Test 1: lecture 7 + 8 T cells cont. Flashcards
T cells are generated by ___
random recombination
activation of T cells requires ___
antigen presenting cell to have the correct:
MHC pepide antigen
costimulatory molecules (CD80, CD86)
cytokines-
CD80 or CD86 binds to ___ on the t cell
CD28
(costimulatory molecules)
what types of cells have MHC class 1
almost all types of cells
CD8 T cells can see these → cytokines or direct lysis of target cells
CD4 T cells can produce ___
help B cells
cytokines
what kind of T cells lead to lysis
CD8
can see MHC class 1
what type of cells have class II MHC?
antigen presenting cells such as:
B cells
Macrophages
DC
as well as epithelial cells of the thymus
class 2 → CD4 → helper B cells and cytokines
Class II is involved in activation of other cells of the immune system
class I pathways gets pathogens from the ___
inside (cytosol)
class II MHC get pathogens from ___
outside cell
__ pathway - peptides from the cytoplasm gain access to this pathway (endogenous).
Class I MHC
CD8 T cells → cytokines and lysis
___ pathway - peptides are within acidified endosomes. They are derived from proteins or pathogens that have been phagocytosed. Thus, they come from outside of the cell (exogenous).
•Class II
CD4 T cells → cytokines and helper B cells
Class I pathway
class 1= intracellular pathogen= CD8 = cytokines and lysis
. Class I made in Endoplasmic Reticulum.
- intracellular proteins from pathogens are degraded by proteasomes.
- Peptides are transported into the ER by TAP (Transporters assoc. w/ Ag processing.
- Peptides bind to Class I
- Peptide loaded Class I molecule goes to cell surface and is expressed .
Class II pathway
Class II = CD4 Tcells = helper B and cytokines
- Class II made in ER
- Invariant chain protects from peptide loading in ER, and targets endosome.
- outside /extracellular Pathogen or Proteins are taken into acidified vesicles and proteases degrade antigen to peptides.
- Invariant chain is degraded, and Class II can bind peptide.
- Peptide loaded Class II molecule is expressed on surface.
invariant chain prevents the breakdown of ___ when it moves from ER to ___
class II
acid vesicle
where do T cells come from?
where do they mature?
from bone marrow → thymus to mature (self vs nonself) → secondary lymphoid tissue (lymphnodes, spleen) to wait for pathogen to trigger
3 main events in the thymus
- TCR gene rearrangement
- Cell selection- positive and negative selection.
- Acquisition of T cell markers (CD4, CD8).
thymus
positive selection in the thymus
•ensures that T cells recognize self-MHC.
T cells that are unable to identify self MHC are killed, the left over T cells that CAN see self MHC are positively selected for
Negative selection in thymus
eliminates many of the T cells that recognize self antigen
T cell presented with self and non self antigens. Those that react to self antigens are killed. Leaving only those that react to non-self
positive selection of T cell
T cell that CAN see self is kept.
negative selection
cells that bind to self antigen are killed
explain + and - selection in thymus
T cells that can identify self MHC are positively selected for. those that can not see self MHC are killed
T cells that react to self antigen are killed. T cells that do not react to self antigen are kept (negative selection)
T cells undergo tolerance induction outside the thymus by ___
peripheral tolerance
anergy
Autoimmune regulator: AIRE- a transcription factor expressed in the thymus that leads to transcription of a wide range of organ-specific genes that are usually only expressed in the ___ tissues
peripheral
how to determine CD4 or CD8
baby T cells have both
in the thymus, pre-T cell will bind to class I or class II
if it binds to class I → CD8+
if it binds to class II→ CD4+
When T cells leave the thymus they have the following characteristics
- They are MHC restricted. (only respond to class I or class II)
- They are self-tolerant (do not react to self antigen)
- They are either CD4 (class 2) or CD8 (class 1)
____ are extensively pleiotropic- having multiple phenotypes, redundant, primarily involved in local effects. They also have a short half-life in vivo, Receptors with several chains, nonantigen-specific.
cytokines
•Binding of a ___ to a receptor induces dimerization or polymerization of receptors
cytokine
•Juxtaposition of the cytoplasmic tails allows engagement of intracellular ___
signaling.
