In epidemiology, environmental diseases are diseases that can be directly attributed to environmental factors (as distinct from genetic factors or infection). Apart from the true monogenicgenetic disorders, which are rare, environment is a major determinant of the development of disease. Diet, exposure to toxins, pathogens, radiation, and chemicals
found in almost all personal care products and household cleaners,
stress, racism, and physical and mental abuse are causes of a large
segment of non-hereditary disease. If a disease process is concluded to
be the result of a combination of genetic and environmental factor influences, its etiological origin can be referred to as having a multifactorial pattern.
There are many different types of environmental disease including:
Disease caused by physical factors in the environment, such as skin cancer caused by excessive exposure to ultraviolet radiation in sunlight
Environmental diseases vs. pollution-related diseases
Environmental diseases are a direct result from the environment. Meanwhile, pollution-related diseases
are attributed to exposure to toxicants or toxins in the air, water,
and soil. Therefore, all pollution-related disease are environmental
diseases, but not all environmental diseases are pollution-related
diseases.
Urban-associated diseases
Urban
areas are highly dense regions that currently hold ~50% of the global
population, a number expected to grow to 70% by 2050, and produce over 80% of the global GDP.
These areas are known to have a higher incidence of certain diseases,
which is of particular concern given their rapid growth. The urban
environment includes many risk factors for a variety of different
environmental diseases. Some of these risk factors, for instance, air-pollution,
are well known, while others such as altered microbial exposure are
less familiar to the general public. For instance, asthma can be induced
and exacerbated by combustion related pollution, which is more
prevalent in urban areas.
On the other hand, urban areas, compared to their rural counterparts,
lack diverse microbial communities, which can help prevent the
development of asthma. Both of these effects lead to a higher incidence of asthma in cities. Infectious diseases
are also often more common in cities, as transfer between hosts is
facilitated by high population densities. However, recent research shows
that increased access to healthcare weakens the urban association with
these diseases, and the net effect is still unclear. Many mental health disorders have also been associated with urban areas, especially in low socioeconomic areas.
Increased levels of stress, air & light & noise pollution, and
reduced "green" space are all urban-associated environmental effects
that are adversely linked to mental health.
Though urban areas are often correlated with dirtiness and disease,
they are likely to have more access to higher quality health care which
can lead to more positive health outcomes. This benefit will continue to
grow as innovation in health technologies steadily rises. Taking this
into account, while overall trends do exist, urban risk factors are
nuanced and often city and context dependent.
There are many other diseases likely to have been caused by common anions found in natural drinking water. Fluoride
is one of the most common found in drier climates where the geology
favors release of fluoride ions to soil as the rocks decompose. In Sri
Lanka, 90% of the country is underlain by crystalline metamorphic rocks
of which most carry mica as a major mineral. Mica carries fluoride in
their structure and releases to soil when decomposes. In the dry and
arid climates, fluoride concentrates on top soil and slowly dissolves in
shallow groundwater. This has been the cause of high fluoride levels in
drinking water where the majority of the rural Sri Lankans obtain their
drinking water from backyard wells. High fluoride in drinking water has
caused a high incidence of fluorosis
among dry zone population in Sri Lanka. However, in the wet zone, high
rainfall effectively removes fluoride from soils where no fluorosis is
evident. In some parts of Sri Lanka iodine deficiency has also been
noted which has been identified as a result of iodine fixation by
hydrated iron oxide found in lateritic soils in wet coastal lowlands.
The U.S. Coast Guard has developed a Coast Guard-wide comprehensive system for surveillance of workplace diseases.
The American Medical Association's
fifth edition of the Current Medical Information and Terminology (CMIT)
was used as a reference to expand the basic list of 50 Sentinel Health
Events (Occupational) [SHE(O)] published by the National Institute for
Occupational Health and Safety (NIOSH), September, 1983.
A protocell (or protobiont) is a self-organized, endogenously ordered, spherical collection of lipids proposed as a rudimentary precursor to cells during the origin of life.A central question in evolution
is how simple protocells first arose and how their progeny could
diversify, thus enabling the accumulation of novel biological emergences
over time (i.e. biological evolution).
Although a functional protocell has not yet been achieved in a
laboratory setting, the goal to understand the process appears well
within reach.
A protocell is a pre-cell in abiogenesis, and was a contained system consisting of simple biologically relevant molecules like ribozymes,
and encapsulated in a simple membrane structure – isolating the entity
from the environment and other individuals – thought to consist of
simple fatty acids, mineral structures, or rock-pore structures.
Overview
Compartmentalization was important in the origin of life.
Membranes form enclosed compartments that are separate from the
external environment, thus providing the cell with functionally
specialized aqueous spaces. As the lipid bilayer of membranes is
impermeable to most hydrophilic
molecules (dissolved by water), modern cells have membrane
transport-systems that achieve nutrient uptake as well as the export of
waste.
Prior to the development of these molecular assemblies, protocells
likely employed vesicle dynamics that are relevant to cellular
functions, such as membrane trafficking and self-reproduction, using amphiphilic molecules. On the primitive Earth, numerous chemical reactions of organic compounds produced the ingredients of life. Of these substances, amphiphilic molecules might be the first player in the evolution from molecular assembly to cellular life. Vesicle dynamics could progress towards protocells with the development of self-replication coupled with early metabolism. It is possible that protocells might have had a primitive metabolic system (Wood-Ljungdahl pathway) at alkaline hydrothermal vents or other geological environments like impact crater lakes from meteorites, which are known to be composed of elements found in the Wood-Ljungdahl pathway.
