L5 Flashcards
which cytokines mediate innate immunity? What triggers them? What produces them?
type 1 IFN: alpha (leukocytes) and beta (fibroblasts)
type 2 IFN: gamma (upregulates INFLAMMATORY cells)
three main actions of type 1 IFN:
-what are they triggered by?
VIRALLY-INFECTED CELLS
1) inhibit viral replication on paracrine cells (protect neighbors)
2) enhance NK cell lysis (sacrifice yourselves!)
3) enhance class 1 MHC –> increases CD8 killers to cause ALL cell lysis (would die anyway)
TNF production is stimulated by which type of bacteria? In response to WHAT in their cell walls?
Main purpose of TNF?
GRAM-NEGATIVE
- ENDOTOXIN
- ->LPS (lipopolysaccharide) - in cell wall
attract INFLAMMATORY cells - cause fever!
How do LOW vs. HIGH amts of TNF affect you?
low TNF: endogenous pyrogen - produces fever
high TNF: sepsis - slows blood flow, causes coagulation - may lead to septic SHOCK
IL-8 (remember your mnemonic 8)- functions as a ____
-two main functions?
1) chemokine (remember C5a - the inflammatory complement)
2) stimulate leukocyte mvmt DIRECTLY - prefers to recruit NEUTROPHILS
- will see again in HIV
IL-4 - activates what?
early B-cell activation, FROM T-helper 2 CELLS
IL-12 - stimulates which cells?
Also promotes what?
T cells - the T CELL STIMULATOR (but not as good as IL-2)
-cell-mediated immunity (TNF, T, NK cells)
What’s the “premier” T cell stimulating factor?
IL-2
TGF-Beta - generally does WHAT to immunity?
-what does it actually STIMULATE (instead of inhibit?)
INHIBITS it - it’s the negative nora.
shuts down MANY of the other cytokines
STIMULATES IgA
Which is the “creme-de-la-creme” cell in activating INFLAMMATION?
-how is it different from type 1 IFN?
IFN - GAMMA (Type 2 interferon)
1) POTENT mononuclear phagocyte ACTIVATOR(phago cells [monocytes + macrophages])
2) Increases Class 1 AND Class 2 expression (inc. cellular AND humoral immunity)
3) DIRECT promoter of differentiation of T and B cells
4) ACTIVATOR of NK cells, neutrophils
IL-6 -her name is ali.
Three main functions?! KNOW! [ALI]
1) Acute phase protein induction
2) LATE B CELL differentiation
3) inflammatory + autoimmune stimulation
IL-1 fxn?
IL-2 fxn?
IL-1: mediates INFLAMM. response - promotes IL-2
IL-2: promotion/proliferation of T cells (like IL-12) that have been stimulated by antigen - autocrine and paracrine growth factor of CD4 AND CD8 - amt of proliferation (replication) of activated T cell is proportional to the amt of IL-2 acting on its own cell
-also stimulates B cells growth/antibody synthesis
IL-5 fxn?
Eosinophil activating factor
2 things required for T cell activation:
1) MHC restriction
2) ACCESSORY molecule: CD28 (on T cell) must bind to either B7-1 or B7-2
Name two CD28 inhibitors:
1) CTLA-4
2) PD-1 - programmed cell death produced by CANCER cells - immunosuppresses T cell rxn in cancer pts
Main fxn of accessory molecule:
1) Strengthen binding
2) Increase transduction of signal
Pair the lymphocyte accessory molecule with its APC target:
- CD4:
- CD8:
- CD2:
- LFA-1: (all bone marrow-derived)
- CD28:
- CD4: Class 2 MHC
- CD8: Class 1 MHC
- CD2: LFA-3 (not now)
- LFA-1: ICAM-1 (hypersens. type 4)
- CD28: B7-1 or B7-2
Clonal selection theory of T cells suggests WHICH mechanism of diversity DOESN’T occur like in immunoglobulins
[remember MMR]
Multiple genes - happens
somatic Recombination - happens
somatic MUTATION - does NOT.
what does CD3 do?
CD3: signal transduction of activating signals from the surface receptor of the APC to the T cell cytoplasm
Which IL factor do you limit in order to limit T cell’s ability to get activated?
IL-2 - it’s the T cell growth factor.
Was activated initially by IL-1 from the APC/epitope, which went on to activate the “naive” T cell
T-helper subsets you’re supposed to know: TH1,2,3,17. What does each do?
TH1: cell-mediated immunity - produces IL-2 (proliferation), TNF (fever) and IFN-gamma (inflamm)
TH2: antibody/humoral immunity - produces IL-4 and IL-10 (EARLY B cell activation- B cell acts as T cell’s APC when PROTEIN antigen present
TH3: SUPPRESSIVE - TGF-beta
TH17: eyeballs - promoted by NK cells; dry eye!
5 steps of cytotoxic T cell-mediated lysis: which two main lytic molecules produced?
GRANZYME, PERFORIN - hole pokers! Result in osmotic lysis.
1) recognition
2) activation
3) LETHAL HIT
4) detachment
5) death of target
ONE cytotoxic T cell can kill MANY other target cells (good!)
When B cells need the help of T cells to respond to antigen, they:
1) incorporate the p___ antigen onto their OWN cell surface class __ molecules (acting as APC)
2) bind their B7 with the T-cell’s ____,
AND
3) bind their CD__ to the T cell’s WHAT?
1) PROTEIN antigen onto their class II (helper T is needed!)
2) CD28
3) B-cell CD40 to T-cell CD40L (LIGAND)
–> results in cytokine release from T cell BACK to B cell for proliferation against that antigen
what are the FOUR mechanisms of DOWNregulation?
1) immunological tolerance (deletion/anergy)
2) T lymphocyte suppression
3) antibody feedback
4) Fas/FasL interactions
what is anergy?
(part of immunological tolerance)
When T cells recognize antigens presented by class II APCs but FAIL to simultaneously bind B7 - leads to functional INACTIVATION of that T cell.
-leads to T cell tolerance developed OUTSIDE the thymus
what is deletion?
(part of immunological tolerance)
-elimination of T cells w/ the ability to bind SELF-antigen (don’t want to react to yourself!)
T/F: CD4 cells can DIRECTLY downregulate immune response
if true, WHAT does it express? using WHAT transcription factor?
true.
(part of T lymphocyte suppression)
mostly IL-2, using factor FOXP3
-levels REDUCED in uveitis
Fas: on (target or cytotoxic) T cell
-how about FasL?
what happens when they’re together?
Fas: on target
FasL: on cytotoxic cell
Merge? Apoptosis to Fas cell (the target cell)
-REGULATES itself as the antigen is eliminated!