•__ kinases phosphorylate tyrosine residues on receptor and on STATs (signal transducers and activators of transcription)
JAK
•STATs dimerize, translocate to ___and bind enhancer regions of genes induced by cytokines
nucleus
how do cytokines work?
binds to receptor
causes dimerization and activation of JAK
this causes phosphorylation of STATs
these dimerize and enter the nucleus and trigger transcription
Xeljanz
Jak3 inhibitor
prevent transcription from cytokine signal
treat RA, alopecia and psoratic arthritis
apoquel is a ___
Jak inhibitor
prevent cytokine signalling
M1 macrophages
interferon gamma tiggers macrophages into classically activated to kill
IL12 trigger T0 → TH1 → produces INF gamma, IL-2, TNF beta → which trigger “killer” macrophages and NK cells
M2 macrophages
macrophages triggered by IL4, 13
wound healing/tissue repair
TH2 cells produce IL13, TH2 mast cells and basophils produce IL4
IL13 + IL4 → T0 → TH2→ produces IL4,IL5, IL10, IL13 → defense against worms, allergies
B cell growth factor, increase TH2, increase IgE isotype, Eosinophil growth factor, inhibit T cells and macrophages, increase wound healing macrophages (type 2)
regulatory macrophages
macrophages that get IL-10
→ anti inflammatory activity
macro, Treg, and other cells produce TGF beta
TGFbeta → T0 → Treg→ will produce TGF beta and IL10
TGF beta→ increases IgA, inhibits immune response, promotes wound healing
IL10→ inhibits T cell and macrophage function
IFN-gamma triggers ___
M1 macrophages to kill
(classically activated)
IFN gamma is made by TH1 and TFH cells, NK and CD8 cells
IL4 and IL13 trigger __
M2 macrophages to become wound healing or tissue repair
TH2 cells produce IL13, TH2 mast cells and basophils produce IL4
IL13 + IL4 → T0 → TH2→ produces IL4,IL5, IL10, IL13 → defense against worms, allergies
B cell growth factor, increase TH2, increase IgE isotype, Eosinophil growth factor, inhibit T cells and macrophages, increase wound healing macrophages (type 2)
IL 10 triggers
regulatory macrophages
→ anti-inflammatory activity
IL10 is made by Treg, TH2, TH1 and TH17 cells
How do M1 macrophages kill
produce Nitric oxide (NO)
respiratory burst (creates reactive oxygen species) that kill things the macrophage eats
macrophages can do what three major things
kill pathogen (M1 → Interferon gamma (made by T cells))
wound healing (M2→type 2 IL4, IL13 (made by T cells))
anti-inflammatory (regulatory→ IL10 (made by T cells))
how does baby T cell get to dendritic cell?
immature DC will sample environment looking for pathogen with TLR
binds to pathogen and eats it
dendritic cell will become active and present MCH class 2, CD80, CD86 and produce IL-12
mature DC will move into lymph node and wait to bind with T cell with the correct receptor
spectral diseases will have high antibodies at what level of pathogen load
high
spectral diseases will have high delayed-type hypersensitivity at what level of pathogen load
low
____– a reaction dependent upon T cells and IFN-g, but not antibodies. Examples- tuberculin skin test; contact dermatitis
DTH- Delayed-type Hypersensitivity
(spectral disease)
subsets of CD4 cells
Th1 → IL-2, IFN- gamma (kill macrophages)
Th2→ IL-4, IL-5 (tissue repair macrophages)
Th1 is a ___
type of CD4 T cell
produces IL-2 and IFN gamma to produce killer macrophages
IL12 trigger T0 → TH1 → produces INF gamma, IL-2, TNF beta → which trigger “killer” macrophages and NK cells
Th2 is a ___
type of CD4 T cell
produced IL-4 and IL-5 → wound healing macrophages (M2)
TH2 cells produce IL13, TH2 mast cells and basophils produce IL4
IL13 + IL4 → T0 → TH2→ produces IL4,IL5, IL10, IL13 → defense against worms, allergies
B cell growth factor, increase TH2, increase IgE isotype, Eosinophil growth factor, inhibit T cells and macrophages, increase wound healing macrophages (type 2)
IFN- gamma
made by Th1 cells, TFH cells, NK cells, CD8 T cells→ killing macrophages
–Activates macrophages(killer), increases Class II and costimulator expression, and enhances IgG2a.
