Where is the pluripotent stem cell found?
Embryonic yolk sac, fetal liver, bone marrow
Pluripotent stem cell can differentiate into two types of cells: _________ and __________.
Myeloid and lymphoid
The stem cell compartment contains which types of cells?
Pluripotent stem cells, myeloid and lymphoid stem cells
Lymphoid cells differentiate into __________, which are found in the progenitor cell compartment.
Pre T cells
Pre B cells
Lymphoid cells can go down two paths of differentiation: list the cells in each path.
Lymphoid stem cell -> pre T cell -> T cell
Lymphoid stem cell -> pre B cell -> B cell -> lymphoblast -> plasma cell
Which types of cells are found in the functional compartment?
T cell, B cell, lymphoblast, plasma cell, granulocyte, macrophage
What is the end maturation cell for a pre B cell?
Plasma cell
What is another name for granulocytes?
PMNs (polymorphonuclear leukocytes)
Myeloid cells can differentiate into two types of cells: ______ and ______.
Granulocytes and macrophages
Why are granulocytes called PMNs?
Because they have a polymorphic nucleus that can easily be identified through the microscope because of their unique shape.
What are the 2 progenitor compartments that a differentiated pluripotent cell can go into?
Thymus and bursa equilvalent
All the cells that go into the thymus will undergo maturation to become __________.
T lymphocytes
The cells in the thymus are: mature OR immature?
Immature
The cells in the thymus are called _______.
Thymocytes
What happens when thymocytes mature?
Immature cells = thymocytes = located inside the thymus
Mature cells = T lymphocytes = move out of thymus into blood
T lymphocytes constitute the part of the immune system called _____.
Cell mediated immunity
T lymphocytes undergo further maturation when they come in contact with _________.
An antigen
When T lymphocytes come in contact with antigen, they undergo further maturation to become _______.
T lymphoblasts
T lymphoblasts can release ________.
Lymphokines
When bursa equilvalent mature, they are called ________ and are released into the _______.
Called B cells, released into blood.
The beginning of all cells in the immune system is the ________.
Pluripotent stem cell
Bursa equilvalent cells are found in the _________.
Fetal liver, bone marrow, GALT ( Gut Associated Lymphoid Tissue)
What makes B lymphocytes and T lymphocytes “mature”?
They have surface receptors for antigens.
When when a B cell comes in contact with an antigen, it becomes a __________.
B cell lymphoblast (aka B cell Blast).
A B cell lymphoblast can undergo further maturation to become a __________.
Plasma cell
Plasma cells produce all ________.
Antibodies.
B cells are responsible for this kind of immunity.
Humoral immunity
True or false: B cells need to signals to undergo maturation.
True.
What are the two signals that a B cell must come in contact with to become mature?
An antigen and a T helper cell.
T cells provide this kind of immunity.
Cell mediated immunity.
Memory cells are also known as ________.
Primed antigen sensitive cells
Another name for you Humoral immunity is ______.
Antibody mediated immunity
What tells B cells to stop producing antibodies?
T cells that are known as suppressor cells.
In which type of immunity, specific or nonspecific, is exogenous stimulation required?
Exogenous stimulation is required in specific immunity.
Which types of cells are involved in nonspecific immunity?
- PMNs (granulocytes)
2. Macrophages (effector cells)
Which types of cells are involved in specific immunity?
- T lymphocytes
- B lymphocytes
- Macrophage (accessory cells)
What is the accessory role of macrophages?
A. Killing antigen
B. Presenting antigen to T cell
C. Presenting antigen to polymorphonuclear cells (PMNs)
B
Explain the accessory role of macrophages.
Pick up the antigen, process it, present it to T cells, then T cells will send signal to B cells.
B cells produce 5 types of antibodies, which are ______.
IgG IgM IgA IgD IgE
T cell lymphocytes can differentiate into 3 types of T cells, which are ______.
T helper cells (2nd signal for B cells) Suppressor cells (suppress B cells) Cytotoxic cells (produce lymphokines)
What are the two components of an antibody structurally?
- Fab = Fragment antigen binding (top of Y)
2. Fc = Fragment constant (bottom of Y)
An antigen usually has multiple antigenic sites, also called ______.
