Prasanna

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Immunodeficiency Diseases

Immunodeficiency results from the failure of one or more components of the immune system. Primary immune deficiencies are caused by genetic developmental defects. Secondary immune deficiencies arise due to various reasons like radiation, use of cytolytic and immunosuppressive drugs and infections. AIDS is an acronym for Acquired Immuno Deficiency Syndrome. It is the deficiency of immune system, acquired during the life time of an individual indicating that it is not a congenital disease. AIDS is caused by Human Immuno Deficiency Virus (HIV).

It selectively infects helper T cells. The infected helper T cells will not stimulate antibody production by B-cells resulting in loss of natural defence against viral infection. On the basis of genetic characteristics and differences in the viral antigens, HIV is classified into the types 1 and 2 (HIV-1, HIV-2).

Structure of HIV

The human immunodeficiency virus belongs to the genus Lentivirus. When observed under the electron microscope, HIV is seen as a spherical virus, 100-120 nm in diameter, containing a dense core surrounded by a lipoprotein envelope. The envelope has glycoprotein (gp) spikes termed gp 41 and gp 120. At the core, there are two large single stranded RNA. Attached to the RNA are molecules of reverse transcriptase.

It also contains enzymes like protease and ribonuclease. The core is covered by a capsid made of proteins. This is followed by another layer of matrix proteins as shown in the Fig 7.18.

HIV Transmission

The HIV is often located within the cells especially in macrophages. HIV can survive for 1.5 days inside a cell but only about 6 hours outside a cell. Routes of HIV transmission include unsafe sexual contact, blood-contaminated needles, organ transplants, blood transfusion and vertical transmission from HIV infected mother to child. HIV is not transmitted by insects or by casual contact.

After getting into the body of the person, the virus enters into macrophages where RNA genome of the virus replicates to form viral DNA with the help of the enzyme reverse transcriptase. This viral DNA gets incorporated into the DNA of host cells and directs the infected cells to produce viral particles.

The macrophages continue to produce virus and in this way acts like a HIV factory. Simultaneously, HIV enters into helper T-lymphocytes, replicates and produces progeny viruses. The progeny viruses released in the blood attack other helper T-lymphocytes.

This is repeated, leading to a progressive decrease in the number of helper T lymphocytes in the body of the infected person. During this period, the person suffers from bouts of fever, diarrhoea and weight loss. Due to decrease in the number of helper T lymphocytes, the person starts suffering from infections and becomes immune defiient and unable to protect against any infection.

A simple blood test is available that can determine whether the person has been infected with HIV. The ELISA test (Enzyme Linked ImmunoSorbent Assay) detects the presence of HIV antibodies. It is a preliminary test. Western blot test is more reliable and a confimatory test. It detects the viral core proteins.
If both tests detect the presence of the antibodies, the person is considered to be HIV positive.

AIDS has no cure. Prevention of AIDS is the best option. Advocating safe sex and promoting regular check-up, safe blood for transfusion, use of disposable needles, use of condoms during sexual contact, prevention of drug abuse, AIDS awareness programme by NACO (National AIDS Control Organisation), NGOs (Non Governmental Organisations) and WHO are to prevent the spreading of AIDS.

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Basic Concepts Of Immunology

Immunology is the study of immune system. This system protects an individual from various infective agents. It refers to all the mechanisms used by the body for protection from environmental agents that are foreign to the body.

When the immune system does not function efficiently in an individual, it leads to infection causing disease. The overall ability of body to fight against the disease causing pathogen is called immunity. It is also called disease resistance and the lack of immunity is known as susceptibility. Immunity is highly specific.

Normally many of the responses of the immune system initiate the destruction and elimination of invading organisms and any toxic molecules produced by them. These immune reactions are destructive in nature and are made in response only to molecules that are foreign to the host and not to those of host itself. This ability to distinguish foreign molecules from self is another fundamental feature of the immune system.

However, occasionally, it fails to make its distinction and reacts destructively against the host’s own molecules; such autoimmune diseases can be fatal to the organism. Almost all the macromolecules e.g. proteins, polysaccharides, nucleic acids, etc., as long as they are foreign to recipient organism can induce immune response. Any substance capable of eliciting immune response is called an ANTIGEN (ANTIbody GENerator). There are two broad classes of immunity responses namely, innate immunity and acquired immunity (Fig. 7.9).

