T cell mediated immunity Flashcards
Which T cell is the direct effector T cell arm?
CD8 T cells
Which T cell is the regulatory T cell arm?
CD4 Th cells
Which T cell has a targeted effector function?
Both CD8 and CD4 Th
Which T cells kill infected or diseased cells?
CD8 cells
Which T cells enhance innate and apaptive immunity?
CD 4 Th cells
What initiates T cell immunity?
Antigen presentation
What is the most common T cell activator?
Dendritic Cells
*DCs must be activated
Where does antigen presentation occur?
In secondary lymphoid organs
Dendritic cells mature through ____________
Antigen activation
Immature dendritic cells in peripheral tissues encounter pathogens and are activated by what?
PAMPs
In dendritic cell maturation, after being activated by PAMPs, ______ signaling induces ____ and enhances processing of _________
- TLR signaling
- CCR7
- Pathogen-derived antigens
What role does CCR7 play in dendritic cell maturation?
- Directs migration into lymphoid tissues
- Augments expression of co-stimulatory molecules and MHC molecules
Mature dendritic cell in ______ primes ______
- T-cell Zone
2. Naive T cells
Dendritic cells are targeted to lymph nodes by ______ binding _____ and ________
- CCR7
- CCL19
- CCL21
Dendritic cells take up _____ in the skin and then move to enter a draining ____
- Bacterial antigens
2. Lymphatic vessel
Dendritic cells bearing antigen enter the draining lymph node, where they settle in the ______
T-cell area
T/F Antigen presenting cells distribute differentially in lymph nodes
True
Dendritic cells are primarily associated with what areas?
T cell areas
Macrophages are primarily associated with what areas?
All areas
B cells are primarily associated with which areas?
B cell areas
Dendritic cells present antigen by ____ and ____
- MHC I
2. MHC II
What is critical for CD8 T cell activation?
Cross-presentation
Circulating naive T cells are exposed to antigens at ______
Lymph nodes
T/F Naive T cell population stays the same through lymph nodes
False, the naive T cell population rotates through lymph nodes
Naive T cells monitor ______ presented by __________
- Antigens
2. Dendritic cells
T cells and Dendritic cells form _______
Immune Synapses
List the steps of a formation of an immune synapse between a T cell and dendritic cell
- T cell initially binds dendritic cell through low-affinity LFA-1:ICAM-1 interactions
- Subsequent binding of T-cell receptors sends signal to LFA-1
- Conformational change in LFA-1 increases affinity and prolongs cell-cell contact
What are the two different regions of the immune synapse formed by T cells and dendritic cells?
- c-SMAC (inner)
2. p-SMAC (outer)
How many signals does T cell activation require?
3
What are the three kinds of signals that APCs deliver to naive T cells?
- Activation
- Survival
- Differentiation
What are the 3 specific things involved with each type of signal received by a naive T cell?
- Activation: T cell receptor
- Survival: Co-Stimulatory molecules
- Differentiation: Cytokines
When signaling activation, name 3 things that are associated with the T cell receptor
- Peptide recognition
- MHC I or II
- CD8 or CD4
When signaling Survival to a naive T cell, name 4 things associated with Co-stimulatory molecules
- Survival signal
- B7 family (APC)
- CD28 family (T cells)
- *B7-CD28 required for T cell activation
When signaling differentiation to a naive T cell, name 3 things associated with cytokines
- Paracrine and autocrine signaling
- Propagation (IL-2)
- Differentiation
IL-2 signals differentiation for which cells?
- CD8
- All Th
IL-4 signals differentiation for which cells?
Th2
IL-6 signals differentiation for which cells?
Tfh
IL-12 signals differentiation for which cells?
Th1
What combination of cytokines signals differentiation for Th17?
TGF-B + IL-16 + IL-23
What cytokine signals differentiation for Treg cells?
TGF-B
List the different cytokines involved with signaling differentiation
- IL-2
- IL-4
- IL-6
- IL-12
- TGF-B + IL-16 + IL-23
- TGF-B
Co-stimulation is required for ______
Activation
What happens when you have a specific antigen and co-stimulator?
T cell is activated and proliferates
What happens when you have the specific antigen alone?
T cell becomes anergic
What happens when an anergic T cell comes in contace with specific antigen and co-stimulator?
T cells stays anergic
T/F B7 is only expressed on APCs that have been activated
True
Naive T cell TCR activation in the absence of co-stimulation leads to _______
anergy
Activation induces what T cell changes?
- Differentiation
- Clonal expansion
- Changes in surface protein expression
- Migration to target tissues
- Effector functions
CD8 T cells differentiate into what?
- Effector cells
- Memory cells
CD4 T cells differentiate into what?
- Th1, Th2, Th17, Tfh, Treg
- Effector cells
- Memory cells
What tissues will T cells migrate to?
- Lymph nodes
- Sites of infection or damage
IL-2 drives _____
Clonal expansion
*for all T cell lineages
Resting T cells express only a ______ IL-2 receptor
Moderate affinity
*IL-2R Beta and gamma chains only
Activated T cells express a ________ IL-2 receptor and secrete _______
- High-affinity
- IL-2
*IL-2 R Alpha, Beta, and Gamma chains
Binding of IL-2 to its receptor signals the cell to _______
Enter the cell cycle
IL-2 induces ________
T-cell proliferation
What type of signaling is prevalent in T cell proliferation and clonal expansion involving IL-2?
