Lecture 2 - Innate Immunity I Flashcards
Innate Immunity
The first and second line of non-specific defenses that exist in all organisms in various ways
1st line of defense
First part of innate immunity.
A non-specific defense that involves skin, mucus, membranes, and chemicals
2nd line of defense
Second part of innate immunity.
A non-specific defense that involves phagocytosis, complement, interferon, inflammation, and fever
Fundamentals of Innate Immunity
- Protective mechanism that exists before infection
- Rapid responses encoded within the germline (DNA in egg and sperm cells)
- Responses are typically identical upon repeat infection
Inflammation
Part of the 1st line of defense
Involves vasodilation, increase in capillary permeability, and influx of immune cells to affected tissues.
Four signs of inflammation
REDNESS: Vessels dilate (vasodilation) and blood volume increases
HEAT: Increased blood volume brings warmth to affected tissue
EDEMA: Swelling due to accumulation of fluid from blood in affected tissue
PAIN: Some inflammatory mediators trigger the pain response
Evidence of Inflammatory Response: Elie Metchnikoff (1800s)
Insult to star-fish larvae with thorn, rapid localization of cells to site of insult, breakdown of thorn by cells
(First observation of phagocytosis)
Inflammatory Response
- Margination: inflammatory chemicals and mast cells leave the bloodstream and move towards infection
- Diapedesis: the Neutrophils leave the bloodstream and head towards the infection
- Chemotaxis: the Neutrophils locate the bacteria through chemical signals
- Phagocytosis: the Neutrophils engulf the bacteria and digest them
Phagocytosis
“Cellular eating”. Process by which a cell engulfs a substance by surrounding it with its membrane
Highly Conserved throughout Evolution
Steps:
1. Phagocytes detects and engages microbe
2. Microbe engagement initiates cytoskeletal rearrangements that drive phagocytosis
3. The microbe is internalized in a specialized phagosome.
4. The phagosome fuses with the lysosome to form a phagolysosome
5. Lysosomal enzymes destroy ingested microbes.
6. Reactive oxygen and nitrogen intermediates destroy microbial proteins, genomes and walls
Phagocytes
“Cell that eats”
Cells that ingest and destroy microbes by a process known as phagocytosis. They also activate neighbouring cells through the release of cytokines and chemokines
Two processes:
1) Chemotaxis — chasing down of microbes
2) Phagocytosis — eating of microbes
Eg. Macrophages, Monocytes, and Neutrophils
Macrophage Development
- Bone Marrow Stem Cell: undifferentiated stem cells in the bone marrow
- Blood Monocyte: differentiation into short-lived monocytes that circulate in the blood
- Tissue Macrophage: Inflammation recruits monocytes to sites of infection where they differentiate into resident macrophages
- Resident macrophages are long-lived “professional” phagocytes that ingest large amounts of extracellular material
Cytokines
Secreted proteins that drive immune and inflammatory reactions.
In innate immunity, cytokines are produced by macrophages and natural killer cells
One effect of cytokines: induce proteins in the endothelium that make the endothelium more adherent for passing leukocytes
Chemokines
A large family of structurally related, low molecular weight cytokines that stimulate leukocyte movement and regulate the migration of leukocytes from the blood to tissues