–Acts on macrophages, dendritic cells, B and T cells.
IL-4
made by Th2 CD4 T cells → wound healing macrophages
–T and B cell growth factor, enhances IgE and IgG1, suppresses macrophage activation.
–Produced by T cells, mast cells, et al.
–Acts on T cells, B cells, macrophages, et al.
TH2 cells produce IL13, TH2 mast cells and basophils produce IL4
IL13 + IL4 → T0 → TH2→ produces IL4,IL5, IL10, IL13 → defense against worms, allergies
B cell growth factor, increase TH2, increase IgE isotype, Eosinophil growth factor, inhibit T cells and macrophages, increase wound healing macrophages (type 2)
Th1 cells help phagocyte mediated elimination of pathogens by ___
IFN gamma → triggering B cells to produce complement binding and opsonizing antibodies
IFN gamma and IL2→activating CD8 T cells → lysis
IFRN gamma → activating M phi (M2- wound healing macrophages)
Th2 cells- mediators of allergy, protection again helminths by ___
IL4 → B cells making IgE (mast cell degranulation)
IL5→ eosinophil recruitment and activation
IL4 and IL13 → alternate way to activate M phi (M2) (wound healing macrophages)
How does Thyroid cell → TH1
IL-12 from macrophage or pathogen tell TH0 to become TH1
TH1 will produce IFN gamma and is important in forming killer macrophages
how does a T cell become TH2
Mast cell and CD4 Tcell produce IL-4
TH2 cells will produce IL 4,IL 13 to create M2 macrophages (wound healing macrophages)
TH2 cells will also create IL-10 to create regulatory macrophages to help with anti-inflammatory activity
___, produced by cells associated with the innate immune response (Macs, DCs), stimulate T cells to develop into Th1 cells.
•IL-12
Th1 produce IFN gamma that stimulate M1 (killer macrophages)
___ produced by T cells, mast cells, basophils, (and other cells) stimulate T cells to develop into Th2 cells.
•IL-4,
Th2 create IL4 IL13→ M2 macrophages (tissue repair)
and IL10 → regulatory macrophages (anti inflammatory)
TH2 cells help basophils, mast cells, eosinophils and B cells respond to parasite infection and mediate ___ responses
allergic
produce IL 4,5, 10,13
IL 4, 13 → M2 tissue repair
IL 10 → regulatory anti-inflammatory
TH1 cells help ___ to suppress intracellular infections
macrophages
produce IL-2, IFN gamma and TNF beta
IFN gamma → killer macrophages
TFH cells
produce IL-21, IL-4, IFN gamma
help B cells become activate, switch isotype and increase antibody affinity
happens in germinal centers
IL-4 → M2 (wound repair)
IFN gamma → killer macrophages
TH17 cells
produce IL-17, IL21
enhance the neutrophil response to fungal and extracellular bacterial infection
T naive (IL6, IL1 TGF beta)→ Th17 (occurs in the lymph node)
____ enhance the neutrophil response to fungal and extracellular bacterial infection
TH17
produce IL-17 and IL21
___ help B cells become activates, switch isotype and increase antibody affinity
TFH cells
produce IL21, IL4 and IFN gamma
Treg cells
produce TGF beta, IL-10
suppress the activities of other effector T cell populations
IL-10 → regulatory macrophages (anti-inflammatory)
Tnaive (TGF beta)→ T reg
___suppress the activities of other effector T cell populations
T reg
produce TFG-Beta, IL-10
IL-10 → regulatory macrophages (anti-inflammatory)
where does CD4 T cell change into TH cells
in the lymph node
high levels of IL4 and IL10 inhibits ___
TH1
high levels of IFN-gamma inhibits ___
TH2
cytotoxic T
CD8 cell
produces cytokines → IFN gamma and TNF
cytotoxins → perforin, granzymes, granulysin
–Perforin- form transmembrane channels
–Enzymes, such as serine esterases and proteoglycans.