Autocrine signaling
What inhibits T cell activation and proliferation?
CTLA-4
What does CTLA-4 stand for?
Cytotoxic T lymphocyte-associated protein 4
T/F CTLA-4 binds B7 with less avidity than does CD28
FALSE, It binds more avidly and delivers inhibitory signals to activated T cells
T/F T cells Die after effector functions are performed
False
CLTA-4 is expressed on which type of T cells activated or resting?
Activated
B7 binds CTLA-4 how much stronger than it will bind CD28?
Twenty fold
CTLA-4 binding an APC after activation leads to what?
T cell inhibition
You could say that CD8 T cells are selective serial killers T/F
True
Do CD8 T cells die once effector functions are complete?
No
CD8 T cells only kill cells expressing what?
Targeted peptide via MHC I
CD8 T cells differentiate into _____ and _______ cells
- Effector
2. Memory
T/F CD8 T cells kill repeatedly
True
How many ways are there to activate Naive CD8 T cells?
Two
What are the two ways to activating a Naive CD8 T cell?
- Dendritic cells infected with some types of virus can activate a naive virus-specific T cell on their own
- Dendritic cells infected with some viruses need help to activate a naive virus-specific CD8 T cell
What are the steps for activating naive CD8 cells via dendritic cells that can activate T cell on their own?
- Dendritic cell sends a sufficiently strong signal to activate the CD8 T cell to effector status
- Activated Virus-specific CD8 T cell makes IL-2, driving its own proliferation and differentiation
What are the steps for activating a naive CD8 T cell by dendritic cells that need help?
- Dendritic cell activates virus-specific CD4 T cell to secrete Il-2 and virus-specific CD8 T cell to express IL-2 receptors
- IL-2 from the CD4 T cell drives the proliferation and differentiation of the virus-specific CD8 T cell
CD8 T cells kill repeatedly, but also _______
specifically
T/F CD8 T cells require a secondary signal to kill
False
Protein granules of Cytotoxic T cells contain what 3 things?
- Perforin
- Granzymes
- Granulysis
What do perforins do?
Aids in delivering contents of granules into the cytoplasm of target cell
What do granzymes do?
They are serine proteases, which activate apoptosis once in the cytoplasm of the target cell
What does granulysis do?
Has antimicrobial actions and can induce apoptosis
What type of apoptosis can be induced via CD8 T cells?
Caspase-mediated apoptosis
CD8 T cells kill through ______ and _______
- Perforin
2. Granzymes
CD4 differentiation involves what 3 things?
- Cytokine Induction
- Transcription factor
- Effector cytokines
Th1 cells are involved in which type of adaptive immunity?
Cellular
Th2 cells are involved in which type of adaptive immunity?
Humoral
What induces CD4 T cell subtype differentiation?
Cytokines
Differentiation is a response to _______
Pathogen exposure
T/F Each T cell has unique effector cytokines
True
Cytokines that induce CD4 differentiation come from what two sources?
- APC itself
2. Immediate environment
Th1 activate ________
Macrophages
What do Activated macrophages do?
- Express co-signaling ligands
- Kill intracellular pathogens
- Release cytokines and antimicrobial effectors
- Present antigen
When pathogens cannot be cleared, what do T cells do?
Form Granulomas
Define Granuloma
A compact aggregate of leukocytes that sequester a pathogen
T/F Pyogenic granulomas are not true granulomas
True
Th1 cytokines enhance Induced innate response T/F
True
Th2 cells promote __________
Tissue protection and repair
What type of cell responds to prolonged extracellular infection?
Th2
What effect do Th2 cells have on Mast cells and eosinophils?
Recruitment and activation
T/F Th2 cells release cytokines
True
T/F Th2 cells do not activate B cells, that’s a Th1 thing
False, they activate a different class than Th1
Granulomas are present in a state of ________
Chronic inflammation
T/F Both infectious and non-infectious agents are contained within Granulomas
True
How many types of granulomas are their?
Several
What do Tfh cells do?
Activate B cells and induce class switching
What are the preliminary steps of B cell activation by Tfh cells?
- The Tfh cell recognizes a peptide derived from the B cell’s antigen
- Naive B cell and Tfh cell exchange signals that begin the process of B-cell activation
Treg cells _______ other T cells
Suppress
T reg cells prevent ___________ in the lymph node
T cell activation
Treg cells stop _________ and prevents _______
- Adaptive immune response
2. Autoimmunity
What is required in order for a Treg to suppress an autoreactive T cell?
It requires them to interact with the same APC
Th17 and Treg cells regulate ________
Mucosal inflammation
What cell inhibits mucosal inflammation?
Treg cells
Th17 and Treg cells are _______ in the gut
enriched
What 3 things do Th17 cells do to regulate mucosal inflammation?
- Neutrophil recruitment
- Antimicrobial peptide production
- Tissue repair
Persistent Th17 involvement is present in some autoimmune conditions. Give 4 examples of such conditions
- Rheumatoid Arthritis
- Multiple Sclerosis
- Psoriasis
- Inflammatory bowl disease