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Principles Of Immunology
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1.Immunology
From Wikipedia, the free encyclopedia
Immunology is a branch of biomedical science that covers the study of all aspects of the immune system in
all organisms.1 It deals with the physiological functioning of the immune system in states of both health and
diseases; malfunctions of the immune system in immunological disorders (autoimmune
diseases, hypersensitivities, immune deficiency, transplant rejection); the physical, chemical and physiological
characteristics of the components of the immune system in vitro, in situ, and in vivo. Immunology has
applications in several disciplines of science, and as such is further divided.
Even before the concept of immunity (from immunis, Latin for "exempt") was developed, numerous early
physicians characterized organs that would later prove to be part of the immune system. The key primary
lymphoid organs of the immune system are the thymus and bone marrow, and secondary lymphatic tissues
such as spleen, tonsils, lymph vessels, lymph nodes, adenoids, andskin and liver. When health conditions
warrant, immune system organs including the thymus, spleen, portions of bone marrow, lymph nodes and
secondary lymphatic tissues can be surgicallyexcised for examination while patients are still alive.
Many components of the immune system are actually cellular in nature and not associated with any specific
organ but rather are embedded or circulating in various tissues located throughout the body.
Classical immunology source |
Classical immunology ties in with the fields of epidemiology and medicine. It studies the relationship between
the body systems, pathogens, and immunity. The earliest written mention of immunity can be traced back to
the plague of Athens in 430 BCE. Thucydides noted that people who had recovered from a previous bout of the
disease could nurse the sick without contracting the illness a second time. Many other ancient societies have
references to this phenomenon, but it was not until the 19th and 20th centuries before the concept developed
into scientific theory.
The study of the molecular and cellular components that comprise the immune system, including their function
and interaction, is the central science of immunology. The immune system has been divided into a more
primitive innate immune system, and acquired or adaptive immune system of vertebrates, the latter of which is
further divided into humoral and cellular components.
The humoral (antibody) response is defined as the interaction between antibodies and antigens. Antibodies are
specific proteins released from a certain class of immune cells (B lymphocytes). Antigens are defined as
anything that elicits generation of antibodies, hence they are Antibody Generators. Immunology itself rests on
an understanding of the properties of these two biological entities. However, equally important is the cellular
response, which can not only kill infected cells in its own right, but is also crucial in controlling the antibody
response. Put simply, both systems are highly interdependent.
In the 21st century, immunology has broadened its horizons with much research being performed in the more
specialized niches of immunology. This includes the immunological function of cells, organs and systems not
normally associated with the immune system, as well as the function of the immune system outside classical
models of immunity (Yemeserach 2010).
Clinical immunology source |
Clinical immunology is the study of diseases caused by disorders of the immune system (failure, aberrant
action, and malignant growth of the cellular elements of the system). It also involves diseases of other systems,
where immune reactions play a part in the pathology and clinical features.
The diseases caused by disorders of the immune system fall into two broad categories: immunodeficiency, in
which parts of the immune system fail to provide an adequate response (examples include chronic
granulomatous disease), and autoimmunity, in which the immune system attacks its own host's body
(examples include systemic lupus erythematosus, rheumatoid arthritis,Hashimoto's disease and myasthenia
gravis). Other immune system disorders include different hypersensitivities, in which the system responds
inappropriately to harmless compounds (asthmaand other allergies) or responds too intensely.
The most well-known disease that affects the immune system itself is AIDS, caused by HIV. AIDS is an
immunodeficiency characterized by the lack of CD4+ ("helper") T cells, dendritic cells andmacrophages, which
are destroyed by HIV.
Clinical immunologists also study ways to prevent transplant rejection, in which the immune system attempts to
destroy allografts.
Developmental immunology source |
The body’s capability to react to antigen depends on a person's age, antigen type, maternal factors and the
area where the antigen is presented.2 Neonates are said to be in a state of physiological immunodeficiency,
because both their innate and adaptive immunological responses are greatly suppressed. Once born, a child’s
immune system responds favorably to protein antigens while not as well to glycoproteins and polysaccharides.
In fact, many of the infections acquired by neonates are caused by low virulence organisms
like Staphylococcus andPseudomonas. In neonates, opsonic activity and the ability to activate the complement
cascade is very limited. For example, the mean level of C3 in a newborn is approximately 65% of that found in
the adult. Phagocytic activity is also greatly impaired in newborns. This is due to lower opsonic activity, as well
as diminished up-regulation of integrin and selectin receptors, which limit the ability of neutrophils to interact
with adhesion molecules in the endothelium. Their monocytes are slow and have a reduced ATP production,
which also limits the newborns phagocytic activity. Although, the number of total lymphocytes is significantly
higher than in adults, the cellular and humoral immunity is also impaired. Antigen presenting cells in newborns
have a reduced capability to activate T cells. Also, T cells of a newborn proliferate poorly and produce very
small amounts of cytokines like IL-2, IL-4, IL-5, IL-12, and IFN-g which limits their capacity to activate the
humoral response as well as the phagocitic activity of macrophage. B cells develop early in gestation but are
not fully active.3
Maternal factors also play a role in the body’s immune response. At birth most of the immunoglobulin is present
is maternal IgG. Because IgM, IgD, IgE and IgA don’t cross the placenta, they are almost undetectable at birth.
