Review of the Immune System

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A)    The Immune System is made up of complex network of white blood cells, otherwise called Leukocytes.

Two general classifications of Leukocytes :
 
1) Granulocytes (basophil, eosinophil, neutrophil)
 
2) Mononuclear cells (Lymphocytes, Monocytes)
Monocytes develop into macrophages
Lymphocytes include B-Cells & T-Cells

Origin of Immune Cells: and Their Functions

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B)     White blood cells in the body proceed from two cell lines

1) Lymphoid Cells
    i. T-Cells
   ii. B-Cells
  iii. Null Cells
 
            2) Myeloid Cells
                i. Monocytes
               ii. Macrophages
              iii. Polymorphs (eg Neutrophil)
              iv. Platelets
 
3) Note: T Cells (or T4 Cells or T helper Cells) is the coordinator of the body's        
     most important defense mechanism cell mediated immunity. This is in
     response to fight invader organisms (antigens); (bacterial, cancer, viral, 
     fungal, protozoal). T-helper cells tell other cells what to do when immune
     response is triggered. Generally T-Cell and other cells of the immune system   
     respond to achieve body defense by a number of processes including
     secreting a number of biochemical's other wise called cytokines (Interleukins,
     inteferons, TNF- a, and TNF - b) Through this interaction a number of body
     defense issues are taken care of.

Generally white blood cell population increases following infections - bacterial  or viral.
When the body is invaded by bacteria antigens, the granulocytes (neutrophil), population increase in number and activity to attack these invader. When the body is invaded by viruses or slow growing bacterial, (TB, Leprosy, fungal organisms), the mononuclear cells, (lymphocytes) increase in number and activity to attack and eliminate these invaders.

Therefore during bacterial infection neutrophil population increases and only returns to the baseline when the infection has resolved.

Otherwise normal Neutrophil count in the body in the absence of  bacterial infection is 1500-7800 cells/MCL of blood.
-         Normal white cell count in absence of an infection is 3.8 ? 10.8 thousands/ MCL of blood.
-         Normally during viral infection the lymphocytes counts rises up so as to wipe out the viral antigen. (Once the viral infection resolves the lymphocytes count returns back to baseline.)
-         Normal lymphocyte count in absence of infection is 850-3900 cells / MCL of blood.
 
Lymphocytes includes T-Cells and B-Cell. T-Cells could be regarded as Generals in this battle, because they coordinate cellular immune response.

B-Cells (B Lymphocytes) response in viral infection is to produce antibodies to that specific antigen. Antibodies are otherwise called immunoglobulbins and there are 5 types.

* Therefore, an active increase in the number of specific antibody to viral antigen is a sign of interct cellular immunity. Once the viral infection resolves, the lymphocyte count returns to normal.  Total white cell count therefore increases during infections-(bacterial or viral)-and returns to normal when the load of antigen is controlled.
 
* If during a infective process total white cell count remains sub-optimal, it means suppressed / compromised immunity this happens in HIV/AIDS.
  

HIV/AIDS: and Immuno compromasation

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Human Immunodeficiency Virus (HIV) antigen is very devastating to the body?s immune system. This is because the virus arrests cellular immune response by destroying CD4, which is the active site of T-Cells. Hence the coordination of Cellular Immune response in the HIV patient is arrested. Cellular immune response is started but, does not continue to be active with time.

Results of this gradual decline in CD4 lymphocyte count, is absence of cellular immunity. There is absence of usual lymphocytosis of viral infections. The body is gradually invaded by bacterial organisms, even by those bacterial that are usually not infective. (Opportunistic Infections)

This results to increased neutrophil count, because of increased bacterial infection. There is decreased CD4 count.

Usually CD4 count showing:
i.    = 500 T-Cell is normal
ii.       200-500 T-Cell indicate immunodeficiency
iii.   < 200 T ? Cells indicates severe immunodeficiency and is the basis for AIDS diagnosis.
 

