Quiz 2 Part 2 Flashcards by amanda kastel

What are the 3 parts of the INDUCED part of innate immunity?

Receptor recognition (self vs non self)
Receptor recognition (signaling)
Extravasation

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approximately how long does the immediate innate immune response last?

0-4 hours

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Approximately how long does the induced innate immune response last?

4 hours-4 days

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Approximately how long does the adaptive immune response last?

4 days - defeat of pathogen, defeat of host, or “truce” of a chronic disease

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Explain the 2 possible routes of the immediate innate immune response

Pathogen invades our tissue and proliferates. From there, the pathogen is recognized by soluble effector molecules (defensins) and resident effector cells (macrophages) within the infected tissue.

The pathogen can be eliminated through this process and infection ends or….

Pathogen is NOT eliminated and the induced innate immune response begins

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Is there any tissue damage in the case of the immediate innate response eliminating the pathogen and clearing the infection?

VERY MINOR tissue damage is repaired

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In which phase of immunity is C3b tagging occurring and macrophage phagocytosis?

During the immediate innate response

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What is occurring during the INDUCED innate response?

Macrophages (resident cells) send out cytokines to recruit effector cells to the infected tissue.
INFLAMMATION, FEVER, THE ACUTE-PHASE RESPONSE

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Once the effector cells (neutrophils, NK cells) and soluble effector molecules (cytokines, chemokines) are recruited and begin fighting off the pathogen , what are the 2 possible routes?

Pathogen is eliminated and infection cleared
Pathogen is NOT eliminated and adaptive response occurs

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If the pathogen is eliminated during the induced response, what can come out of the wound?

pus which is mainly composed of dead neutrophils

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Is there any tissue damage in the induced innate response?

minor tissue damage is soon repaired

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How is the adaptive immune response activated?

dendritic cells carry pieces of the pathogen through an afferent lymphatic to secondary lymphoid tissue. this activates B and T cells and they proliferate and mature to become effector cells

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Is there any tissue damage in the adaptive immune response?

MAJOR tissue damage is gradually repaired

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What happens if the pathogen is NOT eliminated during the adaptive response?

the human host either dies from the acute infection or suffers the disease resulting from the chronic infection

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Name the cells on which innate immune receptors exist

macrophages, neutrophils, NK cells (and others)

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What is the PURPOSE of innate immune receptors?

to distinguish microbial carbohydrates, lipids, proteins, and nucleic acids from host structures —-recognize “self vs non-self”

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Does every cell have the same innate immune recptors?

no! they each have their own subset

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Are innate immune receptors considered specific or nonspecific? why?

nonspecific because each receptor subtype can bind similar structures on DIFFERENT kinds of pathogens. (they do not target any specific pathogen, but to generic structures)

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What is the primary purpose of the innate immune receptors found on the surface of an NK cell?

Receptors on NK cells recognize morphological changes at the surface of human cells that occur because of viral infection. It then kills the whole cell

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Name 4 targets of innate immune receptors on gram POSITIVE bacteria

-Well teichoic acid
-Peptidoglycan
-Lipoteichoic acid
-proteins

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Gram stain stains what structure on a bacterial cell wall? Explain what the colors indicate

gram stain stains PEPTIDOGLYCAN on a bacterial cell wall. If the bacteria is gram positive, purple will appear under a microscope. If the bacteria is gram negative, there will be no color

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Why is it that gram stain does not bond to peptidoglycan to give a purple color in gram negative bacteria

because of the plasma membrane. It prevents stain from getting to the peptidoglycan. The peptidoglycan is “sandwiched” between 2 plasma membrane whereas on gram positive it was on the surface of the membrane

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Name 4 targets of innate immune receptors on gram NEGATIVE bacteria

LPS (lipopolysaccharide) - O polysachharide, Core polysaccharide, and lipid A

Peptidoglycan

lipoprotein

Protein

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Are there more peptidoglycans in gram positive or gram negative bacteria?

gram positive

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What is the name of the receptor on a macrophage that recognizes peptidoglycan?

Lipopolysaccharide receptor (CD14)

Which target on a bacterial cell wall is ONLY found in a gram negative bacteria?

LPS (lipopolysaccharide)

Do neutrophils send signals? What can you conclude from this?

NO - the macrophages do the signaling. Therefore, they will not have signaling receptors like the macrophage

macrophage receptors contain recognition domains for which 3 things on the surface of a microbe?

Carbohydrates --- recognized by Mannose and Dectin-1 receptors Lipoproteins --- recognized by SR-A and SR-B Complement receptors --- CR3 and CR4

Explain why the phagocytic receptors on the surface of the macrophage are important

Ligands on the microbial surface with phagocytic receptors on the macrophage exhibit COOPERATIVE BINDING. This means that there is more than 1 kind of receptor on each macrophage. Therefore, while 1 pathogen has been recognized and engulfed by 1 receptor on the macrophage, somewhere else on the macrophage another pathogen has been recognized by a different receptor

What is the term for phagocytosis through recognition of a ligand on the microbial surface by a phagocytic receptor on the macrophage?

