Ch. 2 Innate Immunity

Question 1

Examples of PAMPs recognized by the innate immune system

Answer 1

• Lipopolysaccharides (LPS)
• mannose residues (more closely spaced on microbes)
• double stranded RNA
• unmethylated CpG nucleotides on DNA

Question 2

Innate Immune cell receptors

Answer 2

• Pattern recognition receptors
• a class of innate cells (macrophages) have many receptors but all the macrophages have the same many receptors (as compared to each B-cell has its own specific receptor and then can clonally divide)
• innate cells have receptors that recognize known danger signals (PAMPS) - vs. adaptivenmakes up new combinations to prep for mutations that could be experienced in the future
• germline encoded - vs. each individual cell does somatic recombination in adaptive

Question 3

Activation of TLR

Answer 3

• On macrophages, neutrophils
• Recognize microbial patterns - flagella, LPS, CpG
• Activation of transcription factor NF-kB
  
  • Leads to anti-microbial functions - inflammation, co-stim molecules, chemokins, endothelial adhesion etc

Question 4

Name other receptors on macrophages

Answer 4

• mannose
• scavenger
• cytokines - INF-gamma - secreted by innate and adaptive immune cells (T-cells) and activates macrophages
• antibodies
• complement proteins - leads to phagocytosis of macrophages coated in complement proteins/antibodies

Question 5

Extravasation steps of leukocytes/macrophages

Answer 5

• macrophage produces IL-1 and TNF when it ingests a microbe
• IL-1 and TNF stimulate endothelial cells to express E-Selectin and P-selectin
  
  • E-selectin and P-selectin on endothelial cells = rolling of leukocytes
• Leukocytes roll on selectins
• Chemokines made in response to IL-1 and TNF increaeses affinity of integrins on leukocytes
• integrins bind at high affinity to ligands on endothelial = adhesion
• Leukocytes move thru the endothelium to the place of infection following the chemokines = motility

Question 6

What is present in phagolysosomes in macrophages that kills microbes?

Answer 6

• ROS
• NO
• lysosomal proteases

Question 7

What cytokine do NK cells produce? and What cytokine stimulates them?

Answer 7

NK cells make INF-gamma - to stimulate macrophages

Macrophages make IL-12 - to stimulate NK cells

Question 8

NK cells and ADCC

Answer 8

ADCC - antibody dependent cellular cytoxicity

• NK cells recognize the Fc portion of IgG antibodies
  
  • IgG antibodies coat microbes and this is then a sign to kill the cell .

Question 9

ITAMs

Answer 9

Immunoreceptor tyr-based ACTIVATION motifs

• activating receptors on NK cells in reaponse to cell damage, malignancy etc
• leads to granule exocytosis - cytotoxic granules
• IFN-gamma production (to stimulate macrophages)

Question 10

ITIMs

Answer 10

immunoreceptor tyr-based INHIBITORY motifs

- inhibitory receptors on NK cells that recognize MHC-I self molecules and prevent NK killing of the cell

Question 11

NK activating Cytokines

Answer 11

IL-15 - development and maturation

INFs, IL-12 (f/macrophages) - enhance killing

Question 12

IL-12

Answer 12

• produced by macrophages/DC cells in response to INF-gamma f/NK cells and microbe presence
• leads to naive T-cells differentiating into effector T-cells