>>>>>>>>>>>>
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
>>>>>>>>>>>>
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.