2-Immunoregulation

Question 1

importance of reg

Answer 1

-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

Question 2

T-reg cell characteristics

Answer 2

-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

Question 3

FoxP3

Answer 3

transcription factor important to function of Treg
-either from recog of self antigen in thymus OR recog of antigen in peripheral tissues

Question 4

CD25

Answer 4

alpha chain of IL2 receptor
-IL2 essential growth factor for Treg

Question 5

Treg mechanism

Answer 5

1. produces suppressive cytokines IL-10 and TGF-beta
2. CTLA-4 binds B7 moles on APCs to reduce ability of APC to act T cells
3. IL2 gets consumed so no growth factor for other cells

Question 6

IL10

Answer 6

inhibits IL12 production by dendritic cells and macros

downregs expression of costimulatory moles and class II MHC

Question 7

TGF -beta

Answer 7

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

Question 8

antibody feedback

Answer 8

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

Question 9

tolerance

definition

Answer 9

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

Question 10

characteristics of tolerance

Answer 10

-antigen specific
-acquired not inborn
-immature lymphocytes are easier to tolerize than mature but can happen

Question 11

clonal anergy

Answer 11

functional inactivation of viable lymphocytes, peripheral tolerance

Question 12

self reactive T cell removal

Answer 12

1. central tolerance removes most in thymus
2. 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

Question 13

B lymphocyte tolerance

Answer 13

since T cells can’t recog self polysaccharides and lipids

either by
1. clonal deletion
2. receptor editing

Question 14

clonal deletion B tolerance

Answer 14

immature B cells exposed to antigen > cell death (central tolerance) or receptor editing

Question 15

receptor editing

Answer 15

B cell rearranges light chain genes again to produce completely diff antigen specificity
-will survive if new antibody not recog self antigen

Question 16

thymocytes

Answer 16

can’t recognize or resp to antigen since no TCR
-can be destroyed by corticosteroids so chronic steroid therapy > state of immunodeficiency

Question 17

thymocyte populations

Answer 17

1. double negative= CD4-CD8- so not express either, thymus
2. double positive= CD4+CD8+ so express both, in thymus
3. single positive= CD4-CD8+ or v/v

double positive > single positive

graph via flow cytometry

Question 18

importance of thymic selection

Answer 18

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

Question 19

positive selection

Answer 19

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

Question 20

negative selection

Answer 20

after positive- thymocytes bind self antigen and self MHC elimated so no autoimmune rxns

dendritic cells at corticomedullary junction

Question 21

autoimmune regulator gene

AIRE

Answer 21

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

Question 22

monokines

Answer 22

produced by macrophages
regulates- phagocytic cells

Question 23

lymphokines

Answer 23

prod by activated T cells
regs- lymphocytes, macros, neutros, eosins

Question 24

colony stimulating factors

Answer 24

prod by lymphos, macros, bone marrow, stromal cells
regs- granulocyte and monocyte prod in marrow

Question 25

cytokine activities

Answer 25

1. autocrine action: act on cells that prod cytokine, can be receptor mediated with IL2
2. paracrine: act on cells in local vicinity of secretion
3. endocrine: act on cells distant from site of prod

Question 26

type 1 IFN

Answer 26

mediates innate immun

alpha and beta interferons upreg expression of class I MHC + act NK cells + block viral replication

Question 27

TNF-alpha

Answer 27

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

Question 28

IL2

Answer 28

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

Question 29

IL4

Answer 29

prod by CD4 T cells, mast cells, basophils
-caused B cell isotypes switch to IgE

induce TH2 immune response

Question 30

Interferon-gamma

Answer 30

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