neonatally thymectomized mice grow up with _______.. Also their ability to reject a foreign skin graft is _______. If a genetically-identical thymus is transplanted, what happens to the mice?
The mice are restored to normal.
What is the only way T cells can see an antigenic determinant?
It must be shown to them by special antigen-presenting molecules. The antigens are on cells.
How many kinds of T cells are there, and what types are they?
5 helper T cells and 1 Killer T cell
All the helper T cells (there are 5 kinds) express the surface marker ______.
What kind of precursor do helper T cells begin as?
an undecided one, typically called Th0.
Helper T cells begin as an undecided precursor. When they are presented with an antigen by a Dendritic cell they begin to ______ and ________.
divide and differentiate
Helper T cells, once presented with an antigen by a DC, can become one of which cells?
Th1, Th17, Th2, Tfh, or Treg cells
What factors are the main determinant of what the Th0 divides and differentiates into?
Basically the experience of the DC:
- What TLR were engaged with the antigen
- what cytokines and chemokines predominated
- and conditions in the periphery when the DC was stimulated
Th1 cells are activated and proliferate what organ?
the lymph node
What happens when circulating Th1 cells encounter antigen?
They secrete lymphokines.
What is the most important lymphokine secreted by Th1?
What are general actions of TNFgamma?
it is pro-inflammatory and chemotactic for blood monocytes (which become macrophages).
INFgamma is a ____
Th1 cells aggregate around macrophages and secrete _____. This turns the macrophages into ______
classically-activated M1 macrophages or angry macrophages.
Macrophages can release cytokines which include_____ and _______. These have the effect of ______.
tumor-necrosis factor alpha (TNFalpha) and IL-1.
In general T cells _______ and macrophages _________.
What does Th1 secrete which helps CTLs get fully activated?
In general what two things does Th1 secrete
IL2 and lymphokines (especially INFgamma)
What does Th17 make?
What is IL17?
an inflammatory lymphokine
The main job of Th17 is to _______. It is especially good at fighting _____
cause inflammation (For this reason it is involved autoimmue diseases).
difficult bacteria and yeast pathogens
In general, Th1 and Th17 are _______. This leads to activation of _______
What are Cytokines?
short range mediators.
What are Lymphokines?
short range mediators. These are a subset of cytokines made only by lymphocytes.
What are Chemokines?
small short range mediators. Primarily cause inflammation
Cyto- short range
lympho- a kind of cytokine
chemo- like a small cyto that causes inflammation.
Th2 and Th1 cells typically encounter antigen in ______
What does Th2 secrete and what do those secretions do?
IL4, IL5, IL13. remember especially IL4.
These attrach macrophages.
Macrophages activated by Th2 are called ______
alternatively activated or M2 macrophages.
What should you think of when you think of M2 macrophages?
healing and repair
scar formation, debris clearing, walling off pathogens
What is special about IL4 (secreted by Th2)?
it is chemotactic for eosinophils (which kill parasites and worms).
Match up the following (one in each category)
Urgent destoyers, healers that appear later
Th1 M1 urgent detroyers
Th2 M2 appear later healers
What is the job of follicular T cells (Tfh)?
They help B cells which have recognized antigen become activated and differentiated. They migrate into the follicles of the lymph node where B cells can be found.
They help B cells switch which antibody they secrete (IgM to another form).
What do Tfhs secrete
a variety of cytokines
Where do Tfhs come from?
They are Th1s and Th2s that acquire a cell marker (CXCR5) which allows them to travel into the follicle.
If Tfh cells do not communicate with B cells which anitbody will you struggle to produce?
Any besides IgM probably. They help the B cells switch from IgM to other forms.
What is the main job of Tregs?
suppress other Th cells. Treg is very potent- one can supress 1000 Th cells
Most Tregs have what phenotype?
Tregs make three things?
Transcription factor Foxp3
All helper T cells have what surface marker?