Although some IgA is provided in breast milk. These passively acquired antibodies can protect the newborn up
to 18 months, but their response is usually short-lived and of low affinity.3 These antibodies can also produce a
negative response. If a child is exposed to the antibody for a particular antigen before being exposed to the
antigen itself then the child will produce a dampened response. Passively acquired maternal antibodies can
suppress the antibody response to active immunization. Similarly the response of T-cells to vaccination differs
in children compared to adults, and vaccines that induce Th1 responses in adults do not readily elicit these
same responses in neonates.3 By 6–9 months after birth, a child’s immune system begins to respond more
strongly to glycoproteins. Not until 12–24 months of age is there a marked improvement in the body’s response
to polysaccharides. This can be the reason for the specific time frames found in vaccination schedules. 45
During adolescence the human body undergoes several physical, physiological and immunological changes.
These changes are started and mediated by different hormones. Depending on the sex
either testosterone or 17-β-oestradiol, act on male and female bodies accordingly, start acting at ages of 12
and 10 years.6
There is evidence that these steroids act directly not only on the primary and secondary sexual characteristics,
but also have an effect on the development and regulation of the immune system.7
There is an increased risk in developing autoimmunity for pubescent and post pubescent females and
males.8 There is also some evidence that cell surface receptors on B cells and macrophages may detect sex
hormones in the system.9
The female sex hormone 17-β-oestradiol has been shown to regulate the level of immunological
response.10 Similarly, some male androgens, like testosterone, seem to suppress the stress response to
infection; but other androgens like DHEA have the opposite effect, as it increases the immune response
instead of down playing it.11 As in females, the male sex hormones seem to have more control of the immune
system during puberty and the time right after than in fully developed adults. Other than hormonal changes
physical changes like the involution of the Thymus during puberty will also affect the immunological response of
the subject or patien
2.Organism
In biology, an organism is any contiguous living system (such as animal, fungus, micro-organism, or plant). In
at least some form, all types of organisms are capable of responding to stimuli, reproduction, growth
and development, and maintenance of homeostasis as a stable whole.
An organism may be either unicellular (a single cell) or, as in the case of humans, comprise many trillions
of cells grouped into specialized tissues andorgans. The term multicellular (many cells) describes any organism
made up of more than one cell.
All organisms living on Earth are divided into the eukaryotes and prokaryotes based on the presence or
absence of true nuclei in their cells. The prokaryotes represent two separate domains,
the Bacteria and Archaea. Eukaryotic organisms are characterized by the presence of a membrane-boundcell
nucleus, and contain additional membrane-bound compartmentalization called organelles (such
as mitochondria in animals and plastids in plants, both generally considered to be derived
from endosymbiotic bacteria).1 Fungi, animals and plants are examples of kingdoms of organisms that are
eukaryotes.
In 2002 Thomas Cavalier-Smith proposed a clade, Neomura, which groups together the Archaea and Eukarya.
Neomura is thought to have evolved fromBacteria, more specifically from Actinobacteria.2 See Branching order
of bacterial phyla.
Etymology source |
The term "organism" (from Greek ὀργανισμός, organismos, from ὄργανον, organon, i.e. "instrument,
implement, tool, organ of sense or apprehension"34) first appeared in the English language in 1703 and took on
its current definition by 1834 (Oxford English Dictionary). It is directly related to the term "organization". There
is a long tradition of defining organisms as self-organizing beings.5
There has been a great deal of recent controversy about the best way to define the organism678910111213 and
indeed about whether or not such a definition is necessary.1415 Several contributions16 are responses to the
suggestion that the category of "organism" may well not be adequate in biology.17
Semantics source |
The word organism may broadly be defined as an assembly of molecules functioning as a more or less stable
whole that exhibits the properties of life. However, many sources propose definitions that exclude viruses and
theoretically possible man-made non-organic life forms.18 Viruses are dependent on the biochemical machinery
of a host cell for reproduction.
Chambers Online Reference provides a broad definition: "any living structure, such as a plant, animal, fungus
or bacterium, capable of growth and reproduction".19
In multicellular terms, "organism" usually describes the whole hierarchical assemblage of systems (for
example circulatory, digestive, or reproductive) themselves collections of organs; these are, in turn, collections
of tissues, which are themselves made of cells. In some plants and the nematode Caenorhabditis elegans,
individual cells are totipotent.
A superorganism is an organism consisting of many individuals working together as a single functional or social
unit.
Viruses are not typically considered to be organisms because they are incapable of
autonomous reproduction, growth or metabolism. This controversy is problematic because some cellular
organisms are also incapable of independent survival (but not of independent metabolism and
procreation) and live as obligatory intracellular parasites. Although viruses have a few enzymes and
molecules characteristic of living organisms, they have no metabolism of their own and cannot synthesize
and organize the organic compounds that form them. Naturally, this rules out autonomous reproduction
and they can only be passively replicated by the machinery of the host cell. In this sense they are similar
to inanimate matter. While viruses sustain no independent metabolism, and thus are usually not
accounted organisms, they do have their own genes and they do evolve by similar mechanisms by which
organisms evolve.
