2-Immunoregulation Flashcards
importance of reg
-not allow immune resp to get out of control
-promote vigorous immune resp then downreg
-prevent immune resp to normal host tissues
-immune resp subject to stimulatory and inhibitory control
T-reg cell characteristics
-express CD4, FoxP3, CD25
-absence leads to autoimmune disease IPEX
-high levels of CTLA-4 that inhibit act of T cells
-require TGF-beta for develop bc it induces FoxP3
-prevent xs immune resp to foreign antigen
-immune responses to self antigen missed by tolerization
FoxP3
transcription factor important to function of Treg
-either from recog of self antigen in thymus OR recog of antigen in peripheral tissues
CD25
alpha chain of IL2 receptor
-IL2 essential growth factor for Treg
Treg mechanism
- produces suppressive cytokines IL-10 and TGF-beta
- CTLA-4 binds B7 moles on APCs to reduce ability of APC to act T cells
- IL2 gets consumed so no growth factor for other cells
IL10
inhibits IL12 production by dendritic cells and macros
downregs expression of costimulatory moles and class II MHC
TGF -beta
suppresses activation of macros and T cells into CTLs and promotes dev of more Treg cells
induces TH17 and B cells to prod IgA antiibody at mucosal sites
initiates wound healing by fibroblasts migration/prolif and inc collagen syn
antibody feedback
either by
1. antibody helps eliminate antigen so no further stimulation
2. immune complex bound antibodies inhibit B lymph activation by binding antibody and Fc receptor
tolerance
definition
block of antigen induced differentiation of B/T aka induced state of unresponsiveness to antigen
-if bone marrow or thymus then called central (death), if periphery then peripheral (inactivation)
good to induce state of tolerance to self antigens bc is lose then autoimmune disease
characteristics of tolerance
-antigen specific
-acquired not inborn
-immature lymphocytes are easier to tolerize than mature but can happen
clonal anergy
functional inactivation of viable lymphocytes, peripheral tolerance
self reactive T cell removal
- central tolerance removes most in thymus
- peripheral Treg cells get rest via costimulatory moles without inflamm
PD1 on T binds PD-L1 or 2 on APC to interrupt signal transduction thru TCR and CD28
T lymph tolerance is long lasting
B lymphocyte tolerance
since T cells can’t recog self polysaccharides and lipids
either by
1. clonal deletion
2. receptor editing
clonal deletion B tolerance
immature B cells exposed to antigen > cell death (central tolerance) or receptor editing
receptor editing
B cell rearranges light chain genes again to produce completely diff antigen specificity
-will survive if new antibody not recog self antigen
thymocytes
can’t recognize or resp to antigen since no TCR
-can be destroyed by corticosteroids so chronic steroid therapy > state of immunodeficiency
thymocyte populations
- double negative= CD4-CD8- so not express either, thymus
- double positive= CD4+CD8+ so express both, in thymus
- single positive= CD4-CD8+ or v/v
double positive > single positive
graph via flow cytometry
importance of thymic selection
due to random gene recombs required to gen the TCR thymocyte pops express all possible antigen specifities
self reactive T need to be deleted
pos/neg selection produces T cells that react only with foreign antigen expressed on self MHC proteins
positive selection
thymocytes bind self MHC proteins are permitted to survive + thymos that recog foreign MHC proteins are eliminated
-aka not beneficial or harmful, just take up space and nutrients
mediated by cortical epithelial cells
negative selection
after positive- thymocytes bind self antigen and self MHC elimated so no autoimmune rxns
dendritic cells at corticomedullary junction
autoimmune regulator gene
AIRE
thymus can express tissue specific self antigens that can aid in neg selection and are under AIRE reg
if mutation in AIRE then widespread autoimmune dis
monokines
produced by macrophages
regulates- phagocytic cells
lymphokines
prod by activated T cells
regs- lymphocytes, macros, neutros, eosins
colony stimulating factors
prod by lymphos, macros, bone marrow, stromal cells
regs- granulocyte and monocyte prod in marrow
cytokine activities
- autocrine action: act on cells that prod cytokine, can be receptor mediated with IL2
- paracrine: act on cells in local vicinity of secretion
- endocrine: act on cells distant from site of prod
type 1 IFN
mediates innate immun
alpha and beta interferons upreg expression of class I MHC + act NK cells + block viral replication
TNF-alpha
tumor necrosis factor
prod by mononuclear phagocytes and T lymphocytes in resp to bacteria lipopolysaccharide aka LPS or endotoxin
will act macros/neutros + inc adhesiveness of vascular endo for neutros + fever generation + neutrophilia + DIC/shock
IL2
prod by CD4 T cells + autocrine and paracrine growth factor got T cells
inc NK cell cytotoxicity and induce NK to become lymphokine activated killer LAK cells (not in body tho in lab
IL4
prod by CD4 T cells, mast cells, basophils
-caused B cell isotypes switch to IgE
induce TH2 immune response
Interferon-gamma
type 2 interferon
prod by CD4, TH1, CD8, NK cells
directs immune resp toward cell mediated immun, most potent act of macros, upregs class I and II MHC expression
isotype switching to IgG
