Induced Innate Immunity Chapter 3

What cell wall differences in Gram (+) and Gram (-) bacteria serve as PAMPs?

Gram (+): sugars, surface proteins, teichoic acid, lipoteichoic acid Gram (-): LPS, surface proteins

A TLR4 must be what kind of dimer?

Homodimer

What are the first effector cells that a pathogen encounters?

macrophages

What do C-type lectin, Class I bind?

mannose, N-acetyl-glucosamine & fucose

Macrophages are a mature form of ______________ that have ______________.

monocytes left the blood and taken up residence in tissue

How many pathogenic species can a receptor recognize in the innate immune system?

multiple pathogens that share particular type of cell-surface carbohydrates

What occurs is CR3 and CR4 bind to iC3b?

opsonization that results in phagocytosis

Unlike most macrophage receptors, the TLR do not cause _____________ but act to ______________ the _______ to _________.

phagocytosis signal macrophage recruit additional cells

List the 3 types of PRPs

* Secreted soluble proteins that circulate in the blood and the lymph * Cell surface receptors that induce phagocytosis following binding *Cell surface receptors that induce the cell to make cytokines following binding

A family of _________ genes encodes for the TLR proteins __________-_________.

10 (possibly 11) TLR1 TLR10

How many domains make up the TLR?

2

What on the Lectin binds to sugars?

3 globular domains on each arm

What is IRAK-4?

A protein kinase

What are the 2 domains of the TLR and how do they differ?

A variable extracellular domain for recognizing pathogens A cytoplasmic domain for signaling

TRAF6 undergoes several steps that eventually leads to _________.

Activation of IKK

What is C-Reactive Protein?

An acute phase reactant, a protein made by the liver and released into the blood within a few hours after tissue injury, the start of an infection, or other cause of inflammation

What type of protein is TRAF6?

An adaptor protein

When PRPs bind with PAMPs what does it trigger?

An inflammation response that is intended to destroy the pathogen

What must TLR4 associate with in order to recognize LPS?

CD14

Give a general list of PRPs on the macrophage What do all of them but TLR induce? What does TLR induce?

C-type Lectin (Class I) --CTLD --RTLD C-type Lectin (Class II) --Dectin-1 Scavenger Receptors (SR) MARCO CR3 & CR4 TLR Phagocytosis Signaling

What are CTLDs and why are they named that?

C-type lectin domains a calcium ion coordinates the interaction of the carbohydrate lignad with the receptor protein

What class macrophage mannose receptor are CTLD and RTLD?

C-type lectin, Class I

What class of mannose receptors in Dectin-1?

C-type lectin, Class II

TLR are an example of what kind of PRP?

Cell surface receptors

What is a structural feature that SR-A and MARCO share?

Collagen-like triple helices with curved type receptors

What are integrins known to do?

Contribute to adhesive interactions between cells that allow for communication between the various cells

What is a special feature that is recognized by Scavenger Receptors?

Dead and dying cells (apoptotic)

SR-B bind to what on bacteria?

Diacylated lipopeptide

All funcional TLR must be __________. But they can be heterodimers or ________________.

Dimers Homodimers

What is RTLDs and why are they named that?

R-type lectin domains THe R-type domain is similar to ricin It is located on the tip of the CTLD

How does IKK activate IκB?

IKK phosphorylates IκB, which then causes the NFκB to be released from inhibition

CR3 and CR4 are members of what family of structurally similar proteins?

Integrins

Where does NFκB go when it is release from IκB? What occurs there?

It goes to the nucleus and initiates the transcription of genes for proteins necessary for establishing a state of inflammation.

What class of PRPs does C-Reactive Protein belong to?

It is a pentraxin

LPS can be picked up by _______ in the plasma and delivered to the CD14.

LBP (LPS-binding protein)

SR-A bind to what on bacteria?

LPS, LTA, proteins, CpG DNA

Cell-surface receptors and proteins that recognize carbohydrates are called ____________.

Lectins

Mannose receptor and dectin-1 are examples of ____________ , specifically ______________ which are present on ______________.

Lectins C-type lectin domains (CTLD) macrophages

What is an LRR?

Leucine-Rich Repeat Region that is found in the amino acid residues of the pathogen recognizing domain of the TLR.

What must the TLR4 associate with in order to form the complex with CD14 and LPS?

MD2

What are MARCOs and what do they do?

Macrophage receptor with collagenous structure Recognize Gram- and Gram+ bacteria

When not in use NFκB is held where by what?

NFκB is held in the cytoplasm as an inactive complex by the inhibitor of κB (IκB)

Is iC3b the only ligand that CR3 and CR4 can bind? If not, what else?

No, several other ligands. They can act as PRPs. In bacteria - oligosaccharides In fungi - β-glucans

Are all TLRs located on the macrophage surface?

No, some are located on the endosome

Are SR-A and SR-B structurally related?

No.

Where is CD14 located?

On the macrophage surface

What do PRPs bind to and why?

PRPs bind to PAMPs on foreign pathogens.

What are PAMPs?

Pathogen-associated molecular patterns

How does the Innate Immune response distinguish self from non-self?

Pattern Recognition Proteins (aka Pattern Recognition Receptors)

What are cytokines?

Protein molecules that act as messengers between cells affecting their behavior

__________________ is when a receptor bound pathogen is surrounded by the macrophage membrane and internalized into a membrane-bound vesicle called an endosome or phagosome that then binds with the lysosome forming a _____________.

Receptor-mediated endocytosis phagolysosome

What are SRs? Where are they found?

Scavenger receptors found on macrophages

Complementing the phagocytic receptors are the ____________ receptors.

Signaling

How does LRR provide variation in TLR?

The # of LRR in the AA sequence provides variability

What does the phosphorylation of IRAK-4 cause?

The IRAK-4 to dissociate from the complex and phosphorylates TRAF6

When the TLR4/MD2 and CD14/LPS complex form what occurs next?

The cytoplasmic TIR domain binds with the MyD88 protein.

After the MyD88 binds with the TIR, what is the next step?

The opposite end of the MyD88 binds to the IRAK4 and causes the IRAK4 to phosphorylate itself

What type of specific domain is the cytoplasmic domain of the TLR?

Toll Interleukin-1 Receptor (TIR)

What is a TLR?

Toll-like receptor that is a signaling receptor

What is the benefit of some TLRs being located on the endosome?

When endocytosis occurs, the macromolecules are degraded when the are exposed to the TLR also they can bind to intracellular pathogens (viruses) to produce a signal

What do CR1 and CR2 do on the surface of the macrophage?

act as phagocytic receptors

What type of protein is the MyD88 protein?

adaptor protein

What does an adaptor protein do?

brings together two signaling proteins

Many of the ligands recognized by phagocytic receptors are bacterial _____________ and _____________.

carbohydrates lipids

Macrophage receptors recognize the _____________ ____________ of bacterial cells but not those of human cells

cell-surface carbohydrates

Natural killer cell receptors recognize________ at the surface of human cells that are caused by viral infections.

changes

CR3 and CR4 bind ________ enabling direct activation of the ______________.

iC3b macrophage

What is IKK?

inhibitor of κB kinase - inhibits the phosphorylation by κB kinase

Give examples of PAMPs

sugars, proteins, lipids, and nucleic acids that are uniquely associated with microbes

What is the function of IKK?

to activate a transcription factor called nuclear factor κB (NFκB)

What do C-type lectin, Class II bind?

β-glucans (LPS, cell walls from bacteria & fungi)