–Cytokines- specifically lymphotoxin (TNF)
–Induction of Apoptosis-
kill virus infected cells
___- form transmembrane channels
–Perforin
made by cytotoxic T cells
how to activate cytotoxic T cell
naive T cells binds with antigen presenting cell and specializes
proliferates
travels to tissues → seek and destroy the pathogen
Three Rs of immune response
recognition
response
regulation
•Th1 and Th2 cytokines cross regulate each other. For example, ___ inhibits the development of Th2 cells, while ___ inhibits the development or function of Th1 cells
IFN-gamma
IL-4
•Certain cytokines are particularly important in suppressing immune responses– ___
IL-10
→ regulatory macrophage (anti-inflammatory)
how to create Treg
T naive (TGF beta)
what are some functions of Treg
- Inhibitory Cytokines
- Metabolic disruption
- Targeting Dendritic cells
- Cytolysis of cells
Treg produce TGF beta and IL10
IL10 can inhibit ___
-antigen presentation and IL-12 production
IL-12 → changes naive T to TH1. TH1 cells produce IFN gamma to create killer macrophages
-inhibit the ability of IFN gamma to activate macrophages/ DC
Th2, Treg, TH1 and Th17 all create ___ which will turn off immune response
IL-10
how to create Th2 and what does it do
how to create TH1 and what does it do
how to create Th17 and what does it do
how to create Tfh and what does it do
how to create Treg and what does it do
•After the expansion of T cells in response to an infection (or immunization), the majority of cells ___
die.
induced cell death
IL-1
produces by
major function
monocytes, many other cell types
pro- inflammatory fever
Tnaive (IL6, IL1, TGF beta)→ TH17 → IL17, IL21
IL2 produced by ___. major function
T cells
T cell growth factor
IL-4 produced by ___, major function ___
Th2 cells, mast cells, basophils
B cell growth factor, promotes Th2 cells, IgE isotype, induces alternatively activated macrophages
(wound healing macrophages)
Th2 also make IL 4,5, 10, 13
naive T (CD40L, IL21, IL4)→ Tfh→ IL21, IL4, IFN gamma
naive T (IL-4) → TH2 → IL 4,5,10,13
IL-5 produced, major function
Th2 cells
eosinophil growth factor
naive T (IL-4) → TH2 → IL 4,5,10,13
IL-6 produced by ___, major function
T cells, many other cell types
pro-inflammatory
naive T cell (IL6, IL1, TGF beta)→ Th17 → IL17 and IL21
IL-7 produced by ___ , major function
stromal cells
T cell and B cell growth factor
IL-10 produced by
major function
T cells (regulatory T cells , Th2, Th1, Th17), macrophages
inhibit T cell and macrophage function
(anti-inflammatory)
naive T (TGF beta)→ Treg → TGF beta, IL10
naive T (IL-4) → TH2 → IL 4,5,10,13
IL-12 made by, major function
dendritic cells, macrophages
stimulate NK cells and TH1 cells to make IFN gamma
IL-13 made by, major function
TH2 cells
induce alternatively activated macrophages (wound healing macrophages) (IL-4 does similar thing)
naive T (IL-4) → TH2 → IL 4,5,10,13
IL15
made by and function
T cells and epithelial cells
T cell growth factor
IL-17
made by, function
Th17 cells
pro-inflammatory, increases neutrophil recruitment (fight against fungal and extracellular bacteria)
Th17 also make IL21
Tnaive (IL6, IL1, TGF beta)→ TH17 → IL17, IL21
IFN gamma made by __ and function
Th1 cells, NK cells, CD8 T cells
Activates macrophages (killer), Upregulates Class II, Promotes IgG2a isotype Abs
TNF
made by ___ function___
macrophages, T cells (Th1), other
pro- inflammatory
killer macrophages
TGF beta
made by. function.
Macrophages, T cells (Treg), many other cell types
Increases IgA, inhibits immune responses, promotes wound healing, promotes Treg cells
naive T cell (IL6, IL1, TGF beta)→ Th17 → IL17 and IL21
naive T (TGF beta)→ Treg → TGF beta, IL10
IL-21
T cells (TH17, Tfh)
important for Tfh help for B cells
naive T cell (IL21, IL4, CD40L)→ TFh → IL21, Il4 and IFN gamma
naive T cell (IL6, IL1, TGF beta)→ Th17 → IL17 and IL21