Another conceptual model of a protocell relates to the term "chemoton" (short for 'chemical automaton') which refers to the fundamental unit of life introduced by Hungariantheoretical biologistTibor Gánti.
It is the oldest known computational abstract of a protocell. Gánti
conceived the basic idea in 1952 and formulated the concept in 1971 in
his book The Principles of Life (originally written in Hungarian,
and translated to English only in 2003). He surmised the chemoton as
the original ancestor of all organisms, or the last universal common ancestor.
The basic assumption of the chemoton model is that life should fundamentally and essentially have three properties: metabolism, self-replication, and a bilipid membrane. The metabolic and replication functions together form an autocatalytic
subsystem necessary for the basic functions of life, and a membrane
encloses this subsystem to separate it from the surrounding environment.
Therefore, any system having such properties may be regarded as alive,
and will contain self sustaining cellular information that is subject to
natural selection. Some consider this model a significant contribution to origin of life as it provides a philosophy of evolutionary units.
Selectivity for compartmentalization
The three main structures phospholipids form in solution: the liposome (a closed bilayer), the micelle and the bilayer.
Self-assembled vesicles are essential components of primitive cells. The second law of thermodynamics requires that the universe becomes increasingly disordered (entropy), yet life is distinguished by its great degree of organization. Therefore, a boundary is needed to separate life processes from non-living matter. This fundamental necessity is underpinned by the universality of the cell membrane which is the only cellular structure found in all organisms on Earth.
In the aqueous environment in which all known cells function, a
non-aqueous barrier is required to surround a cell and separate it from
its surroundings.
This non-aqueous membrane establishes a barrier to free diffusion,
allowing for regulation of the internal environment within the barrier.
The necessity of thermodynamically isolating a subsystem is an
irreducible condition of life. In modern biology, such isolation is ordinarily accomplished by amphiphilic bilayers of a thickness of around 10−8 meters.
Researchers including Irene A. Chen and Jack W. Szostak
have demonstrated that simple physicochemical properties of elementary
protocells can give rise to simpler conceptual analogues of essential
cellular behaviors, including primitive forms of Darwinian competition
and energy storage. Such cooperative interactions between the membrane
and encapsulated contents could greatly simplify the transition from
replicating molecules to true cells.
Competition for membrane molecules would favor stabilized membranes,
suggesting a selective advantage for the evolution of cross-linked fatty
acids and even the phospholipids of today. This micro-encapsulation allowed for metabolism within the membrane, exchange of small molecules and prevention of passage of large substances across it. The main advantages of encapsulation include increased solubility of the cargo and creating energy in the form of chemical gradients. Energy is thus often said to be stored by cells in molecular structures such as carbohydrates (including sugars), lipids, and proteins, which release energy when chemically combined with oxygen during cellular respiration.
When phospholipids
or simple lipids like fatty acids are placed in water, the molecules
spontaneously arrange such that the hydrophobic tails are shielded from
the water, resulting in the formation of membrane structures such as bilayers, vesicles, and micelles. In modern cells, vesicles are involved in metabolism, transport, buoyancy control, and enzyme storage. They can also act as natural chemical reaction chambers. A typical vesicle or micelle in aqueous solution forms an aggregate with the hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic single-tail regions in the micelle center. This phase is caused by the packing behavior of single-tail lipids in a bilayer. Although the spontaneous self-assembly process that form lipid monolayer
vesicles and micelles in nature resemble the kinds of primordial
vesicles or protocells that might have existed at the beginning of
evolution, they are not as sophisticated as the bilayer membranes of today's living organisms.
However, in a prebiotic context, electrostatic interactions induced by
short, positively charged, hydrophobic peptides containing seven amino
acids in length or fewer, can attach RNA to a vesicle membrane, the
basic cell membrane.
Rather than being made up of phospholipids, early membranes may have formed from monolayers or bilayers of simple fatty acids, which may have formed more readily in a prebiotic environment.
Fatty acids have been synthesized in laboratories under a variety of
prebiotic conditions and have been found on meteorites, suggesting their
natural synthesis in nature. Oleic acid vesicles represent good models of membrane protocells
Cohen et al. (2022) suggest that plausible prebiotic production
of fatty acids — leading to the development of early protocell membranes
— is enriched on metal-rich mineral surfaces, possibly from impact
craters, increasing the prebiotic environmental mass of lipids by 102 times.
They evaluate three different possible synthesis pathways of fatty
acids in the Hadean, and found that these metal surfaces could produce
1011 - 1015 kg of 6-18 carbon fatty acids. Of
these products, the 8-18C fatty acids are compatible with membrane
formation. They also propose that alternative amphiphiles like alcohols
are co-synthesized with fatty acid, and can help improve membrane
stability. However, despite this production, the authors state that net
fatty acid synthesis would not yield sufficient concentrations for
spontaneous membrane formation without significant evaporation of
Earth's aqueous environments.
Membrane transport
Schematic
showing two possible conformations of the lipids at the edge of a pore.
In the top image the lipids have not rearranged, so the pore wall is
hydrophobic. In the bottom image some of the lipid heads have bent over,
so the pore wall is hydrophilic.
For cellular organisms, the transport of specific molecules across
compartmentalizing membrane barriers is essential in order to exchange
content with their environment and with other individuals. For example,
content exchange between individuals enables the exchange of genes
between individuals (horizontal gene transfer), an important factor in the evolution of cellular life.