The most common argument in support of viruses as living organisms is their ability to undergo evolution
and replicate through self-assembly. Some scientists argue that viruses neither evolve, nor selfreproduce. In fact, viruses are evolved by their host cells, meaning that there was co-evolution of viruses
and host cells. If host cells did not exist, viral evolution would be impossible. This is not true for cells. If
viruses did not exist, the direction of evolution could be different; however, the ability to evolve would not
be affected. As for the reproduction, viruses totally rely on hosts' machinery to replicate themselves. 20 The
discovery of viral megagenomes with genes coding for energy metabolism and protein synthesis fueled
the debate about whether viruses belong on thetree of life. The presence of these genes suggested that
viruses could metabolize in the past. It was found later that the genes coding for energy and protein
metabolism have cellular origin. Most likely, they were acquired through horizontal gene transfer from viral
hosts
3.Immune system
The immune system is a system of biological structures and processes within an organism that protects
against disease. To function properly, an immune system must detect a wide variety of agents,
from viruses to parasitic worms, and distinguish them from the organism's own healthytissue.
Pathogens can rapidly evolve and adapt, and thereby avoid detection and neutralization by the immune
system, however, multiple defense mechanisms have also evolved to recognize and neutralize pathogens.
Even simple unicellular organisms such as bacteria possess a rudimentary immune system, in the form
of enzymes that protect against bacteriophage infections. Other basic immune mechanisms evolved in
ancienteukaryotes and remain in their modern descendants, such as plants and insects. These mechanisms
include phagocytosis, antimicrobial peptidescalled defensins, and the complement system. Jawed vertebrates,
including humans, have even more sophisticated defense mechanisms,1including the ability to adapt over time
to recognize specific pathogens more efficiently. Adaptive (or acquired) immunity creates immunological
memory after an initial response to a specific pathogen, leading to an enhanced response to subsequent
encounters with that same pathogen. This process of acquired immunity is the basis of vaccination.
Disorders of the immune system can result in autoimmune diseases, inflammatory
diseases and cancer.23 Immunodeficiency occurs when the immune system is less active than normal, resulting
in recurring and life-threatening infections. In humans, immunodeficiency can either be the result of a genetic
disease such as severe combined immunodeficiency, acquired conditions such as HIV/AIDS, or the use of
immunosuppressive medication. In contrast, autoimmunity results from a hyperactive immune system attacking
normal tissues as if they were foreign organisms. Common autoimmune diseases include Hashimoto's
thyroiditis, rheumatoid arthritis, diabetes mellitus type 1, and systemic lupus erythematosus.Immunology covers
the study of all aspects of the immune system.
History of immunology source |
Immunology is a science that examines the structure and function of the immune system. It originates
from medicine and early studies on the causes of immunity to disease. The earliest known reference to
immunity was during the plague of Athens in 430 BC. Thucydides noted that people who had recovered from a
previous bout of the disease could nurse the sick without contracting the illness a second time. 4 In the 18th
century, Pierre-Louis Moreau de Maupertuis made experiments with scorpion venom and observed that certain
dogs and mice were immune to this venom.5 This and other observations of acquired immunity were later
exploited by Louis Pasteur in his development of vaccination and his proposed germ theory of
disease.6 Pasteur's theory was in direct opposition to contemporary theories of disease, such as the miasma
theory. It was not until Robert Koch's 1891 proofs, for which he was awarded aNobel Prize in 1905,
that microorganisms were confirmed as the cause of infectious disease.7 Viruses were confirmed as human
pathogens in 1901, with the discovery of the yellow fever virus by Walter Reed.8
Immunology made a great advance towards the end of the 19th century, through rapid developments, in the
study of humoral immunity and cellular immunity.9Particularly important was the work of Paul Ehrlich, who
proposed the side-chain theory to explain the specificity of the antigen-antibody reaction; his contributions to
the understanding of humoral immunity were recognized by the award of a Nobel Prize in 1908, which was
jointly awarded to the founder of cellular immunology, Elie Metchnikoff.
20 marks
1.Testicular immunology
Testicular Immunology is the study of the immune system within the testis. It includes an investigation of the
effects of infection, inflammation and immune factors on testicular function. Two unique characteristics
of testicular immunology are evident: (1) the testis is described as an immunologically privileged site, where
suppression of immune responses occurs; and, (2) some factors which normally lead to inflammation are
present at high levels in the testis, where they regulate the development of sperm instead of promoting
inflammation.
History of testicular immunology source |

460-377 BC Hippocrates described testicular inflammation associated with mumps

1785 Hunter and Michaelis performed transplant experiments in domestic chickens

1849 Berthold transplanted testes between roosters and showed maintenance of male sex characteristics
only in birds with successfully grafted testes

1
2
2
1899-1900 Sperm recognized as immunogenic (will cause an autoimmune reaction if transplanted from the
testis into a different area of the body) by Lansteiner (1899) and Metchinikoff, (1900)1

1913-1914 Human testis transplants performed by Lespinasse (1913), and Lydson (1914) who performed
a graft on himself!
2

1954 Discovery that sperm autoantibodies contribute to infertility,3

1977 Billingham recognized that the testis is site of immune privilege 4
Immune cells found in the testis source |
Immune cells of the human testis are not as well characterized as those from rodents, due to the rarity of
normal human testes available for experiment. The majority of experiments have studied the rat testis due to its
convenience: it is a relatively large size and is easily extracted from experimental animals.
