Vaccination & Immunisation

Vaccine

A vaccine is a preparation containing whole inactivated pathogens, live attenuated organisms, or antigenic components (proteins, toxoids, polysaccharides or recombinant antigens) of a pathogen, administered orally or by injection to induce protective immunity against that pathogen.

Vaccine

History of Vaccination

• Edward Jenner (1796): Jenner observed that milkmaids who had previously had cowpox were generally protected from smallpox. In 1796 he transferred material from a cowpox sore on a milkmaid to an eight-year-old boy and later exposed the boy to smallpox; the boy did not develop smallpox. Jenner termed this practice vaccination.
• Louis Pasteur: Demonstrated attenuation and inactivation methods for microbes and developed vaccines for anthrax, chicken cholera and rabies.

Principle of Vaccination

Vaccination works on the basis of the immunological memory. When antigenic material is introduced into a healthy person, it elicits a primary immune response during which specific antibodies and memory lymphocytes (memory B cells and T cells) are produced. On subsequent exposure to the same pathogen, these memory cells rapidly recognise the antigen and mount a strong secondary immune response with quick production of antibodies and effector lymphocytes. This rapid, amplified response eradicates the pathogen before disease develops, rendering the person immune or highly resistant to that infection.

Types of Vaccines

• Live attenuated vaccines - contain weakened but replicating organisms (examples: BCG, oral polio vaccine [OPV], smallpox, some influenza vaccines).
• Killed (inactivated) vaccines - contain whole organisms rendered non-infectious (examples: Salk polio, killed typhoid, killed cholera, rabies, plague).
• Toxoid vaccines - contain inactivated bacterial toxins that induce neutralising antibodies (examples: diphtheria toxoid, tetanus toxoid).
• Combination vaccines - include antigens for several diseases in one preparation (examples: DPT - diphtheria, pertussis, tetanus; MMR - measles, mumps, rubella).

Active versus Passive Immunization

• Active immunization - induction of an immune response by administering antigen (vaccine); results in memory cell formation and long-term protection.
• Passive immunization - transfer of preformed antibodies (for example, antitoxin serum); provides immediate but short-term protection without memory formation.

Immune System Disorders

Abnormal or inappropriate immune responses can lead to three broad classes of disorders: (1) hypersensitivity (allergic) disorders, (2) autoimmune disorders, and (3) immunodeficiency disorders.

1. Hypersensitivity (Allergic) Disorders

Hypersensitivity is an exaggerated or inappropriate immune response to normally harmless antigens (allergens). Common allergens include pollen, certain foods (eggs, fish), medications (penicillin), dust, insect venom, cold, heat, sunlight and some fibres.

Mechanism: many allergic responses involve increased production of IgE antibodies and degranulation of mast cells with release of mediators such as histamine, causing local or systemic symptoms.

Common manifestations

• Bronchial asthma - allergic inflammation and spasm of bronchial smooth muscle, increased mucus secretion and narrowed airways leading to coughing and difficulty in breathing, especially during expiration (wheezing).
• Hay fever - allergic rhinitis with watery eyes and nasal mucosal hypersecretion, commonly in response to pollen.
• Urticaria (hives) - raised, itchy, pinkish skin wheals.
• Eczema (dermatitis) - redness, vesicle formation, scaling and itching of the skin.
• Anaphylactic shock - a severe, generalized allergic reaction following systemic entry of an allergen (for example, penicillin, insect sting) causing widespread mast cell degranulation, vasodilation, increased vascular permeability, fluid loss into tissues, fall in blood pressure and potentially fatal circulatory collapse.

Prevention and treatment

• Avoid exposure to known allergens wherever possible.
• Hyposensitisation (desensitisation) - controlled exposure to small doses of allergen to reduce sensitivity.
• Pharmacological therapy - antihistamines, bronchodilators, inhaled corticosteroids for asthma, topical agents for dermatitis; epinephrine injection for anaphylaxis.
• Treat secondary infections with appropriate antibiotics when required.

2. Autoimmune Disorders

Autoimmunity arises when the immune system fails to distinguish self from non-self and produces antibodies or T cells that attack the body's own tissues. Examples include:

• Myasthenia gravis - autoantibodies against acetylcholine receptors at the neuromuscular junction lead to impaired nerve transmission and progressive muscle weakness.
• Pernicious (destructive) anaemia - autoantibodies against intrinsic factor (produced by stomach parietal cells) reduce vitamin B12 absorption and lead to defective RBC production.
• Hashimoto's disease - autoimmune destruction of the thyroid gland causing hypothyroidism.
• Rheumatoid arthritis - presence of rheumatoid factor (an IgM autoantibody) and chronic inflammation of the synovial membrane, leading to pannus formation, cartilage erosion and joint deformity; treatments include anti-inflammatory drugs, physiotherapy and joint replacement in severe cases.

3. Immunodeficiency Disorders

Immunodeficiencies arise from genetic defects, infections, malnutrition or medical treatments and result in increased susceptibility to infections.

• Severe combined immunodeficiency (SCID) - often due to adenosine deaminase deficiency; profound deficiency of both T and B lymphocytes; affected infants have very severe, recurrent infections; gene therapy has been used experimentally and in some clinical settings.
• AIDS (Acquired Immunodeficiency Syndrome) - caused by human immunodeficiency virus (HIV), which infects and destroys T-helper (CD4+) cells. CD4+ counts fall from a normal of about 950/mm3 to below 200/mm3 in advanced disease, leading to opportunistic infections and malignancies.

Selected Genetic and Metabolic Disorders

The following are important genetic or metabolic disorders commonly discussed at the school and undergraduate level.

• Phenylketonuria (PKU) - due to deficiency of the enzyme phenylalanine hydroxylase. Phenylalanine accumulates and is converted to phenylpyruvic acid which accumulates in the brain and causes intellectual disability if untreated. Early dietary restriction of phenylalanine can prevent neurological damage.
• Albinism - deficiency of the enzyme tyrosinase results in decreased melanin synthesis; affected individuals have reduced pigmentation of skin, hair and iris and increased sensitivity to ultraviolet radiation.
• Thalassaemia - inherited disorders of haemoglobin synthesis. Frame-shift or other mutations affect α- or β-globin gene production (α genes on chromosome 16, β genes on chromosome 11). Deficient globin chains cause faulty haemoglobin, red cell deformity and haemolytic anaemia. Management includes blood transfusions and, in some cases, bone marrow transplantation.
• Sickle cell anaemia - a point mutation in the β-globin gene (on chromosome 11) substitutes valine for glutamic acid at the sixth position of the β chain. This produces haemoglobin S (HbS); RBCs become sickle-shaped under low oxygen, undergo haemolysis and cause vaso-occlusive complications. Individuals with sickle cell trait or disease have relative resistance to falciparum malaria.