BIOL 435 Ch. 10 p.2 (T-cell Activation and more) Flashcards
5 distinct subsets of helper T-cells
- TH1
- TH2
- TH17
- Treg
- TFH
- each produce a distinct cytokine profile and regulates distinct activities within the body
TH1
-regulate immunity of intracellular bacteria and viruses
TH2
-regulate immunity to worms
TH17
-regulate immunity to extracellular bacteria and fungi
Treg
- inhibitory in terminating immune responses and inhibiting autoimmunity
- suppress immune response
TFH
- follicular helper
- regulate humoral immunity (B-cells)
- regulates affinity maturation of germinal centre B-cells
polarizing cytokines for TH17
- TGF-beta
- IL-6
- IL-23
effector cytokines from TH17
- IL-17A
- IL-17F
- IL-22
effector functions TH17
-combats extracellular pathogens in barrier tissues
>autoimmunity
>tissue inflammation
polarizing cytokines for TH2
-IL-4
effector cytokines from TH2
- IL-4
- IL-5
- IL-13
effector functions TH2
- combats infection
- activates eosinphils
- involved in allergies
polarizing cytokines for TH1
- IL-12
- IFN-gamma
- IL-18
effector cytokines from TH1
- IFN-gamma
- TNF
effector functions TH1
- combats intracellular pathogens
- activates macrophages
- tissue inflammation
Type 1 response
-intracellular pathogens inducing cell-mediated immunity
>most viruses, some bacteria and fungi
Type 2 reponses
- pathogens inducing humoral immunity
- particullarly extracellular parasites (ex. worms)
cytokines can achieve TH1/TH2 helper subset cross-regulation
- IFN-gamma
- IL-4
- IL-10
IFN-gamma
-from TH1 responses inhibit IgG1/IgE class switching >a common TH2 induced response
IL-4
-from TH2 responses inhibits production of IgG2alpha
>a common TH1-induced response
IL-10
-from TH2 responses inhibit TH1 responses by suppressing the production of inflammatory mediators from APCs
master regulators
- commit T-cells to one subset or the other
- T-Beta
- GATA-3
T-Bet
-suppressess TH2 pathway gene expression
GATA3
-suppresses TH1 pathway gene expression
TFH cells provide
- wide range of help to B-cells
- required for germinal centre formation
- provide signals that drive affinity maturation
- enhance B-cell class switching
helper T-cells commitment to a lineage
- early in differentiation TH subpopulations may be able to shift
- fluidity makes definitive establishment of helper cell lineages difficult
genetic differences in subset differentiation potential
-may lead to different outcomes >leprosy >HIV >reduced TH1 responses >TH17 for controlling infections
tuberculoid leprosy
-stimulates TH1 responses with high levels of IL-2, IFN-gamma and LT-alpha
lepromatous leprosy
-stimulates TH2 responses with high levels of IL-4, IL-5 and IL-10 from other subsets inducing Treg cells
>not as effective at clearing disease
reduced TH1 response
- due to virally produced IL-10 homolog in EBV infections
- confers a survival advantage
HIV progression
- to AIDS
- possibly influenced by a shift from TH1 to TH2 responses over time
differences in surface protein expression
- between naive, effector and memory T-cells
- subsets differentiated by expression of certain cell surface markers
T-cell memory types
- TCM
- TEM
- TRM
- distinguished by locale and commitment to effector function
TCM cells
- central memory T-cells
- reside in/travel between secondary lymphoid tissues
- live longer/divide more times than TEM cells
- rapidly reactivated by second Ag exposure
- can differentiate into several subsets depending on cytokine environment
TEM cells
- effector memory T-cells
- travel to/between tertiary tissues
- contribute better to first-line defenses
- shift right back into effector functions on second Ag exposure
TRM cells
- permanent residents of perviously infected tissue
- respond upon reinfection
- CD8+ TRM found in multiple tissues
when do memory cells arise?
- early in immune response (3 days)
- TCM before TEM
- TEM derived from fully differentiated effector cells
- arise from assymetrical division of activated T-cells
- self-renewing memory SC populations may be generated during T-cell activation
CD4+ vs CD8+ memory T-cells
-more CD8 than CD4
>proliferate more during their responses
>due to differences in life span (CD4) are shorter lived
memory cells maintained for years?
- seems to depend on cytokine input to induce occasional cell divisions
- IL-17 and IL-15 appear important to homeostatic proliferation