Lecture 37 - Immune system: Inflammation and Innate Immunity Flashcards
What are acellular soluble factors?
They are secreted molecules which are involved in immune responses
Name 2 types of cell-mediated immunity that involves acellular soluble factors
- 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 - Complement - a group of plasma proteins that contribute to anti-microbial defenses
What are the 3 basic components of an innate immune response?
- Recognition - identification of pathogens or abnormal cells
- Recruitment - structural and chemical changes that bring WBCs to the site
- Resolution - destruction of pathogens and diseased cells
What is another name of innate immune responses and what are their 2 phases?
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
What are the 5 cardinal signs of inflammation?
- Heat
- Redness
- Swelling
- Pain
- Loss of function
What is the function of resident WBCs (ex. mast cells)?
They recognize tissue damage, pathogen entry, and release signalling molecules. How?
- Mast cell is activated by chemicals released from damaged epithelium
- Mast cell degranulates, releasing granule contents that attract WBCs to move towards it
What occurs when paracrine factors are released from mast cells?
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
Give 2 examples of paracrine factors that promote different processes in local tissue
- Arterioles can dilate, which increases blood flow, causing redness and heat
- Capillary endothelial cells have increased permeability, increasing fluid release into tissue, causing swelling
What happens when cytokines are released into the bloodstream? What are these specific cytokines called?
These cytokines are called interleukins. Their release into the bloodstream can generate body-wide aspects of inflammatory responses
Give 2 examples of how interleukins generate inflammatory responses
- Interleukin 1 can reprogram the hypothalamic set point for temperature, triggering fever
- Interleukin 6 can stimulate proliferation of WBCs (especially neutrophils) in the red bone marrow
What happens when paracrine and hormonal factors are released from mast cells? What are the 2 processes it involves?
It leads to recruitment of circulating WBC through extravasation (movement of WBC through the capillary wall into the surrounding tissues). Extravasation involves:
- Changes in the endothelial wall (allowing WBCs to stick to it)
- Chemotaxis of WBCs into the interstitial space
What is the function of phagocytic myeloid cells?
They resolve infection by engulfing and destroying pathogens
What are the 3 different types of phagocytes and what are their functions?
- Neutrophils - very abundant; the main cell type recruited during innate immune responses
- Eosinophils - mostly phagocytose pathogens that have already been targeted by antibodies
- Macrophages - can be resident or recruited; involved in innate responses, removal of dead cell debris, and sometimes act as antigen-presenting cells (APC)
What are complement proteins? Where are they synthesized?
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
What is the core of the complement cascade? What occurs when it is activated?
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
What are the 3 pathways that can activate the complement system?
- C3 activated by interaction with antibodies - requires an adaptive immune response
- C3 activated by interaction with bacterial cell wall
- C3b stabilized by Complement Factor P (properdin) - stimulated by bacterial secretions
Describe the different components involved in the 3 pathways of the innate immune system when dealing with microbial infections
- The recognition pathway - mast cells and the complement system
- The recruitment pathway - cytokines for vessel dilation, permeability, and chemotaxis and the extravasation of WBCs
- The resolution pathway - phagocytosis (especially by neutrophils and macrophages) and lysis (by complement Membrane Attack Complex)
What are the functions of Natural Killer (NK) cells?
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
What is an abnormal “self cell”?
It’s a body cell that is either:
1. Infected by a virus
2. Part of a tumour
How do NK cells resolve infection?
By releasing substances that trigger cell membrane permeability and lysis
The cytokines released from NK cells attract phagocytes which remove the cellular debris
Describe the different components involved in the 3 pathways of the innate immune system in relation to immune surveillance
- The recognition pathway - interferon-alpha and cell-surface molecules
- The recruitment pathway - interferon-alpha, other cytokines, and enhancing chemotaxis of NK cells
- The resolution pathway - lysis (by perforin) and induction of apoptosis (by TNF-alpha)
