Flashcards in MCM 2-9 Innate Lymphocytes Deck (40)
A patient presents with a common cold. Respiratory epithelial cells begin producing interferon. Which is least likely to be an outcome of the activation of the interferon response?
a. Decreased viral replication within the cell
b. A virus specific, cell mediated immune response
c. Upregulation of NK cell ligands on the infected cell
d. Activation of NK cells
e. Interferon binding to nearby uninfected epithelial cells
A virus specific cell mediated immune response is least likely
Type I interferon. Source? Acts on?
Type 1 interferon is IFN-Alpha and IFN-Beta
Excreted from virally infected cells
Autocrine action (within the cell to decrease syntehsis) as well as paracrine (neighboring cells) acting on NK cells, activating them to kill.
innate vs adaptive
innate - inborn, ready to go, nonspecific, no recombination (mucus, tight junctions, macrophages, neutrophils)
adaptive - tailored to specific antigen, delayed primary response, antigen specific, must ramp up, some recombination necessary
General Innate and Adaptive Bifurkation at the hematopoietic stem cell
Innate - differentiates into common myeloid progenitor which gives rise to innate immune cells
in adaptive - differentiates into common lymphoid progenitor which gives rise to adaptive immune cells
However, there is a class of INNATE that are derived from the common lymphoid progenitor that ussually gives rise to ADAPTIVE immune cells
Natural Killer Cells
are ready to go, do not need priming or proliferation. They can recognize and kill a target cell without priming or sensitization
NK Cells express what cell markers
CD56 (adhesion molecule) and CD16 (an Fc receptor)
-also have cytoplasmic granules to kill target cells
NK cells do not express
CD3, they are CD3-
despite being lymphoid, do not express a BCR or TCR
where do NK cells mature?
unlike T-cells, NK cells mature in the bone marrow, there is no thymic stage. they are ready to go right out of the bone marrow
What do NK cells do?
1. fight viral infection
2. kill tumor cells
3. support placentation (during pregnancy)
describe how an NK cell finds an infected cell?
a virally infected cell excretes type-1 interferon (alpha or beta), which stimulates the NK to divide, and seek out the infected cells to kill.
NK cells and the kinetics of infection response
1. subject infected
2. IFN-1 and other inflammatory mediators released
3. NK cells quickly begin killing
4. much later in response. T-cells begin killing
NK cells are thought to stave off the viral infection until T-cells are ramped up and able to eradicate the infection. NK cells will level out the viral titer. More pronounced in primary infection when T-cells take a few days to activate.
Crosstalk between NK cells and macrophages
NK cells secrete IFN-Gamma (type 2 interferon) to stimulate macrophages, makes macrophage better able to take up antigen and kill
Activated macrophages secrete IL-12
Interferon types 1 and 2
Type 1 - alpha and beta, released by infected cells, stimulates NK cells to activate, divide, and kill
type 2 - interferon gamma - secreted by NK cells to stimulate macrophages, makes them better able to take up antigen and kill
how do NK cells recognize target cells without a TCR?
they have a spectrum of receptors that are either inhibitory or stimulatory. the balance of these receptors determines if the NK cell will kill or not. by default, inhibitory NK signal dominates (protective)
-these receptors are germline encoded, no recombination like B or C receptor
difference between NK receptors and TCR/BCRs?
NK are germline encoded, no recombination like in BCR or TCR
what are the main ligands for the different NK receptors?
most ligands are MHC1 and HLA class molecules
MHC(HLA) Class I types, diversity, and functions
MHC1a - presents antigen to CD8+ cells
A,B,C with 2 alleles each (one per parent)
highly polymorphic in binding pocket. SNPS in this region allow to hold certain peptide better than others
MHC1b - (other functions)
E,F,G, sometimes Mic-a and Mic-b
E has lowest polymorphism
most important inhibitory receptor and activating receptor for NK cells?
CD94:NKG2A inhibitory, interacts with HLA-E which presents fragments from other MHC molecules. Many HLA-E receptors on surface ligated? inhibitory signal dominantes.
-Low HLA-E expression? NK cell sees this as an unhealthy cell, and prepares to kill it. Why? Viruses downregulate MHC1
CD16 - activating. it is an Fc receptor that recognizes IgG antibody. When it sees that there are antibodies on a target, the NK cell kills the target. "Antibody Dependant Cellular cytotoxicity" or ADCC
describe NK cells
what does CD16 see?
what does cd94:nkg2a see?
how does it activate macrophages?
Large granular lymphocytes, CD56+ and CD16+
IFN-gamma (type 2 interferon)
gamma:Delta T-cells have a thymic phase T/F?
True, when lymphoid progenitors enter thymus they can become either an alpha:beta (cd4 or cd8) or gamma:Delta
Alpha Beta T cell Vs Gamma Delta T cell
alpha beta - b chain rearranges first, lots of diversity, positive and negative selection to prevent autoimmunity. tend to move around bloodsteam and lymphatics
gamma delta - gamma and delta chains rearrange first, limited diversity, no selection (limited specificity excludes autoimmunity), tend to be in tissues and express CD3. They are IELS - interepithelial lymphocytes
role of gamma delta T-cells in intestines?
GD t-cells hang out in intestial epithelia
cell becomes infected, gamma delta t-cell is there and responds to stress molecules, kills the cell via lytic granules.
gamma:delta secretes growth factors which then stimulate cell division/repair to fill the gap.
what makes gamma:deta T-cells unique?
they are not MHC restricted and do not need to see peptide cradled in MHC, their receptor is more like an antibody. Can see a limited number of antigens like a B cell would.
can see small phosphoantigens (metabolism of stressed/infected cells)
can see lipid antigens presented in CD1
CD1 molecules do what?
present lipid antigens to gamma:delta T-cells.
CD1's generally present endogenous lipids at the cell surface. When infected, endogenous lipid is exchanged for a bacterial lipid and presented on surface.
do gamma:Delta t-cells have a TCR?
yes, but gamma:delta not alpha:beta
they are cytotoxic to infected/stressed cells, but also contribute to tissue repair
what type of TCR? What diversity?
express alpha:beta TCR with very low diversity (1 possible alpha, 3 possibly beta) - can only see a limited number of lipids
AKA invariant natural killer T cells
NKT cells recognize..
lipids and glycolipids in CD1d
NKT, CD1d, NKT, CD1d, NKT, CD1d
NKT cells would be beneficial against...
what do they excrete?
bacteria excreting lots of weird lipids - like mycobacteria
NKT cells excrete IFN-gamma and IL4
NKT function is very similar to that of...
Helper T cells.
Th - recognize peptide in MHCII, are not directly cytotoxic, and are late cytokine production as effector mechanism
NKT recognize lipid in CD1d, not directly cytotoxic, and their effector mechanisms are EARLY cytokine production (excretes IFN-gamma similarly to TH1, and IL-4 similarly to TH2)