Cytotoxic Cell mediated immune responses Flashcards
Before arriving at CD4+/CD8- and CD8+/CD4- cells, describe the first four cellular stages of the lymphocyte
Stem cell –> Double negative (CD4-/CD8-) –> Pre-T cell –> Double positive (CD4+/CD8+) –> 4 possible outcomes
4 possible outcomes for lymphocytes during selection
strongly recognize Ag-APC –> apoptosis (negative selection)
no recognition Ag-APC—> apoptosis (negative selection)
Weak recognition Ag-APCE –> CD4+/CD8- and CD8+/CD4-
Where does Ag-independent maturation of the T cell occur?
only in the thymus
Thymocytes do what
serve as professional APCs but present BOTH MHC II and MHC I with antigens
activation of T cells occurs in the
LN
Langerhans cells are
immature DCs which do not express B7. found in the epithelia
When do Langerhans cells express B7?
in the LN
what kind of Langerhan cell stimulates naive T cell?
B7 positive
DCs enter the lymph node via the _____ and present AG to naive T cell located in the _______.
afferent lymphatic vessel
parafollicular cortex
CD4/CD8 cells dual function
1) they help FIND the right MHC
2) they help stabilize, “clip” onto the MHC
remember, CDs are signaling coreceptors
B7-CD28 stimulation
co-stimulatory that amplifies the signal
Signal 1 and signal 2
1) Ag-TCR rec
2) B7-CD28 rec
- –> proliferation of T cells specific for bacteria
Activated T cells secrete what to stimulate their own proliferation? The number is increased every ____ hours
IL-2, autocrine stimulation
doubles
APC presents Ag: what are the three subsequent events
1) Activation leads to expression of IL-2R and autocrine IL-2 signaling for proliferation
2) APC detaches before proliferation
NOTE: THEY ARE NOT DIFFERENTIATED YET
in what order is activation, proliferation, and differentiation in?
the one in the question
activation (Ag recognition, followed by IL-2R/IL-2 expression)
proliferation (brought on by IL-2 signaling)
RE-STIMULATION by Ag initiates differentiation
Re-stimulation is required for?
Where does re-stimulation occur?
What cell is responsible for re-stimulation?
differentiation
HOMING: the T cell goes to the tissue from which the Ag was presented in order to be re-stimulated by
tissue macrophages
Steps from naive CD4 T (uncommitted) to fully differentiated TH1/TH2 cell
Naive T cell (uncommitted) + Ag-APC –> Prolif. T cell
Immature effector cell (Th0) + cytokine —> Th1/Th2
differentiation is also called
commitment
restimulation leads to
commitment
Microenvironment includes
macrophages and their secretory products
Why is the microenvironment important
it controls the functional commitments of the T cells
microenvrionment is also called the
cytokine field
the presence of macs and IL-12 drives the Th0 toward
the presence of macs and IL-4 drives the Th0 toward
The absence of IL-12 drives
Th1
Th2
Th2, not necessarily requiring IL-4
Costimulation 1
Costimulation 2
what does the second co-stimulation do?
1 = CD28 --- B7 (APC) 2 = CD40L -- CD40 (APC)
2 increased the expression of MHC and B7
Upregulation of what CD marker is required for B cell activation?
CD40L
To recap:
Th1 —> outcomes
Th2 –> outcomes
Th1
1) Activates macrophages
2) B cell stimulation –> IgG –> complement and opsonization
Th2
1) stimulation of IgE via IL-4–> mast cell degranulation
2) activation of eosinophils via IL-5 (helminth fighting)
Activation of CD8 cells is done via
cross presentation in the LN
DC-Ag presentation just like CD4s
activated CD8s proliferate AND THEN leave the LN
There are three forms of CD8 activation
1) Stimulation+costimulation of CD8 cell without CD4 help
2) Stimulation+costimulation of CD8 with CD4 assistance
3) Stimulation+costimulation of MAC by CD4; Mac goes on to activate CD8s
Three ways CD8 kills infected cells
1) Degranulation of perforin and granzyme
2) Fas-L-Fas (CD95) induced apoptosis
3) IFN-gamma activated MACs
(gamma-delta) T cells. Function:
1) first line of defense
2) regulatory cell
3) bridging innate and adaptive responses
(gamma-delta) T cells. Location
uterus, tongue, intestine
(gamma-delta) T cells. Recognition complex
includes gamma-delta TCR and CD3
What parts of the nontraditional T cell are considered adaptive and what parts are considered innate?
the adaptive = rearrangement of TCRs, development of a memory phenotype
the innate = uses TCR like a PRR
they dont need APCs, and they are not MHC restricted
Slide number 28 has 6 interesting functions listed.
lysis of infected cell apc for alpha-beta t cells helps B cell and IgE production dendritic cell maturation regulation of stromal cell via growth factor production cytokine/chemokine production
(gamma-delta) T cells. Location
uterus, tongue, intestine
(gamma-delta) T cells. Recognition complex
includes gamma-delta TCR and CD3
What parts of the nontraditional T cell are considered adaptive and what parts are considered innate?
the adaptive = rearrangement of TCRs, development of a memory phenotype
the innate = uses TCR like a PRR
they dont need APCs, and they are not MHC restricted
Slide number 28 has 6 interesting functions listed.
lysis of infected cell apc for alpha-beta t cells helps B cell and IgE production dendritic cell maturation regulation of stromal cell via growth factor production cytokine/chemokine production
(gamma-delta) T cells. Location
uterus, tongue, intestine
(gamma-delta) T cells. Recognition complex
includes gamma-delta TCR and CD3
What parts of the nontraditional T cell are considered adaptive and what parts are considered innate?
the adaptive = rearrangement of TCRs, development of a memory phenotype
the innate = uses TCR like a PRR
they dont need APCs, and they are not MHC restricted
Slide number 28 has 6 interesting functions listed.
lysis of infected cell apc for alpha-beta t cells helps B cell and IgE production dendritic cell maturation regulation of stromal cell via growth factor production cytokine/chemokine production