While modern cells can rely on complicated protein machineries to
catalyze these crucial processes, protocells must have accomplished this
using more simple mechanisms.
Protocells composed of fatty acids would have been able to easily exchange small molecules and ions with their environment.
Modern phospholipid bilayer cell membranes exhibit low permeability,
but contain complex molecular assemblies which both actively and
passively transport relevant molecules across the membrane in a highly
specific manner. In the absence of these complex assemblies, simple
fatty acid based protocell membranes would be more permeable and allow
for greater non-specific transport across membranes. Molecules that would be highly permeable across protocell membranes include nucleoside monophosphate (NMP), nucleoside diphosphate (NDP), and nucleoside triphosphate (NTP), and may withstand millimolar concentrations of Mg2+. Osmotic pressure can also play a significant role regarding this passive membrane transport.
Environmental effects have been suggested to trigger conditions under which a transport of larger molecules, such as DNA and RNA, across the membranes of protocells is possible. For example, it has been proposed that electroporation resulting from lightning strikes could enable such transport.
Electroporation is the rapid increase in bilayer permeability induced
by the application of a large artificial electric field across the
membrane. During electroporation, the lipid molecules in the membrane
shift position, opening up a pore (hole) that acts as a conductive
pathway through which hydrophobic molecules like nucleic acids can pass the lipid bilayer.
A similar transfer of content across protocells and with the
surrounding solution can be caused by freezing and subsequent thawing.
This could, for instance, occur in an environment in which day and night
cycles cause recurrent freezing. Laboratory experiments have shown that
such conditions allow an exchange of genetic information between
populations of protocells.
This can be explained by the fact that membranes are highly permeable
at temperatures slightly below their phase transition temperature. If
this point is reached during the freeze-thaw cycle, even large and
highly charged molecules can temporarily pass the protocell membrane.
Some molecules or particles are too large or too hydrophilic to
pass through a lipid bilayer even under these conditions, but can be
moved across the membrane through fusion or budding of vesicles, events which have also been observed for freeze-thaw cycles. This may eventually have led to mechanisms that facilitate movement of molecules to the inside of the protocell (endocytosis) or to release its contents into the extracellular space (exocytosis).
It has been proposed that life began in hydrothermal vents in the deep sea, but a 2012 study suggests that hot springs have the ideal characteristics for the origin of life.
The conclusion is based mainly on the chemistry of modern cells, where
the cytoplasm is rich in potassium, zinc, manganese, and phosphate ions,
not widespread in marine environments. Such conditions, the researchers
argue, are found only where hot hydrothermal fluid brings the ions to
the surface—places such as geysers, mud pots, fumaroles and other geothermal
features. Within these fuming and bubbling basins, water laden with
zinc and manganese ions could have collected, cooled and condensed in
shallow pools. However, a recent discovery of alkaline hydrothermal vents
with an ionic concentration of sodium lower than in seawater suggests
that high concentrations of potassium can be found at marine
environments.
A study in the 1990s showed that montmorillonite clay can help create RNA chains of as many as 50 nucleotides joined together spontaneously into a single RNA molecule. Later, in 2002, it was discovered that by adding montmorillonite to a solution of fatty acid micelles (lipid spheres), the clay sped up the rate of vesicle formation 100-fold.
Some minerals can catalyze the stepwise formation of hydrocarbon tails of fatty acids from hydrogen and carbon monoxide gases—gases that may have been released from hydrothermal vents or geysers. Fatty acids of various lengths are eventually released into the surrounding water,
but vesicle formation requires a higher concentration of fatty acids,
so it is suggested that protocell formation started at land-bound
hydrothermal freshwater environments such as geysers, mud pots, fumaroles and other geothermal features where water evaporates and concentrates the solute.
In 2019, Nick Lane
and colleagues show that vesicles form readily in seawater conditions
at pH between 6.5 and >12 and temperatures 70 °C, meant to mimic the
conditions of alkaline hydrothermal vents, with the presence of lipid
mixtures,
however a prebiotic source to such mixtures is unclear in those
environments. Simple amphiphilic compounds in seawater do not assemble
into vesicles because of the high concentration of ionic solutes.
Research has shown that vesicles can be bound and stabilized by
prebiotic amino acids even while in the presence of salt ions and
magnesium ions.
In hot spring conditions, self-assembly of vesicles occurs, which have a lower concentration of ionic solutes. Scientists oligomerized
RNA in alkaline hydrothermal vent conditions in the laboratory.
Although they were estimated to be 4 units in length, it implies RNA
polymers possibly were synthesized at such environments.
Experimental research at hot springs gave higher yields of RNA-like
polymers than in the laboratory. The polymers were encapsulated in fatty
acid vesicles when rehydrated, further supporting the hot spring
hypothesis of abiogenesis. These wet-dry cycles also improved vesicle stability and binding. UV exposure has also been shown to promote the synthesis of stable biomolecules like nucleotides.
In the origin of chemiosmosis,
if early cells originated at alkaline hydrothermal vents, proton
gradients can be maintained by the acidic ocean and alkaline water from
white smokers while an inorganic membranous structure is in a rock
cavity. If early cells originated in terrestrial pools such as hot springs, quinones present in meteorites like the Murchison meteorite
would promote the development of proton gradients by coupled redox
reactions if the ferricyanide, the electron acceptor, was within the
vesicle and an electron donor like a sulfur compound was outside of the
lipid membrane.
