PASSIVE IMMUNIZATION

Passive immunization against specific infections or in non-specific immunodeficiency states is provided by commercial immunoglobulins (Ig) derived from the pooled plasma of multiple adults.

TABLE 9.8: Immunological preparations for passive immunization

Non-specific immunoglobulins

• Intravenous immunoglobulins

• Intramuscular immunoglobulins

Specific (hyperimmune) immunoglobulins

• Tetanus immunoglobulins (TIG)

• Hepatitis B immunoglobulins (HBIG)

• Varicella-zoster immunoglobulins (VZIG)

• Rabies immunoglobulins (RIG)

• Anti-D immunoglobulins

Anti-sera

• Anti-diphtheria serum (ADS)

• Anti-snake venom (ASV)

Therapeutic immunoglobulin preparations are divided into two types: (a) specific or hyperimmune immunoglobulins, and (b) non-specific immunoglobulins.

Specific (hyperimmune) immunoglobulins are prepared from pooled plasma of immunized or con­valescing adults and contain high titers of specific antibodies against a specific antigen or infection, e.g. tetanus, diphtheria, etc. Being readymade, these antibodies ensure early protection from the specific disease by neutralization of circulating antigen or toxin. However, this protection is limited and temporary, due to quantitatively limited antibodies titers and short-life of immunoglobulins (20-35 day).

Anti-sera are purified concentrates of horse sera, who have been actively immunized with a specific antigen and provide passive immunity to a specific infection, e.g. diphtheria, tetanus and snake bite.

Currently available specific immunoglobulins (Table 9.8) are highly-refined biological products of human, which have gradually replaced earlier products of equine origin.

However two anti-sera of equine origin are still in common use due to lack of alternatives including anti-diphtheria serum (ADS) and anti-snake venom (ASV), which carry high-risk of adverse reactions, e.g.

Non-specific (normal) immunoglobulins are a polyvalent antibody-rich fraction, obtained from pooled human plasma that contains antibodies against several infections prevalent in general population. These immunoglobulins are available as intravenous (IVIG) as well as intramuscular (IMIG) preparations, though IMIG is rarely used at present due to slow and erratic absorption, proteolytic degradation at injection site and high-risk of adverse events, e.g. anaphylaxis. However, IMIG may still be used for post-exposure prevention of measles and hepatitis A in close contacts, with some benefits.

Intravenous immunoglobulins (IVIG) are the most promising immunomodulatory preparations, prepared

TABLE 9.9: Indications for IVIG

Definite indications:

• Immunodeficiency states

- Congenital: X-linked hypogammaglobulinemia, SCID, WAS

- Acquired: AIDS (prophylaxis for recurrent bacterial infection)

• Autoimmune disorders

- Idiopathic thrombocytopenic purpura (ITP)

- Guillain-Barre syndrome

- Kawasaki disease

- Chronic demyelinating inflammatory polyneuropathy

Probable uses:

• Neonatal sepsis, specially in preterms

• Collagen disorders: Dermatomyositis, SLE

• Post-transplants: Prevention of OIs and GVHD

• Autoimmune hemolytic anemia

• Others: Myasthenia gravis, Graves' disease, etc.

SCID: Severe combined immunodeficiency; WAS: Wiskott-Aldrich syndrome; GVHD: Graft versus host disease; OIs: Opportunistic infections

from pooled plasma of at least 1000 donors, with specific WHO standards. For example, (a) at least 90% intact IgG with subclasses in normal ratio, (b) free from IgG aggregates and infectious agents, and (c) low IgA content, etc.

Uses: IVIG is used as: (a) replacement therapy in various immunodeficiency states and/ or (b) immunomodulatory agent in many clinical disorders (Table 9.9). However, their role in some of these conditions is still experimental.

• Direct neutralization of antigens, toxins and auto­antibodies,

• Structural changes and blockade of Fc receptors of autoantibodies in autoimmune disorders,

• Suppression of the synthesis of cytokines and auto antibodies and

• Other modulations in immunological network.

Adverse reactions with IVIG are rare (lt;5%) and usually mild, e.g. local flushing, chills and fever, etc., though fatal anaphylactic reactions have been reported in rare cases of selective IgA deficiency.

BIBLIOGRAPHY

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