Innate Immunity - Binder

Question 1

What does a pathogen have to do to cause an infection (first step)?

Answer 1

They must adhere to the epithelium at the infection site.

Question 2

What are some innate barriers to infection?

Answer 2

1. Tight junctions between epithelial cells.
2. Chemical secretions and mucins to prevent adherence
3. Cilia
4. Normal Flora

Question 3

Describe the recognition-response paradigm in immunity.

Answer 3

The response of the immune system, both innate and adaptive arms rely on the ability of the immune cells to recognize pathogens.

Question 4

What is a pathogen-associate molecular pattern (PAMP)?

Answer 4

PAMPs are conserved features of pathogen groups that serve as recognition sites for innate immune cells. These patterns are absent or shielded in the host to prevent recognition of self.

Question 5

What is a Pathogen Recognition Receptor?

Answer 5

PRRs bind PAMPs to initiate a response. Response can be release of cytokines, complement, phagocytosis, etc. Receptors are present on macrophages, neutrophils, DCs, can be secreted, or can be intracellular.

Question 6

What are the cellular elements of the innate immune system?

Answer 6

• Macrophages
• Dendritic Cells
• NK Cells
• Eosinophils
• Basophils
• Neutrophils
• Mast Cells

Question 7

Where are macrophages and DCs found and what do they do?

Answer 7

Macrophages and DCs mature from monocytes and migrate to the tissues where they stay. Upon pathogen-pattern recognition, they will destroy pathogens without need for adaptive immunity and present antigens for T-cell recognition.

Question 8

Where are neutrophils located?

Answer 8

Neutrophils are resident to the blood and only enter the tissues upon infection.

Question 9

Describe the general phagocytic scheme.

Answer 9

Pattern recognition of pathogen by cell-surface receptors (mannose, scavenger, LPS (CD14) etc.) results in phagocytosis and initiation of inflammation and cytokine release. Pathogen is degraded and presented on MHC-II for T-cell activation.

Question 10

Describe respiratory burst of macrophages.

Answer 10

Increase in oxygen consumption by macrophages. Oxygen will be converted to superoxide and H2O2 as a chemical toxin to pathogens or to form NO, a vasodilator and immune signaling molecule.

Question 11

What are defensins?

Answer 11

A diverse group of small cationic antimicrobial peptides. They can assist with phagocytosis and form aggregates to disrupt pathogen membranes.

Question 12

What are the effector mechanisms of innate immune cells?

Answer 12

1. Phagocytosis
2. Cytokine release
3. Complement
4. Respiratory burst
5. Defensins

Question 13

Describe the complement system

Answer 13

Soluble molecules circulating in blood that recognize and bind to pathogens and aid in opsonization and form membrane attack complexes.

Question 14

PRR: Mannose-binding lectin (MBL)

Answer 14

Free protein in the blood that recognize certain carbohydrates specific to pathogens (by spacing). They opsonize pathogens and activate complement.

Question 15

PRR: Macrophage Mannose Receptor (MMR)

Answer 15

Cell surface receptor of macrophages (CD206) that recognizes patterns similar to MBLs and acts directly as a phagocytic receptor.

Question 16

PRR: Scavenger Receptors

Answer 16

Cell surface receptor (CD204) that recognizes acetylated LDLs and anionic polymers and facilitates phagocytosis. These molecules are shielded by sialic acid on host cells.

Question 17

PRR: fMLP Receptors

Answer 17

Recognize fMet-Leu-Phe, the start of many bacterial proteins. Facilitates cytokine release to induce innate response.

Question 18

PRR: Toll-like Receptors

Answer 18

Broad range of PRRs that initiate a response specific to the pathogen that it recognizes.

For example:
- dsRNA binding to Tlr3 leads to INF production against viruses
- LPS binding to Tlr4 leads to release of TNFa and INF which are antibacterial

Question 19

PRR: NOD proteins

Answer 19

Present in the cytosol and recognize certain microbial products

Question 20

What are the 3 sequential roles of inflammation?

Answer 20

1. Deliver additional immune cells to site of infection
2. Induce local blood clotting to restore barrier
3. Tissue Repair

Question 21

Describe extravasation of neutrophils

Answer 21

Endothelial cells of inflamed blood vessels begin to increase expression of adhesion molecules. Neutrophils are engaged with weak interactions to cause rolling. Chemokines cause conformational changes of integrins on the neutrophil and subsequent strong adhesion to endothelial surface causing arrest. Neutrophils then migrate through endothelial cells to site of infection.

Question 22

What do NK cells do?

Answer 22

NK cells seek and destroy virally infected cells and secrete cytokines to direct other immune cells. Infected cells release TNFs which activate NK cells. Can kill lymphoid tumor cells without immunization.

Question 23

Describe the “surveillance” role of NK cells.

Answer 23

NK cells are thought to survey target cells for self molecules displayed on MHC-I. If self is recognized, the activating receptor on NK cells is over-ridden and no response is initiated. If however, the MHC-I is absent or altered, it cannot stimulate an inhibitory signal and the activation signal takes proceeds leading to NK cell facilitated apoptosis. Complex balance between inhibitory and activation signals.

Question 24

How do NK cells distinguish between virally infected cells and uninfected cells?

Answer 24

Infected cells secrete IFN alpha/beta and increase MHC-I expression.

Question 25

How do NK cells signal to the rest of the immune system upon activation?

Answer 25

Secretion of TNF alpha and INF gamma

Question 26

Which cells secrete IL-6?

Answer 26

Macrophages and dendritic cells, enhances responses

Question 27

Which cells secrete IL-1? What does it do?

Answer 27

Macrophages, enhances responses

Question 28

Which cells secrete CXCL8 (IL-8)? What does it do?

Answer 28

Phagocytes generally, chemoattractant for neutrophils

Question 29

Which cells secrete IL-12? Which cells does it act on?

Answer 29

Macrophages and dendritic cells, acts on naiive T-cells

Question 30

Which cells secrete TNF-alpha? Which cells does it act on?

Answer 30

Macrophages and DCs. Acts on epithelial cells to cause upregulation of adhesion molecules.