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2.4.23 Causes of Cold-like Symptoms and Pneumonia

2.4.23.1 Overview

Cold-like symptoms and pneumonia should be learned to realize COVID-19

2.4.23.2 Details

2.4.23.2.1 An Outline of Causes of Cold-Like Symptoms and Pneumonia

COVID-19 is basically planned disinformation for vaccination. Yet before going into details, preliminary knowledge of colds and pneumonia should be learned.

A cold or a cold-like symptom is typically a disease of acute inflammation of the upper respiratory tract (nasal cavity and throat). The typical symptoms are cough, sneezing, runny nose, nasal congestion, fatigue, headache, sore throat, and fever. Onset of symptoms may begin about 2 days after the causes. Symptoms culminate around 2 - 4 days after the onset. Most patients recover 7 to 10 days after the onset, while some could last for 20 days.
It is commonly said that causes of cold syndromes are mostly viruses (90%) and exceptionally various bacteria (10%). The major types of viruses responsible for colds are rhinoviruses (about 45% × 90%), human coronaviruses (conventional human coronaviruses) (about 15% × 90%), influenza viruses (about 10% × 90%), respiratory syncytial viruses (RSV, Human orthopneumoviruses) (about 8% × 90%), parainfluenza viruses 3 (Human PIV3) (about 8% × 90%), parainfluenza viruses 1 and 4 (Human PIV1 and Human PIV4) (about 7% × 90%), adenoviruses (about 5% × 90%), and human metapneumoviruses (HMPV) (about 2% × 90%). The major types of bacteria responsible for colds are Streptococcus pneumoniae (about 50% × 10%) and Mycoplasma (about 20% × 10%).
The progression of a cold might cause pneumonia, inflammation of the lung affecting alveolar sacs of the lung. In contrast to colds, pneumonia would be rather attributed to bacteria (about 45%). Other attribution would be Accidental taking of foreign liquid into the lungs with the respiratory current (about 25%), viruses (about 20%), and Inhalation of dust such as mold and asbestos (about 10%). The major types of bactera responsible for pneumonia are Streptococcus pneumoniae (about 40% × about 45%), Haemophilus influenzae (about 30% × about 45%), and Mycoplasma (about 20% × about 45%). The major types of viruses responsible for pneumonia are rhinoviruses (40% × about 20%) and influenza viruses (30% × about 20%).

*Attribution: https://en.wikipedia.org/wiki/File:Illu_conducting_passages.svg
* "Respiratory System in Wikipedia" https://en.wikipedia.org/wiki/Respiratory_system


*Attribution: https://commons.wikimedia.org/wiki/File:Relative_sizes_of_microscopic_entities.jpg

Rhinoviruses become infectious when the outside temperature is around 20 degrees celsius (20 °C, 68 °F), because rhinoviruses proliferate in living cells of 33 - 35 degrees celsius (33 - 35 °C, 91 - 95 °F). The incubation period is about 3 days. Symptoms of Rhinovirus infections are mild, they don't lead to death.

Human coronaviruses (conventional human coronaviruses) become infectious when the outside temperature is below 10 degrees celsius (10 °C, 50 °F) and the outside absolute humidity is below 7 g/m3, because human coronaviruses (conventional human coronaviruses) survive well under low temperature and the scattering increases through dust scattering in dry air. Human coronaviruses (conventional human coronaviruses) are easy to infect children under 10 years of age. The incubation period is about 3 days. Symptoms of Human coronavirus infections are mild, they don't lead to death.

Influenza viruses become infectious when the outside temperature is below 10 degrees celsius (10 °C, 50 °F) and the outside absolute humidity is below 7 g/m3, because influenza viruses survive well under low temperature and the scattering increases through dust scattering in dry air. The incubation period is about 2 days. Symptoms of influenza virus infections are sometimes severe, lead to death in some cases.

Respiratory syncytial viruses (RSV, Human orthopneumoviruses) are infectious when the outside temperature is below 10 degrees celsius (10 °C, 50 °F) or humid. Respiratory syncytial viruses are easy to infect babies under 3 years of age. The incubation period is about 4 days. Symptoms of respiratory syncytial virus infections are bronchitis and pneumonia, sometimes severe, lead to death of babies in some cases. Mixed infection with parainfluenza viruses and human metapneumoviruses (HMPV) would occur.

There are some types of parainfluenza viruses. Parainfluenza viruses have nothing to do with influenza viruses. Parainfluenza viruses 3 (PIV3) are infectious when the outside temperature is 20 - 25 °C (68 - 77 °F). Parainfluenza viruses 1 and 4 are infectious when the outside temperature is below 10 °C (50 °F). Parainfluenza viruses are easy to infect 1 or 2 years old babies. The incubation period is about 4 days. Symptoms of PIV are fever and coughing, they don't lead to death. Mixed infection with respiratory syncytial viruses (RSV) and human metapneumoviruses (HMPV) would occur.

Adenoviruses are infectious independently of the outside temperature, while 30 °C (86 °F) might be somewhat more infectious. Adenoviruses are easy to infect children under 10 years of age. The incubation period is about 7 days. Symptoms of Adenovirus infections are mild or rather severe, they don't lead to death.

