Cytotoxic - circulate, recognize MHC I cells, and kill - once activate, secrete interferon |
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Steps of T cell receptor signaling?
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- T cells cluster
- conformational changes in TCR/CD3 subunits - initiates a protein tyrosine kinase pathway --> phosp. ITAMs - ZAP-70/Syk kinases bound to ITAMs phosp. downstream signaling components |
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What do immunosuppressive drugs target?
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the calcineurin pathway
- cyclosporin, FK506 bind to calcineurin, block NFAT activation |
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What generates a positive signal? (2)
What does it result in? |
1. T cell receives signal 1 by recognizing MHC/peptide via TCR
2. receives signal 2 by engagement of the co-stimulatory molecule with its ligand - release of IL-2 and expression of high affinity IL-2 receptors |
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What is the autocrine loop?
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binding of IL-2 to IL-2 receptors that initates a cascade leading to further differentiation of the Tcell
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What does the binding of integrin to its receptors do?
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strengthens the avidity of interaction of the two cells (APC and Tcell)
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What is anergy?
Where is this important? |
TCR-MHC/peptide interaction occurs WITHOUT co-stimulatory signal --> cell is anergized (tolerized) --> no longer differentiate/ will die
- periphery, where self-reactive T cells reside |
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What 3 types of molecules are involved in the interactions b/w T cells an APC's?
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1. TCR's recognize MHC + peptide
2. adhesion molecules "glue" the two cells together 3. co-stimulatory molecules (CS) receptors (R) and ligands (L) interact |
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What is the difference b/w B7 interacting w/ CTLA and CD28?
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B7/CTLA - inhibitory interaction, occurs after T cell activation
B7/CD28 - stimulatory, when T cells initially interact |
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What are 5 subtypes of helper T cells?
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Th1, Th2, Th17, Treg, Tfh
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What are some subtypes of Cytotoxic T cells?
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CTL
CD8 aa Treg |
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Characteristics of NK T cells
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1. Express an invariant TCR (Va18/Ja24)
2. can be CD4+ or CD4- 3. Recognize glycolipids bound by CD1d 4. Produce cytokines such as IL-4 and g-IFN w/in minutes of stimulation 5. Recognize a diacylglycerol glycolipid from Borrelia burgdorferi |
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Naive CD4 T-cell + IL-12 = ?
transcription factor? what cytokine does it secrete? |
Th1 cell
T-bet y-IFN |
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Naive CD4 T-cell + IL-4, IL-25 = ?
what cytokine does it secrete? |
Th2
GATA3 IL-4, 5, 13 |
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Naive CD4 T-cell + IL-1, 6, TGF-B = ?
what cytokine does it secrete? |
Th17
ROR IL-17 |
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Naive CD4 T-cell + Foxp3 = ?
what cytokine does it secrete? |
Treg
Foxp3 IL-6, 10 |
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What cells stimulate macrophages, NK, and CD8 cells?
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Th1
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Which Ig do Th2's work with?
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IgE to stimulate eosinophils, basophils, mast cells
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What do Th2 cells do?
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1. stimulate B cells
2. stimulate antibody switching 3. stimulate Eosinophils, basophils, mast cells via IgE |
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Which cell secretes inhibitory cytokines?
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Treg
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What does Th17 do?
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- activate neutrophils
- fight extracellular pathogens |
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TNF
a. cell source b. effects |
a. Macrophage/T cell
b. Inflammation/fever, acute |
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IL-1
a. cell source b. effects |
a. Macrophage, T cell, Endothelium, epithelium
b. Inflammation, fever (acute), Th17 differentiation |
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IL-12
a. cell source b. effects |
a. Macrophage, Dendritic cell
b. Th1 differentiation, NK activation |
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a/b-IFN
a. cell source b. effects |
a. Macrophage, fibroblast
b. Antiviral, induce class I |
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IL-10
a. cell source b. effects |
a. Macrophage, T cell
b. Blocks IL-12, induce class II |
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IL-6
a. cell source b. effects |
a. macrophage, endothelium, T cell
b. Livier acute phase |
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IL-15
a. cell source b. effects |
a. macrophage
b. NK, CD8 proliferation |
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IL-18
a. cell source b. effects |
a. Macrophage
b. NK, T secretion of IFN |
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IL-23
a. cell source b. effects |
a. Macrophage, dendritic cell
b. Th17 |
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IL-27
a. cell source b. effects |
a. Macrophage, dendritic cell
b. Block Th1 |
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What does TNF secretion cause in low quantities?
Specifically a. endothelial cell b. leukocyte |
Local inflammation
a. Express adhesion molecules, secrete IL-1, chemokines b. Macrophage activation |
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What does TNF secretion cause in medium quantities?
Specifically a. Brain b. Liver c. Bone Marrow |
Systemic effects
a. Fever B. Acute phase proteins secreted C. Release of leukocytes |
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What does TNF secretion cause in high quantities?
Specifically a. Heart b. Blood vessel c. Liver |
Septic shock
a. Low output b. Thrombus, low resistance (low BP) c. Hypoglycemia |
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What makes naive CD4 cells --> Th1 cells?
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IL-12
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What do Th1 cells secrete?
What does this stimulate? (4) |
IFN - gamma, TNF
1. Stimulates macrophages to phagocytose and kill the bacteria 2. Enhances anti-viral responsiveness of cells 3. Increases HLA expression 4. Changes the antigen processing components of the proteosome |
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What is the effect of TH1 cells on B cells?
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TH1 release IFN-gamma --> complement-binding and opsonizing antibodies
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What makes Th2 cells develop?
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IL-4
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What do Th2 cells secrete?
Functions? |
IL-3, -4, -5, -13, and express CCR3
1. Promotes Ig class switching and B cell expansion --> help B cells make antibody responses 2. Critical for immune responses against extracellular pathogens 3. Promote IgE secretion 4. Activate mast cells, basophils 5. Release of mucous |
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What makes Th17 cells develop?
What is special about this pathway in an immune response? |
IL-1 and TGF-B
First adaptive pathway in the course of an immune response |
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What do Th17 cells secrete?
What does it do? |
IL-17, IL-21, IL-22
Il-17 recruits neutrophils Receptor is on most cells, release CXCL8 and CXCL2 |
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What is pleiotropism?
Example? |
Same type of cytokine can have different effects on different cells
IL-4 to B cell --> IgE production IL-4 to CD4 T cell --> Th2 development |
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What is redundancy?
Example? |
2 different cytokines have same effect
IL-2 and IL-4 both cause B-cell proliferation |
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What is Synergy?
Example? |
2 different cytokines have 1 synergistic effect
IFN-gamma and TNF both increase the expression of class I MHC molecules on many cell types |
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What is antagonism?
Example for macrophages? |
Cytokines antagonize each other
IFN-g activates macrophages IL-10 inhibits macrophages |
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What is the oxidative burst?
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Generation of reactive oxygen species (ROS) by the NADPH phagocyte oxidase complex (phox proteins)
Makes NO, O2, also bacteriacidal |
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What are the functions of Treg cells?
What is the transcription factor in their development? |
Suppress T cell activation of self, function in peripheral tolerance
Foxp3 |
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What are CD8 cells?
What does their expansion require? |
Cytotoxic T cells or killer T cells
Expansion requires IL-2 |
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What do CD8 cells release?
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granzyme and perforin to lyse the target cell; also activates caspase
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