Week 2 (Part 1): Innate Immunity - Second Line of Defence

Question 1

What are WBC comprised of?

- What do they include (NEMMB)?

Answer 1

WBC are comprised mainly of leukocytes

- Includes neutrophils, monocytes, macrophages, eosinophils, basophils

Question 2

What are dendritic cells?

Answer 2

Dendritic cells are bone marrow-derived leukocytes

Question 3

What are mast cells?

Answer 3

Mast cells are another type of white blood cell found in connective tissues

Question 4

What are NK cels?

Answer 4

Natural killer cells are white blood cells called lymphocytes they have a role in the innate immune system, as well as the adaptive immune system as well, which is why you can see them sitting in the center of this diagram – remember the B cell and T cells are also lymphocytes…

Question 5

What type of defence to WBC play?

Answer 5

All of these white blood cells have specialized roles within the innate immune system second line of defense

Question 6

What are defensive cells?

- What do they do?

Answer 6

White Blood Cells

• Phagocytes
• Non-specific

Function: To kill extracellular pathogens (dead or damaged cell, unwanted debris) by phagocytosis

Question 7

Who are the early responding cells of the innate system? Why?

Answer 7

Neutrophils

- They are the predominant white cells in the blood

Question 8

What do macrophages arise from? What do they do?

Answer 8

Blood monocytes

- Participate in phagocytosis of larger particles that neutrophils cannot handle

Question 9

What are dendritic cells important for?

- What does it depend on?

Answer 9

Dendritic cells are important intermediary cell between the innate and adaptive immune system

Maturation state
- An Immature dendritic cell is able to be involved in phagocytosis, whereas a mature dendritic cell helps to initiate the adaptive immunity response

Question 10

Describe the steps of phagocytosis:

Answer 10

Steps:

1) Recognition and adherence
- Occurs when pathogen-associated molecular pattern binds with toll-like receptor on phagocyte

2) Engulfment
- Extensions of cytoplasm move around and enclose particle in a phagosome

3) Intracellular Killing
- Once inside cell, phagosome fuses with cytoplasmic lysosome to form phagolysosome, which is killed and digested by enzymes
Removed via exocytosis

Question 11

What does an eosinophil do? (2)

Answer 11

Defense against parasitic infections

• Able to digest much larger particles
• Also have role in allergic reactions (discussed later)

Question 12

What do lymphocytes (NK cells) do?

Answer 12

1) Constantly surveying body for abnormal cells
- Identification
- Must be able to recognize normal vs. abnormal cells

2) Kill INTRAcellular viruses
- Destruction

3) Also has a role in killing cancerous cells
4) Have cytoplasmic granules that contain toxic enzymes which are injected into the abnormal cell – causes degradation of viral RNA/DNA and ultimately destruction of cell through APOPTOSIS

Question 13

How does an NK cell function?

Answer 13

Every NK cell has both an activating receptor, and an inhibitory receptor:

a) On the surface of all NORMAL host cells, a molecule known as Major histocompatibility complex 1 (or MHC 1) is present.
- If the inhibitory receptor on the NK cell binds to this MHC I molecule it is inhibited from activation and the normal host cells are spared from destruction

b) Alternatively, when a host cell is infected, the MHC-1 expression is not present, and therefore there is nowhere for the inhibitory receptor to bind, which allows the activating receptor to work and destroy the infected cell.

Question 14

If activated, what is the fate for the target cell of an NK cell?

Answer 14

NK cells have cytoplasmic granules that contain toxic enzymes which are injected into the cell to degrade it which results in Apoptosis (i.e cell combustion and death

Question 15

What is the complement system?

Answer 15

The complement system is so named because it is complementary to the antibody response of the adaptive immune system
- Complementary to adaptive response of immune system

Question 16

What is the complement system and what does it do?: (3)

Answer 16

Complement system
30 or more plasma and cell surface
proteins that work in concert to fight
invading microorganisms through:

1) Opsonization → phagocytosis
- Complement systems acts as a glue to help attach antigens/complexes to macrophils/neutrophils for easier phagocytosis

2) Inflammation
- Complement system induces histamine release by mast cells and basophils, dilating blood vessels to make them leaky

3) Lysis
- Compliment induces bacterial lysis

Question 17

What is the role of cytokines?

Answer 17

Pro-inflammatory response

Question 18

What types of cytokines are there? What is there role?

Answer 18

A wide range of cytokines are involved in innate immunity including:

• TNF
• Interleuins
• Interferons
• Chemokines

… and there are many different roles that cytokines play!

Question 19

How do cytokines influence events of inflammation?

Answer 19

By producing chemotaxis of leukocytes (chemotaxis means is the movement of an organism in response to a chemical stimulus),
- If we look specifically at proinflammtory cytokines (ones that work to induce the inflammatory response) we look primarily at chemokines and interferons which interfere with viral infections

Question 20

What are key components of inflammation?

Answer 20

Phagocytosis and cytokines

Question 21

What does stimulation of cytokines do? What is the response (2)?

Answer 21

Stimulation of cytokines activates endothelial cells which leads to dilatation of blood vessels, increasing blood flow and allowing permeability of circulating immune cells into the blood vessel.

• Allowing plasma fluid and more immune cells to seep through and accumulate in the inflamed tissue increases the number of phagocytes in the infected tissue for enhanced clearance of extracellular pathogens
• The vasodilation is responsible for the clinical signs inflammation of heat, swelling, and redness

Question 22

Is inflammation bad?

Answer 22

Inflammation is a good thing as it recruits circulating immune cells and plasma proteins into infected tissue to enhance immune defenses.

Question 23

What do cytokines activate during a fever?

Answer 23

Ultimately when inflammation occurs, and cytokines enter the blood circulation, this activates the hypothalamus which is responsible for temperature regulation
- When activated the hypothalamus will produce prostaglandins which results in the clinical sign of an increased temperature or fever.

Question 24

What is a fever an early response to?

Answer 24

Fever is an early response to an infection, the increased body temperature kills most pathogens as most require a lower body temperature to replicate; Slows bacterial growth, speeds body defenses