HIV/AIDS Patients

In HIV/AIDS patients, we have:
 
i.  Decreased Total White Cell count.
ii. Increased Neutrophil Count
iii. Decreased lymphocyte Count
iv.  Decreased T Cells & B ? Cells
v. Decreased CD4 Count.
vi.  Decreased number of anti HIV antibodies as a sign of suppressed B-Cell activity
vii.  Evident viral Load
 
Note: any effective treatment (therapeutic) of HIV/AIDS patients that Re-Activates this suppressed cellular Immunity will demonstrate the following:
 
i. Increased Total White Cell count.
ii. Decreased Neutrophil Count
iii. Increased Lymphocyte
iv. Increased CD4 Count
v. Decreased / zero viral load.
vi.  Increased in the number of circulating anti HIV antibody in such a way as to demonstrate a secondary immune response, (because B-memory Cell and T-memory Cell to HIV are present already in HIV/AIDS), until viral load declines/zeros.

*Therefore Gamma ? globulin antibodies will be involved and shows that the therapeutic agent should have a prenatal application

Note: 1g G (Immunoglobulin G) : is the main antibody in secondary immune response. It is the most abundant immunoglobulin. It fixes complement, crosses the placenta and opsonises bacteria, neutralizes bacteria toxins, and viruses.
 

Cells of Immune System: Formation, Maturation and Differentiation

Formation, Maturation, and differentiation of these immune cells from the blast forms to immune competent cells take place in various organs of the body.
 
* The monocytes and polymorphs (Neutrophils) are normally produced in the bone
    marrow.
 
* T ? lymphocytes are produced from the lymphoid stem cells in bone marrow, but
    matures in the thymus.
 
T-Cells differentiate in the thymus into:
- Cytotoxic T-Cells (MHCL, CD8)
- Helper T Cell (MHCH, CD4)
- Suppressor T-Cells
- Delayed hypersensitivity T-Cells
 
* B-Cells arise from stem cells in bone marrow, matures in bone marrow, migrates to peripheral lymphoid tissues eg: lymph node, spleen, unencapsulated lymphoid tissues (peyers patches). When antigen is encountered, B-Cells differentiate into plasma cell and produce millions of antibodies.
* Monocytes from the bone marrow gets into the circulation, stays for short time and gets into tissues where they differentiate into Macrophages. The blood monocytes are immature cells that have little ability to fight infectious agents, but the tissue macrophages have extreme capability of combating disease agents.
*Macrophages phagocytizes bacteria, cell debris, and senescent red cells and scavenges damaged cells and tissues.
 

CYTOKINES AND THEIR FUNCTIONS

What are these bio-chemicals, otherwise called cytokines. They are secreted by the immune competent cells, macrophages, T-Cell, etc. They are otherwise called inter-leukins, interferons, TNF - a , TNF - b. Etc.

IL-1-- (Interleukin 1) Secreted by macrophages. Stimulate T- Cell , B-Cells,  
                neutrophils, fibroblast and epithelial cells to grow, differentiate  or synthesis
                specific products.
 
IL-2-- (Interleukin 2) Secreted by helper T-Cells. Stimulates growth of helper and  
                 cytotoxic T-Cells
 
IL-3--(Interleukin 3) Secreted by activated T-Cells, support the growth and
                differentiation of bone  marrow stem cells.
 
IL-4--(Interleukin 4) Secreted by T-Cells. Promotes growth of B-Cells. Enhances
                the synthesis of IgE and IgG

IL-5--(Interleukin 5) Secreted by T-Cells. Promotes differentiation of B-Cells.

             --Enhances synthesis of Ig A. Stimulates production and activation of
                 eosinophill
 
IL-8--(Interleukin 8) Major chemotactic factor for neutrophill

             --¡ - Interferons (gamma interferons) secreted by T-helper cells. Stimulates 
                       macrophages.

TNF a-- (Tumor Necrotic Factor Alpha) secreted by macrophages. Increase IL-2
                 receptor synthesis by T-helper Cells. Increases B-Cell proliferation, attracts
                 and activates Neutrophils
          
TNF b--(Tumor Necrotic factor Beta) Secreted by activated T-Lymphocytes.  
                Functional similar to those of TNF - a.
 
 
IL-12--Macrophages as major precursor of IL-2. It is the cytokine central is
               regulating adaptive immunity and haemopoiesis (Production of Red Blood
               Cells.)
Note: Any herbal supplement that supports increased in number and activity of both the macrophages and the T-Cells will mean increased cytokine proliferation with the attendant Benefits as shown above.

The Macrophage system:
(Formation, Maturation, and Differention)

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The macrophage system play very important roles in the immune system. Monocytes from the bone marrow gets into the circulation stays for a short time and gets to these tissues where they differentiate into macrophages.  Naming of these tissue macrophages depends on the tissues where they are found.

