Lecture 37 - Immune system: Inflammation and Innate Immunity

Question 1

What are acellular soluble factors?

Answer 1

They are secreted molecules which are involved in immune responses

Question 2

Name 2 types of cell-mediated immunity that involves acellular soluble factors

Answer 2

1. Cytokine - any signalling molecule that is used as a part of cell-mediated immune responses. Hugely diverse (both chemically and functionally) and can be:
   - paracrine or endocrine
   - released by non-immune cells or by immune cells - acting on non-immune cells or immune cells
   - enhancing immune responses or suppressing them
2. Complement - a group of plasma proteins that contribute to anti-microbial defenses

Question 3

What are the 3 basic components of an innate immune response?

Answer 3

1. Recognition - identification of pathogens or abnormal cells
2. Recruitment - structural and chemical changes that bring WBCs to the site
3. Resolution - destruction of pathogens and diseased cells

Question 4

What is another name of innate immune responses and what are their 2 phases?

Answer 4

Aka inflammatory immune responses

Phase 1 - immediate response: generated by cells and soluble factors already present in the local tissue

Phase 2 - induced response: occurs with the recruitment of WBCs (especially phagocytes) from blood circulation

Question 5

What are the 5 cardinal signs of inflammation?

Answer 5

1. Heat
2. Redness
3. Swelling
4. Pain
5. Loss of function

Question 6

What is the function of resident WBCs (ex. mast cells)?

Answer 6

They recognize tissue damage, pathogen entry, and release signalling molecules. How?

1. Mast cell is activated by chemicals released from damaged epithelium
2. Mast cell degranulates, releasing granule contents that attract WBCs to move towards it

Question 7

What occurs when paracrine factors are released from mast cells?

Answer 7

It leads to structural and physiological changes in the local tissue. These signalling molecules have many non-immune cell targets in local tissue, promoting processes

Question 8

Give 2 examples of paracrine factors that promote different processes in local tissue

Answer 8

1. Arterioles can dilate, which increases blood flow, causing redness and heat
2. Capillary endothelial cells have increased permeability, increasing fluid release into tissue, causing swelling

Question 9

What happens when cytokines are released into the bloodstream? What are these specific cytokines called?

Answer 9

These cytokines are called interleukins. Their release into the bloodstream can generate body-wide aspects of inflammatory responses

Question 10

Give 2 examples of how interleukins generate inflammatory responses

Answer 10

1. Interleukin 1 can reprogram the hypothalamic set point for temperature, triggering fever
2. Interleukin 6 can stimulate proliferation of WBCs (especially neutrophils) in the red bone marrow

Question 11

What happens when paracrine and hormonal factors are released from mast cells? What are the 2 processes it involves?

Answer 11

It leads to recruitment of circulating WBC through extravasation (movement of WBC through the capillary wall into the surrounding tissues). Extravasation involves:

1. Changes in the endothelial wall (allowing WBCs to stick to it)
2. Chemotaxis of WBCs into the interstitial space

Question 12

What is the function of phagocytic myeloid cells?

Answer 12

They resolve infection by engulfing and destroying pathogens

Question 13

What are the 3 different types of phagocytes and what are their functions?

Answer 13

1. Neutrophils - very abundant; the main cell type recruited during innate immune responses
2. Eosinophils - mostly phagocytose pathogens that have already been targeted by antibodies
3. Macrophages - can be resident or recruited; involved in innate responses, removal of dead cell debris, and sometimes act as antigen-presenting cells (APC)

Question 14

What are complement proteins? Where are they synthesized?

Answer 14

They are soluble immune mediators that help resolve microbial infections. When activated, they generate an enzyme cascade that can lead to pathogen death

They are synthesized by the liver, and circulate in the blood plasma

Question 15

What is the core of the complement cascade? What occurs when it is activated?

Answer 15

The core of the complement cascade is the activation of Complement C3, which leads to:

C3a - can initiate or enhance an inflammation response

C3b - leads to the recruitment of other complement proteins that trigger cell lysis and also improves the efficiency of phagocytosis

Question 16

What are the 3 pathways that can activate the complement system?

Answer 16

1. C3 activated by interaction with antibodies - requires an adaptive immune response
2. C3 activated by interaction with bacterial cell wall
3. C3b stabilized by Complement Factor P (properdin) - stimulated by bacterial secretions

Question 17

Describe the different components involved in the 3 pathways of the innate immune system when dealing with microbial infections

Answer 17

1. The recognition pathway - mast cells and the complement system
2. The recruitment pathway - cytokines for vessel dilation, permeability, and chemotaxis and the extravasation of WBCs
3. The resolution pathway - phagocytosis (especially by neutrophils and macrophages) and lysis (by complement Membrane Attack Complex)

Question 18

What are the functions of Natural Killer (NK) cells?

Answer 18

They perform immune surveillance, locating, and destroying abnormal self cells. It can recognize abnormal cells by unusual cell surface proteins or through the secretion of a cytokine called interferon alpha

Question 19

What is an abnormal “self cell”?

Answer 19

It’s a body cell that is either:
1. Infected by a virus
2. Part of a tumour

Question 20

How do NK cells resolve infection?

Answer 20

By releasing substances that trigger cell membrane permeability and lysis

The cytokines released from NK cells attract phagocytes which remove the cellular debris

Question 21

Describe the different components involved in the 3 pathways of the innate immune system in relation to immune surveillance

Answer 21

1. The recognition pathway - interferon-alpha and cell-surface molecules
2. The recruitment pathway - interferon-alpha, other cytokines, and enhancing chemotaxis of NK cells
3. The resolution pathway - lysis (by perforin) and induction of apoptosis (by TNF-alpha)