chapter 3 immunology test 2

how long does the immediate innate immune response take

0-4 hours

how long deso the induced innate immunity response take

4 hours to 4 days

how long does the adaptive immune response take

4 hours until the pathogen is destroyed

which 3 cells are involved in the induced immune response and what is their role

macrophages - first to recognize and respond to the pathogen

leukocytes (specifically neutrophils) - called into the site of infection out of the blood

hepatocytes - make acute phase reactants, aid in the clearance of the pathogen, and direct leukocytes to site of inflammation

which 2 cells help recognize self from nonself

macrophages and NK cells

1st effector cells once the pathogen invades

resident macrophages

where are the resident macrophages located

connective tissues in the linings of GI, respiratory tract, lung alveoli, liver

ligand for macrophage CR1

C3b

pathogen C3b surface fragments + degraded by factor I results in

iC3b

iC3b is a ligand for what

macrophages CR3 and CR4

macrophage surface receptors are efficient why?

combination of opsonization by complement and phagocytosis by macrophages

what 5 ligands do CR3 and CR4 recognize

• iC3b

• LPS (gram - bacteria)

• cell-surface structures on yeast

lectins

carbohydrate-binding proteins

examples of lectins

mannose and glucan

scavenger receptors

preference for molecules that are negatively charged

which are scavenger receptors

nucleic acids, gram + and gram - bacteria

what kind of cells are receptors found in

macrophages, monocytes, dendritic cells, granulocytes, and NK cells

how many PRRs are known

100

PRR

pattern recognition receptors

self

normal healthy cell

nonself

microbial cell

altered cell

cancer cell or apoptotic cell

why is there an unequal distribution of receptors

to make sure that at least some of the leukocytes will be able to recognize the pathogen with their innate receptors.

DAMPs

associated with cells that have been damaged

PAMP stands for

pathogen associated molecular patternw

what are PAMPs

components common to many pathogens and/or altered cells and molecules

soluble PRR example

MBL

TLR-4 ligand

LPS

what microorganism does TLR-4 recognize

gram - bacteria

what cells carry TLR-4

macrophages, dendritic cells, mast cells, eosinophils

TLR-7 ligand

single-stranded viral RNAs

cellular location of TLR-4

plasma membrane

TLR-7 recognizes what microorganisms

RNA viruses

what cells does TLR-7 carry

plasmacytoid dendritic cells, NK cells, eosinophils, B cells

where is TLR-7 located

endosomes

TLR-3 ligand

double-stranded viral RNA

TLR-3 recognizes what microorganisms

RNA viruses

TLR-3 is found in what cells

NK cells, dendritic cells, CD8 T cells, various epithelial cells

TLR-5 ligand

flagellin, a protein

microorganisms recognized in TLR-5

bacteria

cells carrying TLR-5

instestinal epithelium

cellular location of TLR-5

plasma membrane

cellular location of TLR-3

endosomes

what leads to TLR-4

LPS → LBP → CD14 → MD2 → TLR4

adaptor protein

MyD88

kinase

phosphorylation

what does IKK stand for

Inhibition of KappaB Kinase

what is the common pathway of intracellular signaling starting with TLR-4

MyD88 binds TLR-4. IKK ends up being activated and it phosphorylates IkB. NFkB is translocated from cytoplasm to the nucleus. directs the transcription of genes for inflammatory cytokines

NFkB stands for

TF nuclear factor kB

what are NOD-like receptors

cytoplasmic receptors for recognition of pathogens

NOD-1

recognizes a degradation product of Gram (-) peptidoglycan

NOD-2

recognizes a degradation product of most bacteria - muramyl dipeptide

what does recognition lead to

NFkB making inflammatory cytokines

pyroptosis

mechanism of death of the macrophage which allows massive release of IL-1. large number of pores are created for release. extreme circumstances

does pryoptosis happen often?

macrophages most likely dont go through this but instead release IL-1 more slowly

netosis

neutrophil specific death

what is the master regulator for inflammation

IL-1

what is IL-1 exactly

inflammatory cytokine made by macrophages that intiates and activates the creation of other inflammatory cytoknes

what two things activate endothelial cells

TNF-alpha and IL-1

CC or CXC means it’s what?

a chemokine

what are the 5 activated cytokines by resident macrophages

TNF-alpha, IL-6, CXCL8, CCL2, IL-12

what does CCXL8 do

recruits neutrophils from the blood and directs them to infected tissue

what does CCL2 do

recruits monocytres from the blood and directs them to infected tissue

IL-12 does what

recruits and activates NK cells to secrete cytokines that strengthen macrophages’ response to infection

what does CCL2 bind to

CCR2

pryogens

raise temperature

what are the 3 pyrogens

IL-1, IL-6, TNF-alpha

sepsis

infection of the blood

what does IL-6 do

acts on local muscle and fat cells to increase temperature and signals to liver cells (hepatocytes) to make acute phase reactants

what are the acute phase reactants

MBL and CRP

CRP stands for

C-reactive protein

3 properties of macrophages

-long lived

-reside in tissues

-work as infection begins (raise alarm to neutrophils)

4 properties of neutrophils

-short-lived

-circulate in blood

-polymorphonucelar leukocytes (PMNs)

-wait for macrophage to sound alarm to enter tissue

are neutrophils present in healthy tissue

no

what attracts neutrophils

release of inflammatory mediators at infection sites

how many neutrophils enter mouth and throat each day

3 × 10^9

after how many rounds of phagocytosis by apoptosis do neutrophils die

1 round

what are the 4 leukocyte adhesion molecules

selectins, vascular addresins, integrins, immunoglobulin superfamily

leukocyte adhesion molecules

four structural classes of adhesion molecules present on white blood cells

what are selectins

carbohydrate-binding lectins. L-selectin

what are vascular addresins

contain carbohydrate groups to which selectins bind

what are the 3 vascular addresins

CD34, GlyCAM-1, MAdCAM-1

what are integrins

typically bind to Ig superfamily proteins. LFA-1

immunoglobulin superfamily

ICAM-1

C3a and C5a

anaphylotoxins- increase inflammation

chemoattractants

nascent

newly formed

4 steps of extravasation

1. rolling adhesion

2. tight binding

3. diapedesis

4. migration

what receptors are on the surface of a neutrophil

CR1, C3b, CR3 & CR4, CD14, mannose receptors, glycan receptors

primary granular type

azurophilic

secondary granular type

specific

tertiary granular type

gelatinase

H2O2

hydrogen peroxide. necessary for neutrophils to kill bacteria. it is a toxic oxygen-derived product

lactoferrin

iron binding protein that neutrophils release. has antiinflammatory properties

what’s in primary/azurophilic granules

lysozymes, defensins

what’s in secondary/specific molecules

lactoferrin, lysozyme

enzymatic reaction contributing to neutrophil respiratory burst

neutrophil death process

neutrophil → apoptosis → phagocytosed by macrophage

what does NET stand for

neutrophil extracellular trap

what are NETs

the neutrophil’s nucleus swells and leads to the cell bursting (netosis) leaving behind all of the antimicrobial components of the granules as well as DNA and histones that serve to trap the pathogen

chronic granulomatous disease

if macrophages can’t create NADPH oxidase subunit, they don’t kill efficiently. macrophage gets infected and granulocytes surround it