Examples

Kupffer Cells in the Liver
Reticulum Cells in the Lymph nodes, spleen and bone marrow
Alveolar macrophages in the alveolar of the lungs.
In the subcutaneous tissues thy are called
i)   Tissue Histiocytes
ii)  Clasmatocytes
iii) Fixed macrophages
In the brain they are called microglia []
 
 
* HIV-infected microglia fuse to form multi-nucleated giant cells in the Central Nervous system. [  ] Therefore the macrophages in the blood stream, Kuffer cells in the liver, Recticulum Cells in the Lymph nodes, Spleen and bone marrow, Alveolar macrophages in the lungs, Histiocytes / Clasmatocytes and fixed macrophages under the skin, microglia in the brain, and similar macrophages in the lymphoid Linings of the gastro-intestinal system (Tonsils, Peyers patches). All of these play very important role in the Immune system. These system that harbours these macrophages are generally called Reticuloendothelial system

Macrophages are major precursors of  interleukin-12 (IL 12). This is the cytokine  Central in regulating adaptive immunity (Cellular and Humoral) and Hemopoiesis (Production of Blood cells)

Macrophages phagocytize bacteria, macrophages eat up antigen-antibody complexes that may be formed when the body is fighting against viruses, cancer cells etc.

Macrophages phagocytize senescent red cell and scavenges damaged cells and tissues. Thus playing a big role in blood cleansing. Increased activity of macrophages during supplementation with Salvage A may explain the increase in bile production and may be as a result of increased Red Cell metabolism.
   
 

The interplay between microorganisms, macrophages, T-Cells and B-Cells in Stimulating Cellular Immunity is Illustrated in a schematic diagram below:

Micro-Organisms = bacteria, viruses, Helminths, Protozoa

Source:

Comment on the Schematic Diagram

Under normal situation once we get infection (viral, bacteria, etc.), or infestation by helminthes or protozoa, T-Helper naïve cells in our body have two different pathways to undergo to bring about the activation of adaptive immunity ? both cellular and humoral, to fight disease causing organisms.

Pathway I:

Under interleukin-12 (IL-12) induced pathway, T-Helper naïve cells transform into T-Helper I cells, to produce sensitized lymphocytes. T-Helper I cells are involved in activation of both macrophages, and cytotoxic (CD8) cells. Viruses, slow growing bacteria, (TB, Leprosy), fungal organisms, parasitic organisms activate cell-mediated immunity much more. -potentially []
Cytotoxic (CD8) cells are called Natural Killer cells. And they have good application maintaining excellent immunity.

Pathway II:

Under the interleukin-4 (IL-4) induced pathway, T-Helper naïve cells transform into T-Helper  II cells. T-Helper II cells are involved in the activation of B-Lymphocytes to become plasma cells. Plasma Cells produce antibodies. Antibodies neutralize antigens (viruses, cancer cells, fungi, etc) by engaging in antigen antibody reaction. Activated macrophages, eat up antigen/antibody complexes. Thus both pathway I and pathway II are relevant for immunity.
 
Benefits of Adaptive Immunity

• Activated B-Cells become plasma cells
• The antibodies produced by plasma cell aids in host defense by opsonizing bacteria, neutralizing toxins and viruses [ ]
• The organisms resisted by sensitized lymphocytes (Cellular Immunity) generally includes:

1. Tuberculosis, Leprosy: The Cellular immunity is activated much more potently by the slow developing bacteria (eg. Micobacterium Tuberculosis, Micobacterium Leprae)
2. Cancer Cells
3. Viruses
4. Fungal Organisms
5. Parasitic Organisms
6. Active against transplanted organs-tissue rejection
7. Psoriasis- Since M. Leprae, staphylococcus spp are implicated as causative agents of psoriasis.

Thus there is a lot of health benefits in the body where cell mediated immunity is activated. (Use of salvage Herbal supplement to support cellular immunity is therefore highly desirable) This is why most viral infections are self limiting eg. Common cold. HIV/AIDS is very devastating because the virus destroys CD4 cells which are the functional arm of T-Cells - the Coordinator of immune response.
Also HIV infects other cells in the body which are relevant to adaptive immunity viz
- monocytes
- macrophages
- B-Cells []
 
Thus HIV virus arrests cellular immunity by multiple mechanism which we shall discuss in detail in section

Adaptive Immunity: Normal Response to viral infection-

Macrophages inside the lymph node (etc) and their normal response in viral infection could be summarized in the following steps. Normal immune response to viral infection is to activate adaptive immunity (both cellular and humoral) . Let us understand how the immune system fights viral diseases under normal T-Cell response to infection in the following sequence.
 