Macrophages source |
Macrophages are directly involved in the fight against invading micro-organisms as well as being antigenpresenting cells which activate lymphocytes. Testicular macrophages are the largest population of immune
cells in the rodent testis.56 Macrophages have also been found in the testes of humans,7 guinea pigs,
hamsters,8 boars,9 horses 10 and bulls.11 They originate from blood monocytes which move into the testis then
mature into macrophages. In the rat, testicular macrophages have been described as either “resident” or “newly
arrived” from the blood supply.1213
Testicular macrophages can respond to infectious stimuli and become activated (undergo changes enabling
the killing of the invading micro-organism), but do so to a lesser extent than other types of macrophages.1415 An
example is production of the inflammatory cytokines TNFα and IL-1β by activated rat testicular macrophages:
these macrophages produce significantly less TNFα and IL-1β than activated rat peritoneal
macrophages.1516 Aside from responding to infectious stimuli, testicular macrophages are also involved in
maintaining normal testis function. They have been shown to secrete 25-hydroxycholesterol, a sterol that can
be converted to testosterone by Leydig cells.17 Their presence is necessary for the normal development and
function of theLeydig cells,181819 which are the testosterone-producing cells of the testis.
B-Lymphocytes source |
B-lymphocytes take part in the adaptive immune response and produce antibodies. These cells are not
normally found in the testis, even during inflammatory conditions. The lack of B-lymphocytes in the testis is
significant, since these are the antibody-producing cells of the immune system. Since anti-sperm antibodies
can cause infertility, it is important that antibody-producing B-lymphocytes are kept separated from the testis.
T-lymphocytes source |
T-lymphocytes (T-cells) are white blood cells which take part in cell-mediated immunity. They are often found
within tissues where they can be activated by antigen-presenting cells upon infection. They are present in
rat 2021 and human testes,22 where they constitute approximately 10 to 20% of the immune cells present, as well
as mouse 23 and ram 21 testes. Both cytotoxic T-cellsand helper T-cells are found in the testes of rats.24 Also
present in the testes of rats and humans are natural killer cells 124 and natural killer T-cells have been found in
rats and mice.
Mast cells source |
Mast cells are regulators of immune responses, particularly those against parasites. They are also involved in
the development of autoimmune diseases and allergies. Mast cells have been found in relatively low numbers
in the testes of humans, rats, mice, dogs, cats, bulls, boars and deer.2526 In the mammalian testis mast cells
regulate testosterone production.26 There are two lines of evidence that restriction of mast cell activation in the
testis could be beneficial during treatment of inflammatory conditions; (1) In experimental models of testicular
inflammation, mast cells were present in 10-fold greater numbers and showed signs of activation,27 and (2)
Treatment with drugs which stabilize mast cell activation has proved beneficial in treating some types of male
infertility.282930
Eosinophils source |
Eosinophils directly fight parasitic infections and are involved in allergic reactions. They have been found in
relatively low numbers in the rat, mouse, dog, cat, bull and deer testes.25 Almost nothing is known about their
significance or function in the testis.
Dendritic cells source |
Dendritic cells initiate adaptive immune responses. Relatively small amounts of dendritic cells have been found
in the testes of humans,31 rats 32 and mice.3334 The functional role of dendritic cells in the testis is not well
understood, although they have been shown to be involved in autoimmune orchitis during animal
experiments.2532 When autoimmune orchitis is induced in rats, the dendritic cell population of the testis greatly
increases.32 This is likely to contribute to testicular inflammation, considering the well-established role of
dendritic cells in other types of autoimmune inflammation. 35
Neutrophils source |
Neutrophils are white blood cells which are present in the blood but not normally in tissues. They move out
from the blood into tissues and organs upon infection or damage. They directly fight invading pathogens such
as bacteria. Neutrophils are not found in the rodent testis under normal conditions but can enter from the blood
supply upon infection or inflammatory stimulus. This has been demonstrated in the rat after injection with
bacterial cell wall components to produce an immune reaction.36 Neutrophils also enter the rat testis after
treatment with hormones that increase the permeability of blood vessels.37 In humans, neutrophils have been
found in the testis when associated with some tumors.38 In rat experiments, testicular torsion leads to neutrophil
entry into the testis.39 Neutrophil activity in the testis is an inflammatory response which needs to be tightly
regulated by the body, since inflammation-induced damage to the testis can lead to infertility.4041 It is assumed
that the role of the immunosuppressive environment of the testis is to protect developing sperm from
inflammation.
Immune privilege in the testis source |
Sperm are immunogenic - that is they will cause an autoimmune reaction if transplanted from the testis into a
different part of the body. This has been demonstrated in experiments using rats by Lansteiner (1899) and
Metchinikoff (1900),126 mice 42 and guinea pigs.43 The likely reason for this is that sperm first mature at puberty,
after immune tolerance is established, therefore the body recognizes them as foreign and mounts an immune
reaction against them. Therefore, mechanisms for their protection must exist in this organ to prevent any
autoimmune reaction. Theblood-testis barrier is likely to contribute to the survival of sperm. However, it is
believed in the field of testicular immunology that the blood-testis barrier cannot account for all immune
suppression in the testis, due to (1) its incompleteness at a region called the rete testis 26 and (2) the presence
of immunogenic molecules outside the blood-testis barrier, on the surface ofspermatogonia.126 Another
mechanism which is likely to protect sperm is the suppression of immune responses in the testis. 1544 Both the
suppression of immune responses and the increased survival of grafts in the testis have led to its recognition
as an immunologically privileged site. Other immunologically privileged sites include the eye, brain and
uterus.45
The two main features of immune privilege in the rat testis are;

a diminishment in the activation of testicular macrophages by infections such as bacteria, 1544 and

a defect in the activation of T-cells when antigen is presented to them, leading to the absence of
an adaptive immune response to sperm in the testis.26additional citation needed
It is also predicted that the high level of inflammatory cytokines in the testis contributes to immune privilege.26
Immune privilege in rodents and other experimental animals source |
The existence of immune privilege in the testes of rodents is well accepted, due to many experiments
demonstrating prolonged, and sometimes indefinite, survival of tissue transplanted into the testis, 4647 or
testicular tissue transplanted elsewhere.4849 Evidence includes the tolerance of testicular grafts in mice and
rats, as well as the increased survival of transplants of pancreatic insulin-producing cells in rats, when cells
from the testes (Sertoli cells) are added to the transplanted material.50 Complete spermatogenesis, forming
functional pig or goat sperm, can be established by the grafting of pig or goat testicular tissue onto the backs of
mice - however, immunodeficient mice needed to be used.48
Immune privilege in humans source |
The presence of immune-privilege in the human testis is controversial and insufficient evidence exists to either
confirm or rule out this phenomenon.

