The Immune system: review the way I see it but borders on fiction with new hypotheses weaved in

The immune system is very complex but if examined considering the preferred locations of infections the pathways of the immune system are easier to see.  This text will constantly give examples of the type of infection involved with each pathway.

In humans there is an interplay between the Innate immune system we are born with which can recognize the basic characteristics of our enemy and the adaptive immune system that improves upon recognizing our enemy with any “adjustments” they may have made.  This adaptive immune system exists only in vertebrates.  Invertebrates rely only on the basic innate immune system.

The immune system attack is both coordinated and supportive.  Secreted cytokines coordinate the immune system cells to know what kind of infection they are dealing with.  Immune system cells have become specialized to deal with certain infections and to aid the reactions with cytokines which are not their assigned infection.

The innate immune system has several specialized cells.  The Neutrophils who trap and kill bacteria or yeast.  Natural killer cells who destroy stressed and infected cells.  The phagocyte family of Monocytes, Dendritic cells, and macrophages who patrol and consume foreign objects and infected cells. Basophils who contain serotonin and heparin with which to help kill mycobacteria but are also the starting shot for all visible infections.  Eosinophils are the cleaners of the immune system whose priority is parasites but can kill bacteria or fungal infections with acid. Then there are the Mast cells who help innane immune system cells enter infected areas using histamine and when viral infections are involved they awaken the proper T cells of the adaptive immune system.

The Innate Immune system starts with the barrier regions of the skin, the intestine, and the lungs. These regions consist of epithelial cells and connective fibroblast cells. Surface damaged epithelial cells release the cytokine il-6 and infected epithelial cells release TNFalpha.  Immediately the immune system responses.

When the skin surface is damaged the immune system assumes an infection has entered.  The il-6 travels to the lymph gland where it triggers B cells to make IgM.  IgM travels in the blood until it reaches the wound.  If the infection is something like Staph with a smooth surface the IgM antibody easily binds. This IgM antibody method is called complement. Using the Fc back of the antibody small c proteins splice, bind, and slowly build a pore like hole into the bacteria called MAC.

This MAC pore can be formed 3 ways: the complement method just discussed, the Lectin-mannose-binding method, or by the alternative method.

Strep has developed long mannose strings to block antibodies from reaching the surface.  Since antibodies can’t get in a Mannose-binding lectin binds the string and starts the cascade.

E.coli has gone even further to protect itself developing so many surface structures that the pore must form in the cytosol then force itself onto the surface.  The alternative method. 

Infections don’t always enter the body because of damage. Epithelial cells and fibroblasts at the skin surface also have TLRs.  TLRs are the butterfly nets of the innate which have evolved to snare infections as they attempt to invade the body. The TLR senses an infection then triggers a change in gene expression and secretes cytokines warning the immune system what it thinks it saw so the proper defense can be waged.   The patrolling immune system of macrophages, dendritic cells, mast cells, and basophils also use these TLRs. 

TLR2 catches the sugars, the lipopolysaccharides LPS, of infections that like to move into the cell.  Cytosolic viruses and gram negative bacterium are typically the suspects snagged by TLR2.

TLR4 catches the proteins of gram positive bacterium. These are typically large and are often broken down by the innane immune system cells.

TLR3, TLR7, TLR8, and TLR9 tag antigens know to be inside the cell.  TLR3 is the golgi net, TLR7 is the nuclear net, TLR8 is the ER net, and TLR9 is the mitochondria net.

When one of these inside nets are triggered specific cytokines are produced coordinating the attack.  When herpes zoster infects the mitochondria the TLR7 net is triggered.  IFNalphaA is produced which tell macrophages and dendritic cells to wear MET hands so that they can bind and kill cells infected with the herpes virus. TGF-b1 is also produced which helps to activate TH9 cells and TH17 cells.  TH9 causes the development of TH17 from other Thelper cells. The TH17 cells secretes the organelle popping cytokines of the il-20 family. The cytokine that pops the mitochondrial membrane is il-19.  Then il-17F activates the CTL cells.  Any freed viral antigens are bound by IgG3. 

How did IgG3 get produced by B cells? It begins with il-2.   TH9 requires il-2 not just TGF-B1.   High il-2 also causes the development of CTL.  Where did the il-2 come from? Il-2 is secreted by activated Tc (cd8) cells.

How do T cells become "activated" ? When both the TCR and cd28 are stimulated.  This triggers the ability to secrete cytokines and the expression of ICOS.

When the macrophages or dendritic cells digest the viral infected cells they then hold up the viral pieces in HLA mailboxes to T cells and the TCR binds examines it.  When the T cells are activated by these mailboxes with foreign content, these cd8 T cells secrete il-2 and seek out B cells.  Upon finding a B cell with ICOS ligand the T cells COS stimulation secretes il-4 and il-21 resulting in the B cell producing the IgG3 antibodies. 

What happens with cytosol infections like the flu? TLR3 or there are cytosolic receptors that bind cytosolic viral infections’ antigens. The flu would bind the cytosol receptor Rig-1.  The cytokine IFN-beta then coordinates the response. IFNbeta tells dendritic cells and macrophages to wear the tyro3 hands in order to eat virally infected cells.  They also choose to express the HLA-Dr MHC2 mailbox.  The phagocytes also express il-12 and 25HC.  Il-12 is the cytokine stimulates the development of TH1.  TH1 interacts with the mailboxes of the dendritic cells, verifies it is foreign then finds a B cell. Using il-4 and il-21 the cd4 T cell stimulates the B cell to make IgG2 antibodies. 

How do the IgG2 antibodies see the antigens in the cytosol? The 25HC is a specialized cholesterol that binds RNA.  The macrophages secrete these around infected cells.  If the cells contain an excess of RNA in the cytosol the 25HC would bind it and hold it outside of the infected cell.  The IgG2 antibody can then see the antigens.  Complement now be carried out on infected cells where MAC pores can be created on infected host cells. 

How did the IgG3 see inside of the mitochondria or nucleus? TH17 cells appear whenever there is an infection inside an organelle.  When bacterias enter cells through vacuoles or when IgG3 is involved because a virus is in the mitochondria or nucleus.  These interior membranes are popped by the il-20 family cytokines secreted by TH17.    The  il-22 pops vacuoles, il-24  pops the golgi, il-19 pops the mitochondria, and il-26 pops the nucleus based on where the infections are and which cytokine is secreted.  So while the IgG3 antibodies are being produced TH17 cells would be popping the mitochondria where the virus, like herpes zoster, is hiding. Then calling CTL with il-17f.  NK also have receptors for IgG3.  Note that il-26 which locates to the nucleus in host cells has already been found to produce pores on bacterias in addition to binding receptors on immune system cells. 

So TH1 cells secreting il-15 and Tc cells secreting il-2 when activated tell the B cells exiting the bone marrow that the infection is inside of cells, don't bother making IgM.  The B cells respond by making IgD instead when they reach the secondary lymph.  IgD activates Basophils and Mast cells.