Innate immunity

Innate immunity is the natural phenomenon of resistance to infection which an individual possesses right from the birth. The innate defense mechanisms are non-specific in the sense that they are effective against a wide range of potentially infectious agents. It is otherwise known as non-specifi immunity or natural immunity.

A number of innate defense mechanisms are operative non-specifially against a large number of microorganisms as shown in the Table 7.4 and Fig. 7.10.

Acquired immunity

The immunity that an individual acquires after birth is known as acquired immunity. It is the body’s resistance to a specific pathogen. The unique features of acquired immunity are antigenic specificity, diversity, recognition of self and non-self and immunological memory.

Components of acquired immunity

Acquired immunity has two components – cell mediated immunity (CMI) and antibody mediated immunity or humoral immunity.

1. Cell mediated immunity

When pathogens are destroyed by cells without producing antibodies, then it is known as cell mediated immune response or cell mediated immunity. This is brought about by T cells, macrophages and natural killer cells.

2. Antibody mediated immunity or humoral immunity

When pathogens are destroyed by the production of antibodies, then it is known as antibody mediated or humoral immunity. This is brought about by B cells with the help of antigen presenting cells and T helper cells. Antibody production is the characteristic feature of vertebrates only.

Types of acquired immunity

Acquired immunity may be active immunity or passive immunity (Table 7.5).

The immunological resistance developed by the organisms through the production of antibodies in their body is called active immunity. Active immunity is acquired through the use of a person’s immune responses, which lead to the development of memory cells. Active immunity results from an infection or an immunization.

Passive immunity does not require the body to produce antibodies to antigens. The antibodies are introduced from outside into the organism. This, passive immunity is acquired without the activation of a person’s immune response, and therefore there is no memory.

Immune responses

The immune responses may be primary or secondary (Table 7.6).

Primary immune response

The primary immune response occurs when a pathogen comes in contact with the immune system for the first time. During this, the immune system has to learn to recognize the antigen, produce antibody against it and eventually produce memory lymphocytes. The primary immune response is slow and short-lived.

Secondary immune response

The secondary immune response occurs when a person is exposed to the same antigen again. During this time, immunological memory has been established and the immune system can start producing antibodies immediately. Within hours after recognition of the antigen, a new army of plasma cells are generated. Within 2 to 3 days, the antibody concentration in the blood rises steeply to reach much higher level than primary response. This is also called as “booster response”.

Lymphoid organs

Immune system of an organism consists of several structurally and functionally different organs and tissues that are widely dispersed in the body. The organs involved in the origin, maturation and proliferation of lymphocytes are called lymphoid organs (Fig. 7.11).

Based on their functions, they are classified into primary or central lymphoid organs and secondary or peripheral lymphoid organs. The primary lymphoid organs provide appropriate environment for lymphocytic maturation. The secondary lymphoid organs trap antigens and make it available for mature lymphocytes, which can effectively fiht against these antigens.

Primary lymphoid organs

Bursa of Fabricius of birds, bone marrow and thymus gland of mammals constitute the primary lymphoid organs involved in the production and early selection of lymphocytes. These lymphocytes become dedicated to a particular antigenic specificity. Only when the lymphocytes mature in the primary lymphoidal organs, they become immunocompetent cells. In mammals, B cell maturation occurs in the bone marrow and T cells maturation occurs in the thymus.

Thymus

The thymus is a flat and bilobed organ located behind the sternun, above the heart. Each lobe of the thymus contains numerous lobules, separated from each other by connective tissue called septa. Each lobule is differentiated into two compartments, the outer compartment or outer cortex, is densely packed with immature T cells called thymocytes, whereas the inner compartment or medulla is sparsely populated with
mature thymocytes.

One of its main secretions is the hormone thymosin. It stimulates the T cell to become mature and immunocompetent. By the early teens, the thymus begins to atrophy and is replaced by adipose tissue (Fig. 7.12). Thus thymus is most active during the neonatal and pre-adolescent periods.