Evidence for human/primate testicular immune privilege:
Sperm are protected from autoimmune attack, which when it occurs in humans leads to infertility. 51 Local injury
of seminiferous tubules caused by fine-needle biopsies in humans does not cause testicular inflammation
(orchitis).52 Furthermore, human testis cells tolerate early HIV infection with little response.53

Evidence against human/primate testicular immune-privilege:
In transplant experiments, primate testes fail to support grafts of monkey thyroid tissue.54 Human testis tissue
transplanted into the mouse elicited an immune response and was rejected, however, this immune response
was not as extensive as that against other types of grafted tissue
2.Parasitic worm
Parasitic worms, often referred to as helminths /ˈhɛlmɪnθs/, are a division of eukaryotic parasites.1 They are
worm-like organisms living in and feeding on living hosts, receiving nourishment and protection while disrupting
their hosts' nutrient absorption, causing weakness and disease. Those that live inside the digestive tract are
called intestinal parasites. They can live inside humans and other animals.
Helminthology is the study of parasitic worms and their effects on their hosts. The word helminth comes from
Greek hélmins, a kind of worm.
Categorization source |
Parasitic worms belong to four groups: monogeneans, cestodes (tapeworms), nematodes (roundworms),
and trematodes (flukes). The following table shows the principal morphological distinctions for each of these
helminth families:
Cestodes
(tapeworms)
Shape
Body
cavity
Segmented
plane
Unsegmented plane
No
Body
covering
Tegument
Digestive
tube
No
Sex
Trematodes (flukes)
Nematodes (roundworms)
Cylindrical
No
Tegument
Present
Cuticle
Ends in cecum
Ends in anus
Hermaphroditic,
Hermaphroditic exceptschistosomes wh Dioecious
ich aredioecious
Sucker or bothri
Attachme dia,
Oral sucker and ventral
Lips, teeth, filariform extremities, and dentary plates
nt organs androstellum wi sucker or acetabulum
th hooks
Example
diseases
in
humans
Tapeworm
infection
Schistosomiasis, swim
mer's itch
Ascariasis, dracunculiasis, elephantiasis, enterobiasis
(pinworm), filariasis,hookworm, onchocerciasis, trichinosis, t
richuriasis (whipworm)
Note: ringworm (dermatophytosis) is actually caused by various fungi and not by a parasitic worm.
Acquisition source |
Helminths often find their way into a host through contaminated food or water, soil, mosquito bites, and even
sexual acts. Poorly washed vegetables eaten raw may contain eggs of nematodes such as Ascaris, Enterobius,
Thichuris, and/or cestodes such as Taenia, Hymenolepis, and Echinococcus. Plants may also be contaminated
with fluke metacercaria (e.g. Fasciola). Undercooked meats may transmit Taenia (pork, beef and
venison), Trichinella (pork and bear), Diphyllobothrium (fish), Clonorchis (fish),
and Paragonimus (crustaceans). Schistosomes and nematodes such as hookworms
(Ancylostoma and Necator) and Strongyloides can penetrate the skin. Finally, Wuchereria, Onchocerca,
and Dracunculus are transmitted by mosquitoes and flies.
Populations in the developing world are at particular risk for infestation with parasitic worms. Risk factors
include inadequate water treatment,2 use of contaminated water for drinking, cooking, irrigation and to wash
food, undercooked food of animal origin, and walking barefoot. Simple measures can have strong impacts on
prevention. These include use of shoes, soaking vegetables with 1.5% bleach, adequate cooking of foods, and
sleeping under mosquito-proof nets.
Immune response source |
Main article: Effects of parasitic worms on the immune system
Response to worm infection in humans is a Th2 response in the majority of cases. Inflammation of the gut may
also occur, resulting in cyst-like structures forming around the egg deposits throughout the body. The host's
lymphatic system is also increasingly taxed the longer helminths propagate, as they excrete toxins after
feeding. These toxins are released into the intestines to be absorbed by the host's bloodstream. This
phenomenon makes the host susceptible to more common diseases, such as viral and bacterial infections.