Note: T-Lymphocyte manifests the cellular immune response and also regulate B-Lymphocytes and macrophages. 
Now: Normal Body response to viral infection:
 
Except in HIV/AIDS etc)
 
Step 1        Infectious agent, virus enters the body and is eventually taken up in your lymph system
 
Step 2        In the lymph node the infectious agent eg. Virus will bump into a macrophage
 
Step 3        Macrophage ingest/swallows the invaders
 
Step 4        Macrophage opens up the invader, displays viral antigens on its surface for the immune competent cells to read
 
Step 5        Macrophage sends out a message to T-Helper Cells to read and recognize the antigen
 
Step 6        Message activates the T-Helper Cells  and immune response is triggered
 
Step 7        T-Helper cells will
-Read the antigen
                  -Send out messages to activate B-Cells
 
Step 8        B-Cells come and reads the antigens from the Macrophage surface
 
Step 9        Activated B-Cells (Now Plasma Cells) produce millions of antibodies specific for that infectious agent.
Step 10      Antibodies being proteins
- Binds the antigen (virus), thus millions of antibodies outnumber the antigens 
  (virus)
- Once an antibody binds an invader, it signals the macrophages to eat up the 
   antigen / Antibody complex
 
Step 11      Macrophages eats up the Ag-AB Complex.
Note: Macrophage means Large Eater
 
Step 12      Antibody thus outnumbers the antigen (virus), and the antibody effectively helps us to wipe out infectious agent, and there is now a need to deactivate the immune system.
 
Step 13      T-suppressor (T8) will send out message to deactivate the immune response.
 
Step 14      Message Deactivates the immune Response [source:] At this pont the previously increased white cell count and lymphocyte count returns back to normal because the viral antigen have been eliminated.

What are Antibodies?

The antibodies are produced in response to B-Lymphocyte activation. These engage infective agents (bacteria & viruses) in a one to one battle-leading to formation of antigen-antibody complexes before macrophages eat up the complexes. Thus antibodies sacrifices their lives in  the process of this battle against infective agents.
 
Five subtypes of immunoglobulin (antibodies)

V1Z:
 
1g G (immunoglobulin G) : is the main antibody involved in secondary immune response , the most abundant and fixes complements.
 
*1g G crosses the placenta hence any supplementation (therapeutic or prophylactic) that supports secondary immune response should have prenatal application, as the 1g G crosses the placenta to be of immunologic support to the fetus (unborn child)
1g G opsonizes bacteria, neutralizes bacteria toxins, viruses
 
 
Other types of Immunoglobulin
 
Immunoglobulin (A)-(IgA)
Immunoglobulin (M)-(IgM)
Immunoglobulin (D)-(IgD)
Immunoglobulin (E)-(IgE)
 
IGE: mediates immediate (type I) hypersensitivity (allergic) reaction by inducing the release of mediators from mast cells and basophils when exposed to allergen (eg Pollen, etc). 1gE mediates immunity to helminthes (worms).
 
Generally speaking immunoglobulin (antibodies):
i. promotes phagocytocis
ii. prevent attachment of bacteria and viruses to mucous membrane
iii. Activates complement, enhancing opsonisation and lysis
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Complement:
 
A. Worth mentioning is another type of protection our body enjoys through complement        system/ complement fixation. Complement defends against gram negative bacteria.

We have complement { C1, C2, C3, C4, C5, C6, C7, C8, and C9}
 
Functions

B. {C1, C2, C3, AND C4}-Neutralize viruses
     {C3b}-opsonise bacteria.
     {C5a}-Responsible for neutrophil chemotaxis

C. Note: Complement C1 is metablised by the enzyme C1-estarase, and genetic
    deficiency of this C1-estarase leads to hereditary angioedema. (overactive
     complements ) []

*supplementation with salvage A herbal products may supports immunity against sinus infection. Over use (over dosage of Salvage A - Leads to nasal congestion showing that the active principle may have affinityfor the cells of the of the nasal turbinate. (Tissue specifity is one characteristics of different plant anti-oxidants). During Salvage A usage subjects have reported improvement of sinus infections. [see testimony section]