Cell Mediated Immunity Part 1&2 (Exam 1) Flashcards
What are the two major ways in which TCR differ from BCR
TCR is never secreted
TCR must recognize antigen via MHC and not free antigen
What chain in the T cell is synonymous to the heavy chain in B cells
Beta chain
What chain in the T cell is synonymous to the light chain in B cells
alpha chain
Describe the structure of TCR
two chains: one alpha, one beta
each chain composed of two domains
What does a TCR resemble
a Fab fragment (one arm of an Ab molecule)
when are TCR secreted
never
What is the signaling molecule for T cells
CD3
CD3 is analagous to what
Ig alpha and beta
What is CD3 composed of
5 proteins lodged in the membane
What are the 5 proteins of CD3
gamma-epsilon
epsilon delta
zeta zeta or zeta nu
How is CD3 attached to TCR
covalently
What is CD3 important in
t cell activation and differentiation
What marker can be used to measure total counts of T cells in a patient
CD3 as it is found on Th and Tc cells
What is the proportion of Th to Tc in a healthy individual
2 Th per 1 Tc
What would be the result of a CD3 mutation
lack of T cell activation and proliferation
How many isotypes do B and T cell receptors have
B cells: 2 (IgM and IgD)
T cells: 1 (Alpha/beta)
How many combining sites are on B and T cells
B cells 2
T cells 1
What components are involved in signal transduction in B cells and T cells
B cells: Ig alpha and beta, CD19, CD21
T cells: CD3
Compare B and T cell flexibility
B cells: flexible due to hinge
T cell: rigid
How does gene rearrangement occur in T cell receptors
similar to B cell gene arrangement
Which chain of TCR is rearranged first
Beta chain
What chain of TCR is rearranged second
Alpha chain
What segments comprise beta chain
VDJ
What segments comprise alpha chain
VJ
What are the main differences between B and T cell gene rearrangement
T cells can pick more than one D segment in beta chain
TDT is active during alpha and beta chain rearrangement in T cells, while it is turned off after heavy chain rearrangement in B cells
Where are T progenitor cells released from and what happens after release
Bone marrow. Migrate to thymus for maturation
What are the two steps of thymic education on developing T cells
positive selection
negative selection
What is positive selection
ensuring a cell can recognize MHC; if not it dies
What is negative selection
make sure cell does not attack self antigen; if it does it dies
What type of cells are found within the cortex of the thymus
immature lymphocytes and nurse cells
What occurs in the cortex to immature lymphocytes
selection occurs
What type of cells will be seen within the medulla of the thymus
cells that survive selection; many mature thymocytes
Where does the bulk of T cell development occur within the thymus
cortex
What is the function of macrophages and dendritic cells in the cortex of the thymus
provide MHC 2 for developing T cells
During T cell selection, what type of interaction will lead to formation of Th and Tc cells
If interact with MHC2 –> Th cell
If interact with MHC1–> Tc cell
How will an MHC1 and MHC2 deficiency affect T cell development
Patient with deficiency in TAP (associated with class 1 MHC) will prevent the production of CD8+ T cells due to lack of MHC, will still get CD4+ T cells
Class 2 deficiency: prevents production of CD4+ T cells, more severe
What association is required for differentiation of T cells
intimate association with thymic stromal cells (epithelial, macrophages, dendritic)
A cell is positive for CD4, CD8, CD3, and TCR. What type of cell is this
Pre-T cell
What are the cellular markers present on mature Tc cell
CD3
TCR
CD8
What are the cellular markers present on mature Th cell
CD3
TCR
CD4
Where are mature Tc and Th cells found in thymus
medulla
Where are Pro-T cells found
on the way to the thymus
Where are Pre-T cells found
cortex of thymus
What is the function of CD4
stabilizes MHC2/TCR interaction on TH cells
What is the function of CD8
stabilizes MHC1/TCR interaction on TC cells
How will De George’s syndrome affect T cells
lacking a thymus: no T cells will be made. Will have IgM
How will SCID affect T cells
no T cells entering the thymus, causing thymus atrophy
will not have igM
What is the purpose of positive selection in T cells
ensures that the alpha and beta TCRs expressed in an individual will recognize self MHC
How will Th vs Tc decision occur in thymus
whichever the pre-T cell binds to first determines which T cell it will become
What is the purpose of negative selection in T cells
ensures that thymocytes bearing a high affinity for self MHC or self Ag+ MHC are removed
What selection process can lead to immunodeficiencies if deficient
positive selection
What selection process can lead to autoimmune disease if deficient
negative selection
What determines whether a T cell will become Th or Tc
Interaction with MHC, MHC2 will become Th while MHC 1 will become Tc
What type of cell is used for T cell positive selection
double positive T cell
What is a double positive T cell
has both CD8 and CD4
What type of cell will be selected against in T cell negative selection
cells that bind with high affinity to MHC will die via apoptosis
What type of cell will be selected against in T cell positive selection
cells that cannot bind MHC will die via apoptosis
What is bare lymphocyte syndrome
lack of class 1 expression due to a lack of CD8+ T cells caused by a Tap deficiency
Where do T cells initially contact antigen
in secondary lymph tissue
What interaction initiates activation of T cells
TCR with antigen on MHC
List the signals that occur during T cell activation
- MHC class 2 and antigens
- CD28 adn B7 (co-stimulatory molecules)
- cytokines
Which APC is the best. WHy
dendritic cells; always express B7 and only cell that can activate naive T cells
What is required for macrophages to activate naive T cells