Bone marrow

Bone marrow is a lymphoid tissue found within the spongy portion of the bone. Bone marrow contains stem cells known as haematopoietic cells. These cells have the potential to multiply through cell division and either remain as stem cells or differentiate and mature into different kinds of blood cells.

Secondary or peripheral lymphoid organs

In secondary or peripheral lymphoid organs, antigen is localized so that it can be effectively exposed to mature lymphocytes. The best examples are lymph nodes, appendix, Peyer’s patches of gastrointestinal tract, tonsils, adenoids, spleen, MALT (Mucosal-Associated Lymphoid Tissue), GALT (Gut-Associated Lymphoid Tissue), BALT (Bronchial/Tracheal-Associated Lymphoid Tissue).

Lymph node

Lymph node is a small bean-shaped structure and is part of the body’s immune system. It is the first one to encounter the antigen that enters the tissue spaces. Lymph nodes filter and trap substances that travel through the lymphatic fluid. They are packed tightly with white blood cells, namely lymphocytes and macrophages. There are hundreds of lymph nodes found throughout the body.

They are connected to one another by lymph vessels. Lymph is a clear, transparent, colourless, mobile and extracellular fluid connective tissue. As the lymph percolates through the lymph node, the particulate antigen brought in by the lymph will be trapped by the phagocytic cells, follicular and interdigitating dendritic cells.

Lymph node has three zones (Fig. 7.13). They are the cortex, paracortex and medulla. The outer most layer of the lymph node is called cortex, which consists of B-lymphocytes, macrophages, and follicular dendritic cells. The paracortex zone is beneath the cortex, which is richly populated by T lymphocytes and interdigitating dendritic cells. The inner most zone is called the medulla which is sparsely populated by lymphocytes, but many of them are plasma cells, which actively secrete antibody molecules.

As the lymph enters, it slowly percolates through the cortex, paracortex and medulla, giving sufficient chance for the phagocytic cells and dendritic cells to trap the antigen brought by the lymph. The lymph leaving a node carries enriched antibodies secreted by the medullary plasma cells against the antigens that enter the lymph node. Sometimes visible swelling of lymph nodes occurs due to active immune response and increased concentration of lymphocytes.

This swollen lymph nodes may signal an infection. There are several groups of lymph nodes. The most frequently enlarged lymph nodes are found in the neck, under the chin, in the armpits and in the groin.

Cells of the immune system

The immune system is composed of many interdependent cells that protect the body from microbial infections and the growth of tumour cells. The cellular composition of adult human blood is given in Table 7.7.

All these cells are derived from pluripotent haematopoetic stem cells. Each stem cell has the capacity to produce RBC, WBC and platelets. The only cells capable of specifially recognising and producing an immune response are the lymphocytes. The other types of white blood cells play an important role in non specific immune response, antigen presentation and cytokine production.

Lymphocytes

About 20-30% of the white blood cells are lymphocytes. They have a large nucleus filling most of the cell, surrounded by a little cytoplasm. The two main types of lymphocytes are B and T lymphocytes. Both these are produced in the bone marrow. B lymphocytes (B cells) stay in the bone marrow until they are mature. Then they circulate around the body. Some remain in the blood, while others accumulate in the lymph
nodes and spleen. T lymphocytes leave the bone marrow and mature in the thymus gland.

Once mature, T cells also accumulate in the same areas of the body as B cells. Lymphocytes have receptor proteins on their surface. When receptors on a B cell bind with an antigen, the B cell becomes activated and divides rapidly to produce plasma cells. The plasma cells produce antibodies. Some B cells do not produce antibodies but become memory cells. These cells are responsible for secondary immune response. T lymphocytes do not produce antibodies. Thy recognize antigenpresenting cells and destroy them.

The two important types of T cells are Helper T cells and Killer T cells. Helper T cells release a chemical called cytokine which activates B cells. Killer cells move around the body and destroy cells which are damaged or infected (Fig. 7.14).

Apart from these cells neutrophils and monocytes destroy foreign cells by phagocytosis. Monocytes when they mature into large cells, they are called macrophages which perform phagocytosis on any foreign organism.

Antigens

The term antigen (Ag) is used in two senses, the first to describe a molecule which generates an immune response and the second, a molecule which reacts with antibodies. In general antigens are large, complex molecular substances that can induce a detectable immune response. This an antigen is a substance that is specific to an antibody or a T-cell receptor and is often used as a synonym for immunogen.

