immuno lect 2 part 1

PAMPs stands for

pathogen-associated molecular patterns

where are PAMPs found

only pathogens, not on host tissue

DAMPs stands for

danger-associated molecular pattern

when is DAMP released

from damaged or dying host cells following trauma, injury, infection

PRRs stands for

pattern-recognition molecular patterns

what do PRRs do

they are receptors on/in host sentinel cells that recognizes PAMPs and DAMPs

What three general properties make a molecule a good PAMP?

abundant/essential to the microbe, common to many microbes, absent from host tissues

What PAMP is found on gram-positive bacteria?

Peptidoglycans and lipotechoic acid

What PAMP is found on gram-negative bacteria?

Lipopolysaccharide (LPS)

What PAMP is found on acid-fast bacteria?

Glycolipids

What PAMP do most bacteria share in their DNA?

Unmethylated CpG sequences

What PAMP is found on yeasts?

Mannan/beta-glucan

What PAMP is found on viruses?

Double-stranded RNA (dsRNA)

2 types of PRRs

signaling, phagocytic receptors

where are signaling PRRs located

cell surface, cytoplasmic, endosomal

types of signaling PRRs

toll-like receptors, NOD-like receptors, RIG-1-like receptors

Toll-like receptors are

membranous PRRs that recognize a wide variety of ligands

NOD-like receptors are

cytoplasmic PRRs that detect peptidoglycan and muramyl dipeptide

RIG-1-like receptors are

cytoplasmic PRRs that detect viral dsRNA

Signaling PRRs bind to

their PAMP or DAMP

signaling PRRs activate

a signaling cascade that activates transcription factors, and activates transcription of genes

2 types of transcription factors

NF-kB, IRF

categories of genes that get transcribe after PRR signaling

pro-inflammatory cytokines, chemokines, adhesion molecules, co-stimulatory molecules

TLRs that are on the plasma membrane

TLRs 1, 2, 4, 5, 6

TLRs 1,2,4,5,6 detect

bacterial, fungal, and parasite wall components

TLRs that are found on the endosomal membrane

TLRs 3,7,8,9

TLRs 3,7,8,9 detect

bacterial/viral RNA, DNA

all TLRs signal thru

NK-kB or IRF (TLR)

NOD1, NOD2 are found in

the cytosol that detect components of intracellular bacteria

RIG-1, MDA5, LGP2 are found in

the cytosol, detect dsRNA and ssRNA from viruses

what can lead to cell/tissue injury

pathogenic microbes, trauma, injury

pathogenic microbes, trauma, injury must

stimulate an immune response to clean up and start regeneration

what is released when a cell is injured

cytosolic/nuclear proteins and metabolites

what is exposed when tissue is injured

extracellular matrix components

role of DAMPs when released

alert the body to danger, stimulate inflammation, promote healing

4 extracellular DAMPs

Heparan sulfate, hyaluronic acid, fibronectin, peptides from collagen/elastin

5 intracellular DAMPs

Mitochondrial DNA, HMGB-1, adenosine/ATP, uric acid, heat-shock proteins

inflammasome is

a multi-component complex inside cells

function of the inflammasome

acts as an emergency alarm

inflammasome produces

pro-inflammatory cytokines IL-1beta and IL-18 to rapidly fight a pathogen/microbe

1st signal needed to activate the inflammasome

recognition of a PAMP/DAMP via a PRR, activating the NF-kB

2nd signal needed to activate the inflammasome

signal that activates a cytoplasmic NOD-like receptor, activating an enzyme that cleaves and activates the precursors IL-1b and IL-18

phagocytic receptors are on

neutrophils, macrophages, dendritic cells

phagocytic receptors trigger

phagocytosis

phagocytosis leads to

microbe degradation, antigen processing

types of phagocytic receptors

complement receptor (CR), FcyR, mannose receptor

CR recognizes

microbes coated w/complement components

FcyR recognizes

microbes coated w/immunoglobulins/antibodies

mannose receptor recognizes

sugar residues on microbes

opsonization helps with

phagocytosis, making it more efficient than thru PRRs alone

opsonization components

C3b, IgG

C3b is recognized by

the complement receptor

IgG is recognized by

the FcyR

4 steps of phagocytosis of microbes

recognition/attachment, engulfment, phagosome-lysosome fusion, destruction

what happens during recognition and attachment

cytoskeletal rearrangement

4 mechanisms of destruction

lysosomal enzymes, reduced pH, reactive oxygen species, reactive nitrogen intermediates

What happens when PRRs ligate microbe-bound ligands during phagocytosis?

