Outline the mechanism involved in phagocytosis.

 Mechanism involved in phagocytosis:

• Recognition by phagocytic receptor: Mannose receptors, scavenger receptors and receptors for various opsonins bind and ingest microbes, therefore the mannose receptor recognizes microbes and not host cells. The efficacy of phagocytosis is greatly enhanced when microbes are opsonized by specific proteins for which the phagocytes express high affinity receptors
• Engulfment: After a particles is bound to phagocyte receptors, extensions of the cytoplasm flow around it, and the plasma membrane pinches off to form a cytosolic vesicle that enclose the particle.
• Killing and degradation of engulfed material:  The killing of microbes and the destruction of ingested materials are accomplished by reactive oxygen species, reactive nitrogen species, mainly derived from nitric oxide, and lysosomal enzymes. This is the final step in the elimination of infectious agents and necrotic cells. The killing and degradation of microbes and elimination of dead-cell debris within neutrophils and macrophages occur most efficiently after their activation. All these killing mechanisms are normally sequestered in lysosomes, to which phagocytosed materials are brought. Thus, potentially harmful substances are segregated from the cell’s cytoplasm and nucleus to avoid damage to the phagocyte while it is performing its normal function.
  

What is phagocytosis? What are the steps of phagocytosis?

Phagocytosis:

Phagocytosis is the process by which a cell uses its plasma membrane to engulf a large particle, giving rise to an internal compartment called the phagosome. It is one type of endocytosis. In a multicellular organism's immune system, phagocytosis is a major mechanism used to remove pathogens and cell debris.

 

Steps of phagocytosis:

Phagocytosis involves three sequential steps: 

(1) recognition and attachment of the particle to be ingested by the leukocyte

(2) engulfment, with subsequent formation of a phagocytic vacuole

(3) killing or degradation of the ingested material

Describe the degeneration of arachidonic acid metabolites and their role in inflammation.

The lipid mediators prostaglandins and leukotrienes are produced from arachidonic acid present in membrane phospholipids and stimulate vascular and cellular reactions in acute inflammation.

Arachidonic acid is a 20 carbon polyunsaturated fatty acid that is derived from dietary sources or by conversion from the essential fatty acid linoleic acid.

Arachidonic acid derived mediators are synthesized by two major classes of enzymes

1. Cyclooxygenases
2. Lipooxygenases

Cyclooxygenase pathway:

Arachidonic acid - Prostaglandin G2 - Prostaglandin H2 - Prostacyclin PGI2, Thrombaxane A2 - PGD2 - PGE2.

Lipooxygenase pathway:

5HPETE - Leukotriene A4 -  Leukotriene C4 - Leukotriene D4, Leukotriene E4 and Lipoxin A4 and Lipoxin B4

Principal actions of arachidonic acid metabolites in inflammation:

1. Vasodilation - PGI2, PGE1, PGE2, PGD2
2. Vasoconstriction - Thromboxane A2, Leukotrienes C4, D4, E4
3. Increased vascular permeability - Leukotrienes C4, D4, E4
4. Chemotaxis, leukocyte adhesion - Leukotrienes B4

Short note on Chemokines.

Chemokines are a family of small proteins that act primarily as chemoattractants for specific types of leukocytes.
They are classified into four major groups according to the arrangement of cysteine (C) residues in the proteins.

1. C-X-C Chemokines - have one amino acid residue separating the first two of the four conserved cysteine residues.
2. C-C Chemokines - has first two conserved cysteine residues adjacent.
3. C Chemokines - lack the first and third of the four conserved cysteines.
4. CX3C Chemokines - Contain three amino acids between the two cysteines.

Chemokines have two main functions:

1. In acute inflammation - Chemokines stimulate leukocyte attachment to endothelium and they stimulate migration of leukocytes in tissues to the site of infection or tissue damage.
2. Maintanance of tissue architecture - Some chemokines are produced constitutively in tissues and are sometimes called homeostatic chemokines.

State the consequences of complement activation.

The complement system is a collection of soluble proteins and membrane receptors that function mainly in host defense against microbes and in pathologic inflammatory reactions.
The critical step in complement activation is the proteolysis of the third complement, C3. Cleavage of C3 can occur by one of three pathways.

1. The classical pathway - Triggered by fixation of C1 to antibody antigen complex.
2. The alternative pathway - Triggered by microbial surface molecules.
3. The lectin pathway - In which plasma mannose binding lectin binds to carbohydrates on microbes and directly activates C1.

The complement system has three main functions:

1. Inflammation - C3a, C5a and to a lesser extent C4a.
2. Opsonization and phagocytosis - C3b and iC3b acts as opsonins.
3. Cell lysis - The deposition of the MAC on cells makes these cells permeable to water and ions and results in death of the cells.

Write down the functions of complement in inflammation.

Complement:

The complement system is a collection of soluble proteins and membrane receptors that function mainly in host defense against microbes and in pathologic inflammatory reactions.

Functions:

• Increase vascular permeability: C3a C5a and to a lesser extent C3a stimulate histamine release from mast cells and thereby increase vascular permeability and cause vasodilation. They are also called anaphylatoxins because they have effects similar to those of mast cell mediators that involved in the reaction called anaphylaxis.
• Chemotaxis: C5a is a chemotactic agent for neutrophil, monocyte, eosinophils and basophils. C5a also activate lipoxygenase pathway of Arachadonic acid metabolism in neutrophils and monocytes causing further release of inflammatory mediators.
• Opsonization and phagocytosis: C3b and its cleavage product iC3b when fixed to microbial cell wall, acts as opsonins and promote phagocytosis by neutrophils and macrophages.
• Cell lysis: The deposition of the MAC on cells makes these cells permeable to water and ions and results in death of the cell.

What are the function of vasosctive smines.

Histamine and Serotonin are two major vasoactive amines. They are so called because they have important actions on blood vessels.
They are stored as preformed molecule in mast cell, basophils, platelets and on activation these cell release vasoactive amines.

Functions of vasoactive amines:
 Histamine:

• Principal mediators of the immediate transient phase of increased vascular permeability. (Increased vascular permeability)
• Histamine causes dilation of arterioles and increases the permeability of venules. (Vasodilation) 
• Endothelial activation.
• Contraction of some smooth muscles.

Serotonin: 

•  Neurotransmitter in the gastrointestinal tract.
• Vasoconstrictor.