An immunogen is a substance capable of initiating an immune response. Haptens are substance that are non-immunogenic but can react with the products of a specific immune response. Substances that can enhance the immune response to an antigen are called adjuvants. Epitope is an antigenic determinant and is the active part of an antigen. A paratope is the antigen – binding site and is a part of an antibody which
recognizes and binds to an antigen.

Types of antigens

On the basis of origin, antigens are classified into exogenous antigens and endogenous antigens. The antigens which enter the host from the outside in the form of microorganisms, pollens, drugs, or pollutants are called exogenous antigens. The antigens which are formed within the individual are endogenous antigens. The best examples are blood group antigens.

Antibodies

Antibodies are immunoglobulin (Ig) protein molecules synthesized on exposure to antigen that can combine specifically with the antigen. Whenever pathogens enter our body, the B-lymphocytes produce an army of proteins called antibodies to fight with them. Thus, they are secreted in response to an antigen (Ag) by the effect of B cells called plasma cells. The antibodies are classified into five major categories, based on their physiological and biochemical properties. They are IgG (gamma), IgM (mu), IgA (alpha), IgD (delta) and IgE (epsilon).

In the 1950s, experiments by Porter and Edelman revealed the basic structure of the immunoglobulin. An antibody molecule is Y shaped
structure that comprises of four polypeptide chains, two identical light chains (L) of molecular weight 25,000 Da (approximately 214 amino acids) and
two identical heavy chains (H) of molecular weight 50,000 Da (approximately 450 amino acids).

The polypeptide chains are linked together by di-sulphide (S-S) bonds. One light chain is attached to each heavy chain and two heavy chains are attached to each other to form a Y shaped (Fig. 7.15) structure. Hence, an antibody is represented by H₂ L₂. The heavy chains have a flexible hinge region at their approximate middles.

Each chain (L and H) has two terminals. They are C – terminal (Carboxyl) and amino or N-terminal. Each chain (L and H) has two regions. They have variable (V) region at one end and a much larger constant (C) region at the other end. Antibodies responding to different antigens have very different (V) regions but their (C) regions are the same in all antibodies.

In each arm of the monomer antibody, the (V) regions of the heavy and light chains combines to form an antigen – binding site shaped to ‘fit’ a specific antigenic determinant. Consequently each antibody monomer has two such antigen – binding regions. The (C) regions that forms the stem of the antibody monomer determine the antibody class and serve common functions in all antibodies. The functions of immunoglobulin are agglutination, precipitation, opsonisation, neutralization etc.,

Antigen – antibody interaction

The reaction between an antigen and antibody is the basis for humoral immunity or antibody mediated immunity. The reaction between antigen and antibody occurs in three stages. During the first stage, the reaction involves the formation of antigen – antibody complex. The next stage leads to visible events like precipitation, agglutination, etc., The final stage includes destruction of antigen or its neutralization (Fig. 7.16).

Binding force of antigen – antibody reaction

The binding force between antigen and antibody is due to three factors. They are closeness between antigen and antibody, noncovalent bonds or intermolecular forces and affinity of antibody.

When antigen and antibody are closely fitted, the strength of binding is great. When they are apart binding strength is low. The bonds that hold the antigen to the antibody combining site are all non-covalent in nature. These include hydrogen bonds, electrostatic bonds, Van der Waals forces and hydrophobic bonds. Antibody affinity is the strength of the reaction between a single antigenic determinant and a single combining site on the antibody.

The chiefapplication of antigen – antibody reactions are to determine blood groups for transfusion, to study serological ascertainment of exposure to infectious agents, to develop immunoassays for the quantification of various substances, to detect the presence or absence of protein in serum and to determine the characteristics of certain immunodeficiency diseases.

Different types of antigen and antibody reactions

The reaction between soluble antigen and antibody leads to visible precipitate formation, which is called precipitin reaction. Antibodies that bring about precipitate formation on reacting with antigens are called as precipitins.

Whenever a particulate antigen interacts with its antibody, it would result in clumping or agglutination of the particulate antigen, which is called agglutination reaction. The antibody involved in bringing about agglutination reaction is called agglutinin.