Human metapneumoviruses (HMPV) are infectious when the outside temperature is around 20 degrees celsius (20 °C, 68 °F) and humid. Human metapneumoviruses (HMPV) are easy to infect babies and children under 10 years of age. The incubation period is about 5 days. Symptoms of human metapneumovirus (HMPV) infections are bronchitis and pneumonia, sometimes severe. Mixed infection with respiratory syncytial viruses (RSV) and parainfluenza viruses would occur.



* "Rhinovirus in Wikipedia" https://en.wikipedia.org/wiki/Rhinovirus
* "Coronavirus in Wikipedia" https://en.wikipedia.org/wiki/Coronavirus
* "Influenza in Wikipedia" https://en.wikipedia.org/wiki/Influenza
* "Respiratory Syncytial Virus in Wikipedia" https://en.wikipedia.org/wiki/Respiratory_syncytial_virus
* "Human Parainfluenza Viruses in Wikipedia" https://en.wikipedia.org/wiki/Human_parainfluenza_viruses
*Attribution: https://en.wikipedia.org/wiki/File:Adenovirus_4.jpg
* "Adenovirus in Wikipedia" https://en.wikipedia.org/wiki/Adenovirus_infection
* "Human Metapneumovirus in Wikipedia" https://en.wikipedia.org/wiki/Human_metapneumovirus

Bacteria including Streptococcus pneumoniae, Mycoplasma pneumoniae, and Haemophilus influenzae would survive in any outside temperature unless it is over 75 °C (167 °F). They proliferate and become infectious in nutritious and humid conditions of 20 - 50 degree celsius (20 - 50 °C, 68 - 122 °F), particularly 30 - 40 °C (86 - 104 °F). The incubation period of Streptococcus pneumoniae is about 4 days. The incubation period of Mycoplasma pneumoniae is about 15 days. Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma might lead to pneumonia, the symptoms sometimes become serious and lethal.



*Attribution: https://en.wikipedia.org/wiki/File:Streptococcus_pneumoniae.jpg
* "Mycoplasma Pneumoniae in Wikipedia" https://en.wikipedia.org/wiki/Mycoplasma_pneumoniae

Actual causes of cold-like symptoms and pneumonia are multiple. The 2 major factors would be constitutional immunity of individuals and extraneous harmful events, while other factors such as body temperature, contact with pathogenic viruses, and respiratory injury would affect them.
(1) Constitutional Immunity of Individuals
          Overall body temperature including arms, legs, and body surface layers affects immunity
               (commonly affected by atmospheric temperature, room temperature, humidity, and clothes)
          Body condition (old age, fatigue, sleep deprived, chronic disease, etc) affects immunity
          Bacillus Calmette - Guérin (BCG) Tokyo -172 strain vaccination reinforces immunity
          Mental condition affects immunity
(2) Extraneous Harmful Events
          Degree of contact with pathogenic viruses
          Degree of contact with pathogenic bacteria
          Exposure to unfavorable temperature
          Degree of respiratory uncleanness or injury

Details of some factors would be like below.

2.4.23.2.2 Viruses and Immunity

2.4.23.2.2.1 An Outline of Viruses

Viruses are submicroscopic infectious agents that hold DNAs or RNAs and replicate only inside living cells. Viruses are about 20 - 300 nm in length, about 100 nm on average. Form of viruses located outside living cells is called virions. Viruses by themselves have no ability to produce a protein. In combination with living cells, viruses can produce proteins.
When viruses are separated from living things, the viruses would be destroyed in 10 hours. When temperature and humidity of the atmosphere are high, separated viruses would be destroyed in 1 hour.
A virus is at least composed of a capsid (container) enclosing nucleic acid(s) (DNA (s) or mRNA(s)). A capsid is a container made of proteins. Viruses holding DNA (s) are called DNA viruses. Viruses holding mRNA (s) are called RNA viruses. Some species of RNA viruses have enzymes.
A considerable number of species of viruses have an outer layer called "envelope" covering the capsid. An envelope is mostly composed of phospholipid bilayer that was taken from the former host cell (for example from cell membrane) when the virus left the former host cell. Other than that, some glycoproteins are placed on the lipid bilayer (envelope).

A Simple Schematic of a Virus
* https://en.wikipedia.org/wiki/File:Basic_Scheme_of_Virus_en.svg
* "Introduction to Viruses in Wikipedia" https://en.wikipedia.org/wiki/Introduction_to_viruses
There would be nearly hundreds of thousands of species of viruses. Details of most viruses are unknown or unidentified. Yet, they all can survive and multiply at least to a certain extent in living cells. About 6,000 species of viruses are known (identified) as of 2020 CE. Mammalian infectious identified viruses would be about 500 species. Viruses are infectious when the surface structure of the viruses fits a receptor on the surface of a living cell. Human pathogenic identified viruses would be about 100 species as of 2020 CE. Viruses would be pathogenic when the viruses destroy living cells.

Virions (complete virus particle outside host cells) of some common Human Viruses with their relative size
(Fake Viruses such as Ebolavirus are included)
* "Viruses in Wikipedia" https://en.wikipedia.org/wiki/Virus

It is commonly said that about 50% of cold symptoms are attributed to rhinoviruses, 15% to human coronaviruses, 10% to influenza viruses, 5% adenoviruses, 3% human respiratory syncytial viruses (RSV), 2% enteroviruses, 2% human parainfluenza viruses, 2% human metapneumoviruses, and the rest to others.

