Exam 2 -- Induced Innate Immune Response

How do Natural Killer (NK) Cells decide which cells to kill?

Carefully balancing signals of SELF versus NONSELF on the spot

TRUE or FALSE — NK cells must be “activated” before they assess which cells to kill?

TRUE ! — They must be in an ‘active’ state, activated by cytokines

What do NK Cells gather from SELF versus ALTERED/MISSING SELF cells?

SELF — Sufficient inhibitory signals —> No killing!

Missing/Altered Self - Missing/altered inhibitory signals —> Killed

What “conditions” may result in altered/missing inhibitory signal presentation?

Viral infection

Cancer

How does NK-Cell mediated killing occur"?

NK TRAIL receptor binds the Cell’s DR4 and DR5 death receptors, inducing apoptosis

When are DR4 and DR5 receptors expressed?

These ‘death receptors’ are expressed by sick/dying cells

“Kill me” signal

What are some examples of altered/missing self phenotypes caused by viruses?

Lower MHC I expression (Avoid CTLs)

Lower MHC I expression (Inhibit protein synthesis)
Different glycosolation of cellular proteins

What are some examples of altered/missing self phenotypes caused by cancer?

Reduced MHC I receptors on the cell surface (avoid CTLs)

What are two examples of NK Cell Receptors

Lymphocyte Receptor Complex - (Killer Immunoglobin-Like Receptors) — ((KIR))

NK Receptor Complex — (Killer Lectin-Like Receptors) — ((KLR))

TRUE or FALSE — Structural families of NK receptors encode activating and inhibitory receptors

TRUE !

What are the two kinds of NK Receptors that activate and inhibit

ITAMs - Activates

ITIMs - Inhibits

TRUE or FALSE — One KIR gene has 2 alleles, 1 activate and 1 inhibits

TRUE ! — This is a complex system!

What NK Receptor should we be able to recognize (not memorize)

Natural Cytotoxicity Receptors (NCRs)

What’s up with Natural Cytotoxicity Receptors (NCRs)?

Ligands are not well-defined

NKp46 recognizes heparin sulfate proteoglycans

What are some examples of Natural Cytotoxicity Receptors (NCRs)?

NKp30, NKp44, NKp46, NKG2D

When are NKG2D ligands upregulated (+ who are they expressed by)?

Expressed by cells, upregulated during cellular stress and intracellular infections by viruses and bacteria

What do NKG2D ligands resemble?

MHC I molecules

What are NKG2D ligands meant to indicate? (When expressed by cells)

They’re a sort of “danger signal” - Similar to a death receptor when recognized by NK cells

:: NK Cell activation programs result from the integration of many activating and inhibitory signals that vary depending on the nature of the interacting cells

:: NK Cells have many receptors used to detect abnormalities

What do NK Cells look for?

Oddities, Misbehaviors, Altered self