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IMMUNITY & BODY DEFENSES

 The human body is made of 100 trillion cells of which 80 trillion are bacteria and viruses. "So are we the host for the bacteria or is it the other way round"? asks Prof Dr. M. L. Kothari from KEMH Bombay India. whether bacteria cause tissue necrosis or whether it is the body’s over reactive WBC which launches an immune attack on the cells in response to the presence of bacteria, MLK asks .

 

An infection usually steps up the body temperature via cytokines and prostaglandin’s released by WBC's to boost the immune responses causing fever , increases the heart rate and cardiac output to increase the blood flow, stimulates the marrow to increase production of leucocytes, generates immunoglobin’s specific to the bacterial strain as well as memory cells to remember the antigenic structures and increases the cortisone to enhance repair as well as causes heptosplenomegaly where increased destruction of bacterial antigen can occur.    

 

Basic physiology is elaborated upon NOW, as this forms the cornerstone on which rests the body’s defence system  ( against infection )

 

 

IMMUNITY  BASICS

 

(A)      INNATE IMMUNITY

 

a.Acid in stomach destroys swallowed organisms .

b.Mucus in respiratory tract, urinary tract, etc.

c.Complement ( 20 protein enzyme) system in blood destroy bacteria.

       Lysozymes  ( a carbohydrate ) in blood destroys bacteria. 

d.   Neutrophils ( phagocytic ) and lymphocytes ( natural killer type ) destroys foreign   

cells , tumour cells , bacterial and viral cells.

 

(B)      ACQUIRED IMMUNITY .

 

a.HUMORAL IMMUNITY - via  immunoglobins produced by Beta- Lymphocytes.

b.CELL MEDIATED - via direct attack by T- lymphocytes .

c.TYPES OF CELLS  -  involved.

         

         CONNECTIVE              BLOOD

         TISSUE

           Microphage                 Neutrophil/eosinophil

          Plasma cell                   B- lymphocyte

          Macrophages               Monocyte

          Mast cells                     Basophil 

          Fibroblasts                      --

 

       Mast cells play a big role in Allergies and a small role in inflammation. Their function is release of  Heparin to keep circulatory blood liquid.

     " THE IMMUNE RESPONSE "

 

  In response to tissue insult by trauma, organisms, toxins, or autoimmune mechanism.

 

A)      IMMEDIATELY  a few local tissue macrophages start phagocytosis in the affected tissue, local lymph nodes and the spleen , releasing –

 

i)                     (TNF) Tumour Necrosis factor which causes increased blood flow , increased       capillary permeability to enable blood polymorphs to migrate onto the interstitial tissues.

ii)                   (CSF )  Colony Stimulating factor and IL- l ( Interleukin- 1) and Ag (antigen) is released  from the macrophage phagocytosis.

 

B)      Within one hour , the migrated polymorphs begin phagocytosis.

 

C)      Within 8 hours the few monocytes in circulation reach the tissue, mature into macrophages and begin phagocytosis. Though few, they have 5 times the phagocytosis ability of neutrophils.

 

D)      Within 3 - 4 days the CSF stimulates the bone marrow to increase polymorphs and monocytes which then reach the site.

 

E)      Within several days of first days of first exposure the antigens stimulates the B- lymphocyte and T- helper cells to release Interleukins which activate plasma cells to form B- lymphocyte clones. Upto 2000 immunoglobins are released per plasma cell.Secondary response is 10-50 times the magnitude of the primary resonse.

        

a)       IgM is released as a primary response to antigen on first exposure and

            IgG is released as a secondary response to antigen on second exposure

              ( IgM shows active infection ) 

            IgE is present on mast cells.

            IgA is present in secretions and mucosa.[ innate natural immunity ]

            IgD on the surface of B- lymphocyte.[natural – blood ]

 

b)       On  second  exposure immmunoglobins are formed (IgG) immediately due to memory B- lymphocytes which form after first primary exposure which are stored for many months or years. At any given time there are  one million types of memory cells in the blood.

 

 Immunoglobins act via the series of enzymes 20 glycoproteins in the plasma called complement.to destroy the antigen.

 

F)      After several days , pus is formed which is either absorbed or let out through an outlet.

 

G)     Tissue repair occurs

a)       new cells are formed by multiplication of parenchymal cells.- regeneration , wherever possible

b)       Fibroblast lay down fibrous tissue after stimulation by FGF ( Fibroblast Growth Factor ) released by vascular endothelial cells wherever parenchymal regenerartion cannot compensate to maintain integrity and strengthen the repaired tissue.- scarring

 

H) Cortisone is released to nearly five- fold its usual value by the Adrenal Cortex

i)                     which inhibits excessive inflammatory response tp prevent tissue injury.

ii)                   Promotes tissue repair.

 

I)Mast cells release histamine, bradykinin, serotonin, prostaglandins complement and   clotting  factors and play a large role in dealing with allergic inflammatory release.

 

J)Cell  Mediated Immunity is a response to viruses , mycobacteria, protozoan and tumor cells is via stimulation of T- cells by the antigen, & is a secondary response, due to memory cells.

 [HICS]

   1.  T- helper cells release lymphokines (cytokines) called

            a) Interleukins        

            b) Interferon - destroy viruses.

2.       T - inducer cells release Interleukines which help in antibody formation.

3.       Cytotoxic T - cells.

         Cytotoxic T - cells release perforins which perforate the cell- membrane and

        destroy virus and cancer cells.

4.       Supressor T- cells supress excessive immune responses.- regulate

 

 In HIV for e.g. - It takes up to 10 years for full blown aids to develop because of body immunity.

a)       Anti HIV . Antibody develop as humoral immunity.

b)       CD4+ and CD8+  T - Lymphocytes develop as CMI which supress HIV  infection by the cytokines called ' RANTES'

c)       NK ( Natural Killer T cells ) kill organisms or tumor cells .

             Both types of immunity act together in varying proportions during different types of insult.


SUMMARY OF INFLAMMATORY RESPONSE

 


0 HRS              –                LOCAL & LYMPHOID-LN+SPLEEN -MACROPHAGES

[Immediate ]

LESS THAN    –   1 HR  -  CIRCULATION – NEUTROPHIL

  3   DAYS       –   8  HR -  CIRCULATION -MONOCYTES →MACROPHAGES

                                          [ via  TNF ]

 

MORE  THAN  –            -  MARROW– NEUTROPHIL

  3  DAYS         –            -  MARROW –MONOCYTES →MACROPHAGES                via PHAGOCYTOSIS/ETC

                                          [ via CSF  ]

 

 SEVERAL       –                LOCAL PLASMA CELLS -ANTIBODIES +/-

       DAYS        –                LOCAL PLASMA CELLS -CMI

  > 1ST EXPOSURE             [ via IL ]

 

–                        LOCAL ENDOTHELIUM-FIBROBLAST & CORTISONE

                  [ via  FGF ]

–                        MAST  CELLS

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