RECEPTOR MEDIATED ENDOCYTOSIS

In receptor mediated endocytosis, what happens to the endosomes that have been pinched off of the surface of the macrophage?

the endosomes fuse with a lysosome which undergoes hydrolytic activity to destroy the microbes within it. keep in mind: The receptors that first recognized the ligands were pinched off with the endosome! therefore, they are within the cell now and able to recognize microbes that can potentially get into the cell

Name 2 ways in which receptors can recognize a microbe

1. Through a "tag" 2. Through some natural structure on bacteria

A family of ___ genes encodes the Toll-like receptor proteins

10 (TLR1-TLR10)

Explain the structure of the toll-like receptor proteins

they are transmembrane proteins with an extracellular domain for RECOGNIZING PATHOGENS and a cytoplasmic SIGNALING domain for conveying this information to the inside of the cell

What is the cytoplasmic, signaling domain of the TLR receptors called?

TIR -Toll Interleukin-1 Receptor This tells the nucleus to make genes that encode cytokines

What is the term for the variable, extracellular recognition domain of the toll-like receptor proteins?

LRR -Leucine-rich repeat region -Forms homo or hetero dimers

The Toll-like receptor proteins accomplish the ____ cascade

signaling

Which is the most well characterized TLR?

TLR4

TLR receptors can either be found ___ or ___

on the plasma membrane or an endosome (remember: endosome was pinched off of plasma membrane and still has those receptors)

What does TLR4 recognize?

LPS (lipopolysaccharide) -- only on gram negative bacteria. Gram negative bacteria continually produce and shed LPS, making those molecules soluble in the extracellular matrix. their presence signals that a bacteria is nearby

What is the name of the LPS co receptor and the LPS binding protein?

LPS coreceptor = CD14 LPS binding protein = LBP

What is the name of the carrier molecule that carries soluble LPS to the CD14 coreceptor and MD2?

LBP

The TLR4 dimers associate with which molecule

MD2

Name the components of the full, activated TLR4 complex

CD14/LPS/TLR4/MD2

What are the 2 possible routes of LPS after it is shed by a gram negative bacteria?

1. It can bind to a receptor protein on the surface of the macrophage (CD14) 2. LPS can be picked up by a soluble LPS binding protein (LBP) and be delivered to CD14

What is the GOAL of TLR signaling?

to activate the transcription factor NFKB

After the TLR/MD2/LPS/CD14 complex is fully formed, what happens next?

An adaptor protein called MyD88 binds TLR4 to initiate a series of reactions ending in the phosphorylation and activation of IKK

What does a kinase do?

it phosphorylates things (puts a phosphate on)

After IKK is phosphorylated and activated, what happens next?

IKK phosphorylates IKB (the inhibitor present on NFKB), leading to its degradation and removal from the NFKB molecule. NFKB enters the nucleus

What happens after NFKB enters the nucleus

NFKB activates the transcription of genes for inflammatory cytokines (synthesized in cytoplasm and secreted via ER)

What is a locational difference between TLR's (toll-like receptors) and NLR's (NOD-like receptors)

Toll-like receptors are transmembrane NOD-like receptors are soluble INSIDE of the cell within the cytoplasm

What is the purpose of the NOD-like receptors?

to detect degraded bacterial products WITHIN the cell

What are the 3 general domains of NOD like receptors

CARD - caspase recruitment domain NOD - oligomerization domain LRR'S - pathogen recognition (same as TLR!)

What is the goal of NOD-like receptors?

to signal the initiation of a kinase cascade, ending in the release of NFKB to increase cytokine production and activate macrophages

Where are these pieces of degraded bacteria that NLR's are looking for come from?

from pieces of destroyed pathogen from the hydrolytic activities of lysosomes

When do NLR's start to oligomerize?

when they recognize pieces of degraded pathogen leaching out from the phagolysosome into the cytoplasm

Do NOD-like receptors only form dimers?

NOD-like receptors can form dimers or larger

Name the 2 ways in which NFKB can be activated

1. Through molecules of LPS that are shed by gram negative bacteria and recognized by membrane bound Toll-like receptors 2. By the degraded pieces of the pathogen that leech out of a phagolysosome and into the cytoplasm. recognized by NOD-like receptors which are soluble within the cytoplasm

Name the cytokines which induce blood vessels to become more permeable, which enables effector cells and fluid containing soluble effector molecules to enter the infected tissue?

IL-1B TNF-a

What is the function of CXCL8

CKCL8 is a chemokine. It recruits neutrophils from the blood and guides them to the infection

How does CXCL8 achieve its goal

a chemokine receptor on neutrophils binds CXCL8 which makes the neutrophils move up the concentration gradient of CXCL8 to reach the site of infection

besides IL-1B and TNF-a, name 2 other proinflammatory cytokines that are released by macrophages

IL-6 ---- Induces fat and cells to metabolize, producing heat and raising the temperature in the infected tissue IL-12 --- recruits and activates NK cells that in turn also secrete cytokines that strengthen the macrophage's response to infection