Epitopes
Explain the clinal selection theory.
An antigen usually has multiple antigenic sites (aka epitopes), so an antibody needs to be made for each of these sites so that the antigen cannot retain any sites when the antibodies are activated.
Upon initial contact with an antigen, there is a latency period of ______.
10 days
Upon primary antigen exposure and following the 10 day latency period, the first antigen produced is _____.
IgM (which last for a few days then levels come down)
What type of cell causes isotype switching?
T suppressor cells
What is isotype switching?
Upon initial contact with an antigen, after a few days when T suppressor cells tell the B cells to stop producing IgM and to produce IgG, which is the antibody that causes real protection.
When an antigen is encountered a second time, how long is the latent phase?
3 days (vs 10 days with initial contact
Upon 1st antigen exposure when the IgMs are switched to IgGs, how long do the IgG antibodies stick around before going away and memory cells taking over?
3 days
Upon second antigen exposure, what do the memory cells do?
Start proliferating and prodding IgM antibodies, but in lower and slower amount. You get a huge IgG response and this is why you are protected against that antigen when exposed a 2nd time.
What does MHC stand for?
Major Histocompatibility Complex
Explain the accessory cell macrophage role.
Antigen picked up by macrophage, degraded into different components, components come into contact with MHC class II molecules, so the different components get associated with these proteins and expressed on the macrophage surface, which can now be recognized by the T cell.
How many signals does a Macrophage accessory cell need to activate a resting T cell?
Two signals
Once an MHC class II molecule has an antigen associated with it, how does it activate the resting T cell?
It comes into contact with the resting T cell, which has a T cell receptor and a CD4 (T helper cell) and forms a strong bond with the T cell, but it also needs a 2nd signal. The 2nd single comes in the form of interleukin. This 2nd signal will cause activation of the T cell, which means it is now a mature T cell with receptors. The T cell will produce more interleukins (IL2 and IL4), which will stimulate more T cells.
What is the T cell dependent antibody response?
When B cells are stimulated by IL4 and IL5, which is the second signal from T cells, which causes B cell activation and antibody production.
True or False: T cell independent antibody response results in the formation of memory cells.
False! This is when B cells are stimulated only from an antigen without help from T cell, which mainly produces IgM antibodies and DONT result in the formation of memory cells.
How many light and heavy chains does an antibody structure have?
2 light chains
2 heavy chains
Which immunoglobulin class will fix complements?
IgG and IgM
What is the role of IgD?
Unknown
Which immunoglobulin class can cross the placenta?
IgG
_______ is the only antibody that takes immunity from mother to fetus/newborn.
IgG
When IgG antibodies are passed from mother to child, how long do they last before they are broken down and destroyed?
6 months
Which antibody class is responsible for protection against any antigen that is inhaled or ingested?
IgA
This antibody class is only seen in the secretions in the lining of the respiratory tract or GI tract.
IgA
What is the most important antibody in complement fixation and agglutination?
IgM
IgA immunoglobulin class has a main biological function of being _______.
Secretory antibody
_____ means clotting of blood cells.
Agglutination
If you take type A blood and add it to type B, there are ______ antibodies that cause agglutination, which is a type 2 reaction.
IgM
Why is IgM antibody better at agglutination and complement fixation structurally?
Because IgM has 5 Y-shaped structures joined together.
All antibodies have light chains and heavy chains, but it is the ______ chains that are given the designation gamma.
Heavy chains
This immunoglobulin class is known as the homocytotropic antibodies.
IgE
This antibody class is involved in allergic/hypersensitivity reactions.
IgE
Homocytotropic antibodies (aka IgE) bind to ______ cells and are involved in allergic reactions.
Mast cells
A complement has ____ components.
9
The (Fab OR Fc) portion has the receptor for the complement.
Fc
What is the necessary step in the activation of the complement pathway?
C1Q crosslinking 2 antibody molecules that are bound to the microorganism.
____ and ____ components of a complement together are called C3 convertase.
C2 and C4
____ is a component of a complement that is a transmembrane protein that works with the next component to form a membrane channel.
C8
___ and ____ components of complements work together to form a channel in the membrane of an antigen that causes fluid from outside to rush into the cell and cause lysis.