Opsonisation or enhanced attachment is the process by which a pathogen is marked of ingestion and destruction by a phagocyte. Opsonisation involves the binding of an opsonin i.e., antibody, to a receptor on the pathogen’s cell membrane.

After opsonin binds to the membrane, phagocytes are attracted to the pathogen. So, opsonisation is a process in which pathogens are coated with a substance called an opsonin, marking the pathogen out for destruction by the immune system. This results in a much more efficient phagocytosis.

The neutralization reactions are the reactions of antigen-antibody that involve the elimination of harmful effects of bacterial exotoxins or a virus by specific antibodies. These neutralizing substances i.e., antibodies are known as antitoxins. This specific antibody is produced by a host cell in response to a bacterial exotoxin or corresponding toxoid (inactivated toxin).

Vaccines

A vaccine is a biological preparation that provides active acquired immunity to a particular disease and resembles a disease-causing microorganism and is often made from weakened or attenuated or killed forms of the microbes, their toxins, or one of its surface proteins.

Vaccines “teach” our body how to defend itself when viruses or bacteria, invade it. Vaccines deliver only very little amounts of inactivated or weakened viruses or bacteria, or parts of them. This allows the immune system to recognize the organism without actually experiencing the disease. Some vaccines need to be given more than once (i.e., a ‘booster’ vaccination) to make sure the immune system can overcome a real infection in the future.

Vaccine initiates the immunization process. The vaccines are classified as first, second and third generation vaccines. First generation vaccine is further subdivided into live attenuated vaccine, killed vaccine and toxoids (Fig. 7.17). Live attenuated vaccines use the weakened (attenuated), aged, less virulent form of the virus. E.g. Measles, mumps and rubella (MMR) vaccine and the Varicella (chickenpox) vaccine, Killed (inactivated) vaccines are killed or inactivated by heat and other methods. E.g. Salk’s polio vaccine.

Toxoid vaccines contain a toxin or chemical secreted by the bacteria or virus. They make us immune to the harmful effects of the infection, instead of to the infection itself. E.g. DPT vaccine (Diphtheria, Pertussis and Tetanus).

Second generation vaccine contains the pure surface antigen of the pathogen. E.g.Hepatitis-B vaccine. Third generation vaccine contains the purest and the highest potency vaccines which are synthetic in generation. The latest revolution in vaccine is DNA vaccine or recombinant vaccine (Refer Chapter- 9 for details).

Vaccination and immunization

“Vaccination is the process of administrating a vaccine into the body or the act of introducing a vaccine into the body to produce immunity to a specific disease.” Immunization is the process of the body building up immunity to a particular disease.

Immunization describes the actual changes in the body after receiving a vaccine. Vaccines work by fighting the pathogen and then recording it in their memory system to ensure that the next time this pathogen enters the body, it is eliminated far quickly. Once, the body is able to fight against the disease, it is believed to have built the immunity for it, also known as the body being immunized against the disease.

Hypersensitivity

Some of the individuals are very sensitive to some particles present in the environment. The exaggerated response of the immune system to certain antigens present in the environment is called allergy (allo-altered, erg-reaction). The substances to which such an immune response is produced are called allergens. An allergen is an antigen that causes an allergic reaction. Allergic reactions begin within few seconds after the contact with the allergen and last about half an hour.

The common examples of allergens are mites in dust, pollens and some proteins in insect venom. Hay fever and asthma are some common examples of allergy. Symptoms of allergic reactions include sneezing, watery eyes, running nose and difficulty in breathing.

Allergy is a form of over active immune response mediated by IgE and mast cells. It can also be due to the release of chemicals like histamine and serotonin from the mast cells. Anaphylaxis is the classical immediate hypersensitivity reaction. It is a sudden, systematic, severe and immediate hypersensitivity reaction occurring as a result of rapid generalized mast-cell degranulation.

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Maintenance Of Personal And Public Hygiene

Hygiene is a set of practices performed to conserve good health. According to the World Health Organization (WHO), hygiene refers to “conditions and practices that help to maintain health and prevent the spread of diseases.”

Personal hygiene refers to maintaining one’s body clean by bathing, washing hands, trimming fingernails, wearing clean clothes and also includes attention to keeping surfaces in the home and workplace, including toilets, bathroom facilities, clean and pathogen-free.

