Unit 5 - Cell Mediated Immunity Flashcards
True or False:
Complement and antibodies are humoral
True
True or False:
Phagocytes and Cytotoxic t-cells are humoral
False
- they are cell-mediated
What binds to CD4?
MHC-II
What binds to CD8?
MHC-I
What are the primary receptors on a Helper T-cells?
CD4
What are the primary receptors on Cytotoxic T-cells?
CD8
What happens if only IL-2 is secreted?
TH1 response
- cytotoxic
What happens if IL-2 AND IL-4 is secreted?
TH2 response
- antibodies
What do naive helper t-cells divide into?
TH1 cells (cell-mediated response) OR TH2 cells (humoral response)
What happens if a cell is not presenting MHC-I?
Natural killer cells will kill it
Where is MHC-I found?
On all nucleated cells
Where is MHC-II found?
On antigen presenting cells
What happens if a TH1 cell secretes IFN-G and TNF?
Cell-mediated response
- Macrophages!
(unit 5, slide 9)
What happens if a TH1 cell secretes IL-2?
Cell-mediated response
- Cytotoxic T-cells
(unit 5, slide 9)
What happens if a TH2 cell secretes IL-2 and IL-4?
Humoral response
- Antibodies
True or False:
TH1 tends to be proinflammatory
True
True or False:
TH2 tends to be proinflammatory
False
- TH2 tends to be ANTI-inflammatory
- except allergy IgE and when complement accumulates
What are the three outcomes of TH1 cell-mediated immunity?
- Inflammation
- Cytotoxic t-cells
- Macrophages (respond rapidly and stimulate local inflammation)
What kind of immunity is associated with Vaccinia virus or Influenza? Where is the pathogen located? What is the antigen presented on? What is the effector cell? What is the outcome?
Cell-mediated immunity Location = cytosol Antigen presentation = infected cell (MHC-I) Effector cell = CD8 + Tc-cell Outcome = directly kill infected cells
What kind of immunity is associated with TB or leprosy? Where is the pathogen located? What is the antigen presented on? What is the effector cell? What is the outcome?
Cell-mediated immunity Location = Macrophage vesicle Antigen presentation = Macrophage MHC-II Effector cell = CD4 + TH1 Outcome = Activate infected macrophages
What kind of immunity is associated with S. aureus, S. pneumoniae or polio virus? Where is the pathogen located? What is the antigen presented on? What is the effector cell? What is the outcome?
Humoral immunity Location = extracellular Antigen presentation = APC and B-cell MHC-II Effector cell = TH1 and TH2 Outcome = B-cell activation, antibodies
What kind of immune response is diminished during pregnancy, why?
TH1 response is diminished (shifts to Th2 response)
- paternal alloantigenic markers would cause a fetus to be the target of Tc-cell rejection
What immunogenic response is amplified during pregnancy?
Th2 response
- allergies would be worse!
- RA (rheumatoid arthritis) would be better during pregnancy
If during pregnancy, the body switches from a TH1 to a TH2 response, what kind of pathogens should we be concerned about?
Latent viruses and cancerous cells
- INTRAcellular pathogens
True or False:
Cytotoxic T-cells require stimulation by Helper T-cells
False
What role do cyctotoxic t-cells perofrm?
Immunosurveillance
- monitor protein expression of almost every nucleated cell
Define immunosurveillance
Monitoring the protein expression of almost every nucleated cell
- performed by Tc-cells
What is expressed on virtually every nucleated cell?
MHC-I
What is unique to every individual?
MHC-I
What protein is very important in regards to transplant immunology?
MHC-I
- b/c it is unique to every individual
What type of cell does not have MHC-I?
RBCs
If a cell is infected with a virus, what molecule will present it?
MHC-I
If a cell has phagocytosed something, what molecule will present it?
