Topic 9: Neutrophil and Basophil granulocytes

Question 1

What should be mentioned in this topic?

Answer 1

• Basics about WBC
• Neutrophil Granulocyte
• Migration
• Phagocytosis
• Basophil Granulocyte
• Degranulation
• Specific Way of Degranulation
• Nonspecific Way of Degranulation

Question 2

Basics about WBC

Answer 2

• White blood cells are elements of the organism’s immune system.
• they develop in the bone marrow (Except for the lymphocytes)
• Its physiological amount in mammals is 5-15x109/L and in birds is 20-30x109/L.
• There are more factors (species, age, sex, time of the day) that have an effect on the number
  of the white blood cells.
• Increase, leukocytosis, in the number of the white blood cells can be caused in the first place
  by bacterial, viral and parasitic infections, also by inflammatory processes,
• Decrease, leukopenia, can be a result of radioactive radiation, mushroom-toxins or some
  medications.
• Neutrophilic type: horses and carnivores 30% agranulocytes, 60% granulocytes
• Lymphocytic type: ruminant, swine, bird, 60% agranulocytes, 30% granulocytes

Question 3

Neutrophil Granulocyte

Answer 3

• Cells with diameter 10-14micrometers
• Strongly segmented nucleus having small, purple-red-coloured granules in the cytoplasm.
• 80% neutrophil granules and 20% by bigger, asurophil granules.
• The granules: lysosomes that contain the enzymes necessary for perishing and digesting the
  particles of bacteria, funghi and viruses phagocytated by the cell.
• Neutrophil granulocytes are the most important elements of the cellular immunity: proceed a
  very effective phagocytosis, they don’t need previous meeting with the foreign body for its
  recognition and elimination, display their effect immediately.
• PMN Cells: Polymorphonuclear cells
• Lifetime: 6-7 hours in circulation, Tissue: 2-3 days
• Circulating fraction is small
  -A part is adhered to the inner wall of vessels
• Extravascular fraction
  -Bone marrow, spleen
  -Mobilisation: Leukocytosis
• Granula contain enzymes:
  -Lysosyme, Myeloperoxidase, Superoxide dismutase, Acidic, alkali phosphatise, Nuclease, Protease
• Clinically important
  -Pathognostic values in case of infection
• Young forms in the quality blood count: o Stab form (stick shaped)
  -Jugend form (bean shaped)
• Matured neutrophil (3-5 segments)
• Over matured neutrophil (5-10 segments)
• “Shift to the left” in the blood count: Forced hematopoiesis, presence of fresh (acute)
  infection
• “Shift to the right” in the blood count: Presence of aged neutrophil granulocytes, incomplete
  hematopoiesis.

Question 4

Neutrophil Granulocyte

Migration

Answer 4

Neutrophils are able to actively move/migrate.
Movement is based on building up and dissociation of actin chains. As a result of actin polymerisation actin fibers are continuously formed in the cell. These fibers are divided into groups for different tasks by the quality of the actin binding proteins. Contractile actinbundles, gel-forming, actin-bundles or tightly united actin-bundles can be formed. Migration by philopodium

Question 5

Neutrophil Granulocyte

Phagocytosis

Answer 5

Neutrophil granulocytes are not only able to take up bigger particles but also able to engulf molecules. As an example for phagocytosis we show LDL uptake:
- External part of LDL receptor binds an LDL
- Affected by this, the internal clathrin binding site activates and a clathrin coated pit is formed,
that finally ends up with endocytosis and forming of a clathrin coated vesicle
- Calthrin: A complex consisting of three small and three bigger peptides that is inherited
conservatively during evolution.

The phagocyting activity of neutrophil granulocytes goes on basic level under normal circumstances. If specific factors and non specific factors bind a foreign body, the phagocyting ability of neutrophil granulocytes increases to a hundred times higher level.
Opsonisation: There are some natural substances in the blood plasma that can bind foreign antigens similarly to immunoglobulins. They bind with the neutrophil granulocytes and significantly stimulate phagocytosis.
Immune Adherence – The specific immunoglobulin able to bind the antigen is present already and binds the antigen. Because of this specific binding, the Fc part of the IgG binds this complex to the Fc receptor of the neutrophil cell. Results: Increased phagocytosis. The cell expresses the Fc receptors on the surface again making additional phagocytosis possible.

Question 6

Basophil Granulocyte

Answer 6

Rarest WBC
- Diameter 9-10micrometers
- Slightly granular nucleus bent in a horse shoe or an S-like manner.
- Big basophile granules can be found in the cytoplasm. These contain histamine, serotonin and
heparin besides the enzymes. Enzymes: Hyaluronidase, protease, myeloperoxidase.
- Moving capability of the basophil granulocytes is far behind that of the other two granulocyte
types.
- Their main task is to help the immune reactions: They loosen the tissues where the antigens
are present so the other defence elements can more easily get to the place of infection.
- Circulating fraction is small
- No phagocytosis, almost no endocytosis
- Extravasal fraction: Mast cells can be found in the tissues
- These cells loosen the tissues
- Stimulate the elimination of antigens

Question 7

Basophil Granulocyte:

De granulation

Answer 7

• The basophil granulocytes bind IgE type antibodies on their surface. In case an antigen binds to the IgE, the cell quickly releases its enzyme-supply to the environment: degranulation occurs. The released enzymes loosen the environment and give space to additional immune processes.
• Extreme degranulation ends up with pathological damage in the organism’s own tissues: allergy
• Degranulation is stimulated by many different ways of the immune system

Question 8

Basophil Granulocyte:

Specific Way of Degranulation

Answer 8

• on surface of the basophil granulocytes there are receptors that bind the Fc part of the IgE- type immunoglobulins
• The IgE that was produced earlier against another antigen can still bind to the above mentioned receptor if the IgE did not bind the antigen yet.
• The basophil cell “equipped” with IgE roams in the insterstice. In case of meeting an antigen, it binds it.
• The binding itself evokes the vacation of the basophil cell granules. The released materials loosen the tissues. The tissue infected by the antigens becomes accessible for the other cells of the immune apparatus.

Question 9

Basophil Granulocyte:

Nonspecific Way of Degranulation

Answer 9

• Basophil cells cause inflammation
  
  • When an antigen is detected they emit a large amount of a certain material to the
    plasma and the interstitial space that loosens the tissues. This makes it much easier
    for the immune cells and antibodies to get to the antigen..
• The degranulation is stimulated by the C3a and C3b complement factors. The receptor
  specific for these factors is expressed to the surface of the cell again and again.
• Additional products of the degranulation are the heparin (prevents coagulation therefore accelerates the process of the antibodies getting into the interstitium) and the slow reacting
  factor of anaphylaxis (SRS-A).
• This SRS-A causes long lasting inflammation.
• The released histamine and hyaluronidase loosen the tissues so the immune cells and molecules can get to the antigens. Heparin helps by preventing coagulation.