Our public places teem with infection, contamination and germs. It seems that every surface we touch and the air we breathe are with pollutants and microbes. It’s not just the public places that are unclean, but we might be amazed at the number of people who do not wash their hands before taking food, after visiting the restroom, or who sneeze without covering their faces. Many infectious diseases such as typhoid, amoebiasis and ascariasis are transmitted through contaminated food and water.

Advancement in science and technology provide effective controlling measures for many infectious and non-infectious diseases. The use of vaccines and adopted immunization programmes have helped to eradicate small pox in India. Moreover a large number of infectious diseases like polio, diphtheria, pneumonia and tetanus have been controlled by the use of vaccines and by creating awareness among the people.

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Common Diseases In Human Beings

Disease can be defined as a disorder or malfunction of the mind or body. It involves morphological, physiological and psychological disturbances which may be due to environmental factors or pathogens or genetic anomalies or life style changes. Diseases can be broadly grouped into infectious and non infectious types.

Diseases which are transmitted from one person to another are called infectious diseases or communicable diseases. Such disease causing organisms are called pathogens and are transmitted through air, water, food, physical contact and vectors.

The disease causing pathogen may be virus, bacteria, fungi, protozoan parasites, helminthic parasites, etc., Infectious diseases are common and everyone suffers from such diseases at some time or the other. Most of the bacterial diseases are curable but all viral diseases are not. Some infectious disease like AIDS may be fatal.

Non-infectious diseases are not transmitted from an infected person to a healthy person. In origin they may be genetic (cystic fibrosis), nutritional (vitamin deficiency diseases) and degenerative (arthritis, heart attack, stroke). Among non – infectious diseases, cancer is one of the major causes of death.

Bacterial and viral diseases

Bacterial diseases

Though the number of bacterial species is very high, only a few bacteria are associated with human diseases and are called pathogenic bacteria. Such pathogens may emit toxins and affects the body. Common pathogenic bacteria and the bacterial diseases are given in table 7.1.

Bacteria spread through air, water or by inhaling the droplets/aerosols or even by sharing utensils, dresses with an infected person. Typhoid fever can be confirmed by Widal test.

Viral diseases

Viruses are the smallest intracellular obligate parasites, which multiply within living cells. Outside the living cells they cannot carry out the characteristics of a living organism. Viruses invade living cells, forcing the cells to create new viruses. The new viruses break out of the cell, killing it and invade other cells in the body, causing diseases in human beings. Rhino viruses cause one of the most infectious human ailment called the “Common cold”.

Viral diseases are generally grouped into four types on the basis of the symptoms produced in the body organs.

• Pneumotropic diseases (respiratory tract infected by influenza)
• Dermotropic diseases (skin and subcutaneous tissues affected by chicken pox and measles)
• Viscerotropic diseases (blood and visceral organs affcted by yellow fever and dengue fever)
• Neurotropic diseases (central nervous system affcted by rabies and polio).

Some common viral diseases of human beings are given in table 7.2.

Protozoan diseases

About 15 genera of protozoans live as parasites within the human body and cause diseases. Amoebiasis also called amoebic dysentery or amoebic colitis is caused by Entamoeba histolytica, which lives in the human large intestine and feeds on mucus and bacteria (Fig. 7.1).

Infective stage of this parasite is the trophozoite, which penetrates the walls of the host intestine (colon) and secretes histolytic enzymes causing ulceration, bleeding, abdominal pain and stools with excess mucus. Symptoms of amoebiasis can range from diarrhoea to dysentery with blood and mucus in the stool. House flies (Musca domestica) acts as a carrier for transmitting the parasite from contaminated faeces and water.

African sleeping sickness is caused by Trypanosoma species. Trypanosoma is generally transmitted by the blood sucking Tsetse flies. Three species of Trypanosoma cause sleeping sickness in man.

1. T. gambiense is transmitted by Glossina palpalis (Tsetse fly) and causes Gambian or Central African sleeping sickness (Fig. 7.2).