Because of the "water problem", a primitive ATP synthase and other
biomolecules would go through hydrolysis due to the absence of wet-dry
cycles at hydrothermal vents, unlike at terrestrial pools.
Other researchers propose hydrothermal pore systems coated in mineral
gels at deep sea hydrothermal vents to an alternative compartment of
membranous structures, promote biochemical reactions of biopolymers, and
could solve the "water problem".
David Deamer and Bruce Damer argue that biomolecules would become
trapped within these pore systems upon polymerization and would not
undergo combinatorial selection. Catalytic FeS and NiS walls at alkaline hydrothermal vents has also been suggested to have promoted polymerization.
However, Jackson (2016) evaluates how the pH gradient between
alkaline hydrothermal vents and acidic Hadean seawater might influence
prebiotic synthesis.
Three main criticisms emerge from this evaluation. Firstly, the
maintenance and stability of membranes positioned suitably between
turbulent pH gradients seemed implausible. They claim that the
proposition of CaCO3 and Mg(OH)2 precipitates
interacting with fluid mixing in subsurface pores do not produce
satisfactory environments. Secondly, they suggest that the molecular
assemblies required to utilize key energetic gradients available at
hydrothermal systems were too complex to have been relevant at the
origin of life. Lastly, they argue that even if a molecular assembly
could have harvested available hydrothermal energy, those assemblies
would have been too large to operate within the proposed membrane
thicknesses accepted by proponents of the hydrothermal vent hypothesis.
In 2017, Jackson takes a further stance, suggesting that even if an
organism successfully originated in alkaline hydrothermal pores,
exploiting natural pH gradients for energy, it would not be able to
withstand the drastic change of environment after emergence from the
vent environment in which it had solely evolved.
This emergence, however, is essential to the niche differentiation of
life, allowing for the diversification of habitats and energetic
strategies. Counters to these arguments suggest that the close
resemblance between biochemical pathways and geochemical systems at
alkaline hydrothermal vents gives merit to the hypothesis, and that
selection on these protocells would improve resilience to environmental
change, allowing for emergence and distribution.
It has been considered by other researchers that life originating
in hydrothermal volcanic ponds exposed to UV radiation, zinc sulfide
photocatalysis, and occurrence of continuous wet-dry cycling would not
resemble modern biochemistry.
Maximal ATP synthesis is shown to occur at high water activity and low
ion concentrations. Despite this, hydrothermal vents are still
considered to be a feasible environment as some shallow hydrothermal
vents emit freshwater and the concentration of divalent cations in
Hadean oceans were likely lower than in modern oceans. Nick Lane and
coauthors state that "alkaline hydrothermal systems tend to precipitate
Ca2+ and Mg2+ ions as aragonite and brucite, so
their concentrations are typically much lower than mean ocean values.
Modelling work in relation to Hadean systems indicates that hydrothermal
concentrations of Ca2+ and Mg2+ would likely have
been <1 mM, which is in the range that enhanced phosphorylation
here. Other conditions considered here, including salinity and high
pressure, would have only limited effects on ATP synthesis in submarine
hydrothermal systems (which typically have pressures in the range of 100
to 300 Bars). Alkaline hydrothermal systems might also have generated
Fe3+ in situ for ADP phosphorylation. Thermodynamic modelling
shows that the mixing of alkaline hydrothermal fluids with seawater in
submarine systems can promote continuous cycling between ferrous and
ferric iron, potentially forming soluble hydrous ferric chlorides, which
our experiments show have the same effect as ferric sulphate".
Montmorillonite bubbles
Another
group suggests that primitive cells might have formed inside inorganic
clay microcompartments, which can provide an ideal container for the
synthesis and compartmentalization of complex organic molecules. Clay-armored bubbles form naturally when particles of montmorillonite
clay collect on the outer surface of air bubbles under water. This
creates a semi permeable vesicle from materials that are readily
available in the environment. The authors remark that montmorillonite is
known to serve as a chemical catalyst, encouraging lipids to form
membranes and single nucleotides to join into strands of RNA. Primitive
reproduction can be envisioned when the clay bubbles burst, releasing
the lipid membrane-bound product into the surrounding medium.
Membraneless droplets
Another
way to form primitive compartments that may lead to the formation of a
protocell is polyesters membraneless structures that have the ability to
host biochemicals (proteins and RNA) and/or scaffold the assemblies of
lipids around them. While these droplets are leaky towards genetic materials, this leakiness could have facilitated the progenote hypothesis.
Coacervates
Researchers have also proposed early encapsulation in aqueous phase-separated droplets called coacervates.
These droplets are driven by the accumulation of macromolecules,
producing a distinct dense phase liquid droplet within a more dilute
liquid medium.
These droplets can propagate, retaining their internal composition,
through shear forces and turbulence in the medium, and could have acted
as a means of replicating encapsulation for an early protocell. However,
replication was highly disordered and droplet fusion is common, calling
into question coacervates true potential for distinct
compartmentalization leading to competition and early
Darwinian-selection.
Sexual reproduction
Eigenet al. and Woese proposed that the genomes of early protocells were composed of single-stranded RNA, and that individual genes corresponded to separate RNA segments, rather than being linked end-to-end as in present-day DNA genomes. A protocell that was haploid
(one copy of each RNA gene) would be vulnerable to damage, since a
single lesion in any RNA segment would be potentially lethal to the
protocell (e.g. by blocking replication or inhibiting the function of an
essential gene).