Treg disfunction leads to ______
T or F. suppression of other T cells by Treg is antigen-specific.
F Tregs only require antigen-specificity to interact with their corresponding antigen. Tregs are able to suppress all nearby T cells when activated regardless of the antigen specificity of the T cell.
How do CTLs work?
These are killer t cells. They signal the target cell to undergo apoptosis which leads to DNA fragmentation and nuclear collapse.
The way Killer T cells work would be most effective against what?
Virtually all T cells have what surface marker?
CTLs have what surface marker?
What is MHC restriction (basic overview)?
Basically it explains CTL immunological specificity. For instance if person A has virus E, his CTLs will only kill target fibroblasts from person A with that are infected with virus E. If the cell is not infected or infected with another virus, or infected with the same virus but the cell is from an unrelated person then no CTL killing happens.
Both B Cells (and their antibodies) and T cells interact with free floating antigen. T or F?
F. B cells focus on free floating antigens while T cells focus on antigens on cell surfaces not free floating antibodies. They only see antigen when it is bound to to MHC molecules on the surface of cells (such as DCs).
T cells are _____-specific and _____-restricted.
T cells do not see antigen alone, they only see antigen that is what?
presented on the surface of genetically identical cell.
How genetically identical do cells have to be for T cells to recognize their antigens?
The cells must come from individuals who have the same alleles at a group of loci called the MHC.
The MHC loci code for what?
surface glycoprotein molecules
Describe the process of antigen presentation to T cells.
A virus is ingested by a dendritic cell (it is taken into a cell via an endosome). The virus is broken into peptides within the endosome. Another vesicle containing MHC molecules (they are embedded in the membrane and faces inward) fuses with the endosome. The peptides associate with the MHC molecules. Next, the endosome travels to the cell surface and fuses with the plasma membrane. Doing this causes the MHC molecules (now bound with virus peptide) to face the outside of the Dendritic cell. A cell that does this is called an antigen presenting cell or APC.
What is the mechanism called when an antigen comes from the outside and then ends up in the membrane of an antigen presenting cell?
The extrinsic pathway.
Dendritic cells actually present the appropriate helper T cell with ____
an MHC-antigen complex
What type of MHC contains an alpha chain and a beta chain and binds antigen fragments?
MHC class II
What are the two chains that make up a T cell receptor on a T cell?
alpha and Beta
T cells receptors are made out of _____. How are these related to B cells?
V (D) and J regions. They are not related to B cell VDJ regions.
How many CDRs does a T cell have?
which chain on a TCR has a transmembrane domain?
both (alpha and beta). There are 2 chains.
The actual signal that turns on the T cell, once its TCR is bound to a antigen + MHC complex is _____
What are the three sorts of signals, or three steps, to activate a T cell?
- TCR-pMHC (interaction between TCR, antigenic peptide, and MHC)
- accessory molecular interactions which can only be provided by true APC (these modify activation (enhance or diminish)).
- The APC may secrete cytokines which modify activation of the T cell.
Class I MHC products are on ______
all nucleated cells.
Class II MHC products are on______
the surfaces of dendritic cells and macrophage-like cells; it includes most cells that are involved in some way in presenting antigenic peptides to Th cells.
What are the five types of Helper T cells?
Th1, Th2, Th17, Thf, Treg
Which helper T cells are designed to recognize peptides on class II molecules?
all (Th1, Th2, Th17, Thf, Treg)
Class I MHC are from peptides made and found _______. Because of this they are not taken up by _________
within the cell
Class I MHC molecules go through the _____ pathway.
What sort of antigens do MHC class I molecules pick up?
mutated or abnormal proteins from inside the cell. These could come from viruses or the cell itself.
Helper T cells see antigen with class ____ molecules while CTL see antigen with class_____ molecules
What is cross presentation?
This is when a dendritic cell eats an antigen and then allows some of the peptide to leak over into class I MHC. This allows for class I and II MHC presentation at the same time.
do dendritic cells present to CTL or Th?
