Handout 10: Differentiation and Functions of CD4+ T cells Flashcards
How many T cells have a specific TCR that can recognize a given pathogen? What do these T cells with specific TCRs that recognize pathogens do?
1 in 10^6 T cells
These T cells are mobilized and activated
Specific T cells are made by the immune system _____
On demand
Most of the T cells in ciruculation (90-95%) have what type of TCRs?
They have alpha beta TCRs
What do alpha beta TCRs recognize/bind to? What kind of co-receptors do they express?
They recognize/bind to both peptides presented within the MHC molecules and MHC itself
They express either CD4 or CD8 co-receptors
alpha Beta T cells are ______
MHC restricted
Ag recognition involves _______
clustering of TCRs
How is activation of T cells initiated?
By a signaling cascade after TCRs (at least two) recognize a specific Ag
Which parts of the alpha beta TCR signals and which parts are not long enough to signal?
The alpha and Beta chains have only a very short intracellular domain so signaling is mediated by other proteins comprising the TCR complex. CD3 proteins (gamma, delta, epsilon and zeta) have cytoplasmic tail that is long enough to signal
What components are required to activate a T cell?
TCR, CD4 or CD8, and CD3 to activate a T cell. CD4 is needed for T helper cells while CD8 is needed for cytotoxic T lymphocytes (CTLs)
What marker is used for counting total numbers of T cells (CD4 + CD8 T cells)
CD3
What is required to interview naive T cells? How many T cells can in interview per hour?
Activated DC required. Interviews about 500 naive T cells per hour
______ are immature dendritic cells that do not express high levels of B7
Langerhans’ cells
What is the process by which dendritic cells stimulate naive T cells?
- Ag uptake by Langerhan’s cells in the skin
- Langerhan’s cells leave the skin and enter the lymphatic system
- Langerhan’s cells enter the lymph node to become dendritic cells expressing B7
- B7-positive dendritic cells stimulate naive T cells
After the TCR is engaaged and activates T cell, what must the T cell receive?
Co-stimulatory signal
What are the co-stimulatory molecules expressed on professional APC?
B7 proteins (CD80/CD86)
B7 molecules plug into _____ expressed on T cells
CD28 receptor
What is the purpose of co-stimulation?
It’s an amplifier that improves the signal; with co-stimulation, we need about 100 fewer clustered TCRs for activation
What does CD80-CD26 Co-stimulation lead to?
Leads to proliferation and differentiation of T cells specific for a bacterial protein
What happens after T cell activation is completed?
The T helper cell and the APC are separated, and the APC goes on to activate other T cells. The T cells proliferate to increase their numbers.
What is required for the proliferation of T cells and is also called T cell growth factor?
IL-2
Do all T cells have IL-2 receptors (IL-2R) expressed on their surface? If not, which which T cells express IL-2R and which do not?
No, naive T cells do not have IL-2R expressed on their surface. Activated T cells, in contrast produce large amounts of IL-2 and express IL-2R.
Aside from T cell proliferation, what is another function of IL-2?
It enhances resistance of activated T cells to apoptosis
What are the steps in T cell proliferation?
- T cell is activated by Ag and costimulator
- IL-2 is secreted
- IL-2R alpha chain is expressed which results in formation of a high-affinity IL-2R alpha-beta-gamma complex (without the alpha chain, there is low affinity for the T cell)
- IL-2 induced T cell proliferation occurs
What are the phenotypic subsets of CD4 + T cells? These are all what kinds of cells?
Th1, Th2, & Th17 cells. These are all CD4 positive helper cells
Th1 cell Cytokine required to convert CD4+ into Th1 subtype: Signature cytokines: Immune reactions: Host defense: Role in diseases:
Cytokine required to convert CD4+ into Th1 subtype: IL-12
Signature cytokines: IFN gamma
Immune reactions: Macrophage activation; IgG production
Host defense: Intracellular microbes
Role in diseases: Autoimmune diseases; tissue damage associated with chronic infections
Th2 cell Cytokine required to convert CD4+ into Th2 subtype: Signature cytokines of Th2: Immune reactions: Host defense: Role in diseases:
Cytokine required to convert CD4+ into Th2 subtype: IL-4
Signature cytokines: IL-4, IL-5, IL-13
Immune reactions: Mast cell, eosinophil activation; IgE production; “alternative” macrophage activation
Host defense: Helminthic parasites
Role in diseases: Allergic diseases
Th 17 cell Cytokine required to convert CD4+ into Th17 subtype: Signature cytokines: Immune reactions: Host defense: Role in diseases:
Cytokine required to convert CD4+ into Th17 subtype: IL-23
Signature cytokines: IL-17A, IL-17F, IL22
Immune reactions: Neutrophilic, monocytic inflammation
Host defense: Extracellular bacteria, fungi
Role in diseases: Autoimmune inflammatory diseases
Activated T cells do no produce cytokines randomly. Each subset of T helper cells produces particular set of cytokines to carry out specific functions. What are the functions of each subset of T helper cells (Th1, Th2, Th17)? What is this process called?
Th1 cells are used to activate a cell-mediated immune response
Th2 cells activate an Ab-mediated immune response
Th17 cells are involved in inflammation and anti-bacterial response
Process is called differentiation or commitment of T helper cells
What is the sequence of events leading to T helper cell subtype differentiation?
Naive CD4 uncommitted cell–>proliferating T cell–>Immature T cell (Th0)–>Th1 cell or Th2 cell
What is the function of Th1 cell? What is the function of Th2 cell?
Th1 cell: Activates macrophages, induces B cells to produce opsonizing Ab
Th2 cell: Activates B cells to make neutralizing Ab; has various effects on macrophages
What forms an important bridge between innate and adaptive immunity?
Pathogen recognition by immature Dendritic Cells through Pattern Recognition Receptors (PRRs)
- Pattern Recognition Receptor (PRR) signaling causes activation and maturation of ______ which processes Ag and is presented to _____.
- _____ assists in the development and differentiation of Th1 cell
- Differentiation of _____ and ____ occurs in similar manner
- Antigen Presenting Cell, naive Th0 cells
- IL-12
- Th2 and Th17
What produces IL-12? What produces macrophages and IFN-gamma?What does IL-12 and IFN-gamma activate? This stimulates what?
DCs produce IL-12, NK cells produce macrophages and IFN gamma
IL-12 and IFN-gamma activate transcription factors T-bet, STAT1, and STAT4, which stimulates differentiation of naive CD4+ T cells into Th1 subset