(12) Acquired Immunity Flashcards
Suppose you suffer repeated exposure to small amounts of pathogen leading to a very mild infection that clears in 2-3 days. Would you expect your immune system to respond more rapidly and effectively each time?
Why or Why not?
NO
Why:
- Threshold for Acquired response is never reached, this is indicated by the mild infection that clears before an acquired response.
- If acquired response is never triggered then the memory lymphocytes will never be created and there will be no change in the body’s response to the pathogen because it being controlled by the INNATE IMMUNITY
Around what day is the adaptive response induce and in general, what happens at this time to/for:
- Barrier Functions
- Extracellular Pathogens
- Intracellular Pathogens
- Viruses
Day 4, Innate system will notify acquired system that there is a problem
Barrier Function:
- IgA bumped up in LUMINAL SPACES
- IgE antibodies on Mast Cells
- Local Inflammation
Extracellular Pathogens:
- IgG and Fc receptor bearing cells IgG
- IgM + Classical Complement
Intracellular Bacteria:
- T-cell activation of Macrophages by IFN-gamma
Viral Response:
- Cytotoxic T cells IFN-gamma
T or F: dendritic cells can squeeze between epithelial cells in order to test for PAMPs in the gut lumen
True
What are the two primary effector functions of a CD4 effector T cell?
- Supply Second signal of activation to B-cell
2. Activate Macrophages
Reconcile the affinity of effector CD8 cells for MHC class I. Why not MHC class II only?
MHC class I is expressed on all host cells
CD8 T cells kill infected cells
*it is logical that MHC class I is accessible to CD8 T cells because they need to travel around the body and be able to sample any tissue they choose for infection
***What would be the implications of losing the cross-presentation mechanisms of MHC class I and II?
- TH1 would never be able to recognize and intracellular pathogen, because it is a CD4 cell and they only have access to MHC class II
- It would be impossible to generate an acquired antibody response to an intracellular pathogen because they also only recognize MHC class II
What are the two signals needed to activate a T-cell and why are these two types needed?
- MHC class II (APC) binds to TCR (T-cell)
- B7 (APC) binds to CD28 (T-cell)
**Both signals are needed to prevent autoimmune diseases from manifesting, B7 is only upregulated in Macrophages and B-cells when they bind a pathogen via a PRR or BCR
**This serves as a DOUBLE CHECK for pathogenicity because two independent cells are recognizing something as foreign in TWO DIFFERENT ways (b/c they probably aren’t recognizing the same antigen)
T-CELLS ACTIVATED IN THE ABSENCE OF B7 ON APCs ARE LIKELY RECOGNIZING SELF ANTIGEN
Once T-cells are activated, what do they secrete, and what do they differentiate into?
- Secrete IL-2 causing proliferation
- Differentiate in to Effector cells (SHORT LIVED) move out of 2˚ lymph tissue and Memory cells (LONG LIVED) stay in 2˚ lymph tissue
How do memory cells lead to a more rapid response on second exposure to the same pathogen?
- They proliferate and their CONCENTRATION shoots up, this means the next time we encounter that pathogen and the APC brings it in, a cell containing the receptor for that antigen will be contacted quickly
Differentiate an effector CD4 cell from a naive CD4 cell?
- Effector T cells DO NOT REQUIRE CO-STIMULATORY signalling
- they UPREGULATE most RECEPTORS TO GIVE THEM GREATER ACCESS to DIFF. TISSUEs.
What one thing makes it possible for Naive T Cells to have access to Secondary lymph tissues?
- what allows them to interact with APCs?
- What would happen with deficiencies in either?
L-selectin allows T cells to bind to CD34 and move through High Endothelial Venules
LFA-1 is essential for interactions with APCs (via so that the Naive cells can test the environment
**LFA-1 deficiency would lead to SCID because T-cells would never get activated, lack of L-selectin would do the same because T-cells would lack access to 2˚ lymph tissue
What is the point of the upregulation of VLA-4 and LFA-1 on Effector T cells
VLA-4 is needed to Leave the vasculature
LFA-1 is needed to interact with APCs, upregulation allows even more interaction
T or F: CTLs require B7 to degranulate
False, this would make no since because no cells except APCs (the cells you dont want to kill) have B7
***What important molecules are produced by CD8 T-cells?
- Perforin
- Granzymes
- Granulysin
- Fas Ligand
***What important molecules are produced by TH1 cells?
- IFN-gamma
- CM-CSF
- TNF-alpha
- CD40 Ligand
- Fas Ligand
***What important molecules are produced by TH2 cells?
- IL-4
- IL-5
- IL-13
- CD40 ligand
***What important molecules are produced by TH17 cells?
- IL-17
- IL-6
***What important molecules are produced by Treg cells?
- IL-10
- TGF-beta
What cytokines turn TH0 cells into TH1 cells?
- IL-12
- INF-gamma
What cytokines turn TH0 cells into TH2 cells?