Intestinal helminths source |
Intestinal helminths, a type of intestinal parasites, reside in the human gastrointestinal tract. They represent
one of the most prevalent forms of parasitic disease. Scholars estimate over a quarter of the world’s population
is infected with an intestinal worm of some sort, with roundworms, hookworms, and whipworms infecting 1.47
billion people, 1.05 billion people, and 1.30 billion people, respectively.3 Furthermore, the World Bank estimates
100 million people may experience stunting or wasting as a result of infection.4
Because of their high mobility and lower standards of hygiene, school-age children are particularly vulnerable
to these parasites.5 Overall, an estimated 400 million, 170 million, and 300 million children are infected with
roundworm, hookworm, and whipworm, respectively.6 Children may also be particularly susceptible to the
adverse effects of helminth infections due to their incomplete physical development and their
greater immunological vulnerability.5
Costs of intestinal helminth infection source |
Symptoms source |
In patients with a heavy worm load, infection is frequently symptomatic. Conditions associated with intestinal
helminth infection include intestinal obstruction, insomnia, vomiting, weakness, and stomach pains,7 and the
natural movement of worms and their attachment to the intestine may be generally uncomfortable for their
hosts.3 The migration of Ascaris larvae through the respiratory passageways can also lead to
temporary asthma and other respiratory symptoms.7
In addition to the low-level costs of chronic infection, helminth infection may be punctuated by the need for
more serious, urgent care; for example, the World Health Organization found worm infection is common reason
for seeking medical help in a variety of countries, with up to 4.9% of hospital admissions in some areas
resulting from the complications of intestinal worm infections and as many as 3% of hospitalizations attributable
to ascariasis alone.8
Also, the immune response triggered by helminth infection may drain the body’s ability to fight other diseases,
making affected individuals more prone to coinfection.3 Reasonable evidence indicates helminthiasis is
responsible for the unrelenting prevalence of AIDS and tuberculosis in developing, particularly African,
countries.9 A review of several data clearly revealed the effective treatment of helminth infection reduces HIV
progression and viral load, obviously by improving helminth-induced immune suppression.10
Nutrition source |
One way in which intestinal helminths may impair the development of their human hosts is through their impact
on nutrition. Intestinal helminth infection has been associated with problems such as vitamin
deficiencies, stunting, anemia, and protein-energy malnutrition, which in turn affect cognitive ability and
intellectual development.8 This relationship is particularly alarming because it is gradual and often relatively
asymptomatic.11
Parasite infection may affect nutrition in several ways. Some scholars argue worms may compete directly with
their hosts for access to nutrients; both whipworms6 and roundworms4 are believed to impact their hosts in this
way. Nonetheless, the magnitude of this effect is likely to be minimal; after all, the nutritional requirements of
these intestinal worms is small when compared with that of their host organism.3
A more probable source of infection-induced malnutrition is the nutrient malabsorption associated with parasite
presence in the body. For example, in both pigs and humans, Ascaris has been tied to temporarily
induced lactose intolerance and vitamin A,12 amino acid, and fat malabsorption.8 Impaired nutrient uptake may
result from direct damage to the intestines' mucosal walls as a result of the worms’ presence, but it may also be
a consequence of more nuanced changes, such as chemical imbalances caused by the body’s reaction to the
helminths.13 Alternatively, the worms’ release of protease inhibitors to defend against the body’s digestive
process may impair the breakdown of other nutritious substances, as well.36 Finally, worm infections may also
cause diarrhea and speed “transit time” through the intestinal system, further reducing the body’s opportunity to
capture and retain the nutrients in food.8
Worms may also contribute to malnutrition by creating anorexia. A decline in appetite and food consumption
due to helminthic infection is widely recognized by the literature,4 with a recent study of 459 children
in Zanzibar reporting even mothers noticed spontaneous increases in appetite after their children underwent a
deworming regimen.14 Although the exact cause of such anorexia is not known, researchers believe it may be a
side effect of body’s immune response to the worm and the stress of combating infection.3 Specifically, some of
the cytokines released in the immune response have been tied to anorexic reactions in animals. 6
Helminths may also affect nutrition by inducing iron-deficiency anemia. This is most severe in
heavy hookworm infections, as N. americanus and A. duodenale feed directly on the blood of their hosts.
Although the impact of individual worms is limited (each consumes about .02-.07 ml and .14-.26 ml of blood
daily, respectively), this may nonetheless add up in individuals with heavy infections, since they may carry
hundreds of worms at a given time.8 One scholar went so far as to predict, “the blood loss caused by
hookworm was equivalent to the daily exsanguination of 1.5 million people”,3 while a study in Zanzibar showed
a 15¢ triannual application of mebendazole could avert 0.25 l of blood loss per child per year. Although
whipworm is milder in its effects, it may also induce anemia as a result of the bleeding caused by its damage to
the small intestine.38
The connection between worm burden and malnutrition is further supported by studies indicating deworming
programs lead to sharp increases in growth; the presence of this result even in older children has led some
scholars to conclude, “it may be easier to reverse stunting in older children than was previously believed
3.
Microorganism
A microorganism (from the Greek: μικρός, mikrós, "small" and ὀργανισμός, organismós, "organism")
or microbe is a microscopic organism, which may be a single cell1 or multicellular organism. The study of
microorganisms is called microbiology, a subject that began with Anton van Leeuwenhoek's discovery of
microorganisms in 1675, using a microscope of his own design.
