lecture 4 exam 2 Flashcards
adaptive immunity relies on APC to process antigen and present it to T cells via
peptides on MHC molecules
MHC molecules are on the surface of antigen presenting cells (DC, B cells, macrophages)
cytosolic pathogens
obligate intracellular
viruses
some bacteria
any cell
extracellular (vesicular pathogen)
bacteria
protozoa
infected apoptotic cells
macrophage
extracellular pathogens
bacteria
toxins
b cell
macrophage as pro APC
main function is to trap and destroy
phagosomes are very acidic
cannot engage in prolonged interactions w t cells
present antigens to effector and memory t cells but NOT naive t cells
b cell as pro APC
process and present protein antigens in blood and lymphoid organs to helper t cells to activate immune response
dendritic cell as pro APC
most important full time professional APC
ONLY cell w ability to present to naive T cell
100x more effective at presenting antigen than macrophage and B cell
dendritic cells
- derived from bone marrow
- found in most tissues and blood
- long thin cytoplasmic processes called dendrites
- increase cell SA -> increased efficiency in trapping and presenting ag - immature DC are good at capturing antigen (phagocytosis, pinocytosis)
- mature DC are best at processing the internalized antigen and presenting antigens to naive T cells in lymph nodes
- can produce diff cytokines depending on binding to PAMPs and alarmins that lead to activation of various T cell subsets
- act as sentinel cells
classical DC
langerhans cells - immature DC in skin
origin of histiocytomas in dogs
interdigitating, thymic, follicular
interdigitating DC
mature DC interacts w T cells in the lymph node
thymic DC
in thymus important for presenting self antigens to developing T cells
follicular DC
confined to follicles of lymph nodes
present antigen to B cells as immune complexes (antigen + fdc)
plasmacytoid DC
derived from plasma cell rather than myeloid precursor
long lived cells
found in blood, bone marrow and lymphoid organs
not as effective at APC
essential in anti-viral responses
-rapidly activated by viral nucleic acids
-professional producers of type 1 IFN
-activate NK cells
immature vs mature DC
as they mature they change their function
immature: specialized antigen trapping cells - increased tolerance, decreased immunity
mature: specialized antigen processing cells - increased immunity, decreased tolerance
- increase surface epression of MHC 2, upregulate costimulatory molecules tat are needed for T cell activation (CR3), secrete cytokines needed for T cell proliferation and differentiation
through maturation interact w pathogens, PAMPS, DAMPS, inflammation
produce CD80, CD40, CD86
processing and presentation of cytosolic (endogenous) antigens to MHC 1
intracellular
proteasome cleaves proteins into peptides (8-10aa)
ubiquitin - recycles proteins and targets viral proteins to proteasome
transporter proteins (TAP) carry the antigen peptides to ER
approx 200 MHC 1 to stimulate a CD8+ t cell
MHC antigen complex get imbedded in cell membrane
presentation of vesicular or exogenous antigens to MHC 2
extracellular (vesicle or normal)
invariant chain prevents peptide from binding to MHC 2 in the ER
infected cell enters and fuses w lysosome
antigenic peptide exchanges for invariant chain and creates complex w MHC 2
MHC 2 ag complex goes to membrane
approx 200-300 peptide MHC complexes required to activate CD4+ t cell
MHC 1
intracellular antigens
CD8+ T cells
cell mediated immunity
MHC 2
extracellular antigens
CD4+ T cells
humoral immunity
T cell subsets
alpha beta: - CD4+: t helper 1, 2, 17, tregulatory - memory t cells -CD8+: cytotoxic/cytolytic gammadelta innate lymphoid - NK
naive t cells and dc migrate to lymph node for priming
chemokines signal movement to ln
selectins & integrins support migration across endothelial cells (vessels & lymphatics)
DC enter afferent lymphatic
naive t cells enter HEV
-interact w thousands of DC in paracortex
-TCR recognizes specific antigenic peptide/MHC of DC
-adhesion molecules cause firm binding (immunological syapse)
T cell activation requires 3 signals
- antigen specific - TCR & CD3 (TCR complex), CD4& CD8 (coreceptor) - CD3 helps signal transduction
- costimulatory - CD28 binds to B7 (CD80/86)
- cytokines - IL 2 for proliferation, others for differentiation of thelper cells
signal 2 costimulatory signals
CD40L on T cell binds to CD40 on APC
-DC releases cytokines
-upregulates CD28 on T cell
CD28 on t cell binds costimulatory molecule B7 (CD80/86) on APC
-CD80 on macrophages and DC
-CD86 on B cells
-enhances cytokine expression and survival genes in T cell
-upregulates CTLA-4 (CD152) expression
CD152 binds CD80/86 after 2-3 days to STOP activation
CD152 bound to CD80/86 bw T cell and APC does what?
stops activation of costimulatory signals
immunological synapse
t cell and DC must be in contact for 12-24 hours to complete T cell activation
co receptors and adhesion molecules strengthen T cell:APC interactions via this synsapse
SMACs
after complete, the synapse is endocytosed and degraded terminating the cell interactions
