Adaptive 2 Flashcards
What is cell mediated immunity?
Antigen-receptor effector T cells dominate
T help CD4 and cytotoxic CD8
Responsible for chronic inflammation, tumor immunity and graft rejection
What are the subtypes of CD4 helper T cells?
TH1 activate macrophages
TH2 activate B cells
Tregs: suppressor aberrant pathological immune responses
TH17: assist B cells to make antibodies, activate macrophages, recruit immune cells (loss linked to chronic inflammation)
What are the subtypes of CD8 cytotoxic T cells?
TH17 cells: create inflammation and tissue injury in autoimmune disease
T regulatory cells (Tregs): shut down immune responses after they have successfully eliminated invading organisms and prevent autoimmunity
How do T cells differ form B cells?
TCR bind antigen but not native antigen (unlike antibodies)
TCR binds antigens already broken down and present on surface of APC
Cell to cell contact is always required between T cell and APC
T cells never secrete their antigen specific receptor
Describe antigen presentation to T cells. How are antigen presented?
T cells do not recognize intact antigens
T cells recognize antigens that have been digested into peptides and combined with MHC
MHC bring peptides to cell surface and display do they can be recognized by T cells
MHC proteins plus antigen fragments= antigen presentation
What are MHCs (human leukocyte antigen)?
Dimeric surface glycoproteins that control adaptive immune response (on chromosome 6)
Present antigens to T cells to distinguish self and non self
Each has one binding site, no capacity to rearrange or structurally change (similar to immunoglobulin)
In the transplantation process what is MHC used for?
Tissue typing, determination of HLA genotypes of donor and recipient (only identical twins have same MHC 1)
Describe the differences between MHC 1 and MHC 2. What are they regulated by?
MHC 1: Present on the surface of all nucleated cells (so
excludes mature RBCs), samples the internal contents of a cell and displays peptides to the immune system.
MHC 2: Present only on APCs, Associates with peptides from within vesicles (i.e. acquired outside the cell), nonidentical polypeptide chain
Expression regulated by cytokines
What are MHC 1 and 2 each recognized by?
MHC 1: CD8
MHC 2: CD4
Describe APCs, Examples?
Internalize and degrade antigens into 10-30 amino acids for loading onto MHC 1 and 2
Ex: dendritic cells, macrophages, langerhans cells, B cells
What are considered the professional APCs?
Dendritic cells are most efficient
Found in tissues in contact with external environment
Only cells that present antigen to naive T cells
What MHC complex forms on vaccinated cells?
MHC 1
Spike proteins form spikes that migrate to cell surface
Vaccinated cells also break up some of the proteins and present them
MHC plus spike binds on cell surface
What kind of MHC complex forms on dead vaccinated cells?
MHC 2
Debris from dead cell contains spike proteins can be taken up by APC
Describe T cell Receptors, What do they bind, what is the most abundant, what are they made out of?
Bind to MHC peptide complexes
Most abundant is a disulfide-linked heterodimer transmembrane complex of alpha and beta chains
Constant and variable region, constant region anchored in cell membrane
Do T cell receptors go through somatic mutations?
No
What region of the T cell receptors recognize antigens? How do they diversify? Where does this occur?
Variable
diversity in T cells receptors is generated during gene rearrangement focused on CDR 3 regions (hyper variable)
Occurs in the thymus
For a T cell to be functional what does it need?
TCR that can recognize antigen with MHC
Expression of CD4 or CD8 coreceptor
TCR must be linked to another cell surface molecule
When are CD4 and CD 8 cells expressed?
Once cells reach the thymus
Describe the process of thymic education that TCR undergo.
Eliminates self reactive T cells and require that T cells recognize either MHC 1 or 2
Epithelial cells in Cortex mediate positive selection
Dendritic cells in medulla mediate negative selection
Describe the positive and negative selection that occurs during T cell development.
TCR must recognize MHC and pathogen peptides
Positive selection: T cells with low affinity for self MHC survive, decides if T cell becomes CD 4 or CD8
Negative selection: deletes T cells that have high affinity for self peptides and self MHC
What CD cells are MH 1 and 2 accociated with?
T cells that recognize MHC 1 receive a survival
signal for CD8 and stop expressing CD4.
T cells that recognize MHC 2 receive a survival
signal for CD4 and stop expressing CD8
What happens to mature naive T cells that are self MHC-restricted and tolerant to many self antigens?