Vulnerability to damage could be reduced by maintaining two or
more copies of each RNA segment in each protocell, i.e. by maintaining
diploidy or polyploidy. Genome redundancy would allow a damaged RNA
segment to be replaced by an additional replication of its homolog.
For such a simple organism, the proportion of available resources tied
up in the genetic material would be a large fraction of the total
resource budget. Under limited resource conditions, the protocell
reproductive rate would likely be inversely related to ploidy number,
and the protocell's fitness would be reduced by the costs of redundancy.
Consequently, coping with damaged RNA genes while minimizing the costs
of redundancy would likely have been a fundamental problem for early
protocells.
A cost-benefit analysis was carried out in which the costs of
maintaining redundancy were balanced against the costs of genome damage.
This analysis led to the conclusion that, under a wide range of
circumstances, the selected strategy would be for each protocell to be
haploid, but to periodically fuse with another haploid protocell to form
a transient diploid. The retention of the haploid state maximizes the
growth rate. The periodic fusions permit mutual reactivation of
otherwise lethally damaged protocells. If at least one damage-free copy
of each RNA gene is present in the transient diploid, viable progeny can
be formed. For two, rather than one, viable daughter cells to be
produced would require an extra replication of the intact RNA gene
homologous to any RNA gene that had been damaged prior to the division
of the fused protocell. The cycle of haploid reproduction, with
occasional fusion to a transient diploid state, followed by splitting to
the haploid state, can be considered to be the sexual cycle in its most
primitive form. In the absence of this sexual cycle, haploid protocells with damage in an essential RNA gene would simply die.
This model for the early sexual cycle is hypothetical, but it is
very similar to the known sexual behavior of the segmented RNA viruses,
which are among the simplest organisms known. Influenza virus, whose genome consists of 8 physically separated single-stranded RNA segments,
is an example of this type of virus. In segmented RNA viruses, "mating"
can occur when a host cell is infected by at least two virus particles.
If these viruses each contain an RNA segment with a lethal damage,
multiple infection can lead to reactivation providing that at least one
undamaged copy of each virus gene is present in the infected cell. This
phenomenon is known as "multiplicity reactivation". Multiplicity
reactivation has been reported to occur in influenza virus infections
after induction of RNA damage by UV-irradiation, and ionizing radiation.
Starting with a technique commonly used to deposit molecules on a
solid surface, Langmuir–Blodgett deposition, scientists are able to
assemble phospholipid membranes of arbitrary complexity layer by layer. These artificial phospholipid membranes support functional insertion both of purified and of in situ expressed membrane proteins. The technique could help astrobiologists understand how the first living cells originated.
Surfactant molecules arranged on an air–water interface
Jeewanu protocells are synthetic chemical particles that possess cell-like structure and seem to have some functional living properties. First synthesized in 1963 from simple minerals and basic organics while exposed to sunlight, it is still reported to have some metabolic capabilities, the presence of semipermeable membrane, amino acids, phospholipids, carbohydrates and RNA-like molecules. The nature and properties of the Jeewanu remains to be clarified.
In a similar synthesis experiment a frozen mixture of water, methanol, ammonia and carbon monoxide
was exposed to ultraviolet (UV) radiation. This combination yielded
large amounts of organic material that self-organised to form globules
or vesicles when immersed in water.
The investigating scientist considered these globules to resemble cell
membranes that enclose and concentrate the chemistry of life, separating
their interior from the outside world. The globules were between 10 and
40 micrometres (0.00039 and 0.00157 in), or about the size of red blood
cells. Remarkably, the globules fluoresced,
or glowed, when exposed to UV light. Absorbing UV and converting it
into visible light in this way was considered one possible way of
providing energy to a primitive cell. If such globules played a role in
the origin of life, the fluorescence could have been a precursor to
primitive photosynthesis.
Such fluorescence also provides the benefit of acting as a sunscreen,
diffusing any damage that otherwise would be inflicted by UV radiation.
Such a protective function would have been vital for life on the early
Earth, since the ozone layer, which blocks out the sun's most destructive UV rays, did not form until after photosynthetic life began to produce oxygen.
The synthesis of three kinds of "jeewanu" have been reported; two of
them were organic, and the other was inorganic. Other similar inorganic
structures have also been produced. The investigating scientist (V. O.
Kalinenko) referred to them as "bio-like structures" and "artificial
cells". Formed in distilled water (as well as on agar gel) under the
influence of an electric field, they lack protein, amino acids, purine
or pyrimidine bases, and certain enzyme activities. According to NASA
researchers, "presently known scientific principles of biology and
biochemistry cannot account for living inorganic units" and "the
postulated existence of these living units has not been proved".
Analogous Research: Fuel Cells
In March 2014, NASA's Jet Propulsion Laboratory demonstrated a unique way to study the origins of life: fuel cells.
Fuel cells are similar to biological cells in that electrons are also
transferred to and from molecules. In both cases, this results in
electricity and power. The study of fuel cells suggest that an important
factor in protocell development was that the Earth provides electrical
energy at the seafloor. "This energy could have kick-started life and
could have sustained life after it arose. Now, we have a way of testing
different materials and environments that could have helped life arise
not just on Earth, but possibly on Mars, Europa and other places in the Solar System."
Ethics, controversy, and research considerations
Protocell research has created controversy and opposing opinions, including criticism of vague definitions of "artificial life".
The creation of a basic unit of life is the most pressing ethical
concern, although the most widespread worry about protocells is their
potential threat to human health and the environment through
uncontrolled replication.
