Phagocytosis Flashcards
1
Q
What is phagocytosis?
A
- 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.
2
Q
What are the main roles of phagocytosis?
A
Roles are:-
- 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.
3
Q
What are the effector (and other) cells of the innate immune system?
A
- 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).
4
Q
Describe neutrophils.
A
- 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.
5
Q
Describe macrophages.
A
- 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).
6
Q
Describe dendritic cells.
A
- They have extensions that allow them to sample the environment and detect pathogens.
- They are found in the skin, mucosa (mucus membrane) and tissues.
- Not only do they phagocytose, but they also present the pathogen antigens to T cells, which activates the adaptive immune system.
7
Q
Describe how dendritic cells signal for T cell activation.
A
- T cells require two signals to become fully activated.
- A first signal, which is antigen-specific, is provided through the T cell receptor (TCR) which interacts with peptide-MHC molecules on the membrane of antigen presenting cells (APC) [Here it is DC].
- A second signal, the co-stimulatory signal, is antigen nonspecific and is provided by the interaction between co-stimulatory molecules expressed on the membrane of APC and the T cell.
- One of the best characterized co-stimulatory molecules expressed by T cells is CD28, which interacts with CD80 and CD86 on the membrane of APC.
- The third signal can be the cytokines (they vary depending on the type of pathogen) released by the dendrites.
- These cytokines tell the cell what type of T-cells it needs to differentiate into.
8
Q
What are the four steps of phagocytosis?
A
- CHEMOTAXIS - The cells need to get to the site where the pathogen has entered the body or to the site where the cells are damaged and need to be eliminated.
- RECOGNITION AND ATTACHMENT to microbes/dead cells
- ENGULFMENT
- KILLING/DIGESTION of ingested microbes/dead cells
Chemotaxis meaning - movement of a motile cell or organism, or part of one, in a direction corresponding to a gradient of increasing or decreasing concentration of a particular substance.
9
Q
Describe chemotaxis, ie. phagocyte mobilisation (the first step of phagocytosis).
A
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 which 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.
10
Q
Describe the recognition and attachment of foreign bodies (the second step of phagocytosis).
A
- 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 (no reaction) and non-self (reaction) 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 present 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.
11
Q
Describe Toll-like receptors (TLRs).
A
- They are receptors that play essential roles in innate immunity.
- They have been conserved throughout evolution as they are vital for the survival of many organisms.
- Human TLRs recognise PAMPs (eg. lipoteichoic acid, lipopolysaccharides) and stimulate the production of inflammatory cytokines.
12
Q
Describe opsonisation.
A
- This process facilitates phagocytosis.
- It is the coating of microbes with opsonins. There are two classes of opsonins “-
- Proteins of complement systems (C3b, C4b).
- Antibodies (Immunoglobulin, Ig).
- 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.
13
Q
Describe engulfment (the third step of phagocytosis).
A
- 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.
14
Q
Describe pathogen destruction (the fourth step of phagocytosis).
A
- 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 wall.
15
Q
Describe the two different ways in which phagocytes kill pathogens.
A
- Phagocytes can kill pathogens in an oxygen-dependant or oxygen-independant manner.
- A superoxide is biologically toxic and is deployed by the immune system to kill invading microorganisms.
- In phagocytes, superoxide is produced in large quantities by the enzyme NADPH oxidase for use in oxygen-dependent killing mechanisms of invading pathogens.
- Oxidising radicals, such as NOS and ROS, kill phagocytosed microbes; however, they can also damage other tissues, so they need to be carefully controlled.
- There are some enzymes that work in an oxygen-independent manner, ie. they can work under anaerobic conditions.
17
Q
Describe the other types of prey that phagocytes go after.
A
- In addition to pathogens, phagocytes also target:
- microorganisms
- Damaged or dying cells:
- This happens when cells undergo apoptosis; it is a fast, efficient removal by phagocytes.
- It is a ‘silent removal’ in the sense that there is no inflammation with this removal.
