Lecture 5 - Innate Immunity (Basics, Phagocytosis, and Migration)

Question 1

How can pathogens enter the body?

Answer 1

Pathogens can enter the body through mucosal surfaces (mouth/respiratory tract, gastrointestinal tract, reproductive tract) and external epithelial surfaces (external surface, wounds/abrasians, insect bites).

Question 2

True or False?:

Saliva, hair, mucus, and tears all contribute to adaptive immunity.

Answer 2

False

Saliva, hair, mucus, and tears all contribute to innate immunity.

Question 3

What provides the first barrier against infection?

Answer 3

Epithelial surfaces like skin, gut epithelium, and, and respiratory eptithelium provide the first barrier against infection.

Question 4

What cells are involved in innate immunity?

Answer 4

Neutrophils & Other Granulocytes, Monocytes & Macrophages, Dendritic Cells, and Natural Killer & Innate Lymphoid Cells

Question 5

Enzymes, anti-microbial peptides, and complement are all involved with which type of immunity?

Answer 5

Innate Immunity

Question 6

True or False?:

Infectious agents must overcome innate host defenses to establish a focus of infection.

Answer 6

True

Question 7

What is phagocytosis?

Answer 7

Phagocytosis is the internalization of pathogens or their components upon their binding to receptors on the cell surface of phagocytes.

Question 8

Which types of cells is phagocytosis mediated by?

Answer 8

Phagocytosis is mediated by phagocytes – macrophages, granulocytes (neutrophils), and immature DCs.

Question 9

Which of the following does phagocytosis not lead to?

• Removal and Killing of Pathogens.
• Clearing of Debris
• Complete Stop of the Immune Response
• Generation of Antigenic Peptides for Presentation to T-Cells

Answer 9

Complete Stop of the Immune Response

Question 10

True or False?:

Macrophages have phagocytic receptors that bind microbes and their components.

Answer 10

True

Question 11

What are the four steps of phagocytosis?

Answer 11

1. Bacterium becomes attached to membrane evaginations called pseudopodia.
2. Bacterium is ingested, forming phagosome.
3. Phagosome fuses with lysosome.
4. Bacterium is killed and then digested by lysosomal enzymes.

Question 12

How are phagolysosomes able to kill microbes?

Answer 12

Phagolysosomes contain products (reactive oxygen species, enzymes, antimicrobial peptides) and an environment (acidification) that can kill microbes.

Question 13

What does phagocytosis ligand binding trigger?

Answer 13

Phagocytosis ligand binding triggers signaling that results in a cellular change.

Question 14

How are phagocytes “turned on”? What does this lead to?

Answer 14

Phagocytes are turned on by phagocytosis. It leads to the digestion of pathogen.

Question 15

How does the phagosome contribute to adaptive immunity?

Answer 15

The phagosome contributes to adaptive immunity through its role in antigen degradation, antigen processing, antigen presentation (MHCII), and antigen presentation via cytosol (MHCI).

Question 16

What are microglia?

Answer 16

Microglia are CNS-residents responsible for establishing proper neuronal connections. They play a role in brain development, learning, and memory. They are often considered to be the “macrophages of the brain”.

Question 17

What is multiple sclerosis?

Answer 17

Multiple sclerosis is a complex inflammatory disease characterized by myelin breakdown. It leads to lots of toxic debris in brain lesion microenvironments.

Question 18

True or False?:

Microglia and peripheral infiltrates of macrophages participate in debris clean-up in MS. Various animal models show that this is required for CNS repair.

Answer 18

True

Question 19

The picture below is from research published by Lou et al. in 2016. They used a laser to injure mouse CNS tissue with normal microglia (left) and microglia with receptors knocked out (right). What are the results and conclusions of their research?

Answer 19

Results: In the wildtype microglia tissue, pseduopodia are extended into the region where the damage was inflicted. This does not occur in the receptor KO microglia tissue.

Conclusions: Microglia’s role in CNS damage repair is dependent upon receptors expressed by microglia.

Question 20

What experimental set-up is used to measure phagocytosis?

Answer 20

To measure phagocytosis, a substrate is dyed with a pH-sensitive fluorophone that only fluoresces under low pH conditions (like those in a phagolysosome). You feed the substrate to macrophages or microglia and measure the fluorescence

Question 21

What are the four steps of recruitment of leukocytes to sites of infection?

Answer 21

1. Cytokines produced by macrophages cause dilation of local small blood vessels.
2. Leukocytes move to periphery of blood vessel as a result of increased expression of adhesion molecules by endothelium.
3. Leukocytes extravasate at site of infection.
4. Blood cloting occurs in microvessels.

Question 22

Which types of cells are recruited to sites of infection?

Answer 22

Monocytes and Neutrophils

Question 23

What do monocytes bind to to allow them to migrate into surrounding tissues?

Answer 23

Adhesion Molecules

Question 24

What are the three main classes of adhesion molecules?

Answer 24

Selectins, Integrins, and the Immunoglobulin Superfamily

Question 25

What do selectins do?

Answer 25

Selectins bind carbohydrates and initiate leukocyte-endothelial interaction.

Question 26

What do integrins do?

Answer 26

Integrins strongly bind to cell-adhesion molecules and extracellular matrix molecules.

Question 27

What do leukocytes roll along?

Answer 27

Vascular Endothelium

Question 28

What are the four steps to leukocyte migration into tissues?

Answer 28

1. Rolling Adhesion
2. Tight Binding
3. Diapedesis
4. Migration

Question 29

Which non tissue-resident cell is recruited to the site of infection to ingest and kill microgranisms via phagocytosis?

Answer 29

Neutrophils

Question 30

What is pus the result of?

Answer 30

Pus is the result of dead and dying neutrophils.

Question 31

What can neutrophils produce?

Answer 31

Neutrophils can produce an extracellular matrix called a NET (neutrophil extracellular trap) to trap microorganisms.