2.4.23.2.2.2 Process of Infection and Immune Response

Human cold pathogenic viruses would infect and replicate like below.
Most part of the outer layer of skin is keratinized, covered with stratum corneum. Most viruses wouldn't infect on stratum corneum. In contrast, mucous membranes such as nasal cavity and throat are not keratinized, they are slightly protected by body fluid and so on, they tend to be infected.
Wearing clean surgical masks prevents mucosal dryness, prevents fingers from touching the lip, reduces the risk of infection.
Scattered viruses would accidentally encounter human living cells of mucos membranes around the nasal cavity and the throat. When defense of the mucos membranes is weak and the surface structure of a virus fits a receptor on the surface of a human living cell, the virus adheres to the receptor and enter the living cell in 10 - 20 minutes. DNA (s) or mRNA (s) of the virus are released in the living cell and enzymes to generate replicated viruses are produced. A part of the replicated viruses would go out of the living cell like other Extracellular Vesicles, when the living cell is living. (Living cells would generally discharge various vesicles called Extracellular Vesicles, enclosing various substances such as DNAs and RNAs.)
From one virus, about 100 viruses are generated (replicated) in the living cell in 10 hours, then the cell is destroyed, rest of the replicated viruses in the cell are released. The released replicated viruses (and replicated viruses that went out of the living cells) would enter other living cells.

When many viruses are released from living cells, human immune system would respond to them.
Human immune system consists of the innate immune system and the adaptive immune system. The innate immune system mentioned below would respond in this early stage. For example, 75% of Influenza infection would be resolved before the onset by the innate immune system. 75% of Influenza infection would not develop into the onset.

Human immune system would be encouraged by high body temperature. Keeping the body warm encourages human immune system. Good body condition and mental condition encourage human immune system. Fatigue, sleep deprived, chronic diseases, and so on would reduce human immune system.

Aside from that, BCG (Bacillus Calmette - Guérin) Tokyo-172 strain vaccination would encourage human immune system. BCG vaccine is made of a strain of the attenuated Mycobacterium tuberculosis bacteria, which has ability to multiply but lost ability to cause disease or damage in humans. BCG vaccine is primarily used against tuberculosis, which is caused by Mycobacterium tuberculosis bacteria, expecting to obtain adaptive immunity against turberculois.
However, particularly BCG Tokyo-172 strain also encourages innate immunity over a long period of time. The attenuated bacteria may be activating innate immunity over a long period of time. The mechanism might be that the attenuated bacteria cause state like chronic infection with no disease, the state like chronic infection weaken winding of DNAs about innate immunity onto histon, consequently interrupt formation of nucleosome about innate immunity.

* "BCG Vaccine in Wikipedia" https://en.wikipedia.org/wiki/BCG_vaccine
* "Tuberculosis in Wikipedia" https://en.wikipedia.org/wiki/Tuberculosis

Additionally, similar to the above, temporary pathogen infections may also temporarily boost innate immunity. This is a phenomenon in which when infected with one pathogen, it becomes difficult to be infected with other pathogens at the same time.

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DNAs show some types in shape.

Shapes of DNA
from left to right
(1) DNA Double-Stranded Helix, (2) Nucleosome, (3) 10 nm "Beads-on-a-String" Chromatin Fibre,
(4) 30 nm Chromatin Fibre, (5) 30 nm Chromatin Fibre (wide view),
(6) Active Chromosome, (7) Active Chromosome (wide view),
(8) Metaphase Chromosome, (9) Metaphase Chromosome (wide view)
*Attribution: http://en.wikipedia.org/wiki/File:Chromatin_Structures.png

(1) A double-stranded helix DNA is basically a twisted long ladder.

(2) Nucleosome
On the other hand, since Human DNAs in a cell are some 2 m in total and they should be housed in a nucleus some 10 μm in diameter, double-stranded helix DNAs are commonly shrunken (wound). Double-stranded helix DNAs are shrunken (wound) mediated by Histone.
Histone is a kind of proteins. 8 molecules of histone form a "histone octomer." Double-stranded helix DNA usually winds itself around "histone octomers" and forms "nucleosome." Double-stranded helix DNA winds 2 turns around each histone octomer as nucleosome.

Nucleosome
*Attribution: http://en.wikipedia.org/wiki/File:Nucleosome_organization.png

* "Nucleosome in HubPages" http://nathanielzhu.hubpages.com/hub/Nucleosome-Structure-Part-1
* "Nucleosome in Wikipedia" http://en.wikipedia.org/wiki/Nucleosome

(3) Chromatin (10 nm Beads-on-a-String Chromatin Fibre)
A chain of nucleosomes is a chromatin. Then the length of double-stranded helix DNA is shortened in the shape of nucleosome or chromatin. Nucleosomes firstly form 10nm Beads-on-a-String Chromatin Fibre.
10 nm Beads-on-a-String Chromatin Fibre is active in transcription (protein synthesis), supposedly because DNAs are partly wound and strings are still quite exposed.

