L5

Question 1

which cytokines mediate innate immunity? What triggers them? What produces them?

Answer 1

type 1 IFN: alpha (leukocytes) and beta (fibroblasts)

type 2 IFN: gamma (upregulates INFLAMMATORY cells)

Question 2

three main actions of type 1 IFN:

-what are they triggered by?

Answer 2

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)

Question 3

TNF production is stimulated by which type of bacteria? In response to WHAT in their cell walls?

Main purpose of TNF?

Answer 3

GRAM-NEGATIVE

• ENDOTOXIN
• ->LPS (lipopolysaccharide) - in cell wall

attract INFLAMMATORY cells - cause fever!

Question 4

How do LOW vs. HIGH amts of TNF affect you?

Answer 4

low TNF: endogenous pyrogen - produces fever

high TNF: sepsis - slows blood flow, causes coagulation - may lead to septic SHOCK

Question 5

IL-8 (remember your mnemonic 8)- functions as a ____

-two main functions?

Answer 5

1) chemokine (remember C5a - the inflammatory complement)
2) stimulate leukocyte mvmt DIRECTLY - prefers to recruit NEUTROPHILS
- will see again in HIV

Question 6

IL-4 - activates what?

Answer 6

early B-cell activation, FROM T-helper 2 CELLS

Question 7

IL-12 - stimulates which cells?

Also promotes what?

Answer 7

T cells - the T CELL STIMULATOR (but not as good as IL-2)

-cell-mediated immunity (TNF, T, NK cells)

Question 8

What’s the “premier” T cell stimulating factor?

Answer 8

IL-2

Question 9

TGF-Beta - generally does WHAT to immunity?

-what does it actually STIMULATE (instead of inhibit?)

Answer 9

INHIBITS it - it’s the negative nora.
shuts down MANY of the other cytokines

STIMULATES IgA

Question 10

Which is the “creme-de-la-creme” cell in activating INFLAMMATION?

-how is it different from type 1 IFN?

Answer 10

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

Question 11

IL-6 -her name is ali.

Three main functions?! KNOW! [ALI]

Answer 11

1) Acute phase protein induction
2) LATE B CELL differentiation
3) inflammatory + autoimmune stimulation

Question 12

IL-1 fxn?

IL-2 fxn?

Answer 12

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

Question 13

IL-5 fxn?

Answer 13

Eosinophil activating factor

Question 14

2 things required for T cell activation:

Answer 14

1) MHC restriction

2) ACCESSORY molecule: CD28 (on T cell) must bind to either B7-1 or B7-2

Question 15

Name two CD28 inhibitors:

Answer 15

1) CTLA-4

2) PD-1 - programmed cell death produced by CANCER cells - immunosuppresses T cell rxn in cancer pts

Question 16

Main fxn of accessory molecule:

Answer 16

1) Strengthen binding

2) Increase transduction of signal

Question 17

Pair the lymphocyte accessory molecule with its APC target:

• CD4:
• CD8:
• CD2:
• LFA-1: (all bone marrow-derived)
• CD28:

Answer 17

• 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

Question 18

Clonal selection theory of T cells suggests WHICH mechanism of diversity DOESN’T occur like in immunoglobulins

Answer 18

[remember MMR]

Multiple genes - happens
somatic Recombination - happens

somatic MUTATION - does NOT.

Question 19

what does CD3 do?

Answer 19

CD3: signal transduction of activating signals from the surface receptor of the APC to the T cell cytoplasm

Question 20

Which IL factor do you limit in order to limit T cell’s ability to get activated?

Answer 20

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

Question 21

T-helper subsets you’re supposed to know: TH1,2,3,17. What does each do?

Answer 21

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!

Question 22

5 steps of cytotoxic T cell-mediated lysis: which two main lytic molecules produced?

Answer 22

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!)

Question 23

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?

Answer 23

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

Question 24

what are the FOUR mechanisms of DOWNregulation?

Answer 24

1) immunological tolerance (deletion/anergy)
2) T lymphocyte suppression
3) antibody feedback
4) Fas/FasL interactions

Question 25

what is anergy?

Answer 25

(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

Question 26

what is deletion?

Answer 26

(part of immunological tolerance)

-elimination of T cells w/ the ability to bind SELF-antigen (don’t want to react to yourself!)

Question 27

T/F: CD4 cells can DIRECTLY downregulate immune response

if true, WHAT does it express? using WHAT transcription factor?

Answer 27

true.
(part of T lymphocyte suppression)

mostly IL-2, using factor FOXP3
-levels REDUCED in uveitis

Question 28

Fas: on (target or cytotoxic) T cell
-how about FasL?

what happens when they’re together?

Answer 28

Fas: on target
FasL: on cytotoxic cell

Merge? Apoptosis to Fas cell (the target cell)
-REGULATES itself as the antigen is eliminated!