They are capable of presenting to both (at the same time) through cross-presentation.
CD4 is on the surface of _____ cells and binds to MHC class ____.
CD4 binds MHC class II where? CD8 binds to MHC class 1 where?
both at the base (which is unvarying in everyone) not at the peptide binding groove.
CD8 is on the surface of ______ cells and binds to MHC class _____
what does CD binding achieve? (CD8 or CD4 for instance)
it just increases binding affinity of CTL or Th for MHC. Without TCR binding it cannot activate the T cell on its own.
What are the four experimental observations about how Tfh cells help a B cell get activated?
- T cells and B cells must be from a donor with same MHC class II
- T cell and B cell are not specific for same epitope but both their epitopes are both located on the same antigen molecule
- If you block a B cells ability to endocytose, a T cell cannot help it make antibody
- the Tfh must contact the B cell
Are MHC class II molecules found on B cells?
yes. the whole process of ingesting antigens works for them just like a dendritic cell. They present antigen + MHC class II to Tfh cells which help them make antibodies.
For some antigens no T cell help is available. What are these called and what molecule are they typically?
they tend to be carbohydrates.
The response to t-independent antigens is almost all done by whaty kind of antibody?
What is an example of a T-independent antigen?
the capsular polysaccharide S. pneumoniae.
With protein T-independent antigens what kind of antibodies are made?
a little IgM and no IgG.
What is a lectin?
a protein that binds a sugar not typically made in the person. They can function as innate immune molecules such as MBP.
This is a bean lectin which stimulates all T cells to divide.
what is PHA (phytohemaglutinin)?
For 500 point
What is a mitogen?
something which stimulates cell mitosis such as PHA or Con A and sometimes antibody to CD3 (these all work for T cell mitosis only). These will stimulate ALL T cells to divide (they are non-specific).
What mitogen stimulates both B and T cells to divide?
Pokeweed mitogen (PWA).
The thymus consists of epithelial cells which arise from the III and IV pharyngeal pouches in fetal life, _________, and __________
macrophages derived from the bone marrow,
thymocytes derived from the bone marrow
Describe the way T cells mature.
Lymphoid precursors arrive from the bone marrow, interact with Notch receptors and begin to divide rapidly in the thymus. They are double negative at this point. As they mature they become double positive (CD4+/CD8+). Then during selection one of the genes is turned off. Very few become single positive.
How many T cells become single positive and leave the thymus?
fewer than 2%. MOst stay double positive and die in the thymus.
What 3 things must a T cell do?
- not recognize self
- Not recognize free antigen
- Recognize antigenic peptide plus self MHC
All cells express Class ___ MHC
What are the three options for a maturing T cells
What happens in positive selection?
2 of 3 CDRs of t cells bind to the MHC (class I or II) on a cell within the thymus. The binding affinity is low. The idea is that when the MHC is bound with foreign antigen, the binding will be high (as it is bound with self antigen now)
How does the thymus keep foreign antigens out
Describe negative selection.
Immature T cells bind to MHC with self antigen with High affinity. This means that all of the CDRs are bound. This T cell would result in autoimmunity and is triggered to either become a Treg or undergo apoptosis.
What are the two possible fates of an immature T cell that is negatively selected?
apoptosis or differentiated into a Treg.
What is AIRE and what does it do?
Autoimmune regulator. It is a gene. This gene causes stromal cells in the thymus to express a wide variety of extrathymic peptides. thus, T cells can be negatively selected for MHC + self antigen complexes that would match in other parts of the body besides the thymus.
What happens in non-selection?
The TCR has no affinity for the MHCs. The T cell fails to mature and dies within 2-3 days by apoptosis.
how do B cells bind antigen?
surface Ig bind an epitope of antigen. They internalize it and load it onto class II MHC.
what cells are capable of cross presentation?
What class MHC would a liver cell use to present antigen?