Adaptive Immune Response to Intra- and Extracellular Pathogens Flashcards
The goal of the immune response to intracellular pathogens are to _____ against infection (B Cells) and _____ an established infection (NK Cells or CD8+).
Protect
Eradicate
NK cells are used by the _____ immune system; whereas CD8+ CTL are used by the _____ immune system to eradicate an established infection.
innate
adaptive
_____ mediates enhancement of the cytotoxic activity of NK cells and CD8+ cytotoxic T lymphocytes
IL-12
Activation of NK cells lead to __________ which kills the infected cell.
Degranulation
Antigen specific ______T Cells and cytotoxic ______ T Cells are involved with eradicating intracellular pathogens.
CD4+
CD8+
How is NK cell activity inhibited?
The inhibitory receptor binds Self MHC I-self peptide complex
If the NK cell is activated, what has the virus inhibited?
MHC Class I Expression
Naive T cells come into contact with _____ in lymph nodes which is necessary for activation of the T cell.
Antigen Presenting Cell
T cells become activated by:
- TCR recognition of _______ on APC
- _________ molecule binding
Peptide:MHC
Co-Stimulatory (ex. CD28-B7)
The interaction between dendritic cell and naive T cell and binding of co-stimulatory molecules CD28 and _____ causes activation of the T cell.
B7
Which co-stimulatory molecules are necessary for the T cell dependent pathway to activate B cells?
CD40L with CD40
If an infected cell is negative for MHC class I, what will happen to the cell?
The infected cell will be killed by NK cells
The receptor for naive T cells is ___-selectin; whereas, the receptor for activated T cells is ____ or ____ selectin ligand.
Naive = L-selectin Effector = E- and P-selectin Ligand
The receptor for naive T cells is ___-selectin; whereas, the receptor for activated T cells is ____ or ____ selectin ligand.
Naive = L-selectin Effector = E- and P-selectin Ligand
Activated T cells must migrate to __________ and be retained so that they can express their effector functions and eradicate virally infected cells.
the site of infection
Macrophages ______ and T cells ________.
Kill
Protect
Macrophages are activated by CD___: CD_____ and by ______.
CD40L:CD40
IFN-gamma
What are three responses that occur due to activation of macrophages?
- Killing of phagocytosed microbes
- Increased expression of MHC molecules and co-stimulatory molecules (B7)
- Secretion of cytokines (TNF, chemokines, IL-1, IL-2)
If a dendritic cell or macrophage ingests a microbe, it will release IL-12 and cause the differentiation of Naive CD4+ T Cell into ______ which will release IFN-gamma for the activation of macrophage.
Effector T Cell (T helper I Cell)
What are the three common cytokines that Th2 Cells will release in order to inhibit macrophage activation?
IL-10
IL-4
IL-13
What is CTL targeting?
A CTL will kill targets that express the same Class I-associated antigen that triggered the proliferation and differentiation of naive CD8+T cells to become CTLs.
What is CTL targeting?
A CTL will kill targets that express the same Class I-associated antigen that triggered the proliferation and differentiation of naive CD8+T cells to become CTLs.
What are the three important biochemical signals (kinases) that activate CD8+T cells to proliferate and differentiate into CTLs?
MAP kinases (AP-1)
Protein Kinase C (NF-kB)
Calcineurin (NFAT)
How does the CTL lyse a target cell?
Lytic Granules
Fas-FasL
What are the proteins within lytic granules of cytotoxic T Cells?
Perforin
Granzymes
Granulysin
What is perforin?
A protein in lytic granules that polymerizes to form a pore in the target membrane
What is a granzyme?
A serine protease (protein in lytic granule of T cell) that activates apoptosis in the cytoplasm of the target cell
What is granulysin?
A lytic granule protein of cytotoxic T cells that induces apoptosis of the target cell
What is granulysin?
A lytic granule protein of cytotoxic T cells that induces apoptosis of the target cell
How do granzymes enter the target cell?
A cytotoxic T lymphocyte releases Granzyme B and Perforin (lytic granules) via exocytosis.
- Perforin molecules create a Polyperforin Pore in the target cells membrane that allows entry of apoptotic Granzyme molecules
- ALSO, CI-MPR (receptor) will bind Granzyme and the complex will be engulfed in a vesicle and brought into the target cell
______ creates pores in the target cell membrane.
Perforin
What are the three pathways that Granzyme B uses to induce apoptosis of the target cell?