Beads-on-a-String
*Attribution: http://en.wikipedia.org/wiki/File:Chromatin_Structures.png

(4) Chromatin (30 nm Chromatin Fibre)
When 10 nm Beads-on-a-String Chromatin Fibre is furthermore wound, it would be 30 nm Chromatin Fibre.
30 nm Chromatin Fibre is less active in transcription (protein synthesis), supposedly because double-stranded helix DNA string is less exposed.
Since Nucleosomes partly stick to double-stranded helix DNAs, Nucleosomes partly oppose DNA transcription. Then it should be noted that situation of Nucleosomes or Chromatin affects specific transcription, protein biosynthesis, and consequently determines cellular property.
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When many cells are destroyed, it would be the onset and pathogenic. Cold-like symptoms would appear around the nose and the throat 48 hours after the first infection. Assuming that the first infection occurred in 10 living cells, viruses after 45 hours would be like 10,000,000,000 around the nasal cavity and the throat. Assuming volume of body fluid associated with the nasal cavity and the throat to be 500 mL (500 g), 1 mL (1 g) of body fluid includes 20,000,000viruses.
Coughing twice would spread 15 μL (15 mg) of body fluid including saliva, which might include 300,000 viruses. Sneezing once would spread 100 μL (100 mg) of body fluid including saliva, which might include 2,000,000 viruses.

A Typical Virus Replication Cycle (from left to right)
*Attribution: https://en.wikipedia.org/wiki/File:HepC_replication.png

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Mammalian (including human) immune system is responsible for excluding or destroying foreign matter. Mammalian (including human) immune system consists of two systems.
One is the innate immune system (natural immune system), the other is the adaptive immune system (acquired immune system).
The innate immune system (natural immune system) first responds less specific to the foreign matter. When the innate immune system fails to exclude and destroy the foreign matter, the adaptive immune system (acquired immune system) responds relatively efficiently creating efficient cells decently specific to the foreign matter.
A major function of the innate immune system is providing innate immune cells such as Macrophages, Neutrophils, Dendritic cells, and Natural killer cells. These cells are created from (Multipotential) Hematopoietic Stem Cells in bones like below.

Development of Blood Cells
*Attribution: https://en.wikipedia.org/wiki/File:Hematopoiesis_(human)_diagram_en.svg

Multi potential Hematopoietic Stem Cells reside in bones along with bone marrow. Bone marrow is a fluid substance in bones. Bone marrow is a mixture of body fluids, fats, and various cells mostly from Hematopoietic Stem Cells.

Components of Bone Marrow
*Attribution: http://en.wikipedia.org/wiki/File:Gray72-en.svg

For example, a Multipotential Hematopoietic Stem Cell changes into a Promonocyte (Promonocyte cell) in the bone marrow, it drifts into blood vessels and changes into a Monocyte (Monocyte cell), drifts into a part of body and changes into a Macrophage. Innate immune cells such as Macrophages, Neutrophils, Dendritic cells, and Natural killer cells are distributed into various organs and other parts of the human body. When the innate immune cells such as Macrophages, Neutrophils, and Dendric cells encounter various foreign matter such as pathogens, they swallow and destroy various foreign matter and discharge its fragments. Other than that, Natural killer cells destroy mostly specific cells such as cancer cells and virus-infected cells.

* "Macrophage in Wikipedia" https://en.wikipedia.org/wiki/Macrophage
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Virus-infected cells can be distinguished from common cells through fragmentary peptides (on the MHC (Major Histocompatibility Complex) molecules) on the surface of the cells.
Most cells (except for red blood cells) have MHC (Major Histocompatibility Complex) molecules on the surface. A MHC molecule has ability to hold a fragmentary peptide which was in the cell. A schematic diagram of a MHC molecule holding a fragmentary peptide would be like below. As suggested in the larger diagram below, proteins in a cell are disassembled into some fragmentary peptides, a fragmentary peptide is caught by a MHC molecule in the cell, then the MHC molecule holding the fragmentary peptide is transferred to the surface of the cell, the fragmentary peptide is exposed (on the MHC molecule) on the surface of the cell. In short, a fragmentary peptide in a cell would be presented (on a MHC molecule) on the surface of the cell. The exposed fragmentary peptide basically consists of 10 - 20 amino acids.
Virus-infected cells expose fragmentary peptides from viruses. Then virus-infected cells can be distinguished from common cells.




* https://en.wikipedia.org/wiki/File:MHC_Class_I_processing.svg
* "Major Histocompatibility Complex in Wikipedia" https://en.wikipedia.org/wiki/Major_histocompatibility_complex

Macrophages and Neutrophils release specific proteins called Cytokine. Cytokine raises body temperature, high body temperature encourages Leucocytes (Granulocytes (Neutrophils and others), Monocytes (develop into Macrophages and Dendritic Cells), and Lymphocytes) and the immune system.
Many patients recover within 7 days.

When the cold last long, the adaptive immune system appears.