IFN gamma
When can B cells activate naive T cells
after contact with an antigen
What are the only cells that can present antigen to Th cells. Why
APCs; due to co-stimulatory molecules present
What are the APCs
dendritic cells
macrophages
B cells
Where are APCs found
DC: paracortex
B: cortex in germinal centers
M: everywhere
What type of receptors are dendritic and macrophages
innate receptors
What shares a similar structure to CD28
CTLA-4
What do the 3 seignals required to activate T cells have in common
all are pro-inflamamtory cytokines
List the steps in Th cell and macrophage interaction
- MHC and TCR complex with antigen
- Co-stimulatory molecules needed for activation of T cells
- cytokines: IL-1 drives T cell into activation
Once activated, how does a Th cell upregulate
IL-2 receptor with higher affinity will then make IL-2
IL-2 made by T cells for Tcells will lead to production of IFN gamma
IFN gamma activates macrophages
What is the function of IgCAM on T cells
tether t cells and macrophages long enough for interactions to occur
How does a T cell shut itself off
downregulates CD28 and Upregulates CTLA
What is a clinical use of CTLA-4 downregulator
may be manipulated in certain cancer: can be turned off to keep the immune system on
What type of reaction does a Th1 mimic
type 4 hypersensitivity reaction
How might a Th1 reaction be seen clinically
tuberculosis with granuloma
Which cytokine from TH cells activates macrophages
IFN gamma
Which cytokine from Th cells can be used to diagnose TB
IFN gamma through a quanteferon test
Which cytokine from Th cells activates B cells
IL-4
What cytokines do macropahges secrete
IL-1
IL-6
TNF alpha
What are superantigens
viral or bacterial proteins that bind MHC outside of the peptide binding cleft
What effects do superantigens have on T cells
causes less specificty and activation of numerous clones of T cells
What is a disease caused by superantigens
toxic shock syndrome
How is toxic shock syndrome caused
more T cells and macrophages are activate, leading to increased pro-inflammatory cytokines causing a cytokine storm
What is ZAP 70
specific tyrosine kinase seen in T cell signaling
What does activation mean in terms of T cells
changes in gene expression functional changes differentiation cell division cytokine production
What effect would a gain of function mutation in ZAP70 have
excess T cell activation
What could result from a loss of function mutation in ZAP70
T cells do not activate
What are extracellular infections cleared by
antibody, complement, and phagocytes
What type of pathogen always requires CMI for effective clearance
viral
What is the goal of CMI
to destroy intracellular agent by destroying the host cell that harbors it
What type of hypersensitivity reaction will be induced by intracellular bacteria or parasites
delayed type 4 through Th1 and macropahge activation
How do Th1 affect class switching in B cells
release IFN gamma that promotes class switching to IgG
What type of T cell will IL4 act on
Th2
What is the affect of IL4 on T cell
Causes the release of IL4, IL10, IL13, and GF beta
In which type of infection will IL 12 be made
intracellular infections
In which type of infection will IL 4 be made
parasitic infections
In which types of infections will IL6 and TGF beta be made
extracellular bacteria and fungal infections
What type of T cell will IL12 act on
Th0
What does IL 12 do to Th0
causes it to become Th1
What cytokines drive isotype switching to IgE
IL4 and IL13
What cytokine drives isotype switching to IgA
TGF beta
What type of T cell will IL6 and TGF beta act on
Th0
What do IL6 and TGF beta do to Th0
cause to become Th17
What does Th17 secrete
IL17 and IL 22
What is the function of IL 17
activates tissue cells and leukocytes to secrete inflammatory cytokines leading to recruitment of neutrophils
How do Th0 cells differentiate into Th1 cells
when macrophages become activated they make IL12, which acts on Th0
Which cytokine can inhibit TH1
IL10 and IL4 from Th2
Which cytokine can inhibit Th2
IFN gamma from Th1
What is the function of autocrine signaling of IL2 in TH1 cells
induces the t cell to stay activated
also activates Tc cells
What is the function of regulatory T cell
prevents limits the activation of TH1 cells by releasing IL10
What do T reg cells require for development
TGF beta
What is the main cytokine produced by Tregs
IL10
What would be the result in a lack of Tregs
IBS and other autoimmune diseases
Which type of cells are often targeted by intracelllular infections
macrophages
What is perforin
membrane punching, pore forming molecule
What are granzymes
enzymes that damage the target cell
What is a CTL
Tc that bind with class 1 MHC restricted endogenous peptides. Requires IL2 from activated Th1 cell
What does CTL bind to
MHC class 1
WHat receptors interacting on Tc cells will cause a cell to undergo apoptosis
FAs and FASL
What are two ways in which a CTL can kill
- Binding MHC with antigen leads to holes in membrane of cell lackign MHC. Will release perforin leading to damage of membrane
- If Tc recognizes FAS will bind with it using FASL causing cells to die
What cell markers are found on NK cells
CD16 and CD56
What type of cell will recognize a lack of expression of class 1 MHC
NK cells
What are the 2 types of receptors on NK cells
Inhibitory: killing inhibitory receptor (KIR)
Activating: killing activation receptor (KAR)
What do inhibitory on NK cells recognize
MHC alpha chains
What do activating receptors on NK cells recognize
possibly lectins conserved among many pathogens
What receptor if present on any cell can bind to and kill a target cell
Fc gamma receptor
What must be present on a cell that can undergo ADCC
anything with CD16 that can bind IgG can undergo ADCC
What are the effector cells in cell-mediated immunity
CTL
NK cells
macrophages