Microorganisms are very diverse; they include all of the prokaryotes, namely the bacteria and archaea; and
various forms of eukaryotes, comprising the protozoa, fungi, algae, microscopic plants (green algae),
and animals such as rotifers and planarians. Some microbiologists also classify viruses as microorganisms, but
others consider these as nonliving.23 Most microorganisms are microscopic, but there are some
likeThiomargarita namibiensis, which are macroscopic and visible to the naked eye.4
Microorganisms live in every part of the biosphere including soil, hot springs, on the ocean floor, high in
the atmosphere and deep inside rocks within the Earth's crust (see also endolith). Microorganisms are crucial
to nutrient recycling in ecosystems as they act as decomposers. As some microorganisms can fix nitrogen,
they are a vital part of the nitrogen cycle, and recent studies indicate that airborne microbes may play a role
inprecipitation and weather.5
On 17 March 2013, researchers reported data that suggested microbial life forms thrive in the Mariana Trench.
the deepest spot on the Earth.67Other researchers reported related studies that microbes thrive inside rocks up
to 1900 feet (580 metres) below the sea floor under 8500 feet (2590 metres) of ocean off the coast of the
northwestern United States.68 According to one of the researchers,"You can find microbes everywhere —
they're extremely adaptable to conditions, and survive wherever they are."6
Microbes are also exploited by people in biotechnology, both in traditional food and beverage preparation, and
in modern technologies based on genetic engineering. However there are manypathogenic microbes which are
harmful and can even cause death in plants and animals.9
Evolution source |
Further information: Timeline of evolution and Experimental evolution
Single-celled microorganisms were the first forms of life to develop on Earth, approximately 3–4 billion
years ago.101112 Further evolution was slow,13 and for about 3 billion years in thePrecambrian eon, all organisms
were microscopic.14 So, for most of the history of life on Earth the only forms of life were
microorganisms.15 Bacteria, algae and fungi have been identified inamber that is 220 million years old, which
shows that the morphology of microorganisms has changed little since the Triassic period.16
Microorganisms tend to have a relatively fast rate of evolution. Most microorganisms can reproduce rapidly,
and bacteria are also able to freely exchange genes through conjugation, transformationand transduction, even
between widely divergent species.17 This horizontal gene transfer, coupled with a high mutation rate and many
other means of genetic variation, allows microorganisms to swiftly evolve (via natural selection) to survive in
new environments and respond to environmental stresses. This rapid evolution is important in medicine, as it
has led to the recent development of "super-bugs", pathogenic bacteria that are resistant to
modern antibiotics.18
Pre-microbiology source |
The possibility that microorganisms exist was discussed for many centuries before their actual discovery in the
17th century. The existence of unseen microbiological life was postulated byJainism, which is based
on Mahavira's teachings as early as 6th century BCE.19 Paul Dundas notes that Mahavira asserted existence of
unseen microbiological creatures living in earth, water, air and fire.20 Jain scriptures also describe nigodas,
which are sub-microscopic creatures living in large clusters and having a very short life and are said to pervade
each and every part of universe, even in tissues of plants and flesh of animals.21 However, the earliest known
idea to indicate the possibility of diseases spreading by yet unseen organisms was that of
the Romanscholar Marcus Terentius Varro in a 1st-century BC book titled On Agriculture in which he warns
against locating a homestead near swamps:
… and because there are bred certain minute creatures that cannot be seen by the eyes, which float in the air
and enter the body through the mouth and nose and they cause serious diseases.22
In The Canon of Medicine (1020), Abū Alī ibn Sīnā (Avicenna) hypothesized that tuberculosis and other
diseases might be contagious2324
In 1546, Girolamo Fracastoro proposed that epidemic diseases were caused by transferable seedlike entities
that could transmit infection by direct or indirect contact, or even without contact over long distances.
All these early claims about the existence of microorganisms were speculative and were not based on any data
or science. Microorganisms were neither proven, observed, nor correctly and accurately described until the
17th century. The reason for this was that all these early studies lacked the microscope.
4.
Genetic disorder
A genetic disorder is an illness caused by one or more abnormalities in the genome, especially a condition
that is present from birth (congenital). Most genetic disorders are quite rare and affect one person in every
several thousands or millions.
Genetic disorders are heritable, and are passed down from the parents' genes. Other defects may be caused
by new mutations or changes to the DNA. In such cases, the defect will only be heritable if it occurs in the germ
line. The same disease, such as some forms of cancer, may be caused by an inherited genetic condition in
some people, by new mutations in other people, and by nongenetic causes in still other people.
Some types of recessive gene disorders confer an advantage in certain environments when only one copy of
the gene is present.1
Single gene disorder source |
Prevalence of some single gene disorderscitation needed
Disorder prevalence (approximate)
Autosomal dominant
Familial hypercholesterolemia
1 in 500
Polycystic kidney disease
1 in 1250
Neurofibromatosis type I
1 in 2,500
Herary spherocytosis
1 in 5,000
Marfan syndrome
1 in 4,000 2
Huntington's disease
1 in 15,000 3
Autosomal recessive
Sickle cell anaemia
1 in 625
Cystic fibrosis
1 in 2,000
Tay-Sachs disease
1 in 3,000
Phenylketonuria
1 in 12,000
Mucopolysaccharidoses
1 in 25,000
Lysosomal acid lipase deficiency
1 in 40,000
Glycogen storage diseases
1 in 50,000
Galactosemia
1 in 57,000
X-linked
Duchenne muscular dystrophy
1 in 7,000
A single gene disorder is the result of a
single mutated gene. Over 4000 human
Hemophilia
1 in 10,000
Values are for liveborn infants
diseases are caused by single gene defects.