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Some Macrophages and Dendritic cells drift holding some fragments of the destroyed foreign matter.
When the innate immune system is struggling to annihilate the foreign matter, the adaptive immune system responds. The first step of the adaptive immune system is Helper T-cells' acceptance of foreign matter's fragmentary peptides. The major cells of the adaptive immune system are Helper T-cells (Helper T lymphocyte cells or T helper cells), killer T-cells (killer T lymphocyte cells), and B cells (B lymphocyte cells). They are created from (Multipotential) Hematopoietic Stem Cells in bones as shown above and distributed into various organs and other parts of the human body. (Helper T-cells and killer T-cells are created from T-cells (T lymphocyte cells).) T-cells and B-cells have millions of variations in their fine structure (in T-cell receptor and B-cell receptor).

When a Helper T-cell encounters a Macrophage or a Dendritic cell holding a fragment (peptide) of the destroyed foreign matter on its surface (on a molecule called MHC) and the fragments (peptide) fit the specified variation (T-cell receptor) of the Helper T-cell, the Helper T-cell is activated. When the activated Helper T-cell encounters the specified variation (T-cell receptor) of killer T-cells or the specified variation (B-cell receptor) of B-cells holding fragments (peptides) of the destroyed foreign matter, the killer T-cells change into activated killer T-cells or the B-cells change into Plasma cells. Plasma cells produce antibodies. Then the activated killer T-cells and the antibodies attack the foreign matter. (Other pathways of the adaptive immune system are left out for now.)


Acceptance of Helper T-Cell and Contact to B-Cell for B-cell Activation
* "T Helper Cell in Wikipedia" https://en.wikipedia.org/wiki/T_helper_cell
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Schematic View of a T-Cell with TCR Complex


Schematic View of a B-Cell with BCR
* "B Cell in Wikipedia" https://en.wikipedia.org/wiki/B_cell

MHC molecules would be categorized into MHC Class I and MHC Class II. Most cells except for red blood cells, Macrophages, and Dendritic Cells form MHC Class I molecules. In contrast, Macrophages and Dendritic Cells form MHC Class II molecules. Class I and Class II are basically similar in shape.

The basic mechanism of MHC Class I and Class II are similar. Yet, Class II on Macrophages and Dendritic Cells is different from Class I in function. When Macrophages or Dendritic Cells swallow viruses, proteins of viruses are disassembled and some fragmentary peptides derived from viruses are exposed on MHC Class II molecules.
On the other hand, Helper T-cells have special parts (protein complexes) called TCR (T-cell receptor). Fine structure of the TCR of a Helper T-cell is basically different from other Helper T-cells' TCR. Fine structure of Helper T-cells' TCR is diverse. T-cells are produced, it become millions of variations of TCR's fine structure. The diversity of TCR is created through DNA recombination.
A few TCR out of millions of TCR would fit a specific peptide in several days. When a MHC Class II on Macrophages or Dendritic Cells holding a fragmentary peptide of foreign matter enters a lymph node and accidentally encounter a suitable TCR of Helper T-cells, the Helper T-cell would be activated. The activated Helper T-cell would multiply. (There are about 600 lymph nodes in a human body)
Other than that, B-cells similarly have special parts (protein complexes) called BCR (B-cell receptor). Fine structure of a B-cell is basically different from other B-cells' BCR. Fine structure of B-cells' BCR is diverse. There would be millions of variations of BCR's fine structure. The diversity of BCR is created through DNA recombination.
A few BCR out of millions of BCR would suit the foreign matter. The suitable BCR can activate B-cells. T-cell dependent activation would be the major pathway of B-cell activation. In T-cell dependent activation of B-cell, when a part of foreign matter encounters a suitable BCR of B-cells in a lymph node, the B-cell takes in the part of foreign matter, disassembles it, and exposes a fragmentary peptide on its MHC Class II. Subsequently, when the activated Helper T-cell encounters the B-cell exposing (presenting) the fragmentary peptide, the activated Helper T-cell activates the B-cell through Cytokines. The activated B-cell would multiply and change into Plasma cells and memory B-cells.
The Plasma cells release their Y-shaped proteins, BCRs. The Y-shaped proteins are antibodies called Immunoglobulins. Immunoglobulins would stick to the specified foreign matter and destroy them in combination with Phagocytes such as Macrophages. The major Immunoglobulins are Immunoglobulin M (IgM) and Immunoglobulin G (IgG).
Immunoglobulin M (IgM) starts to appear about 7 days after the infection, about 5 days after the onset. IgM culminates about 14 days after the infection, about 12 days after the onset. IgM disappears about 21 days after the infection, about 19 days after the onset. Immunoglobulin G (IgG) instead starts to appear about 14 days after the infection, about 12 days after the onset. IgG culminates about 25 days after the infection, about 23 days after the onset. IgG slowly decreases, yet is provided for several months or several years.
In addition, the activated Helper T-cells would activate specific killer T-cells that fit the fragmentary peptide. The activated killer T-cells would destroy virus-infected cells.
Then, memory B-cells remain for a long time in the body, they quickly produce antibodies when the same foreign matter enters the body.
(Other pathways of the adaptive immune system are left out for now.)
Yet, there are other variations of symptom transitions. The variations are shown like below.






