Innate Immunity (Module 2) Flashcards
What is inflammation?
Complex biological response to pathogens, trauma, or chronic illness that is characterized by redness, heat, swelling, pain, and loss of function.
Is inflammation always an indication of infection?
Often yes, but there are also many chronic disease states where inflammation is the result such as arthritis.
What protein fragments released during the complement cascade increase inflammation?
Examples are C3a, C4a, and C5a.
Is inflammation caused by pathogens?
Not directly, but inflammation is a result of the innate immune system preventing damage by that pathogen.
What are the symptoms of inflammation?
Redness, heat, swelling, pain, and loss of function each correlate to a phase of acute inflammation.
What does the cytokine, IL-1 (Interleukin-1) do when released in response to a pathogen?
Interleukin-1 (IL-1) causes capillaries in the immediate area to dilate which triggers endothelial cells to separate and become leaky. This allows blood (plasma, RBC, WBC, and platelets) to pass through into the area of tissue injury from the blood vessel (vasculature).
This creates redness, heat and swelling in the tissue which is not its normal state. The increased fluid pressure on nerve endings causes pain and loss of function.
Phagocytes migrate in from blood vessels and engulf and remove the pathogen.
What are the stages of inflammation?
Table 2-6
Vascular Permeability - vasculature dilates in response to IL-1, hyperemia (blood rushes in), transudation (passage of fluid through membranes) and fibrin plug formation results.
Emigration of Neutrophils - Neutrophils migrate through capillary endothelium to infection site and attach.
Emigration of Macrophages - Monocytes and macrophages travel to the site of infection (4-24 hrs)
Cellular Proliferation and Repair - Cells begin to repair in area (~18 hrs and peak at 48-72 hrs)
What is phagocytosis?
Process where cells internalize particulates, pathogens, dying cells and debris through endocytosis.
What are phagocytes? Name two common phagocytes.
Cells that specialize in phagocytosis.
Macrophages and neutrophils are two of the most efficient cells at removing pathogens via phagocytosis.
What two myeloid cells circulate in the body looking for an infection on a continuous basis as part of the innate immune function?
macrophages and neutrophils
They look for non-self and remove it.
What are the precursor cells for macrophages?
Monocytes
In a normal healthy individual are 3-11% of the total circulating WBC population.
What happens to the monocytes in the blood circulation?
The monocytes then leave the blood and reside in the various body tissues where they change to macrophages but each tissue has a specific name for their macrophages, e.g. in the liver – Kupffer cells, central nervous system - microglial cells.
What do the various macrophages do in the body tissues?
Act as the clean-up crew. Remove anything that is non-self or dying.
Most abundant cell in the body - more than red blood cells and skin.
What is the most abundant white blood cell circulating in a normal healthy individual?
Neutrophils
What word is used to describe neutrophils nucleus’ appearance?
Polymorphonuclear
How do neutrophils get though blood vessels to the area of infection?
Squeeze through blood vessels to infection site by diapedesis.
Neutrophils are ___________ lived than macrophages
shorter
True / False. Neutrophils are programmed to die.
True
What happens to neutrophils after they have engulfed pahtogens?
- Neutrophils will undergo programmed cell death, apoptosis, as a means of containing and preventing infection.
- Macrophages will consume the dead or dying neutrophils (your pus!).
What body part holds reserves of neutrophils?
Large reserves are maintained within the bone marrow and are released in times of infection.
What happens to the neutrophil population circulating in the blood during an infection?
Neutrophil population will increase above the normal reference range 50-70%.
How do macrophages recognize pathogens? (at least one way)
On the surface of macrophages are many receptors that are specific for particular components of pathogens. These receptors on the pathogens are shared among a variety of pathogens so it is still non-specific and part of the innate immunity.
In response to a receptor signal, macrophages release cytokines.
Name some examples of macrophage receptors
Table 2-7
Toll-like Receptor 4 (TLR4) - specific for the bacterial lipopolysaccharide present in gram negative bacterium cell walls.
Complement Receptor 1 (CR1) - binds to C3b
Complement Receptor 3 (CR3) - binds to iC3 fragments
Complement Receptor 4 (CR4) - binds to iC3 fragments
What are the first four of the eight phases of phagocytosis?
First four - extravasation - migration out of blood vessels into infected tissue.
- Adherence - Cytokines cause Weibel-palade bodies (selectins in endothelial cells) to express on the surface as P and E selectins. Glycolipids and glycoproteins on the leukocyte surface then stick to the selectin molecules on the endothelial surface and are guided to the inflamed tissue.
- Locomotion - phagocyte crawls along the surface of endothelium via expressed P and E selectins.
- Diapedesis - Leukocytes (mostly neutrophils) squeeze through the tissue by diapedesis. It forms pseudopods to make it through.
- Chemotaxis - leukocytes are drawn towards the area of pathogen invasion based on the chemical gradient created in the area of inflammation.