MHC-II
True or False:
All t-cells have a t-cell receptor
True
- ALL t-cells have CD3
True or False:
Helper t-cells use CD8 to bind to MHC-II on APCs
False
- they use CD4
(unit 5, slide 18)
True or False:
Cytotoxic t-cells use CD4 to bind MHC-I on nucleated cells
False
- theu use CD8
True or False:
Helper t-cells are … CD3+, CD4+, CD8-
True
True or False:
Cytotoxic t-cells are …
CD3-, CD8+, CD4-
False
- it must be CD3+ because it’s a t-cell!
True or False:
Dendritic cells are CD3+
False
- they have toll-like receptors, not t-cell receptors
What syndrome results if you are born without a thymus?
DiGeorge Syndrome
- patient will not have t-cells (helper or cytotoxic)
If a patient has DiGeorge Syndrome, what kind of pathogens are they susceptible to and why?
Cannot combat intracellular pathogens
- b/c they don’t have Tc-cells
- generally they are able to cope with extracellular bacteria
What are the two functions of CD3, CD4, and CD8?
- Integrins - adhere t-cells to the target cell
2. Signal transduction receptors - send messages into the cell
What are the three things that can be triggered by signal transduction receptors?
- Activation
- Differentiation
- Proliferation
* Reminder = signal transduction receptors are CD3, CD4, and CD8
(unit 5, slide 20)
True or False:
The affinity of the TCR-antigen association is quite low
True!
- a single TCR (cytotoxic t-cell receptor) + antigen interaction is NOT sufficient for the Tc-cell to kill the target cell
Since there is a weak cytotoxic t-cell + antigen association, what are the three ways that it is overcome?
- A large number of TCR + antigen interactions
- MHC-I + CD8 co-receptor interactions
- Expression of ICAMs on the surface of Tc (cytotoxic t-cell)
Describe how perforin kills a cell?
Basically “pokes holes” in the cell membrane
- related to complement C9
- results in cell LYSIS
Describe how granzymes kill a cell?
It is an enzyme that is injected into a cell, which induces APOPTOSIS
- if a cell is infected with a virus, we don’t want to induce lysis, b/c then the cell contents will spill out into extracellular space
How does Fas Ligand kill cells?
When FasL (fas ligand - on Tc-cells) interacts with FasR (receptor - on all nucleated cells in the body), it signals to the cell to die
- basically a self-destruct button on the cell
- induces apoptosis
What immune cells mature in the thymus?
T-cells
What are the three thymic peptide hormones that influence the maturation and differentiation of t-cells?
- Thymulin
- Thymosi
- Thymopoietin
What are the steps involved in t-cell education/maturation?
- Immature lymphocytes migrate to thymic subscapular cortical region
- Recombination generates a random antigen binding site = double negative thymocyte
- Thymocytes express CD3, CD4, AND CD8 = double positive thymocyte
- thymocytes undergo apoptosis unless they bind MHC-I or MHC-II of CORTICAL EPITHELIAL CELLS - Dendritic nurse cells phagocytose autoreactice t-cells
True or False:
Sheep RBCs are able to bind with human t-cells
True
What was the erythrocyte rosette test in the 1970’s?
Sheep RBCs bind with t-cells in a rosette structure
- this makes them heavier
- we could precipitate out the t-cells from the other leukocytes
- instead of centrofusion (which got ALL WBCs = 80% neutrophils)
Instead of using sheep RBCs, what method do we use now to separate out different t-cell types?
StemSep
Antibodies specific to any cell, are conjugated to a magnetic bead
- Antibodies + CD4 = helper t-cells will be collected
- Antibodies + CD8 = Tc-cells collected
- Antibodies + CD3 = all t-cells
Where is CD34 found?
On stem cells
hematopoietic stem cell
Where are CD19 and CD20 found?
On immature leukocytes in lymphoma and leukemia
What is the key marker for the hemtopoietic stem cell?
CD34
Rituxan (Rituximab) is the antibody marker for which CD?
CD20
- for lymphoid progenitors
- lymphoma and autoimmune disorders
In regards to thymic education, what cells perform positive selection?
Cortical epithelium
In regards to thymic education, what cells perform negative selection?