* "T Helper Cell in Wikipedia" https://en.wikipedia.org/wiki/T_helper_cell

Lymph Nodes in Human Body
* "Lymph Node in Wikipedia" https://en.wikipedia.org/wiki/Lymph_node


Schematic Diagram of Immunoglobulin
*Attribution: https://en.wikipedia.org/wiki/File:AntibodyChains.svg


Process Destroying Foreign Matter in Combination with Immunoglobulins and Phagocytes.
1. Antibodies (A) and pathogens (B) drift in the blood.
2. The antibodies bind to pathogens.
3. A phagocyte (C) approaches the pathogen.
4. Phagocytosis occurs as the pathogen is ingested.
*Attribution: https://en.wikipedia.org/wiki/File:Antibody_Opsonization.svg

* "Memory B Cell in Wikipedia" https://en.wikipedia.org/wiki/Memory_B_cell

2.4.23.2.2.3 Types of Viruses

2.4.23.2.2.3.1 Introduction to Types of Viruses

There would be basically 7 types of viruses from the viewpoint of DNA and RNA. Yet, before going into detail about this, structure of DNA and RNA, complementarity of bases, directionality of strands, synthesis mechanism of peptides, proteins, and enzymes, replication mechanism, and "sense" of a DNA strand and a RNA strand should be learned.

2.4.23.2.2.3.2 Details of DNAs and RNAs

A DNA is a strand basically consisting of 4 nucleotides, Adenine nucleotide, Thymine nucleotide, Guanine nucleotide, and Cytisine nucleotide. Each nucleotide consists of a sugar, a phosphate, and a nitrogenous base. Nitrogenous bases are Adenine, Thymine, Guanine, and Cytosine. Sugar-phosphate parts bond in a chain (strand) through Phosphodiester bonds.
Assuming 2 strands of DNAs, a nitrogenous base of a DNA strand sticks exclusively to its complementary nitrogenous base of the other DNA strand forming hydrogen bonds. Adenine's complementary nitrogenous base is Thymine. Thymine's complementary nitrogenous base is Adenine. Guanine's complementary nitrogenous base is Cytosine. Cytosine's complementary base is Guanine.
Then the 2 strands form a double-stranded helix. The sugar in DNA is deoxyribose, nucleotide of DNA is deoxynucleotide.


Schematic of DNA
*Attribution: https://commons.wikimedia.org/wiki/File:DNA_simple2.svg

DNA and nucleotides


Structure of a Nucleotide
*Attribution: https://en.wikipedia.org/wiki/File:0322_DNA_Nucleotides.jpg

Bonding of Complementary Nitrogenous Bases
*Attribution: https://en.wikipedia.org/wiki/File:DNA_chemical_structure.svg

In addition, directions of a strand of DNA is defined as directionality. 5 "carbon numbers" are assigned to 5 carbons of each sugar of nucleotides. The end of a DNA strand with carbon number 3 bearing a hydroxyl group is called "3' end." In contrast, the other end with carbon number 5 bearing a phosphate group is called "5' end."

Assignment of Numbers on Sugar Carbons
*Attribution: https://en.wikipedia.org/wiki/File:Nukleotid_num.svg

Structural Formula of a Simplified DNA
*Attribution: https://en.wikipedia.org/wiki/File:Phosphodiester_Bond_Diagram.svg
* "Phosphodiester Bond in Wikipedia" https://en.wikipedia.org/wiki/Phosphodiester_bond

Sequences of nitrogenous bases of DNAs contain information of peptides, proteins, and enzymes to be synthesized. (A peptide is a chain of amino acids, a protein is a large molecule mostly consisting of a large peptide or a lump of peptides. An enzyme is a kind of proteins with specific function, for example producing new biochemical substances such as ethyl alcohol and DNAs and changing biochemical substances. DNA polymerase, DNA dependent RNA polymerase, and RNA dependent RNA polymerase are all enzymes.) Sequences of nitrogenous bases of DNAs are transcribed to mRNAs through DNA dependent RNA polymerase to synthesize peptides, proteins, and enzymes.
* "RNA Polymerase in Wikipedia" https://en.wikipedia.org/wiki/RNA_polymerase

mRNA is similar to DNA, yet there are some differences.
The differences are


mRNA

DNA

Type of Sugar

Ribose

Deoxyribose

Bonding between Bases

Basically Unbonded

Basically Bonded

Structure

Single Helix

Double Helix

Pyrimidine Base

Cytosine and Uracil

Cytosine and Thymine


*Attribution: https://commons.wikimedia.org/wiki/File:Difference_DNA_RNA-EN.svg


*Attribution: https://commons.wikimedia.org/wiki/File:Difference_DNA_RNA-EN.svg

2.4.23.2.2.3.3 Production of mRNA

Assuming it to synthesize the peptide in the order of Tryptophan, Lysine, Aspartic acid, and Phenylalanine, an outline would be like below.

A double-stranded DNA like below should be assumed, the double-stranded DNA is partly torn, a DNA dependent RNA polymerase moves on a strand of DNA from 3' end (3') to 5' end (5'), it produces a strand of mRNA.