Leave the thymus and populate lymph nodes, spleen and MALT
Describe the process by which T cell are activated and lymphokines are released.
T-cells recognize antigen in the context of an MHC molecule on the cell surface.
The 3 hypervariable regions (CDRs) in the variable domain recognize antigen.
Upon recognition of a specific antigen, the signal is passed to CD3 (required for T cell activation), which relays the signal, prompting T-cell activation and the release of lymphokines.
Compare B and T cells.
Effector B cells secrete antibodies; heavy chain constant (C)
region isotypes trigger distinct effector mechanisms.
Effector T cell functions depend on cell to cell contact and are not mediated directly by the T cell receptor, which serves only for antigen recognition.
THERE IS NO CLASS SWITCHING IN T CELLS!
What is cluster of differentiation (CD)?
CD antigens are proteins on surface of leukocytes, recognized by specific antibodies
Often act as receptors or ligands, other functions such as adhesion
What is the function of CD4? What cytokines do the subgroup produce?
Main regulators of immune defense
Interacts with antigen displayed by MHC2
Respond to exogenous antigens (inhaled, ingested or injected)
TH1: Ifn g, Il-2, TNF-a (tumor necrosis factor) associated with inflammation
TH2 : Il-4, Il-10, TGF-b (transforming growth factor)
What is the function of CD8?
Destroy virus infected, tumor and cells with intracellular bacteria
T cell must stimulated by cytokine (IL-2) from TH1
By what 3 mechanisms do CD8 cells kill?
Secrete cytokines, primarily TNF-α and IFN-γ, which have anti-tumor and anti-viral microbial effects.
Release perforin and granzymes.
Induce apoptosis via Fas/FasL receptor interactions.
(May be overactive causing damage, respond to endogenous antigens )
What two cells have perforins and granzymes?
NK cells
CD8 cells
What are the functions of regulatory (suppressor) T cells? What disease does it protect against?
Maintain peripheral tolerance
Mostly CD4
Ensure tolerance to self antigens
Limit excess immune response
Regulate fetoplacental immunity
Homeostasis and regenerations
Prevents graft-verses host disease in transplantations
Describe the purpose of immunotherapy. What is one common method?
Block cancer cells from shutting down the immune system
Checkpoint inhibition: prevent shut down of immune system to allow it to attack cancer, antibodies that block the receptor or its ligand that induces immune suppression
May attack healthy vital organs
What are checkpoint proteins and how do checkpoint inhibitors work (checkpoint blockade)? What are 2 examples of checkpoint inhibitors?
Checkpoint proteins turn down immune system to reduce autoimmunity, protect self from getting attacked
Checkpoint inhibitors are monoclonal antibodies that inhibit proteins that suppress immune system
Attack cancer cells
PD1 and CTLA4 receptors to which monoclonal antibodies attack
What occurs when a cancer cell expresses PD-L1? How does the immun system oppose this
Prevents T cells from attacking the tumor and these T cells remain in the margin of the cancer suppress immune system, allowing tumor cells to grow
Checkpoint inhibitors physically block the ligand or its receptor on T cells, which frees the immune system to attack the cancer.
What are nivolumab and ipilimumab in the treatment of cancer?
Nivolumab (opdivo): PD-1 blockade
Ipilimumab (yervoy): CTLA-4 blockade
How can vaccines be used to fight cancer?
Present immune system with piece of cancer, allowing it to attack
Ex:Provenge
BCG: TB vaccine used to treat bladder cancer
How are Bi-specific antibodies used to treat cancer?
Not individualized for each patient
Antibodies that attach to both cancer cell and a T cells bringing them close together so T cells can attack
Describe how Car-R cells can be used to treat cancer.
Revs up a person’s immune system
Extract a patient’s T cells from blood and train them to recognize and kill cancer
T cells modified with viral vector to express Car-T so they recognize cancer antigen
Ex: enable T cells to express CD19 receptor (receptor expressed on normal and cancerous B cells)
What are 3 ways in which cell mediated immunity protects us?
- Activation of NK cell and macrophages
- Stimulates cells to secrete cytokines that influence other cells involved in adaptive and innate immune responses
- CTLs induce apoptosis, CTLs are not injured when they kill target cells and can kill again
- Generate memory cells