- IL-4
- IL-6
What are the 3 primary effector functions of TH1 cells?
- Macrophage Activation
- Production of IL-2 to drive proliferation
- Production of cytokines and chemokines that production of neutrophils and macrophages (GM-CSF, IL-3) and moving them to the inflammatory site (TNF-alpha, LT)
What is the points of a granuloma?
- cell types?
TH1 cells surround macrophages that have been infected with bacteria and can’t kill it and wall it off from the body
What are the signals needed for macrophage activation?
- CD40 Ligand (T-cell) binds to CD40 (macrophage)
2. IFN-gamma secreted from T cell binds receptor on Macrophage
Of the following processes, which can occur OUTSIDE of the germinal center reaction?
- B cell proliferation
- Somatic Hypermutation
- Affinity Maturation
- Isotype Switching
ALL MUST OCCUR IN GERMINAL CENTER RXN
- Minor exception is non-specific proliferation driven by PAMPs binding PRRs and antigens binding BCRs
You are infected with a virus and a week later you get blood work done. What antibody would you think is highest in the blood at this time?
- what if you get sick again by the same virus?
IgM, your first response to a pathogen will be making a lot of IgM because your B-cells proliferate and young B-cells will still be making IgM
***ON Second exposure this spike is not as prominent in IgM and is more prominent in IgG because your B-cells have now isotype switched
T or F: a neutralizing antibody can also be opsonized
True, this is possible but it is not always the case
What are the 5 ways that an dimeric IgA cell can act as a neutralizer?
In to Out
1. Bind antigen in subendothelium and expel it to lumen
- Bind antigen inside endosome when passing through endothelial cell and push it into the lumen
- *Most Important IgA is secreted then neutralized material in the gut lumen
Out to In
4. IgA binds antigen at M-cell surface then get put through the galt
- IgA binds antigen in endosome inside M-cell then takes it to a APC
What is ADCC?
- cell type?
- Mechanism
Fc(gamma)RII receptors on NK cell bind IgG1 or IgG3 that is bound to the antigen. NK cell then secretes death signals to the antibody-bound cell
What are mast cells the most defensive against and where does this occur?
- Most defensive against parasites particularly in the GI TRACT
What is protective immunity?
- what does it allow for?
Protective Immunity - Immunity to Re-infection by a particular Pathogen
- pre-formed T cell and/or B cell-mediated immune response can prevent or rapidly remove infectious agents
What is immunological memory?
The ability or the immune system to respond very rapidly and more efficiently to pathogens that it has encountered before
What allows for a QUICKER, MORE SENSITIVE, and MORE SPECIFIC response on second exposure to a pathogen?
Quicker:
- Isotype switching has already occured so we have the correct isotype to use on reinfection
More Sensitive:
- there are 10-100x as many more cells specific for that pathogen as there were on the 1st exposure, this means that APC with the antigen will be detected much faster in the 2˚ lymph. tissue.
More Specific:
- With each exposure somatic hypermutation occurs and even better antibodies are selected for
Before the process of immunological memory occurs, why is the immune system so good at knocking out the infection quickly and effectively on reexposure?
All of the same effector T cells and Ab are present in the blood still and can quickly sniff out the disease
What cell has more inflammatory mediators than any other immune cell?
Mast Cells
What is the difference between an acute phase serum and a convalescent serum?
Acute phase serum has high IgM and Low IgG
Convalescent serum has Low IgM and High IgG
Serum becomes covalescent 2-3 weeks after exposure to the pathogen
What is the window of time for protective immunity?
- what will happen if your are reexposed during this time period?
- what cells and molecules are primarily responsible for this response?
~3 weeks - 3.5 months after the primary exposure to the pathogen
- If you are re-exposed during this time you’re body will very rapidly kill the pathogen
- B cells producing IgG are mainly responsible for this quick response because T cell taper off after about 3 weeks
Compare the secondary adaptive response to the primary adaptive response in terms of speed and intensity.
Primary:
- takes about a week to kick in
- Not nearly as many cells are activated in this response compared to the secondary
Secondary:
- Kicks in much faster
- many more cells are produced and the response is much more intense
T or F: memory T cells exist as well as memory B cells
True
Why is the secondary response to a pathogen so much better?
Memory T cells with antigen specific for that pathogen are found more easily by APCs.
Memory B cells with Ab specific for that pathogen are much more easily found by T cells and can be activated
What is the CD8 response to Virally Infected cells that have been affected for an extensive period of time by the virus?
CD8 will not be responsive most likely because MHC class I is probably no longer expressed on the cell surface of the virally infected cell. Thus NATURAL KILLER cells will take over at this time by recognizing the presence of MIC or the absence of MHC class I.
T or F: protective immunity occurs with the 1st exposure to the pathogen, but does not occur on second exposure
False, Protective immunity follows for 2-3 months following the clearance of the infection with every single exposure