C8 and C9
Antibodies cannot kill the cell themselves, but require help from _____.
Complements
True OR False: the components of a complement anchored in a cell have a large molecular weight and cause destabilization of the cell membrane, causing rupture.
True
What is complement fixation?
The anchoring of complement components to the cell that cause water to rush in/ cell lysis.
When antibodies coat an antigen, bring it in front of phagocytic cell (macrophage) that has Fc receptors and produces projections similar to amoeba that will cause engulfing and destruction of the antigen, it is called _____.
Opsonization
True or False: T-independent antibody response can produce IgG.
False! Can never produce IgG, only IgM.
Name the 5 approaches for immunocompetence evaluation.
- Check body and organ weights
- Hematologic parameters
- Serum chemistry
- Bone marrow status (CFU = colony forming units, reduction in CFU means immunosupression)
- Histpathology
If tier 1 immunocompetence evaluation testing is positive, what is required?
Must move on to tier 2 immunotoxicology testing
In a Tier 1 immunosupression test, you do a primary PFC (Plaque Forming Cell) assay, which looks for ______ antibody.
IgM
In a Tier 2 immunosupression test, you do a secondary PFC (Plaque Forming Cell) assay, which looks for ______ antibody.
IgG
List some procedures categorized as Tier 2 immunotoxicology testing procedures (5 total).
- Surface marker analysis
- Secondary PFC assay (IgG)
- CTL assay
- DHR assay
Host resistance
What is the difference between innate immunity and acquired immunity?
Innate = immunity we are born with
Acquired = immunity we get over time, acquired not initial
To test a person’s innate immunity, you want to test for ______. (3 mechanisms employed)
- Phagocytosis
- NK cell activity
- Chemotaxis
Explain the process of radioactive phagocytosis in detecting/testing innate immunity.
Macrophages are involved in phagocytosis, so you take some chromium labeled sheep RBCs (cRBC) which are radioactively labeled and take some macrophages from person, mix them together in a Petri dish, leave them for a period of time, wash them and remove supernatural, which contains the unbound RBCs. Treat with ammonium chloride to remove bound RBCs to the outside of the macrophage. Competent macrophages will have engulfed the cRBCs, so it should be inside. Use sodium hydroxide (NaOH) to digest the macrophages, suspend them, and look to see if there is 51Cr (Chromated, cRBCs).
Explain the process of nonradioactive phagocytosis in detecting/testing innate immunity.
Add macrophages to latex spheres and let them sit. Stain with methylene blue . The samples that picked up the latex spheres and are functioning normally will stain differently than the ones that didn’t pick up the latex.
What is mixed with the macrophages in nonradioactive phagocytosis innate immunity testing?
Latex spheres
What is mixed with the macrophages in radioactive phagocytosis innate immunity testing?
Chromated (51Cr) cRBCs (chromium labeled sheep RBCs)
When testing natural killer (NK) cell activity for innate immunity, if there is 51Cr in the supernatant, it means that the splenocytes(NK cells) are (functioning properly OR not functioning properly).
Functioning properly
Explain the process of testing NK cell activity to test innate immunity.
You take splenocytes (NK cells) from a healthy animal (control) and an animal that has been exposed to a chemical that may have compromised the NK cells. Add chromium labeled tumor cells (51Cr tumor cells) and incubate. If there is 51Cr in supernatant following incubation, it means that the NK cells are functional because they killed the tumor cells and liberated the 51Cr.
Explain the process of chemotaxis in testing innate immunity.
When injured, a chemical mediator (lymphokines) is released that sends signal for macrophages and neutrophils to come to site of injury (chemotaxis). So take two animals (one control and one exposed to chemical), remove animal macrophages from blood, place in chamber, put chemoattractor at bottom of tube and see if macrophages move across. After 30 min, add formaldehyde to stop macrophage movement and examine under microscope. Lots of macrophages = normal response.
What is humoral immunity?
Comes as a result of B cells
Antibody production
In acquired immunity, the _____ cell response is the antibody response.
Humoral
An example of a B cell mitogen is _______.
LPS
An example of a T cell mitogen is _______.
PHA