Additionally, postulation into the conditions for protocellular
origins of life on Earth remain debated. Scientists in the field
emphasize the importance of further hypothesis based experimentation
over theoretical conjecture to more concretely constrain the prebiotic
plausibility of different protocell morphologies, geologic conditions,
and synthetic schemes.
act as a physical and chemical barrier to infectious agents; via
physical measures such as skin and mucus, and chemical measures such as clotting factors and host defence peptides.
Anatomical barriers
Anatomical
barriers include physical, chemical and biological barriers. The
epithelial surfaces form a physical barrier that is impermeable to most
infectious agents, acting as the first line of defense against invading
organisms. Desquamation
(shedding) of skin epithelium also helps remove bacteria and other
infectious agents that have adhered to the epithelial surface. Lack of
blood vessels, the inability of the epidermis to retain moisture, and
the presence of sebaceous glands in the dermis, produces an environment unsuitable for the survival of microbes. In the gastrointestinal and respiratory tract, movement due to peristalsis or cilia, respectively, helps remove infectious agents. Also, mucus traps infectious agents. Gut flora
can prevent the colonization of pathogenic bacteria by secreting toxic
substances or by competing with pathogenic bacteria for nutrients or
cell surface attachment sites. The flushing action of tears and saliva helps prevent infection of the eyes and mouth.
Inflammation
is one of the first responses of the immune system to infection or
irritation. Inflammation is stimulated by chemical factors released by
injured cells. It establishes a physical barrier against the spread of
infection and promotes healing of any damaged tissue following pathogen
clearance.
The process of acute inflammation is initiated by cells already present in all tissues, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells, and mast cells. These cells present receptors contained on the surface or within the cell, named pattern recognition receptors (PRRs), which recognize molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns
(PAMPs). At the onset of an infection, burn, or other injuries, these
cells undergo activation (one of their PRRs recognizes a PAMP) and
release inflammatory mediators,
like cytokines and chemokines, which are responsible for the clinical
signs of inflammation. PRR activation and its cellular consequences have
been well-characterized as methods of inflammatory cell death, which
include pyroptosis, necroptosis, and PANoptosis. These cell death pathways help clear infected or aberrant cells and release cellular contents and inflammatory mediators.
Chemical factors produced during inflammation (histamine, bradykinin, serotonin, leukotrienes, and prostaglandins) sensitize pain receptors, cause local vasodilation of the blood vessels, and attract phagocytes, especially neutrophils.
Neutrophils then trigger other parts of the immune system by releasing
factors that summon additional leukocytes and lymphocytes. Cytokines produced by macrophages and other cells of the innate immune system mediate the inflammatory response. These cytokines include TNF, HMGB1, and IL-1.
The inflammatory response is characterized by the following symptoms:
The complement system is a biochemical cascade
of the immune system that helps, or "complements", the ability of
antibodies to clear pathogens or mark them for destruction by other
cells. The cascade is composed of many plasma proteins, synthesized in
the liver, primarily by hepatocytes. The proteins work together to:
trigger the recruitment of inflammatory cells
"tag" pathogens for destruction by other cells by opsonizing, or coating, the surface of the pathogen
form holes in the plasma membrane of the pathogen, resulting in cytolysis of the pathogen cell, causing its death
rid the body of neutralised antigen-antibody complexes.
The three different complement systems are classical, alternative and lectin.
White blood cells (WBCs) are also known as leukocytes.
Most leukocytes differ from other cells of the body in that they are
not tightly associated with a particular organ or tissue; thus, their
function is similar to that of independent, single-cell organisms. Most
leukocytes are able to move freely and interact with and capture
cellular debris, foreign particles, and invading microorganisms
(although macrophages, mast cells, and dendritic cells
are less mobile). Unlike many other cells, most innate immune
leukocytes cannot divide or reproduce on their own, but are the products
of multipotent hematopoietic stem cells present in bone marrow.
Mast cells are a type of innate immune cell that resides in
connective tissue and in mucous membranes. They are intimately
associated with wound healing and defense against pathogens, but are
also often associated with allergy and anaphylaxis. When activated, mast cells rapidly release characteristic granules, rich in histamine and heparin, along with various hormonal mediators and chemokines, or chemotactic cytokines into the environment. Histamine dilates blood vessels, causing the characteristic signs of inflammation, and recruits neutrophils and macrophages.
The word 'phagocyte' literally means 'eating cell'. These are immune cells that engulf, or 'phagocytose', pathogens or particles. To engulf a particle or pathogen, a phagocyte extends portions of its plasma membrane,
wrapping the membrane around the particle until it is enveloped (i.e.,
the particle is now inside the cell). Once inside the cell, the invading
pathogen is contained inside a phagosome, which merges with a lysosome.
The lysosome contains enzymes and acids that kill and digest the
particle or organism. In general, phagocytes patrol the body searching
for pathogens, but are also able to react to a group of highly
specialized molecular signals produced by other cells, called cytokines. The phagocytic cells of the immune system include macrophages, neutrophils, and dendritic cells.
Phagocytosis of the hosts' own cells is common as part of regular tissue
development and maintenance. When host cells die, either by apoptosis or by cell injury due to an infection, phagocytic cells are responsible for their removal from the affected site.
By helping to remove dead cells preceding growth and development of new
healthy cells, phagocytosis is an important part of the healing process
following tissue injury.