- Activation of Caspase 3
- Activation of CAD directly
- Activation of BID (mitochondria)
Describe how Granzyme B induces apoptosis (starting with caspase 3).
- Granzyme B activates Caspases, especially Caspase 3
- Caspase 3 leads to Caspase Activated DNAse (CAD)
- CAD causes DNA fragmentation = Apoptosis
What is the action of Caspase Activated DNAse?
CAD causes DNA fragmentation and, thus, apoptosis
What is the action of Caspase Activated DNAse?
CAD causes DNA fragmentation and, thus, apoptosis
Granzyme B has three pathways leading to apoptosis, two of which use CAD to fragment DNA. The third pathway cleaves DNA through activation of ________.
ENDOG
Describe the Granzyme B pathway that begins with activation of BH3-interacting domain death agonist (BID).
- Granzyme B enters the target cell and activates BID
- BID destroys the integrity of the mitochondrial outer membrane and induces the formation of the BAD/BAX channel
- Pro-apoptotic factors are released from the mitochondrial membrane
- Cytochrome C will activate Caspase 9 and endonuclease G (ENDOG) = cleaves DNA = apoptosis
Granzyme B cleaves DNA through either _____ or ______.
CAD
(two pathways: caspase 3 or CAD directly)
ENDOG
(BID >BAD/BAX>Cyto C > Caspase 9 >ENDOG)
Granzyme B cleaves DNA through either _____ or ______.
CAD
(two pathways: caspase 3 or CAD directly)
ENDOG
(BID >BAD/BAX>Cyto C > Caspase 9 >ENDOG)
The release of T cell granules occurs over a somewhat specific time line:
T zero = cell binds to target cell, no granules nearby
T 1min - 4min = granules move toward point of contact
T 40mins = ______________
Release of granules into space between T cell and Target cell. Target cell has begun apoptosis at this time.
Other than lytic granules, how can cytotoxic T cells lyse a target cell?
Fas:FasL
FasL is on the ______ and Fas is on the ________.
CTL
Target Cell
Interaction = apoptosis (death receptor pathway)
How do Fas:FasL interactions eradicate cells infected with intracellular pathogens?
- Fas receptor trimerization activates the death domain
- FADD leads to signaling cascade that activates caspase 8
- Caspase 8 activates BID and/or Caspase 3
- The caspase cascade leads to DNA fragmentation
Bax/Bak is associated with the ________ pathway of apoptosis, whereas BAD/BAX is associated with the _____ pathway of apoptosis.
Fas/FasL
Granzyme B
Bax/Bak is associated with the ________ pathway of apoptosis, whereas BAD/BAX is associated with the _____ pathway of apoptosis.
Fas/FasL
Granzyme B
Fas-mediated killing is important for the maintenance of T Cell _______.
Self-tolerance
Both Fas and FasL are members of the _____ family of proteins.
TNF
Which cells produce IFN-gamma in order to activate macrophages?
CD4+ T Cells
Which cells produce cytokines to provide stimulation for CD8+ T cell activation?
CD4+ T Cells
Which cells produce cytokines to enhance the activity of APCs?
CD4+ T Cells
Why are CD4+ T Cells important (3 main functions)?
- Production of cytokines to stimulate CD8+ T Cells
- Production of cytokines to enhance APC activity
- Production of IFN-gamma for activation of macrophages
How do intracellular pathogens try to thwart the immune response?
- Inhibit ______ activity
- Block _____ transport
- Block _______ synthesis or retention
- Removal of _____ from the ER
- Interfere with ________ by “decoy”
- proteasomal
- TAP
- MHC
- Class I
- Cytotoxic T Lymphocytes
The immune response to EXTRAcellular pathogens is initiated by ______ and _______.
Macrophages
Neutrophils
The immune response to EXTRAcellular pathogens is initiated by ______ and _______.
Macrophages
Neutrophils
Once inside a lysosome, microbes are killed via _____ and/or ______.
ROS
NO
_____ Immunity is referred to as a driver of cell mediated immunity.
Th1
Which cell type will activate IFN-gamma?
Th1
What does IFN-gamma do?
- Increases MHC expression
- Activates macrophages
- Activates class switching
- Induces formation of Th1 effector cells
Isotype switching occurs when _____ acts on B cells.
