In Brutons aganunaglobulinemia opsonisation is not affected [Ref : Harrison 171h/e p. 381; Bobbin's 7"Ve p. 60, 61, 62, 210, 591 During phagocytosis there is rapid respiratory burst which is brought about by rapid burst in the activity of NADPH oxidase. Increased NADPH oxidase activity leads to increased oxidative proesses and there by increased production of superoxide anion (02-) Superoxide is then conveed to hydrogen peroxide (1-1,02) free radical. The 11,0, generated by NADPH oxidase system is not able to kill the bacteria itself However, the azurophilic , granules of the neutrophils contain the enzyme myeloperoxidase (MPO) which in presence of halide such as Cl? conves H202 to hypochlorite (HOCI). Hypochloth'e (HOCI) is a potent antimicrobicidal agent that destroys microbes by halogenation. The H20,- MPO - halide system is the most efficient bactericidal system in neutrophils. Chediak higashi syndrome It is an autosomal recessive disorder. Chediak higashi syndrome is caused due to mutation in the LYST gene. This gene provides instructions for making a protien known as lysosomal trafficking regulator. This protein plays a role in transpo of materials into lysosomes. Lysosomes contain several enzyme. They use these enzymes to kill various microorganism, break down several toxins. During phagocytosis, lysosomes fuse with phagosome, forming phagolysosome. Once the phagolysosomes are formed, lysosomes secrete enzymes to kill the bacterial. Mutation in the LSYT protein disrupts the size, structure and function of lysosomes. Lysosomes cannot fuse with phagosome to form phagolysosome. Thus this syndrome is a disease with impaired bacteriolysis due to impaired phagolysosome formation. As a result, most people with chediak higashi syndrome have repeated and persistent infections, staing in infancy or early childhood. These infections are life threatening. Besides, the granules of lysosomes, the secretory / storage granules of various other cells are also affected. The other cells involved are ? - Melanosotnes of melanocytes - Dense bodies of platelets - Granules of schwann cells In pigment cells called melanocytes the melanosome become abnormally large so there is reduced production of melanin. Thus people with chediak Higashi syndrome have occulocutaneous albinism i.e the colour (-)f skin, hair and eye is reduced. Abnormality in platelets produce bleeding disorders. Defective granules in schwann cells lead to neurological symptoms e.g. peripheral neuropathy. More on chediak higashi syndrome Most children with chediak Higashi syndrome ultimately reach a stage of the disorder known as accelarated phase (lymphoma like stage). This severe phase of the disease is thought to be triggered by viral infection (E.B.virus). In the accelarated phase, defective white blood cells divide uncontrollably and invade many of the body's organs. The accelarated phase is associated with fever, episodes of abnormal bleeding, overwhelming infections and organ failure. They are usually life threatening and lead to death. Bruton's agammaglobulinemia Bruton's agammaglobulinemia is an X-linked disease that occurs mainly in males. It is caused due to defect in the gene Bruton's tyrosine kinase. Bruton's tyrosine kinase plays a crucial role in B cell maturation as well as mast cell activation. Defect in Bruton's tyrosine kinase leads to failure of maturation of B cells. B cells cannot mature beyond pro B cell stage. In the absence of mature B cell, patient lacks lymphoid tissue and fails to develop plasma cells, (the cells that produce antibodies). Thus there is absence of immunoglobulins of all classes in Bruton's agammaglobulinemia. Germinal centres, where B cells proliferate and differentiate are poorly developed, in all lymphoid tissues including the .spleen, tonsils, adenoids, peripheral lymph nodes. Peyer patches in the intestine are small or absent. Clinical features Patients with Bruton's agammaglobulinemia do not manifest any symptoms till 6 months of life (due to the presence-of maternal antibodies). These patients are susceptible to infections with capsulated bacterias because antibody response is vital to kill encapsulated bacterias. Antibodies help in opsonization of encapsulated bacterias such as staphylococcus aureus, 11 ifluenzae, streptococcus pneumoniae. The polysaccharide capsule that surrounds the encapsulated bacteria is a potent virulent agent. It protects the bacteria from phagocytosis. These bacterias can only be phagocytosed when they are opsonised (coated) with specific proteins (opsoni us). Opsonized (coated) bacterias become attractive targets for phagocytes because phagocytes express high affinity receptors for opsonins. The major opsonins present in the body are IgG antibody and C3b complement. In Bruton's agammaglobulinemia antibodies are absent therefore opsonisation is defective.