What are the co-receptors also expressed in T cells?
CD4 and CD8
What percentage of T cells in circulation have alpha/beta TCRs?
How many TCRs have to recognize a specific antigen, in order for the signaling cascade to be initiated?
True/False: alpha/beta chains have long intracellular domains.
False; they have short intracellular domains
Signaling is mediated by other proteins comprising TCR complex, which proteins have cytoplasmic tails long enough to signal?
CD3 proteins (gamma, delta, epsilon, zeta)
What is CD3?
A marker for counting the amount of T cells (CD4+ and CD8 T cells)
What components are needed to activate a T cell?
TCR, CD4 or CD8, and CD3
Where does activation of T cells occur?
About how many naive T cells do dendritic cells “interview” every hour?
~500 naive T cells per hour
What are immature dendritic cells called, and do they express high levels of B7?
Langerhan’s cells; No
Describe the development of Langerhan’s cells into mature dendritic cells.
Antigen uptake from Langerhan’s cells in the skin –> Langerhan’s cells leave skin –> then enter lymphatic system –> then enter lymph node, once they enter the lymph node they become dendritic cells expressing B7 –> B7 dendritic cells then stimulate naive T cells
What are B7 proteins (CD80/CD86) and what are they expressed on?
Co-stimulatory molecules; expressed on professional antigen presenting cells
What is the receptor for B7 molecules and what kind of cell is this receptor expressed on?
CD28 receptor; expressed on T cells
Co-stimulation does what to the signal?
amplifies and improves the signal
bonus info: w/ co-stimulation ~100-fold fewer clustered TCRs are needed for activation
T cells proliferate in order to increase their numbers, what drives the proliferation?
IL-2 (T cell growth factor)
Do naive T cells have IL-2 receptors on their surface?
True/False: Activated T cells produce high numbers of IL-2 and express IL-2R.
What is IL-2’s function?
It is the T cell growth factor; it enhances resistance of activated T cells to apoptosis
Are Th1, Th2, and Th17, all CD4+ helper T cells or CD8 cytotoxic T cells?
They are all CD4+ helper T cells
What is(are) the cytokines associated with the Th1 molecule?
What are the immune reactions and roles in disease for Th1 molecules?
Macrophages activate IgG production; They play a role in autoimmune diseases, and tissue damage associated with chronic infections
What is(are) the cytokines associated with Th2 molecule?
IL-4, IL-5, IL-13
What are the immune reactions and roles in disease for Th2 molecules?
Mast cell and eosin activation, IgE production, “alternative” macrophage activation; they play a role in allergic diseases
What is(are) the cytokines associated with Th17 molecules?
IL-17A, IL-17F, IL-22
What are the immune reactions and roles in disease for Th17 molecules?
Neutrophilic, monocytic inflammation; they play a role in autoimmune inflammatory diseases
What type of response is induced by each subset of the T helper cells?
Th1 = activate cell-mediated immune response Th2 = activate Ab-mediated immune response Th17 = involved in inflammation and anti-bacterial response
The pathway of differentiation of T helper cells is?
Naive CD4 T cells (uncommitted)
What is the development of Th1 cells?
IL-12 and IFN-gamma activate transcription factors (T-bet, STAT1, and STAT4) which stimulate differentiation of naive CD4+ T cells –> this lead to the development of Th1 subset
Which inhibits the development of Th2 and Th17 and amplifies the Th1 cell response?
What is the development of Th2 cells?
IL-4 activates GATA3 and STAT6, which stimulate differentiation of naive CD4+ T cells –> this leads to the development of the Th2 subset
What is the development of Th17 cells?
IL-1, IL-6, IL-23 activate the transcription factors RORyt and STAT3 –> these stimulate the differentiation into the Th17 subset
IL-23 most important cytokine
Which cytokine(s) promote the Th17 response by suppressing Th1 and Th2 and which amplify the response?
What is the principal action of IL-2?
