Phagocytosis Flashcards
What is phagocytosis?
It is a mechanism of the innate immune system where phagocytes internalise certain matter (in this case, pathogens, dying cells, etc.).
It then destroys the pathogen by digesting it.
What are the main roles of phagocytosis?
- to protect the body from pathogens
- to dispose of damaged/dying (apoptotic) cells
- to process and present antigens (Ag)
This processing/presenting of antigens activates the adaptive immune system. It, in essence, links the innate and adaptive immune system.
What are the effector (and other) cells of the innate immune system?
The effector cells are phagocytes. Most cells will phagocytose, but there are special cells that excel at it. These cells are:
- neutrophils
- macrophages
- dendritic cells
Their origin is the myeloid lineage, so they are generated in the bone marrow.
Other cells in the innate immune system include:
- mast cells (myeloid lineage)
- eosinophils (myeloid lineage)
- basophils (myeloid lineage)
- natural killer (NK) cells (lymphoid lineage, made in bone marrow)
Describe neutrophils.
They are polymorphonuclear (PMN) leukocytes. They are the most abundant WBC circulating in the blood.
They respond early to infection (inflammation). They have a lifespan of about 8-10 hours in the blood and about 4-5 days in the tissue.
Their function is to phagocytose and kill microbes that enter the body. They release enzymes, such as lysozymes, collagenases and elastases, which help destroy the pathogen.
Describe macrophages.
Monocytes have a kidney-shaped nucleus, and when they enter the tissue, they differentiate into macrophages.
They are very efficient at phagocytosis, the killing of microbes; they secrete inflammatory factors (cytokines).
Describe dendritic cells.
They have extensions that allow them to sample the environment and detect pathogens.
They are found in the skin, mucosa and tissues.
Not only do they phagocytose, but they also present the pathogen antigens to T cells, which activates the adaptive immune system.
Describe how dendritic cells signal for T cell activation.
The first signal is the antigen recognition by the T cell receptor (TCR). However, this may not be enough to activate naïve T cells, so we have a second signal (a costimulation) by CD80/CD86 in the antigen-presenting cell and CD28 in T cells. The third signal can be the cytokines released by the dendrites.
What are the four steps of phagocytosis?
1) CHEMOTAXIS (mobilisation of site of infection/injury)
2) RECOGNITION AND ATTACHMENT to microbes/dead cells
3) ENGULFMENT
4) KILLING/DIGESTION of ingested microbes/dead cells
Describe chemotaxis, ie. phagocyte mobilisation (the first step of phagocytosis).
It is the movement of cells towards the site of infection.
When a foreign body enters the tissue, the resident macrophages, etc. go towards and attach themselves to it. This causes it to release certain substances called chemoattractants; they attract phagocytic cells. Chemoattractants are released by many cells, such as bacteria, inflammatory cells and damaged tissues. These chemoattractants create a chemoattractive gradient towards the tissue, spreading out to surrounding blood vessels.
Neutrophils that are circulating in the bloodstream have receptors on them that allow them to follow the chemoattractive gradient, and migrate towards the infected tissue. They can then aid in the removal of the foreign bodies.
Describe the recognition and attachment of foreign bodies (the second step of phagocytosis).
The recognition of pathogens can occur because they present PAMPs (protein-associated molecular patterns). These are present on pathogens and not on host cells, helping the phagocyte differentiate between self and non-self cells. They are invariant structures that are shared by an entire class of pathogen. These are essential for the survival of the pathogens, and they need to be so that they erase the possibility of the pathogen mutating and not expressing that PAMP anymore. Some examples of PAMPs would be double-stranded viral RNA, or lipopolysaccharides (LPS) found in bacterial membranes.
The PAMPs are recognised by PRRs (pattern recognition receptors) that are present on phagocytes. They, in essence, help detect foreign bodies or aged/damaged cells.
Another way in which foreign bodies can be recognised is through opsonisation.
List the five PRRs.
- TOLL-LIKE RECEPTORS:
found on the plasma membrane and endosomal membrane - C-TYPE LECTIN RECEPTORS (CTLRs):
eg. mannose receptor - NOD-LIKE RECEPTORS (NLRs):
reside as free proteins in the cytoplasm - RIG-LIKE HELICASE RECEPTORS (RLRs):
cytosolic receptors for viral double-stranded RNA - SCAVENGER RECEPTORS:
they scavenge dead/damaged cells, but can also detect various bacterial cell wall components (CD14 scavenges LPS-LBP)
Describe Toll-like receptors.
They are receptors that play essential roles in innate immunity. They have been conserved throughout evolution.
Human TLRs recognise PAMPs (eg. lipoteichoic acid, lipopolysaccharides) and stimulate the production of inflammatory cytokines.
Describe opsonisation.
This process facilitates phagocytosis.
It is the coating of microbes with opsonins (such as proteins of the complement system, C3b, C4b, and antibodies, immunoglobulin). Opsonised microbes can be phagocytosed easier (via receptors for opsonins on phagocytes).
This, however, is REQUIRED for encapsulated bacteria. The capsule on these bacteria deflect phagocytes, so the opsonin coating helps the phagocytes get access to these kinds of microorganisms.
Describe engulfment (the third step of phagocytosis).
When the microbe makes contact with the membrane, the actin cytoskeleton rearranges to make membrane protrusions called pseudopods that surround the microbe, bringing it inside of the cell. This vesicle that it is encapsulated in is called a phagosome.
Then, this phagosome combines with lysosomes in the cell to form a phagolysosome. This is done so that the enzymes present in the lysosome can get access to the microorganism to destroy it.
Describe pathogen destruction (the fourth step of phagocytosis).
The pathogen destruction occurs because of the lysosome. It contains digestive enzymes that it releases into the phagolysosome. Some of these enzymes are:
- proteolytic enzymes (cathepsins): degrade microbes
- lysozyme: breaks bacterial walls
- lactoferrin: binds iron, stealing it away from the bacteria
- defensins: destroy bacterial walls