* https://en.wikipedia.org/wiki/File:Simple_transcription_elongation1.svg



2.4.23.2.2.3.4 Synthesis of Peptide, Proteins, or Enzymes

Generally, peptides, proteins, and enzymes are synthesized on ribosomes in the living cell, mRNA is acquired by a ribosome, 3 consecutive nitrogenous bases (nucleobases) of part of mRNA (codon) (as shown below, for example, UUC from 5' end to 3' end) are arranged on the synthetic site of the ribosome, tRNA holding 3 consecutive nitrogenous bases complementary to the 3 nitrogenous bases of the mRNA (codon) is introduced to the synthetic site. (As shown below, for example, AAG are complementary to UUC.) The tRNA holds an amino acid. (As shown below, for example, tRNA complementary to UUC holds a Phenylalanine.) 20 types of amino acids are employed for the synthesis, there would be 20 types of tRNAs.

Components of a Typical Animal Cell
* "Ribosome in Wikipedia" https://en.wikipedia.org/wiki/Ribosome


Schematic of Peptide/Protein Synthesis
*Attribution: https://en.wikipedia.org/wiki/File:Peptide_syn.svg

The relationship between combinations of 3 consecutive nitrogenous bases of mRNA (codons) and amino acids that tRNAs are holding is specified. The relation is shown in the Genetic Code.

*Attribution: https://en.wikipedia.org/wiki/File:GeneticCode21-version-2.svg
* "Genetic Code in Wikipedia" https://en.wikipedia.org/wiki/Genetic_code

Then, the mRNA with the sequence of UGGAAAGAUUUC from 5' to 3' can be translated into the peptide in the order of Tryptophan, Lysine, Aspartic acid, and Phenylalanine. In this case, the mRNA is called "positive-strand." (It's complementary strand is called "negative-strand.")
In contrast, the DNA with the sequence of ACCTTTCTAAAG from 3' to 5', GAAATCTTTCCA from 5' to 3', is called "antisense strand (template strand)." The DNA with the sequence of TGGAAAGATTTC from 5' to 3' is called "sense strand (coding strand)."

2.4.23.2.2.3.5 Types of Viruses and Outlines

There would be basically 7 types of viruses from the viewpoint of DNA and RNA.

(I) Double-stranded DNA Viruses
A double-stranded (ds) DNA virus holds a double-stranded DNA in its capsid. When it enters a living cell, it releases the ds DNA, mRNA is produced through DNA-dependent RNA polymerase of the living cell, and peptides, proteins, and enzymes for replication of the virus are synthesized. Examples are Adenoviruses and Smallpox viruses.

(II) Single-stranded DNA Viruses
A single-stranded (ss) DNA virus holds a single-stranded DNA in its capsid. When it enters a living cell, it releases the ss DNA, the complementary strand of DNA is produced through DNA polymerase of the living cell. Then a double-stranded DNA is formed, mRNA is produced through DNA-dependent RNA polymerase of the living cell, peptides, proteins, and enzymes for replication of the virus are synthesized. An example is Adeno-associated viruses.

(III) Double-stranded RNA Viruses
A double-stranded RNA virus holds a double-stranded mRNA and RNA-dependent RNA polymerase in its capsid. When it enters a living cell, it releases the ds mRNA and RdRp, new mRNAs for replication of the virus would be produced through RdRp, and peptides, proteins, and enzymes for replication of the virus are synthesized. An example is Rotaviruses.

(IV) Positive Sense Single-stranded RNA Viruses
A positive sense single-stranded RNA virus holds a positive sense single-stranded mRNA in its capsid. When it enters a living cell, it releases the positive sense mRNA, peptides, proteins, and enzymes including RdRp are synthesized. New positive sense mRNAs for replication of the virus would be produced through RdRp. Examples are Rhinoviruses, Human coronaviruses (conventional human coronaviruses) and Hepatitis C viruses (HCV).

(V) Negative Sense Single-stranded RNA Viruses
A negative sense single-stranded RNA virus holds a negative sense single-stranded mRNA and RNA-dependent RNA polymerase in its capsid. When it enters a living cell, it releases the negative sense mRNA and RdRp, the positive sense mRNA would be produced through RdRp, peptides, proteins, and enzymes for replication of the virus are synthesized. Examples are Influenza viruses and Human respiratory syncytial viruses (RSV).

(VI) Single-stranded RNA Viruses with a DNA Intermediate (Retroviruses)
A single-stranded RNA virus with a DNA intermediate holds a positive sense single-stranded mRNA and RNA-dependent DNA polymerase (reverse transcriptase) in its capsid. When it enters a living cell, it releases the positive sense mRNA and RdDp, double-stranded DNAs (viral DNAs) are produced, the viral DNAs are integrated into DNAs of the living cell. From the viral part of DNAs, peptides, proteins, and enzymes for replication of the virus are synthesized. Examples are Human T-cell lymphotropic viruses and alleged Human Immunodeficiency Viruses.

(VII) Double-stranded DNA Viruses with an RNA Intermediate
A double-stranded (ds) DNA virus with an RNA intermediate holds a double-stranded DNA in its capsid. When it enters a living cell, it releases the ds DNA, mRNA is produced through DNA-dependent RNA polymerase of the living cell, a new ds DNA is produced through RNA-dependent DNA polymerase (reverse transcriptase) for replication of the virus, peptides, proteins, and enzymes for replication of the virus are synthesized. An example is Hepatitis B viruses (HBV).