T-cell growth stimulation
What is the principal action of IL-4?
B cell switching to IgE
What is the principal action of IL-5?
activation of eosinophils
What is the principal action of IFN-gamma?
activation of macrophages
What is the principal action of TGF-beta?
Inhibition of T cell activation
What is the principal action of IL-17?
Protection from extracellular pathogens, inflammation and auto-immunity
What is the main function of classical macrophage activation and what T cell subset induces classical macrophage activation?
enhanced microbial killing; Th1 cell
What is the main function of the alternative macrophage activation pathway and which subset of T helper cells induces alternative macrophage activation?
Complement binding and opsonizing IgG antibodies
What are the functions of Th17 cells?
- secrete IL-17 and IL-22
- secretion of the cytokines causes inflammation, neutrophil response, anti-microbial peptides, and increased barrier function
- main function: recruiting leukocytes and inducing inflammation
How are CD8+ T cells activated?
cross-presentation of antigens to CD8+ T cells
What are the steps of CD8+ T cell activation?
activated in the lymph node by dendritic cells loaded with antigens (recognize class I MHC) –> activated CD8+ cells proliferate and leave lymph nodes
What is cross-presentation?
specialized dendritic cells ingest infected cells, transfer the protein antigens into the cytosol and process the antigens to enter the class I MHC antigen presentation
What is the role of helper T cells in the activation of CTLs?
They produce cytokines that stimulate CTL differentiation
CD8+ T cells are activated in the lymph nodes, and recognize class I MHC-associated antigen, once activated they leave the lymph nodes. CTLs are activated to release what?
granule contents = perforin and granzyme
Do the gamma/delta T cells recognize the MHC-associated peptide antigens?
What do gamma/delta cells NOT express?
What are the functions of gamma/delta cells?
- first line of defense
- regulatory cell
- bridge between adaptive and innate responses
How are the gamma/delta cells a component of adaptive immunity?
- provide junctional diversity via the rearrangement of TCR genes
- develops a memory phenotype
How are gamma/delta cells considered to be part of the innate immunity?
A restricted TCR may be used as a pattern recognition receptor.
Are gamma/delta TCRs more or less diverse than alpha/beta TCRs?
What type of antigens do gamma/delta TCRs recognize?
What other molecules do NKT cells share properties with?
Natural Killer cells and T cells
What kinds of molecules do NKT cells recognize?
Self and foreign lipids and glycolipids
How are lipids and glycolipids presented in regards to NKT cells?
They should be presented within non-polymorphic CD1d molecule (Ag presenting complex like MHC)
IFN-gamma, IL-4 and GM-CSF are produced in large quantities in what cells?
Deficiency or dysfunction of NKT cells leads to..?
- Progression of asthma
T cells which specific recognize antigens, receive signals through their antigen receptors, that increase the affinity integrins for their ligands. What are these two integrins?
VLA-4 and VLA-5
Th1 cells but NOT Th2 cells express high levels of which chemokine receptors?
CXCR3 and CCR5
Which T cell subset expresses high levels of E and P selectin?
Th2 cells express which chemokine receptors
CCR3, CCR4, CCR8
Th17 cells express which types of chemokine receptors?
CCR6 which binds to chemokine CCL20
What is IFN-gamma’s effect on B cells?
promotes switching to certain IgG subclasses (IgG2a or IgG2c) and inhibits switching to IL-4-dependent isotypes (IgE)
What is the negative feedback loop associated with Th1 cells?
Th1 cells produced IL-10 which functions mainly to inhibit dendritic cells and macrophages, which suppresses Th1 activation
Th1 CD40 signals activate transcription factors NF-kB and AP-1, and IFN-gamma activates STAT1. These stimulate expression of enzymes of macrophages. What are these enzymes? What type of macrophage activation is this?
Phagocytic oxidase (creates ROS), inducible nitric oxide synthase (creates NO) and lysosomal enzymes