Clinical Immunology - Neutrophils

Pluripotent

Neutrophils are generated from ___ stem cells

True

True or False: Neutrophils are one of the most common cells in circulation

60-75%

What percentage of circulating white blood cells are neutrophils?

6-12 hours

In circulation, the life span of a neutrophil is, on average...

Phagocytosis and killing pathogens

What is the main function of neutrophils in circulation?

Rabbits, birds, and amphibians

Heterophils are seen in what animal types?

Granulopoiesis; within the bone marrow

The formation of neutrophils, also known as ___, takes place in which part of the body?

Granulocyte-monocyte progenitor cell -> myeloblast

After which step in the granulopoiesis process does it become specific to neutrophils?

Metamyelocytes and band neutrophils

If there is extreme inflammation in the body, what abnormal neutrophil types may be seen in circulation?

Secretory vesicles

What structures are only seen in mature, segmented neutrophils?

Shape and position of the nucleus as well as types of granules

How are the cells in the different steps of granulopoiesis differentiated?

Azurophilic/primary, specific/secondary, and tertiary granules

What three general granule types do neutrophils have?

They must be recruited to tissue by a signal given by chemokines

Neutrophils are normally confined to circulation. What process must occur in order for them to migrate to tissue?

10-fold

During bacterial infections, the number of circulating neutrophils may increase by?

Selectins

The first adhesion molecules to play a role in extravasation are?

Carbohydrates

Lectins are a group of adhesion molecules which bind to what type of molecule?

Rolling adhesion; slows neutrophils in order for them to migrate through to tissues

Adhesion molecules mediate what process? What is the function of this process?

P and E selections

Which selections are generally found on the endothelium?

On a neutrophil

Where are L selectins found?

Weak

Selectin-mediated binding is (weak/strong)

Activated integrins

In the extravasation process, strong bonds are forged with what molecules?

Rolling, tethering, adhesion, crawling, and transmigration

What are the steps of the extravasation process?

Proinflammatory cytokines

What induces the expression of adhesion molecules on endothelial cells?

Phagocytosis, degranulation, and NETosis

What are the main antimicrobial mechanisms of neutrophils?

Activation, adherence, digestion, destruction

What are the steps of phagocytosis?

Cluster of differentiation

Neutrophils express multiple ___ on their surface

Antibodies, leukotrienes, complements, cytokines, and attachment to blood vessel wall

The most relevant surface receptors on neutrophils are those for...

Both are negatively charged and tend to repel each other, considered 'slippery'

To adhere to a microbe, the neutrophil must 'grab' it. Why is this difficult?

Opsonins; makes it more positively charged

What molecule can attach on the surface of the microbe to make it easier to grab? Why does this make it easier?

Phagosome

Bacteria is engulfed within the neutrophil in a vacuole known as a?

The lysosome

The phagosome of a neutrophil joins with what cellular organelle in order to destroy the microbe?

Respiratory burst or granule-associated lytic enzymes and antimicrobial peptides

Within phagolysosomes, what two processes can be used to kill microbes?

Reactive oxygen species which damage microbial membranes

In the process of a respiratory burst, the microbe is damaged via?

NADPH

Which enzyme within the respiratory burst process is responsible for making reactive oxygen species?

Proteolytic enzymes, lactoferrin, and defenses

What are the three granule-associated methods of microbial destruction?

Binds iron, which is necessary for bacterial life

How does lactoferrin kill microbial species?

Bactericidal, also recruit and activate other WBCs

What is the role of defensins?

Degranulation

Which antimicrobial mechanisms is used to execute a rapid response to infection?

Release of contents of granules of neutrophils into extracellular space

What occurs during the process of degranulation?

Proteases, reactive oxygen species, lysozyme, and cationic proteins

What are some of the enzymes included in neutrophilic granules?

Can induce a potent pro inflammatory response due to granule contents released in the extracellular space

What is the main downside of degranulation?

Neutrophil extracellular traps

What does NETs stand for?

Nuclear delobulation, disassembly of nuclear envelope, chromatin decondensation, and plasma membrane rupture

What are the main steps of NETosis?

Inflammatory stimuli

Apoptosis of neutrophils occurs in the presence of ___

Macrophages

Apoptotic neutrophils are removed by which cells?

Secretion of anti-inflammatory cytokines which induce the resolution of inflammation

Ingestion of apoptotic neutrophils triggers what?

Efferocytosis

Phagocytosis of apoptotic neutrophils by macrophages is known as?

Selectins, interns, and chemokines

What molecules are involved in the extravasation process?