2. T. rhodesiense is transmitted by Glossina morsitans causing Rhodesian or East African sleeping sickness.

3. T. cruzi is transmitted by a bug called Triatoma megista and causes Chagas disease or American trypanosomiasis.

Kala – azar or visceral leishmaniasis is caused by Leishmania donovani, which is transmitted by the vector Phlebotomus (sand fly). Infection may occur in the endothelial cells, bone marrow, liver, lymph glands and blood vessels of the spleen. Symptoms of Kala azar are weight loss, anaemia, fever, enlargement of spleen and liver.

Malaria is caused by different types of Plasmodium species such as P. vivax, P. ovale, P. malariae and P. falciparum (Table 7.3). Plasmodium lives in the RBC of human in its mature condition it is called as trophozoite. It is transmited from one person to another by the bite of the infected female Anopheles mosquito.

Life cycle of Plasmodium

Plasmodium vivax is a digenic parasite, involving two hosts, man as the secondary host and female Anopheles mosquito as the primary host. The life cycle of Plasmodium involves three phases namely schizogony, gamogony and sporogony (Fig. 7.3).

The parasite first enters the human blood stream through the bite of an infected female Anopheles mosquito. As it feeds, the mosquito injects the saliva containing the sporozoites. The sporozoite within the blood stream immediately enters the hepatic cells of the liver. Further in the liver they undergo multiple asexual fission (schizogony) and produce merozoites. After being released from liver cells, the merozoites penetrate the RBC’s.

Inside the RBC, the merozoite begins to develop as unicellular trophozoites. The trophozoite grows in size and a central vacuole develops pushing them to one side of cytoplasm and becomes the signet ring stage. The trophozoite nucleus then divides asexually to produce the schizont. The large schizont shows yellowish – brown pigmented granules called Schuffers granules. The schizont divides and produces mononucleated merozoites.

Eventually the erythrocyte lyses, releasing the merozoites and haemozoin toxin into the blood stream to infect other erythrocytes. Lysis of red blood cells results in cycles of fever and other symptoms. This erythrocytic stage is cyclic and repeats itself approximately every 48 to 72 hours or longer depending on the species of Plasmodium involved. The sudden release of merozoites triggers an attack on the RBCs.

Occasionally, merozoites diffrentiate into macrogametocytes and microgametocytes. When these are ingested by a mosquito, they develop into male and female gametes respectively.

In the mosquito’s gut, the infected erythrocytes lyse and male and female gametes fertilize to form a diploid zygote called ookinete. The ookinete migrates to the mosquito’s gut wall and develop into an oocyte. The oocyte undergoes meiosis by a process called sporogony to form sporozoites. These sporozoites migrate to the salivary glands of the mosquito. The cycle is now completed and when the mosquito bites another human host, the sporozoites are injected and the cycle begins a new.

The pathological changes caused by malaria, affects not only the erythrocytes but also the spleen and other visceral organs. Incubation period of malaria is about 12 days.

The early symptoms of malaria are headache, nausea and muscular pain. The classic symptoms first develop with the synchronized release of merozoites, haemozoin toxin and erythrocyte debris into the blood stream resulting in malarial paroxysms – shivering chills, high fever followed by sweating. Fever and chills are caused partly by malarial toxins that induce macrophages to release tumour necrosis factor (TNF-α) and interleukin.

Prevention

It is possible to break the transmission cycle by killing the insect vector. Mosquitoes lay their eggs in water. Larvae hatch and develop in water but breathe air by moving to the surface. Oil can be sprayed over the water surface, to make it impossible for mosquito larvae and pupae to breathe.

Ponds, drainage ditches and other permanent bodies of water can be stocked with fishes such as Gambusia which feed on mosquito larvae. Preparations containing Bacillus thuringiensis can be sprayed to kill the mosquito larvae since it is not toxic to other forms of life. The best protection against malaria is to avoid being bitten by mosquito. People are advised to use mosquito nets, wire gauging of windows and doors to prevent mosquito bites.

In the 1950’s the World Health Organisation (WHO) introduced the Malaria eradication programme. This programme was not successful due to the resistance of Plasmodium to the drugs used to treat it and resistance of mosquitoes to DDT and other insecticides.

Fungal diseases

Fungi was recognized as a causative agent of human diseases much earlier than bacteria. Dermatomycosis is a cutaneous infection caused by fungi belonging to the genera Trichophyton, Microsporum and Epidermophyton.