Single gene disorders can be passed on to
subsequent generations in several ways. Genomic imprinting and uniparental disomy, however, may affect
inheritance patterns. The divisions between recessive and dominant types are not "hard and fast", although the
divisions between autosomaland X-linked types are (since the latter types are distinguished purely based on
the chromosomal location of the gene). For example,achondroplasia is typically considered a dominant
disorder, but children with two genes for achondroplasia have a severe skeletal disorder of which
achondroplasics could be viewed as carriers. Sickle-cell anemia is also considered a recessive condition,
but heterozygous carriers have increased resistance to malaria in early childhood, which could be described as
a related dominant condition.4 When a couple where one partner or both are sufferers or carriers of a single
gene disorder and wish to have a child, they can do so through in vitro fertilization, which means they can then
have a preimplantation genetic diagnosis to check whether the embryo has the genetic disorder.5
Autosomal dominant source |
Main article: Autosomal dominant#Autosomal dominant gene
Only one mutated copy of the gene will be necessary for a person to be affected by an autosomal dominant
disorder. Each affected person usually has one affected parent.6 The chance a child will inherit the mutated
gene is 50%. Autosomal dominant conditions sometimes have reduced penetrance, which means although
only one mutated copy is needed, not all individuals who inherit that mutation go on to develop the disease.
Examples of this type of disorder are Huntington's disease,7 neurofibromatosis type 1, neurofibromatosis type
2, Marfan syndrome, herary nonpolyposis colorectal cancer, and herary multiple exostoses, which is a highly
penetrant autosomal dominant disorder. Birth defects are also called congenital anomalies.
Autosomal recessive source |
Main article: Autosomal dominant#Autosomal recessive allele
Two copies of the gene must be mutated for a person to be affected by an autosomal recessive disorder. An
affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are
referred to as carriers). Two unaffected people who each carry one copy of the mutated gene have a 25%
chance with each pregnancy of having a child affected by the disorder. Examples of this type of disorder
are Medium-chain acyl-CoA dehydrogenase deficiency, cystic fibrosis, sickle-cell disease, Tay-Sachs
disease, Niemann-Pick disease, spinal muscular atrophy, and Roberts syndrome. Certain other phenotypes,
such as wet versus dry earwax, are also determined in an autosomal recessive fashion.89
X-linked dominant source |
Main article: X-linked dominant
X-linked dominant disorders are caused by mutations in genes on the X chromosome. Only a few disorders
have this inheritance pattern, with a prime example being X-linked hypophosphatemic rickets. Males and
females are both affected in these disorders, with males typically being more severely affected than females.
Some X-linked dominant conditions, such as Rett syndrome,incontinentia pigmenti type 2 and Aicardi
syndrome, are usually fatal in males either in utero or shortly after birth, and are therefore predominantly seen
in females. Exceptions to this finding are extremely rare cases in which boys with Klinefelter
syndrome (47,XXY) also inherit an X-linked dominant condition and exhibit symptoms more similar to those of a
female in terms of disease severity. The chance of passing on an X-linked dominant disorder differs between
men and women. The sons of a man with an X-linked dominant disorder will all be unaffected (since they
receive their father's Y chromosome), and his daughters will all inherit the condition. A woman with an X-linked
dominant disorder has a 50% chance of having an affected fetus with each pregnancy, although it should be
noted that in cases such as incontinentia pigmenti, only female offspring are generally viable. In addition,
although these conditions do not alter fertility per se, individuals with Rett syndrome or Aicardi syndrome rarely
reproduce.citation needed
X-linked recessive source |
Main article: X-linked recessive
X-linked recessive conditions are also caused by mutations in genes on the X chromosome. Males are more
frequently affected than females, and the chance of passing on the disorder differs between men and women.
The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will carry one
copy of the mutated gene. A woman who is a carrier of an X-linked recessive disorder (XRXr) has a 50%
chance of having sons who are affected and a 50% chance of having daughters who carry one copy of the
mutated gene and are therefore carriers. X-linked recessive conditions include the serious diseases hemophilia
A, Duchenne muscular dystrophy, and Lesch-Nyhan syndrome, as well as common and less serious conditions
such as male pattern baldness and red-green color blindness. X-linked recessive conditions can sometimes
manifest in females due to skewed X-inactivation or monosomy X (Turner syndrome).
Y-linked source |
Main article: Y linkage
Y-linked disorders are caused by mutations on the Y chromosome. Because males inherit a Y chromosome
from their fathers, every son of an affected father will be affected. Because females only inherit an X
chromosome from their fathers, and never a Y chromosome, female offspring of affected fathers are never
affected.
Since the Y chromosome is relatively small and contains very few genes, relatively few Y-linked disorders
occur.citation needed Often, the symptoms include infertility, which may be circumvented with the help of some
fertility treatments. Examples are male infertility.citation needed
Mitochondrial source |
Main article: Mitochondrial disease
This type of inheritance, also known as maternal inheritance, applies to genes in mitochondrial DNA. Because
only egg cells contribute mitochondria to the developing embryo, only mothers can pass on mitochondrial
conditions to their children. An example of this type of disorder is Leber's herary optic neuropathy.
Multifactorial and polygenic (complex) disorders source |
Genetic disorders may also be complex, multifactorial, or polygenic, meaning they are likely associated with the
effects of multiple genes in combination with lifestyles and environmental factors. Multifactorial disorders
include heart disease and diabetes. Although complex disorders often cluster in families, they do not have a
clear-cut pattern of inheritance. This makes it difficult to determine a person’s risk of inheriting or passing on
these disorders. Complex disorders are also difficult to study and treat because the specific factors that cause
most of these disorders have not yet been identified.
On a pedigree, polygenic diseases do tend to "run in families", but the inheritance does not fit simple patterns
as with Mendelian diseases. But this does not mean that the genes cannot eventually be located and studied.
There is also a strong environmental component to many of them