Phagocytes and NK Cells

Question 1

Primary activators of the innate immune system, but NOT the first responder

Answer 1

• sentinel cells

Question 2

What cells are sentinel cells?

Answer 2

1. Macrophages
2. Dendritic Cells
3. Mast Cells

Question 3

Sentinel cells express Pathogen recognition receptors (PRRs) which can recognize?

Answer 3

1. PAMPS - pathogen associated molecular patterns
   - on microbes
2. DAMPS - damage associated molecular patterns
   - expressed on damaged host cells

Question 4

Macrophages

Answer 4

• sentinel and phagocytic cells
• > can capture microbes and kill microbes
• > can also be antigen presenting cells

Question 5

The major antigen presenting cell

Answer 5

• Dendritic cells

Question 6

Plays a key role in allergies and can trigger inflammation

Answer 6

• Mast cells

Question 7

Types of Cytokines

Answer 7

1. Interleukins
2. Lymphokines
3. Chemokines
4. Interferons

Question 8

Cytokines that act as growth and differentiation factors for cells of the immune system

Answer 8

• Interleukins

Question 9

Pro-inflammatory and chemotactic cytokines

Answer 9

• Chemokines (IL-8)

Question 10

Cytokines that can interfere with viral replication

Answer 10

• interferons

Question 11

Most important cytokines released by the sentinel cells are?

Answer 11

• TNF, IL-1, IL-6

- > proinflammatory

Question 12

Main result of cytokine release by sentinel cells

Answer 12

• INFLAMMATION

Question 13

What are phagocytic cells?

Answer 13

1. Polymorphonuclear cells
   - granulocytes (neutrophils)
2. Monocytes/Macrophages
   - monocytes when in the blood
   - macrophages when in the tissue

Question 14

What are complement proteins produced by?

Answer 14

• Macrophages and hepatocytes primarily

Question 15

Chemical gradient to attract inflammatory cells

Answer 15

• chemotaxis

Question 16

Proteins that coats microbes and enhances phagocytosis

Answer 16

• opsonins

Question 17

Integrins

Answer 17

• surface protein molecules (adhesion proteins)

- active during chemotaxis to emigrate from vessels

Question 18

Phagocytosis Steps

Answer 18

1. Chemotaxis
   - via chemokines and PAMPS
2. Adherence
   - via receptors on the surface of phagocytes
3. Ingestion
   - phagocytosis
4. Destruction
   - oxygen dependent killing
   - oxygen independent killing

Question 19

Directed migration according to a chemical gradient

Answer 19

• chemotaxis

Question 20

Receptor to bind complement opsonizing microbes

Answer 20

• CR

Question 21

Receptors to bind antibody opsonizing microbes

Answer 21

• FcR

Question 22

Neutrophil Enzymes

Answer 22

1. Myeloperoxidase (MPO)
   - only cell with this, most potent antimicrobial
2. Lysozyme
3. Collagenases
4. Lactoferrin

Question 23

First phagocyte to respond to infections after sentinel detection

Answer 23

• Neutrophil

Question 24

Neutrophil characteristics

Answer 24

• Short life span
• dying neutrophils attract macrophages
• not proliferative, there to kill and die (can not sustain killing)
• > phagocytosis leads to death
• active immediately after release from bone marrow
• rapidly exhausted

Question 25

Monocytes/Macrophages characteristics

Answer 25

- Long life span - maintain sustained phagocytosis - slower speed of response for phagocytosis - limited potent antimicrobial capacity - > less degranulation and no MPO in most mammals - tissue repair - activated AFTER exposure to bacterial proteins (PAMPS) and inflammatory molecules (cytokines) - "PACMAN" - essential for homeostasis (recycling RBCs) and recovery

Question 26

What almost exclusively makes IL-8?

Answer 26

- neutrophils

Question 27

Which cells secrete Cytokines?

Answer 27

- Sentinel cells - > TNF, IL-6, IL-1 - > IL-8 (chemokines) - Macrophages - > TNF-a, IL-1, IL-6, IL-12!!

Question 28

What are the major cytokines of Macrophages

Answer 28

1. IL-1 2. IL-6 3. IL-12 (acts on T and NK Cells) 4. TNF-a

Question 29

NK cells

Answer 29

- cells of the innate immune system - kill virally infected host cells and tumor cells - > antigen independent, whereas cytotoxic T cells (CTLs) are antigen dependent - > kill host cells infected with microbes, not microbe directly - can express FcR and bind to antibody - receptor for some complement proteins - MHC-1 Expression by host cells inhibits - recognize proteins on target cells expressed under stress - regulated by cytokines

Question 30

Antibody dependent cell-mediated cytotoxicity (ADCC)

Answer 30

- if target host cell has antibody attached to it - > expresses FcR so can bind to antibody - kills host cell with cytotoxic granules

Question 31

Effect of MHC-1 Expression by host cells on NK cells

Answer 31

- NK cells are inhibited by cells that express MHC-1 - > says "im normal leave me alone" - > if does not express the NK cell will see and kill it