2.4.23.2.3 Extracellular Vesicles

Aside from viruses, confusing things with viruses, Extracellular Vesicles, should be learned.
Extracellular Vesicles are particles covered with phospholipid bilayer. Extracellular Vesicles are generally released from living cells. Unlike viruses, they have no ability to be replicated. The smallest would be around 20 - 30 nm in diameter, larger one would be like 10 μm, while the majority would be smaller than 200 nm. They look like some viruses.
They are categorized into 3 types fom the viewpoint of the production process.
(1) Microvesicles 100 - 1,000 nm (2) Exosomes 50 - 150 nm, (3) Apoptotic bodies 3,000 nm
Microvesicles start with protrusion (budding) of cell membrane (phospholipid bilayer). Exosomes start with Endocytosis (phenomena of living cells ingesting foreign matter). Apoptotic bodies start with Apoptosis (spontaneous programmed cell death under specific conditions).
They sometimes contain DNAs and RNAs, Exosomes are particularly similar to viruses from the viewpoint of electron microscope.




Schematic of Exosome and MVB (multi-vesicular body)
*Attribution: https://en.wikipedia.org/wiki/File:Exosome_kalamedits.jpg

* "Extracellular Vesicle in Wikipedia" https://en.wikipedia.org/wiki/Extracellular_vesicle
* "Exosome (vesicle) in Wikipedia" https://en.wikipedia.org/wiki/Exosome_(vesicle)
* "Endocytosis in Wikipedia" https://en.wikipedia.org/wiki/Endocytosis
* "Apoptosis in Wikipedia" https://en.wikipedia.org/wiki/Apoptosis

2.4.23.2.4 Bacteria

Bacteria are microscopic single-celled organisms holding DNA, yet lacking a distinct nucleus (prokaryotes), and proliferate outside other living cells, while nutrients are required. They are typically a few micrometers in length. Organelles bound to membrane are not basically seen. (Organelles are specialized small organs that have no nucleic acids.) The bacterial cell is surrounded by a cell membrane, phospholipid bilayer. The membrane encloses contents of the cell.

There would be a million species or genus of bacteria. Details of most bacteria are unknown or unidentified. About 7,000 species or genus of bacteria are known (identified) as of 2020 CE. Plant pathogenic identified bacteria would be about 250 species. Human pathogenic identified bacteria would be about 50 species as of 2020 CE. Most bacteria are non-pathogenic. There are usually about 700 species of harmless indigenous bacteria in a mouth cavity.
Bacteria are about 0.2 - 5 μm in length.
Pathogenic bacteria produce bacterial toxins such as specific lipopolysaccharides and specific proteins.
The immune system would respond them like viruses.


A Schematic View of a Typical Bacterium

* "Bacteria in Wikipedia" https://en.wikipedia.org/wiki/Bacteria

The most typical cold or pneumonia pathogenic bacterium would be Streptococcus pneumoniae. It would cause human pneumonia. It is about 1 μm in size.

Streptococcus Pneumoniae
*Attribution: https://en.wikipedia.org/wiki/File:Streptococcus_pneumoniae.jpg
* "Streptococcus Pneumoniae in Wikipedia" https://en.wikipedia.org/wiki/Streptococcus_pneumoniae

Staphylococcus aureus might follow. It might cause human pneumonia. It is about 500 nm in size.

Staphylococcus Aureus
*Attribution: https://en.wikipedia.org/wiki/File:Staphylococcus_aureus_01.jpg
* "Staphylococcus Aureus in Wikipedia" https://en.wikipedia.org/wiki/Staphylococcus_aureus

Another example could be Mycoplasma pneumoniae. It might cause human pneumonia. It is about 200 nm in length. It might cause human pneumonia. It is about 200 nm in length.


A Schematic View of Mycoplasma Pneumoniae
* "Mycoplasma Pneumoniae in Wikipedia" https://en.wikipedia.org/wiki/Mycoplasma_pneumoniae

Another example could be Chlamydia pneumoniae. It might cause human pneumonia. It is about 200 nm in length.

Chlamydia Pneumoniae
*Attribution: https://en.wikipedia.org/wiki/File:Chlamydia_pneumoniae.jpg
* "Chlamydia Pneumoniae in Wikipedia" https://en.wikipedia.org/wiki/Chlamydia_pneumoniae

Another possible cold or pneumonia pathogenic bacterium could be Mycobacterium avium complex. It might cause atypical pneumonia. The appearance of Mycobacterium avium complex is similar to Coronaviruses.

Mycobacterium Avium
*Attribution: https://en.wikipedia.org/wiki/File:Mycobacterium_avium-intracellulare_01.png
* "Mycobacterium Avium Complex in Wikipedia" https://en.wikipedia.org/wiki/Mycobacterium_avium_complex

2.4.23.2.5 Respiratory Uncleanness and Injury

Accidental taking of foreign liquid into the lungs with the respiratory current would provide nutrients for bacteria. It would encourage bacterial infection.

Respiratory including lungs can be injured by chemical means such as harmful substances and physical means such as electromagnetic waves. Cells and microstructure of lungs can be destroyed. When cells and microstructure of lungs are destroyed, nutrients of cell contents and body fluid are supplied, various bacteria start to multiply. It causes serious bacterial pneumonia.






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