Immunology 4 Innate Immune System

Front 1

what is the first thing that happens when a microbe gets past the epithelium

What is the cool thing about thses cells being activated?

Back 1

1. dendritic cells & macrophages gobble up the microbe

**PMN (neutrophiles) are not on scene yet and so dont phago at this

**cool thing that macro and dendritic are APC!

Front 2

what is O2 dependent killing of microbes by phago

O2 INdependent?

Back 2

O2: make ROS (NO & superoxide anion)
No O2: proteolytic enzymes

Front 3

which receptors on phagocytes stim migration

Back 3

chemokine
N formylmethionyl receptors

Front 4

which receptors on phago stim immune response

Back 4

TLR
cytokine

Front 5

what do cytokines do

Back 5

promote immune response
guide cell migration

Front 6

where are most TLR's found, what happens when the ligand binds

Back 6

mainly in innate though some on adaptive cells

**when ligand binds NFkB (inflammation and prepares innate to talk to adaptive) and IRF3 (block viral replication and make NK) are stim to be made

Front 7

so a microbe enters the epithelium and macro and dendritic are on it with phago, what allows them to become APC?

Back 7

TLR binding and NFkB (molecule produced when TLR is bound with ligand, promotes inflammation and gets adaptive and innate talking)

With TLR and NFkB the cell expresses B7 (CD80 & CD86)


COSTIMULATION, CD80 and CD86 are costim molecules

Front 8

IFN a
IFN b

What stim secretion, who secretes them, what o they do

Back 8

secreted wwhen TLR binds
secreted by macro

causes:
1. antiviral mech in surrounding cells
2. increase MHC I to present AG to CD8 T cells
3. Stim NK

Front 9

what do NK cells do?
what stim NK
How do NK recognize bad guys

Back 9

NK stim by type 1 interferons (IFNa/b)
Control viral replication before adaptice starts
recognize cells with less MHC I

Front 10

what two granules are in NK cells? what do they do

Back 10

1. perforin: make pores
2. granzymes: serine esterase

Front 11

what two cells secrete the majority of cytokines

are cytokines innate or adaptive

Back 11

1. macro (innate)
2. Th (adaptive)

**innate, there is NO SPECIFICITY to target cells

Front 12

what is the fx of the following innate cell

1. Basophile/Mast
2. Eosinophile/NK
3. PMN
4. Macro/Mono

Back 12

1. Baso/Mast: degranulate, release histamine promote inflammation

2. Eosinophils/NK: release cytotixins and kill bugs

3. PMN: phago to kill

4. Mono/Macro: phago and APC

Front 13

what are the 2 main PRR for phago? *name 3 specifics for each category

Back 13

1. Opsonin- host molecules that coat the pathogen: complement, CRP, AB

2. PAMP- mannose, scavenger, LPS

Front 14

so PAMP is a type of PRR that is specific for phago, what are 3 types of PAMP

Back 14

1. mannose
2. scavenger
3. LPS

Front 15

what are 3 types of opsonins, what do they do

Back 15

1. AB
2. complement
3. CRP

**they are host molucules that coat the bug and icnrease phago

Front 16

when proteolytic cleave is used in phago is this O2 dependent

Back 16

nope

**O2 dependent make ROS- NO, O2-, H2O2, ClO-

Front 17

what cells kill fungal infections?

Back 17

well anthing that kills INTRACELLULAR

1. CD8
2. NK
3. PMN
4. Macro/Mono

Cell mediated

Front 18

name 3 consequences of ineffective phagocytosis

Back 18

1. recurrent bacterial infections
2. hard to treat infections bc bug stays in macro w/o being degraded (persistant IR)
3. macro spread bug around body (reticuloendothelial system)

Front 19

what is commonly ineffective with ineffective phagocytes?

Back 19

NADPH oxidase, chronic granulatoma disease

**phago use ROI, NO, and proteolytic enzymes to kill

Front 20

what is defective in chronic granulatomas disease, why

Back 20

defective phago due to defective NADPH oxidase system

**cant make H2O2 and O2- to kill the bug once its ingested

Front 21

why do granulomas form in CGD

Back 21

cant kill the bug once its ingested bc no NADPH oxidase to make O2 dependent killing mechs

**the phago keeps IR going, chronic inflammation leads to granuloma

Front 22

do phagocytes (macro, PMN) just gobble things up and be done?

Back 22

nope, they indice other IR

1. cell migration, chemokine, N formyl methionyl

2. Promote IR: TLR, Cytokine

**phago do other IR by their other receptors as well as the cytokines they secrete

Front 23

what cell type has TLR, where
what do TLR recognize
what does binding do

Back 23

1. phago have TLR on cell surface and internally on endosome

2. TLR recognize PAMP (mannose, LPS, scavenger)

3. when bound: NFkB & IRF3

Front 24

what does PAMP stand for

Back 24

pathogen associated molecular pattern

Front 25

how many TLR are there
what is the cytoplasmic domain
what is the extracellular domain

Back 25

11
TIR domain
leucine

**TLR recognize PAMP, mannose, LPS, scavenger

Front 26

what are the TF that are stim when pathogens bind to TLR on phago

Back 26

1. NFkB: promote inflammation, prepare for interaction with adaptive

2. IRF3: stim NK, make interferons to block virus

Front 27

what does NFkB do? when is it made

Back 27

1. promote imflammation
2. prepare innate to interact with adaptive (costim, B7 CD80/86)

**bug binds TLR and NFkB is made, IRF3 is also made

Front 28

what does IRF 3 do? when is it made

Back 28

1. makes type 1 interferons (IFNa/b), block viral replication

2. stim NK cells

Front 29

when we talk about bug binding to TLR and NFkB being made what specifically does NFkB do