Macrophages, from the Greek, meaning "large eaters", are large
phagocytic leukocytes, which are able to move beyond the vascular system
by migrating through the walls of capillary
vessels and entering the areas between cells in pursuit of invading
pathogens. In tissues, organ-specific macrophages are differentiated
from phagocytic cells present in the blood called monocytes. Macrophages are the most efficient phagocytes and can phagocytose substantial numbers of bacteria or other cells or microbes.
The binding of bacterial molecules to receptors on the surface of a
macrophage triggers it to engulf and destroy the bacteria through the
generation of a "respiratory burst", causing the release of reactive oxygen species. Pathogens also stimulate the macrophage to produce chemokines, which summon other cells to the site of infection.
Neutrophils, along with eosinophils and basophils, are known as granulocytes due to the presence of granules in their cytoplasm, or as polymorphonuclear cells (PMNs) due to their distinctive lobed nuclei.
Neutrophil granules contain a variety of toxic substances that kill or
inhibit growth of bacteria and fungi. Similar to macrophages,
neutrophils attack pathogens by activating a respiratory burst. The main products of the neutrophil respiratory burst are strong oxidizing agents including hydrogen peroxide, free oxygen radicals and hypochlorite.
Neutrophils are the most abundant type of phagocyte, normally
representing 50–60% of the total circulating leukocytes, and are usually
the first cells to arrive at the site of an infection.
The bone marrow of a normal healthy adult produces more than 100
billion neutrophils per day, and more than 10 times that many per day
during acute inflammation.
Dendritic cells (DCs) are phagocytic cells present in tissues that are in contact with the external environment, mainly the skin (where they are often called Langerhans cells), and the inner mucosal lining of the nose, lungs, stomach, and intestines. They are named for their resemblance to neuronaldendrites, but dendritic cells are not connected to the nervous system. Dendritic cells are very important in the process of antigen presentation, and serve as a link between the innate and adaptive immune systems.
Basophils and eosinophils are cells related to the neutrophil. When activated by a pathogen encounter, histamine-releasing basophils are important in the defense against parasites and play a role in allergic reactions, such as asthma. Upon activation, eosinophils secrete a range of highly toxic
proteins and free radicals that are highly effective in killing
parasites, but may also damage tissue during an allergic reaction.
Activation and release of toxins by eosinophils are, therefore, tightly
regulated to prevent any inappropriate tissue destruction.
Natural killer cells (NK cells) do not directly attack invading microbes. Rather, NK cells destroy compromised host cells, such as tumor
cells or virus-infected cells, recognizing such cells by a condition
known as "missing self". This term describes cells with abnormally low
levels of a cell-surface marker called MHC I (major histocompatibility complex) - a situation that can arise in viral infections of host cells.
They were named "natural killer" because of the initial notion that
they do not require activation in order to kill cells that are "missing
self". The MHC makeup on the surface of damaged cells is altered and the
NK cells become activated by recognizing this. Normal body cells are
not recognized and attacked by NK cells because they express intact self
MHC antigens. Those MHC antigens are recognized by killer cell immunoglobulin receptors (KIR) that slow the reaction of NK cells. The NK-92 cell line does not express KIR and is developed for tumor therapy.
Like other 'unconventional' T cell subsets bearing invariant T cell receptors (TCRs), such as CD1d-restricted Natural Killer T cells,
γδ T cells exhibit characteristics that place them at the border
between innate and adaptive immunity. γδ T cells may be considered a
component of adaptive immunity in that they rearrange TCR genes to produce junctional diversity and develop a memory phenotype.
The various subsets may be considered part of the innate immune system
where a restricted TCR or NK receptors may be used as a pattern recognition receptor. For example, according to this paradigm, large numbers of Vγ9/Vδ2 T cells respond within hours to common molecules produced by microbes, and highly restricted intraepithelial Vδ1 T cells will respond to stressed epithelial cells.
Increased levels of lactoferrin and transferrin inhibit bacterial growth by binding iron, an essential bacterial nutrient.
Neural regulation
The
innate immune response to infectious and sterile injury is modulated by
neural circuits that control cytokine production period. The inflammatory reflex is a prototypical neural circuit that controls cytokine production in the spleen. Action potentials transmitted via the vagus nerve to the spleen mediate the release of acetylcholine, the neurotransmitter that inhibits cytokine release by interacting with alpha7 nicotinic acetylcholine receptors (CHRNA7) expressed on cytokine-producing cells. The motor arc of the inflammatory reflex is termed the cholinergic anti-inflammatory pathway.
Pathogen-specificity
The parts of the innate immune system display specificity for different pathogens.
Type I interferons (IFN), secreted mainly by dendritic cells, play a central role in antiviral host defense and a cell's antiviral state. Viral components are recognized by different receptors: Toll-like receptors are located in the endosomal membrane and recognize double-stranded RNA
(dsRNA), MDA5 and RIG-I receptors are located in the cytoplasm and
recognize long dsRNA and phosphate-containing dsRNA respectively. When the cytoplasmic receptors MDA5 and RIG-I recognize a virus the conformation between the caspase-recruitment domain
(CARD) and the CARD-containing adaptor MAVS changes. In parallel, when
TLRs in the endocytic compartments recognize a virus the activation of
the adaptor protein TRIF is induced. Both pathways converge in the recruitment and activation of the IKKε/TBK-1 complex, inducing dimerization of transcription factorsIRF3 and IRF7,
which are translocated in the nucleus, where they induce IFN production
with the presence of a particular transcription factor and activate
transcription factor 2. IFN is secreted through secretory vesicles, where it can activate receptors on both the cell it was released from (autocrine) or nearby cells (paracrine). This induces hundreds of interferon-stimulated genes to be expressed. This leads to antiviral protein production, such as protein kinase R, which inhibits viral protein synthesis, or the 2′,5′-oligoadenylate synthetase family, which degrades viral RNA.