Tight adhesion and receptor clustering, which signals cytoskeletal rearrangement

What structure forms once the plasma membrane closes around an attached microbe?

phagosome

How does phagosome pH change during maturation?

goes from neutral to acidic

What forms when the phagosome fuses with granules/lysosomes, and what does it

bring in?

phagolysosome, which brings in hydrolytic enzymes and antimicrobial peptides

What is generated during the oxidative/respiratory burst?

reactive oxygen species (ROS)

What else is generated alongside ROS during phagosome maturation?

reactive nitrogen species

What does NADPH oxidase produce first during phagosome maturation?

Superoxide anion (O2-)

What does superoxide anion become after reacting with H+ and H2O?

Hydrogen peroxide (H2O2)

What can H2O2 be converted into?

The hydroxyl radical (·OH)

What does myeloperoxidase do?

In neutrophils, it combines H2O2 with Cl⁻ to make hypochlorite (ClO⁻), essentially bleach

What does inducible nitric oxide synthase (iNOS) do?

It converts arginine into nitric oxide (NO)

What does NO combine with superoxide to form?

Peroxynitrite (ONOO·)

Why are these free radicals effective?

They severely damage lipids, DNA, and proteins inside the phagosome

What does phagocyte activation upregulate?

Respiratory burst enzymes, phagocytic receptors, and antigen-presenting molecules.

What does cytokine production do?

It induces production of more leukocytes and starts the inflammatory cascade.

What does chemokine production do?

It recruits leukocytes.

Why are adhesion molecules expressed on leukocytes?

So leukocytes can stop and migrate from blood into tissue.

What other mediators are produced to recruit leukocytes?

The arachidonic acid cascade (prostaglandins, leukotrienes) and platelet-activating factor.

What are the 6 neutrophil extracellular effector tools?

Proteases, myeloperoxidase, defensins, cathelicidins, NADPH oxidase, and the respiratory burst

Is NET formation active or passive?

Active

What triggers NETs?

Cytokines (IL-8) and PAMPs (LPS).

What are NETs made of?

DNA, histones, elastase, defensins, and myeloperoxidase.

What do NETs do?

They are microbicidal, meaning they kill microbes.

What does major basic protein do?

It is cytotoxic to helminths (worms).

What does eosinophil cationic protein do?

It forms pores in membranes and digests RNA

What is eosinophil-derived neurotoxin?

A ribonuclease with antiviral properties

What does eosinophil peroxidase do?

It causes oxidative damage via H2O2.

What does NADPH oxidase on the eosinophil membrane do?

It produces the oxidative burst.

What lineage are NK cells, and how do they differ from T and B cells?

They are lymphoid but need no prior sensitization and have no T or B cell receptors.

What does the NK activation receptor recognize?

Viral proteins, altered surface glycoproteins, and antibody-coated cells.

What does the NK activation receptor recognize?

Viral proteins, altered surface glycoproteins, and antibody-coated cells

What does the NK inhibitory receptor recognize?

Normal MHC class I, a “self” marker on all nucleated cells. It overrides the activation signal

When does an NK cell kill?

When the inhibitory signal is absent, meaning MHC I is missing.

How does an NK cell kill?

Perforin inserts into the membrane and makes a pore. Granzyme enters through the pore and triggers apoptosis.

What are the 3 innate effector mechanisms?

Phagocytosis and degradation, extracellular granule release, and NK cell cytotoxicity

Which infections is phagocytosis best for?

Extracellular and intracellular infections.

Which infections is granule release best for?

Extracellular and helminth infections.

What do NK cells mainly fight?

Viruses and cancer.

What is phagosomal maturation?

Acidification, fusion with lysosomes, and the respiratory burst.