Dendritic nurse cells
Why are antibodies useless in fighting off TB and EBV?
They are INTRAcellular pathogens
True or False:
T-cells that are exposed to tumors can be “trained” to recognize tumor antigens
True
What is a tumor-infiltrating lymphocyte?
A cell that can fight cancer
What are the steps involved in using tumor-infiltrating lymphocytes to fight off cancer?
- Tumor-infiltrating lymphocytes are extracted from within the tumor
- T-cells are engineered to over-produce cytokines (TNF)
- T-cells are cultured with IL-2
What effect does the cytokine TNF have?
Calls out for help from macrophages
What does HIV impair?
Impairs the function of the MHC-II response (TH1 and TH2)
- targets helper t-cells
True or False:
HIV-specific Tc will lyse HIV-infected cells
True
True or False:
The HIV Nef protein reduces the cellular expression of MHC-II
False
- reduces the expression of MHC-I
Why is it important to know that HIV Nef proteins reduce the cellular expression of MHC-I?
Natural killer cells will attack cells that are not expressing MHC-I
- means that NKC are more likely to attack healthy cells (?)
(unit 5, slide 40)
True or False:
AIDSVAX GP120 is an attentuated vaccine
False
- it is a subunit vaccine
Why was HIV GP12- genetically engineered to incorporate inactivated canarypox virus?
B/c canarypox virus causes a very strong CD8+ response (cytotoxic t-cell response)
What is canarypox virus when it is added to HIV?
It’s an adjuvant
- creates a stronger than normal immune response
True or False:
Epstein Barr Virus is an opportunistic herpes virus
True
What does EBV cause?
Infectious mononucleosis
If EBV is reactivated later in life, what is it associated with?
Burkitt and Hodgkins lymphoma
What happens to EBV if you get an organ transplant?
Reactivation!
- you have to receive immunosuppressive drugs for the transplant and EBV is opportunistic
- will lead to the pathogen to re-emerge
What kind of cells patrol for and eliminate cells that are expressing EBC antigens?
Cytotoxic t-cells
True or False:
You can get EBV from a transplanted organ
True!
True or False:
Cytotoxic t-cells cannot act independently from other t-cells
False
- Tc ARE able to act independently from helper t-cells
What is an example of an allogentic Tc-cell transplant?
- EBV seropositive person
- Take out EBV-specific CD8+ leukocytes
- Enhanced the Tc-cell leukocytes to secrete more IL-2
- Re-introduce them to people immunosuppressed with EBV
What phagocytoses M. Tuberculosis?
Macrophages of the alveoli
Why doesn’t TB get digested by phagocytes in the lungs?
TB disrupts the fusion of the lysosome
- so it doesn’t get digested
- prevents the fusion of lysosomes
- they will divide in the cell until they are released by exocytosis
True or False:
Intracellular parasites are protected from antibodies
True
What kind of parasite is Mycobacterium Tuberculosis?
Intracellular parasite
What does the body do to protect itself from TB?
Macrophages and t-cells surround the parasitized cells
- creates a granuloma (mass of leukocytes)
What kind of immune response is very important to fight off TB?
Cell-mediated
- (a humoral response “antibodies”, wouldn’t do anything … b/c it is intracellular
- NEED Tc-cells
How does the t-cell response compare to a b-cell response?
3 things
- T-cell respond faster
- Response is shorter
- Not as effective as b-cells
What is involved in a TB skin test?
Small amount of tuberculin (protein) antigen is administered INTRADERMALLY
- does not induce sensitization (does not cause antibodies to be made)
- generates a response in people who were previously sensitized
True or False:
When you get a TB skin test, they inject a small amount of the bacterium intradermally
False
- they do not inject the bacterium
- they are putting in tuberculin, a protein
Why will a blister form on some people when they get a TB skin test?
If they were previously exposed to TB, they have antibodies made against the antigen AND
infiltration of pro-inflammatory sensitized t-cells and macrophages cause local inflammation
True or False:
Vaccines that stimulate a modest Tc-cell response have a small protective effect against HIV
True