IFN-gamma
Th2 immunity drives the ______ response.
antibody (humoral)
Interleukin 4 and co-stimulatory molecules ________ induce the production of IgG and ______.
CD40/CD40L
IgE
Which cytokine will activate eosinophils in the presence of parasites?
IL-5
Which cytokine is closely associated with isotype switching?
IL-4
What is the “default” antibody that does not require any isotype switching?
IgM
The humoral immune response involves _____ production.
Antibody
How are B cells activated?
- Recognition by B cells leads to a signal transduction cascade that ultimately activates the B cell
- Soluble antigen initiates crosslinking of immunoglobulin receptor which results in production of IgM
B cells do not need MHC for activation because they themselves are ________ cells.
Antigen-Presenting
______ are the receptors on B cells.
Antibodies
True or False: All B Cells produce antibodies.
False. Naive B cells canNOT produce antibody, they must become activated.
B cells can be activated by _______ or soluble _______.
Microbes
antigen
When a soluble antigen activates B cells through its IgM receptor, proliferation will result in what kind of B cells?
B cells that have IgM receptors
When a soluble antigen activates B cells through its IgM receptor, proliferation will result in what kind of B cells?
B cells that have IgM receptors
What two changes can result from B Cell exposure to microbes?
Changes in phenotype and function
Where do T cells and B cells interact?
Lymph Nodes
How is Isotype switching in B cells dependent on T cell interactions?
A dendritic cell may present antigen to a helper T cell through interaction of B7 and CD28. The T cell expresses CD40 ligand and begins releasing cytokines. Through the CD40L and the cytokines, the T cell will now activate a specific B cell.
Isotype switching in B cells is dependent on T cells (interaction through CD40-CD40L) and the released _______.
Cytokines
Activated B cells will go through isotype switching after T helper cell interaction and will respond to different cytokines. To change to the IgG isotype, B cells will interact with _____ cytokine. To change to the IgE isotype, B Cells will interact with _____ cytokines.
IFN-gamma = IgG IL-4 = IgE
_____ is secreted onto mucosal surfaces.
IgA
What type of B cell-derived cells will produce and secrete antibody?
Plasma cells
High-affinity Ig-expressing B cells are also known as _____.
Memory B cells
Plasma cells take up residence in _______.
Bone marrow
Memory B cells take up residence in _________.
Secondary Lymph Nodes
What is the effect of complement activation?
Inflammation (due to “a fragments”) and cascade effect (due to “b fragments”)
What is the effect of complement activation?
Inflammation (due to “a fragments”) and cascade effect (due to “b fragments”)
NK cells are part of which arm of the immune system?
Innate (even though they are lymphoid derived)
What is active immunization?
Vaccination
What is induced by vaccination?
Adaptive Immunity
Immunological Memory
Protection
Vaccinations can be of what two forms?
Live-attenuated
Killed (inactive)
What is passive immunization?
Passive injection of preformed antibodies
True or False: The two public health interventions that have had the greatest impact on the world’s health are clean water and vaccines.
True
To which category of vaccines do most successful viral vaccines belong?
Live Attenuated
What are heterologous vaccines?
Vaccination through the use of closely related organisms of lesser virulence that share many antigens with the virulent organism (i.e. Smallpox eradication through vaccinia or cowpox)
What are live recombinant vaccines?
Vaccines that have been genetically engineered to contain a gene that codes for an immunogenic protein of interest but came from a different organism.
Which category of vaccines has good immune response in a single dose, danger of reversion, and is inexpensive?
Live Vaccines
Killed vaccines have a poor immune response because it has primarily an ______ response and very little ______ .
Antibody response
Very little cell-mediated
A vaccine is considered to be very good if it produces what two responses?
Humoral Immunity: Protection against infection
Cell-Mediated Immunity: Eradication of infection
True or False: Antibodies can only neutralize microbes.
False: antibodies can neutralize microbes or toxins
True or False: Antibodies can only neutralize microbes.
False: antibodies can neutralize microbes or toxins
Through which receptor will antibody-opsonized microbes bind to a phagocyte?
Fc Receptors will bind a microbe that has been opsonized by antibody.
_______ Activity is enhanced by antibody.
Complement
Which complement fragments will recruit and activate leukocytes?
C3a and C5a