Ringworm is one of the most common fungal disease in humans (Fig. 7.4). Appearance of dry, scaly lesions on the skin, nails and scalp are the main symptoms of the disease. Heat and moisture help these fungi to grow and makes them to thrive in skin folds such as those in the groin or between the toes. Ringworms of the feet is known as Athlete’s foot caused by Tinea pedis (Fig. 7.5). Ringworms are generally acquired from soil or by using clothes, towels and comb used by infected persons.

Helminthic diseases

Helminthes are mostly endoparasitic in the gut and blood of human beings and cause diseases called helminthiasis. The two most prevalent helminthic diseases are Ascariasis and Filariasis.

Ascaris is a monogenic parasite and exhibits sexual dimorphism. Ascariasis is a disease caused by the intestinal endoparasite Ascaris lumbricoides commonly called the round worms (Fig. 7.6). It is transmitted through ingestion of embryonated eggs through contaminated food and water.

Children playing in contaminated soils are also prone to have a chance of transfer of eggs from hand to mouth. The symptoms of the disease are abdominal pain, vomiting, headache, anaemia, irritability and diarrhoea. A heavy infection can cause nutritional deficiency and severe abdominal pain and causes stunted growth in children. It may also cause enteritis, hepatitis and bronchitis.

Filariasis is caused by Wuchereria bancroft, commonly called fiarial worm. It is found in the lymph vessels and lymph nodes of man (Fig. 7.7). Wuchereria bancroft is sexually dimorphic, viviparous and digenic. The life cycle is completed in two hosts, man and the female Culex mosquito The female fiarial worm gives rise to juveniles called microfiariae larvae.

In the lymph glands, the juveniles develop into adults. The accumulation of the worms block the lymphatic system resulting in inflammation of the lymph nodes. In some cases, the obstruction of lymph vessels causes elephantiasis or fiariasis of the limbs, scrotum and mammary glands (Fig. 7.8).

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Origin And Evolution Of Man

Mammals evolved in the early Jurassic period, about 210 million years ago (mya). Hominid evolution occurred in Asia and Africa. Hominids proved that human beings are superior to other animals and efficient in making tools and culture.

The earliest fossils of the prehistoric man like Ramapithecus and Sivapithecus lived some 14 mya and were derived from ape like Dryopithecus. Dryopithecus and Ramapithecus were hairy and walked like gorillas and chimpanzees. Ramapithecus is regarded as a possible ancester of Australopithecus and therefore of modern humans. They were vegetarians (Fig 6.10).

Australopithecus lived in East African grasslands about 5 mya and was called the Australian ape man. He was about 1.5 meters tall with bipedal locomotion, omnivorous, semi erect, and lived in caves. Low forehead, brow ridges over the eyes, protruding face, lack of chin, low brain capacity of about 350 – 450 cc, human like dentition, lumbar curve in the vertebral column were his distinguishing features.

Homo habilis lived about 2 mya. Their brain capacity was between 650 – 800cc, and was probably vegetarian. They had bipedal locomotion and used tools made of chipped stones.

Homo erectus the fist human like being was around 1.7 mya and was much closer to human in looks, skull was flitter and thicker than the modern man and had a large brain capacity of around 900 cc. Homo erectus probably ate meat Homo ergaster and Homo erectus were the first to leave Africa.

Neanderthal human was found in Neander Valley, Germany with a brain size of 1400 cc and lived between 34,000 – 1,00,000 years ago. They differ from the modern human in having semierect posture, flat cranium, sloping forehead, thin large orbits, heavy brow ridges, protruding jaws and no chin. They used animal hides to protect their bodies, knew the use of fie and buried their dead. They did not practice agriculture and animal domestication.

Cro-Magnon was one of the most talked forms of modern human found from the rocks of Cro-Magnon, France and is considered as the ancestor of modern Europeans. They were not only adapted to various environmental conditions, but were also known for their cave paintings, failures on flours and walls. Homo sapiens or modern human arose in Africa some 25,000 years ago and moved to other continents and developed into distinct races. They had a brain capacity of 1300 – 1600 cc. They started cultivating crops and domesticating animals.