Some viruses evade this by producing molecules that interfere with IFN production. For example, the Influenza A virus produces NS1 protein, which can bind to host and viral RNA, interact with immune signaling proteins or block their activation by ubiquitination, thus inhibiting type I IFN production. Influenza A also blocks protein kinase R activation and establishment of the antiviral state. The dengue virus also inhibits type I IFN production by blocking IRF-3phosophorylation using NS2B3 protease complex.
Beyond vertebrates
Prokaryotes
Bacteria (and perhaps other prokaryotic organisms), utilize a unique defense mechanism, called the restriction modification system to protect themselves from pathogens, such as bacteriophages. In this system, bacteria produce enzymes, called restriction endonucleases, that attack and destroy specific regions of the viral DNA of invading bacteriophages. Methylation of the host's own DNA marks it as "self" and prevents it from being attacked by endonucleases. Restriction endonucleases and the restriction modification system exist exclusively in prokaryotes.
Invertebrates
Invertebrates
do not possess lymphocytes or an antibody-based humoral immune system,
and it is likely that a multicomponent, adaptive immune system arose
with the first vertebrates. Nevertheless, invertebrates possess mechanisms that appear to be precursors of these aspects of vertebrate immunity. Pattern recognition receptors
(PRRs) are proteins used by nearly all organisms to identify molecules
associated with microbial pathogens. TLRs are a major class of pattern
recognition receptor, that exists in all coelomates (animals with a body-cavity), including humans. The complement system exists in most life forms. Some invertebrates, including various insects, crabs, and worms utilize a modified form of the complement response known as the prophenoloxidase (proPO) system.
Antimicrobial peptides are an evolutionarily conserved component of the innate immune response found among all classes of life and represent the main form of invertebrate systemic immunity. Several species of insect produce antimicrobial peptides known as defensins and cecropins.
Proteolytic cascades
In invertebrates, PRRs trigger proteolytic cascades that degrade proteins and control many of the mechanisms of the innate immune system of invertebrates—including hemolymph coagulation and melanization.
Proteolytic cascades are important components of the invertebrate
immune system because they are turned on more rapidly than other innate
immune reactions because they do not rely on gene changes. Proteolytic
cascades function in both vertebrate and invertebrates, even though
different proteins are used throughout the cascades.
Clotting mechanisms
In the hemolymph, which makes up the fluid in the circulatory system of arthropods,
a gel-like fluid surrounds pathogen invaders, similar to the way blood
does in other animals. Various proteins and mechanisms are involved in
invertebrate clotting. In crustaceans, transglutaminase
from blood cells and mobile plasma proteins make up the clotting
system, where the transglutaminase polymerizes 210 kDa subunits of a
plasma-clotting protein. On the other hand, in the horseshoe crab
clotting system, components of proteolytic cascades are stored as
inactive forms in granules of hemocytes, which are released when foreign
molecules, like lipopolysaccharides enter.
Members of every class of pathogen that infect humans also infect
plants. Although the exact pathogenic species vary with the infected
species, bacteria, fungi, viruses, nematodes, and insects can all cause plant disease. As with animals, plants attacked by insects or other pathogens use a set of complex metabolic
responses that lead to the formation of defensive chemical compounds
that fight infection or make the plant less attractive to insects and
other herbivores. (see: plant defense against herbivory).
Like invertebrates, plants neither generate antibody or T-cell
responses nor possess mobile cells that detect and attack pathogens. In
addition, in case of infection, parts of some plants are treated as
disposable and replaceable, in ways that few animals can. Walling off or
discarding a part of a plant helps stop infection spread.
Most plant immune responses involve systemic chemical signals
sent throughout a plant. Plants use PRRs to recognize conserved
microbial signatures. This recognition triggers an immune response. The
first plant receptors of conserved microbial signatures were identified
in rice (XA21, 1995) and in Arabidopsis (FLS2, 2000).
Plants also carry immune receptors that recognize variable pathogen
effectors. These include the NBS-LRR class of proteins. When a part of a
plant becomes infected with a microbial or viral pathogen, in case of
an incompatible interaction triggered by specific elicitors, the plant produces a localized hypersensitive response
(HR), in which cells at the site of infection undergo rapid apoptosis
to prevent spread to other parts of the plant. HR has some similarities
to animal pyroptosis, such as a requirement of caspase-1-like proteolytic activity of VPEγ, a cysteine protease that regulates cell disassembly during cell death.
"Resistance" (R) proteins, encoded by R genes, are widely present in plants and detect pathogens. These proteins contain domains similar to the NOD Like Receptors and TLRs. Systemic acquired resistance (SAR) is a type of defensive response that renders the entire plant resistant to a broad spectrum of infectious agents. SAR involves the production of chemical messengers, such as salicylic acid or jasmonic acid.
Some of these travel through the plant and signal other cells to
produce defensive compounds to protect uninfected parts, e.g., leaves.[43]
Salicylic acid itself, although indispensable for expression of SAR, is
not the translocated signal responsible for the systemic response.
Recent evidence indicates a role for jasmonates in transmission of the signal to distal portions of the plant. RNA silencing mechanisms are important in the plant systemic response, as they can block virus replication. The jasmonic acid response is stimulated in leaves damaged by insects, and involves the production of methyl jasmonate.
