What genes are expressed by an activated T-cell and what are their roles? (3)
1) IL-2 cytokine - secreted by the T-cell and has autocrine activity to stimulate proliferation
2) IL2R(alpha) chain - a chain of the IL-2 receptor that establishes its high affinity so that only activated cells will proliferate upon IL-2 release
3) CD40L - binds to CD40 on APC cells providing an amplification signal to maintain APC immune response.
How do CD4+ T cells differentiate into TH1 cells? Cytokine? (2) Microbe? Effect? Role in disease? (2)
Cytokine: IFNy, IL12
Microbe: intracellular bacteria
Effect: activate macrophage --> kill bacteria
Role in Disease: autoimmune, tissue damage associated with infection
How do CD4+ T cells differentiate into TH2 cells? Cytokine? Microbe? Effect? Role in disease?
Effect: Activate B cells --> secrete antibodies to parasites and allergens
Role in disease: Allergies
How do CD4+ T cells differentiate into TH17 cells? Cytokine? (3) Microbe? (2) Effect? Role in disease?
Cytokine: TGF-B, IL6, IL23
Microbe: Extracellular bacteria and fungi
Effect: Activates PMNs --> kill bacteria and fungi
Role in disease: Organ specific autoimmunity
How do effector T cells recognize antigen?
Only needs the first signal to recognize antigens: TCR and CD4/CD8 co-receptor recognize MHC/antigen complexes presented by APC's
Generally, how do effector T cells know where to go to fight infection?
The inflammatory response releases cytokines TNF and IL-1 and chemokines that bind to the endothelial cells and increase in concentration at the site of infection T cells have high-affinity forms of LFA-1 and VLA-4 that bind to the endothelium at the site of infection
What is the role of L-selectin, E-Selectin, and P-Selectin in the immune response?
L-selectin: effector T-cells lose the expression of L-selectin, which prevents it from migrating back to lymph (along with CCR7)
E and P-Selectin: Effector T-cells increase expression - increase ability to migrate to site of infection (along with CXCR10)
How is the site of infection marked? (3)
1) cytokines (TNF and IL1) and chemokines are released by macrophages 2) vasodialation and increased vascular permeability cause redness, heat and swelling 3) inflammatory cells migrate into tissue releasing mediators that cause pain
What cytokines are released at the site of infection? (2)
TNF and IL-1
What types of T cells will go towards the site of infection?
ALL effector T cells, recognizing an array of antigens, will become concentrated at the site regardless of which antigen they recognize.
What T-Cell receptors mediates trafficking to lymphatic tissue? (2)
CCR7 and L-selectin
What T-Cell receptors mediates trafficking to peripheral tissue? (2)
CXCR10 and E/P-Selectin
What is the role of TH1 cells? Produce? Express? Functions? (3)
Functions: 1) induce isotype switching in B Cells
2) Increase microbial killing capacity of phagocytes (marcrophages and PMNs)
3) induce b7 from APC so that CD8 cells can differentiate into CTL
What is the response of an activated macrophage? (3)
1) production of reactive oxygen spcies
2) Secretion of cytokines (TNF, IL-2, IL-12)
3) increased expression of MHC molecules and costimulators
What is the positive feedback loop between TH1 cells and marcrphages and how do you stop it?
1) TH1 cells secrete IFN-y cause macrophages to secret IL-12
2) IL-12 causes CD4+ T Helper cells to differentiate into more TH1 cells
To stop it: kill/remove all pathogens
What is the role of TH2 cells? Produce? Functions? (4)
Produce: IL-4, IL-5, IL-13, IL-10
Functions: 1) induce isotype switching in B cells to produce antibodies (IgE is main one)
2) Increase tissue repair processes of marcophages
3) inhibit macrophage killing
4) Activate eosinaphils
What cytokine from what cell activates eosinophils?
IL-5 from TH2 cells
How do the functions of TH1 cells and TH2 cells interact?
The functions "do not get along". IL-4, IL-10 and IL-13 from TH2 cells inhibit macrophage killing, therby counteracting the effects of TH1 cells, which release IFN-y and TNF to increase macrophage killing
What is the role of TH17 cells? Produce? Functions? (3)
Produce: IL-17, IL-22
Functions: 1) stimulate inflammation increase recruitment of PMNs, monocytes to sites of infection (early stages of inflamation)
2) Maintain epithelial barrier integrity
3) stimulate antimicrobial peptides to kill bacteria
What does IL-17 do? (2) What cell releases it?
TH17 secret IL-17
IL-17 increases the inflammation response and causes the secretion of antimicrobial peptides
How do CTL cells kill?
Secretes: Perforins: creates pore in cell Granzymes: serine protease which activates apoptosis in infected cell Fast Ligand: induces apaptosis by binding fas receptor on target cell
How does CTL get activated from naive CD8 positive T Cells? (2)
Direct: Recognize antigen/MHC Class I complex (first signal) plus HIGH levels of costimulatory molecules (2nd signal - CD28 from T-cell binds with B7 from APC)
Indirect: First signal is normal but second signal not adequate. TH1 cells express CD40L and secrete IFNy which upregulate the co-stimulatory molecules (more B7 to provide second signal)
What is Toxic Shock Syndrome?
A bacterial "superantigen" activates T cells by binding outside binding cleft of many MHC molecules, bypassing the specificity of MHC molecules. Massive unregulated release of cytokines leads to a NON-CLONAL expansion of T cells. Symptoms: Hypotension, change in vascular permeability, change in live function
What types of antigens do BCR and TCR recognize?
TCR: Peptides BCR: protein, lipid or lipoprotein