9 - Adapt 3: T Cell Activation Flashcards
CD4 cells are:
T helper cells
what are the four main Th cells?
Th1
Th2
Th17
Treg
what stimulates differentiation into Th1
IL-12 and IFN-y
what stimulates Th2
IL-4
what stimulates Th17
TGF-B, IL-6, IL-21, IL-1B, and IL-23
where do the cytokines that stimulate differentiation come from
APCs
what stimulates Treg
TGF-B and Foxp3
what is Th1 involved in
cell-mediated immunity (intracellular bacteria and virus, autoimmunity)
what is Th2 involved in
humoral immunity (extracellular parasites, allergy, asthma)
what is Th17 involved in
cell-mediated inflammation, autoimmune diseases (extracellular pathogens and fungi, autoimmunity). Mainly neutrophils
what is Treg involved in
immunoregulation (switching off immune response)
what cell type does Th1 activate, and its effect
macrophages, via IFN-y, leading to cell mediated immunity
what cell type does Th2 activate and its effect
B cells, via IL-4, leading to class switching to neutralize antibodies and IgE
what cell type does Th17 activate and its effect
Neutrophils, via IL-17, to increase acute inflammation
bacteria + partial activation of macrophage with IFN-y =
granulomas in bovine tuberculosis
what is the pathogenesis of Th2 in response to parasites
parasites -> Th2 response -> IL-4, IL-5 and IL-13 -> decrease in parasites from direct killing (from class switching)
what is class switching?
idk I’ll fill this in later
pathogenesis of Th17 for extracellular pathogens
Th17 cells > Th17 cytokines >the
production of pro-inflammatory
cytokines > increase acute
inflammation through the recruitment of
innate immune cells such as neutrophils
> also promote further Th17 activation
in a positive feedback manner >
autoimmune diseases
T/F Treg subtypes activate Th1, Th2 and Th17
false, they suppress it
What causes feline immunodeficiency?
FIV activates Treg cells and replicates within these cells, and the Tregs become a virus reservoir for FIV, improving the viral survival and maintenance in the host. Therefore it is a lifelong disease
Porcine reproductive and respiratory syndrome virus (PRRSV) increase blood Tregs. T or F
true, leading to decreased immune response (because the Tregs are shutting it off)
Tregs in cattle in blood after BLV infection, T or F
true.
What are Memory T cells>
T cells that are first made in response to an antigen, that persist in the body so that a secondary antigenic response can be quicker and faster becuase the cells “remember” the antigen and can recognize is quickly
what happens during immunization
DCs take up antigens and present to naive T cells. Then the T cells are stimulated to proliferate and differentiate into effector and memory T cells
what are the three subsets of memory Tcells
central memory
Effector memory
Resident memory
function of central memory (Tcm) cells
live longer, reside and travel between in
secondary lymphoid organs
function of effector memory T cells (Te)
contribute better at first line of defense
function of resident memory t cells (Trm)
permanent residents of previous infected tissues
CD4 t cell memory
upon reinfection, CD4 memory cells can amount anamnestic responses that are quicker and of higher magnitude than a primary source
CD8 T cell memory
5-10% of CTLs survive after primary infection to become memory CD8 T cells.
Memory CD4 vs Memory CD8 T cells (NOT ON EXAM ACCORDING TO PROF)
Number of memory CD8T > memory CD4T cells
* Memory CD4 T cells proliferate > memory CD8T cells during secondary infection
* Memory CD8T cells more long lived than memory CD4T cells
* Following infection, memory CD4+ T cell help is necessary for the induction of a
memory CD8+ T cell pool
* Memory CD4+ T cell help promotes the induction of tissue-resident memory
CD8+ T cells during mucosal infection
* Regulatory T (T Reg) cells act during the resolution phase of infection to protect
CD8+ T cells from inflammatory signals and promote the survival of memory
CD8+ T cell pool
when do memory T cells arise
within 3 days during the infection
how are memory T cells maintained
IL-15 and IL-7 inputs allow for the maintenance of Memory T cells in the absence of the initial antigen
what is the significance of IL-15 and IL-7
induce occasional division of memory T cells, which is involved in maintaining memory T cells without antigen input
what are the three subsets of cytotoxic effector cells
CTLs, NK T cells, and NK cells
what is the purpose of cytotoxic effector cells
eliminate infected cells and abnormal tumor cells (aka target cells)
what are the two pathways in which CTLs can kill targets
- perforin/granzyme pathway
- Fas (CD95) - FasL (CD95-L) pathway
what are the granules released by CTLs
granzyme, perforin and serglycine
describe the perforin/granzyme pathway
granzymes enter the cell via receptor-mediated endocytosis, and enter the cytoplasm after perforin makes holes in the cell wall (activates apoptotic pathways)
What is critical in the perforin granzyme pathway
ability to bind to target cells proficiently
what is important for receptor phosphorylation in the perforin granzyme pathway
LcK
T/F co-stimulation/signal II is required in the perforin granzyme pathway
false. it is not always required
steps of granzyme perforin pathway
- conjugate formation
- CTL cytoplasmic rearrangement
- CTL granule exocytosis
- Dissociation
- apoptosis of target, recycling of CTL
Describe the Fas (CD95) - FasL (CD95L) pathway
Fas is bound to FasL, which initates a death signal leading to apoptosis (cute lil pathology reminder)
How do NK cells recognize their targets
they recognize the absence of MHC I on their targets and KILL EM
How do NK cells react to healthy cells
healthy cells have lots of MHC I, so they induce a STRONG INHIBITORY signal in the NK cells
how do NK cells react to tumor cells or virally infected cells
tumor cells or virally infected cells often downregulate MHC I, so there will be REDUCED INHIBITION and the NK cells will kill em
how do NK cells react to transformed or some infected cells>
transformed or infected cells sometimes increase the expression of molecules that are recognized by activating NK cell receptors (activating ligands). Thist results in STONG ACTIVATION THAT OVERRIDES INHIBITION and the NK cell will kill em
how do NK cells induce apoptosis of their targets
very similar to CTL, use perforins/granzymes at the junction between the two cells
when are NK cells recruited
earlier than CTLs because they are part of innate response (day 1 ish)
What are NKT cells
cells that are neither NK cells or T cells, and bridge the innate/adaptive immune systems.
do NKTs have a TCR
yes but it is invariant and recognizes glycolipids presented by CD1d
TF: NKT cells only act as killer cells
false. they can act as helper cells by secreting cytokines
TF: NKT cells can form memory cells
false
NKT posses T cell surface proteins rather than NK surface proteins
false. they have NK surface proteins rather than T cell varieties
NKT kill primarily via the __ pathway, but can also kill via the ___ pathway
Fas-FasL, perforin/granzyme
NKT have both ___ and ____ cell types
CD4+ and CD4-
what do both the fas-fasL pathways activate
Caspase-3, which induces apoptosis
What is a clinical application of cell mediated killing?
Chimeric antigen receptors (CARs)
describe CAR immunotherapy
CAR immunotherapy
> modifying a cancer patient’s
own NK or T cells to express CAR and
antigen-specific antibody that
target tumor antigen > re-infusing these modified NK or T
cells back into the patient >
attack and kill cells expressing
the target antigen
what is CAR therapy being used for in vetmed
Canine and feline lymphoma
There is a slide called “Functions of T helper cell subsets”. go review it cuties
did you review it? Did you? D i d y o u?
good job
