Innate Immunity #2

Innate Immunity is essential for what stage of infection?

Early

Adaptive immunuity is essential for what?

Microbe clearance

Extracellular infection is accessible to what? what is the defense mechanism?

Soluble macrophages and phagocytes. Complement macrophages, neutrophils and antimicrobial peptides

Intracellular infection requires what? by what cells?

Killing or activation of infected cells by NK cells and activated macrophages

Innate immunity recognizes structures on what that is not present in normal host cells

Structures shared by microbes

Pattern Recognition Receptors (PRR) encoded in germ line for innate immunity possesses what?

Limited diversity

Molecules expressed and or produced solely by microbes?

Pathogen assoc. Molecular Patterns (PAMPs)

PRR expression is what?

Redundant, it is in multiple spots (plasma memb., endosomal membrane, cytosol)

TLR-4 reconizes what?

LPS

TLR-3 Recognizes what?

dsRNA

TLR signal recruits what Adaptor proteins

MyD88 and TRIF

TLR signal activates what transcription factors?

NF-kB and IRF

NF-kB triggers what cytokines?

IL-1, TNFalpha, IL-12

IRF triggers what cytokines?

IFNalpha/beta

NLRP3 inflammasome assembly does what?

• Caspase-1 activation

• Cleavage of pro-IL-1B

• secretion of IL-1B

IL-1B induces what?

accumulation of neutrophils and monocytes

Chemical barrier component of epithelia

Kill microbes by releasing peptide antibiotics that disrupt the outer membrane

Neutrophil characteristics

• 3-5 lobule

• Most abundant 1×10^11 per day

• Short lived (6 hrs in blood)

What cell is the first responder in inflammatory response?

Neutrophils

Monocytes characteristics

• 10x less abundant in blood that neutrophils

• long lived

• become macrophages in tissue

Monocytes mediate what stage of innate response?

Later, 1 or 2 days after (second responder). Divide and persist at site.

Function of macrophages?

Trigger inflammation, kill microbes

Dendritic Cells (DC) have and do what?

Have dendrites and phagocytosis

DCs link what?

Innate and Adaptive responses, capture microbe antigens to naive T cells, secrete cytokines

Plasmacytoid DC make what?

IFNalpha/beta (interferon type 1)

NK cells kill what? how?

Host cells, not microbes. Release Perforin/granzyme.

Mast, Eosinophil, and basophils function?

Once activated, release proteolytic enzymes that contribute to inflammation

Enzymes released that contribute to inflammation

Histamines, prostaglandins, heparin, leukotrienes, TNFalpha

Mast, Eosiniphil, and basophils important in protecting against what?

Helminths

Lymphocyte (adaptive) cell activation requires what?

• Signal 1: antigen binding to antigen receptor

• Signal 2: molecules provided by innate cells.