Back 29

1. promote inflammation

2. prepare phago with TLP to become APC. Increase expression of B7 (CD80/86) for costimulation

Front 30

along with MHC what else is required for APC to T cells, how is this does

Back 30

COSTIMULATION

**when bug binds TLR on the phago, the phago make NFkB which makes the phage express B7 (CD80, 86). this increases surface molecules for APC fx

Front 31

what is IFNa/b
when is it stimulated
what does it do

Back 31

type 1 interferons

*when bug binds TLR on phago IRF3 is stimulated, IRF3 makes IFNa/b

**kill infected cells
**increase MHC 1
**stim NK cells

Front 32

how is MCH1 increased

Back 32

bug binds TLR on phago
makes IRF3
IRF3 makes IFNa/b
IFNa/b increase MHC for presentation of AG to T

Front 33

NFkB
IRF3

**when are they made, what do they do

Back 33

made when bug binds TLR

NFkB: promote inflammation, prepare phago for APC

IRF3: make type 1 interferons, IFNa/b to kill virus, increase MHC1 and stim NK

Front 34

what is one type of interferon that stim NK cells

Back 34

type 1

IFNa/b

Front 35

how do NK cells work to kill infected cells

Back 35

they bind cells, when they see MCH 1 they are inhibited

**if they bind a cell with decreased MHC 1 they arent inhibited and will release preformed granules (perforin, granzymes)to kill the cell

**NOTE: MCH 1 is a normal molecule on all cells, tumors can sometimes decrease MHC 1 to evade T cell elimination

Front 36

what is perforin, what cell uses it, does it work alone

Back 36

Granule in NK cell. When an NK cell does not bind MCH is is not inhibited and releases its granules

1. Perforin: makes a pore in infected cell

2. Granzymes: serine esterase, enter through the pore that was formed and induce apoptosis

Front 37

what causes NK degranulation, what granules are released

Back 37

normal, NK binds MCH and is inhibited

infected cell with decreased MHC, no MHC --> no inhibition

**perforin makes a hole in infected cell membrane, granzymes then enter and activate apoptosis (serine esterases to activate caspases involved in forming apoptosis complex)

Front 38

what cell type makes the majority of cytokines? are they innate or adaptive

are cytokines themselves innate or adaptive

Back 38

1. macrophages, innate
2. T helper, adaptive

Cytokines are innate, no specificity to a target cell

Front 39

are cytokines made on the spot or premade and stored

Back 39

made on the spot

**made in respone to bug

Front 40

how can a cells response to a give cytokine be altered

Back 40

1. number of receptorrs
2. affinity of receptor for cyto

Front 41

what are the 6 major classes of cytokines

Back 41

1. interleukins (IL)
2. interferonf (IFN)
3. Tumor Necrosis Factor (TNF)
4. Colony Stim Factor (CSF)
5. Growth Factors (GF)
6. Chemokines

Front 42

which IL is stil with lymphoid but not myeloid

Back 42

IL7

**IL3 for both

**IL7 for lymphoid
**CSF GM for myeloid

Front 43

cytokines activate/inhibit/modify IR, HOW?!

Back 43

activate signal transduction to make TF

Front 44

cytokines are diverse

1. pleitropy
2. redundant
3. synergy
4. antagonism

Back 44

1. pleitropy: 1 cytokine has diff effects on dif cells

2. redundant: 2 cytokines do same fx

3. synergy: the action of 2 cyto together gives a greater response than one alone

4. antagonism: cytokines work in opposition

Front 45

what is the name of a common signal transduction pathway that is activated by a cytokine

Back 45

JAK/STAT

1. Cytokine binds
2. receptor dimerizes
3. receptor cross Pi JAK
4. Pi-JAK then Pi the receptor
5. Pi receptor gives binding for STAT
5. STAT then Pi and dimerize
6. STAT-Pi enters nucleus and acts at TF

Front 46

in the JAK/STAT path who acts at TF?

Back 46

STAT

Front 47

how is CGD treated (3)

Back 47

1. IFNg
2. Bone marroe transplant
3. gene therapy

Front 48

what does IFNg do?

Back 48

exogenous sytokine therapy for CGD

1. enhance ROS
2. stim antimicrobial responses of macro

Front 49

what cells release IFNg? what is the effect

Back 49

T cells
NK

**increase microbial activity of macrophages and increase ROS

**also stimulates LOT of other cells

Front 50

what causes NK to release IFNg

Back 50

another cyto!

IL12 released by macrophages that need help killing ingested bug

Front 51

when is IL12 secreted, who secretes it

Back 51

macrophages secrete IL12, its SOS!!! HELP ive swallowed something and I need help

**IL12 activates NK, NK makes IFNg, IFNg increases ROS in macro

Front 52

so, IL12 is secreted by a macro who needs help, IL12 activates NK, NK then makes IFNg which increases ROS for macrophage

Back 52

coo teamwork

Front 53

what are 3 ways NK are activated

Back 53

1. IL12 from macrophages that need help

2. decreased MHC 1

3. IFNa/b

Front 54

4 major components of innate

Back 54

1. cytokines
2. phagocytes
3. APC
4. NK

Front 55

name the fx of the following innate cell

1. Neutrophile
2. macro
3. dendrite
4. NK
5. eisonophil
6. mast
7. basophile

Back 55

1. PMN: phago, ROS, antimicrobial peptide

2. Macrophage: cyto, phago, APC

3. dendrties: APC, costimulatory, ROS, IFN, cytokines

4. NK: lysis of viral infected cells, activate macrophage

5. eosinophile: parasites

6. Mast cell: histamine, allergy

7. Basophile: histamine, allergy