INTRODUCTION
Body is protected against invading organisms by physical barriers like skin and other epithelial linings which constitute the first line of defence. If these mechanisms fail to control the invading organisms, then the second line of defence, the immune system is activated.
Lymphoid tissues are fundamentally involved in the process of immunity i.e. body protection power against invasion by undesirable agents like microorganisms,viruses, tumour cells and parasites.
The responses of the immune system of each division (natural
and acquired) are divided into two types: Humoral and Cellular (cell mediated).
The Humoral responses are effected by elements free in the serum or body fluids:
whereas cell mediated responses involve cells directly eliminating the invading
organisms. (The main differences between natural and acquired immune system are
given in Table 15.1)
THE NATURAL (OR INNATE) IMMUNE SYSTEM ----
A. Natural Humoral Responses These are effected by soluble factors in the serum and body fluids, e.g.
1. The complement system
2. C-reactive protein
3. Interferons
4. Natural killer cells
1. The Complement System
The cell-killing effect of circulating antibodies and cellular immunity are mediated by a system of plasma enzymes, called the Complement System.
The enzymes are identified by the numbers C1 to C9.
Cl is made up of 3 subunits, Clq, Clr and Is, therefore, there are 11 proteins in the system. Activation of this system triggers a sequence of 'cascade reactions that activates other components of the system.
The system gets activated by three pathways:
(i) Classical pathway -
initiated by antibody binding to antigen. C1 binds to the antibody-antigen complex (i.e. immune complex) and thus triggers a sequence of events that activates C3.
(ii) Mannose binding lectin pathway initiated when lectin binds mannose groups in bacteria; and
(iii) Alternative or properdin pathway -
initiated by polysaccharides in bacterial cell wall (endotoxin), yeast cell wall ( zymosan ) and tumour cells.
Interaction of factor I with polysaccharides in cell membrane of invading cells triggers reactions that activate C3 and C5. Properdin (a circulating protein) stabilizes the activating enzyme complex.
Once activated, the complement system helps in lysing foreign invaders by the following mechanisms:
(i) Insertion of pore-forming molecules (perforins) in the cell membranes of foreign invaders. Ions move through these pores and the cells become lysed by osmosis.
(ii) Formation of the activated fragments C3a and C5a from C3 and C5 respectively. These fragments release histamine from granulocytes, mast cells and platelets. Histamine dilates the blood vessels and increased capillary permeability
(a) C5b, C6 and C7 are chemotactic and attract leucocytes to the site of the antigen-antibody reaction.
(b) C3b is responsible for opsonization and phagocytosis of bacteria . It also initiates reactions that activate the rest of the complement enzymes.
2. C-Reactive Protein
Entry of foreign invaders (antigens) activates concentration of many plasma proteins, specially of C-reactive protein (CRP) which coats the invading antigen. CRP-coated organisms activate the complement system which in turn, facilitates phagocytosis.
Normal plasma level: <1 mg/dL
3. Interferons
Virally infected cells release 'interferons' into ECF which:
(i) forms a protective ring of uninfected cells, thus limits the spread of infection; (1) inhibits protein synthesis by promoting degradation of mRNA thereby inhibits replication of viruses.
4. Natural Killer Cells (NK Cells)
These are special type of cytotoxic lymphocytes, also called non-T, non-B lymphocytes. These are large lymphocytes that make up 10-15% of the circulating agranulocytes.
Characteristic features:
(i) They kill cells without any apparent prior sensitization and without the involvement of major histocompatibility antigen.
(ii) They destroy cells that have undergone malignant transformation, thus help prevent the establishment of cancerous tumours.
(iii) They attack viruses and kill antibody-coated viruses.
(iv) Their activity is increased by interleukin-2 (IL-2).
(v) They represent
(a) an important natural first line of defence against viral infections
(b) combating the spread of disease while more specific T and B cell responses are activated.
(vi) They may represent a primitive immune system from which Tand B cell system evolved
B. Natural Cellular Responses
Foreign substances entering the blood stream are dealt win by circulating phagocytes in neutrophils and monocytes Cell mediated 1st and 2nd line of defence respectively
If initial inflammatory response by neutrophils and monocytes does not prevent the spread of the foreign material further than, the 'fixed' macrophages, in the liver spleen, lymph nodes and other body tissues may succeed in eliminating it from the tissue fluid.
THE ACQUIRED IMMUNE SYSTEM
If the invaders overcome the natural immune system, then the acquired immune system comes into play.
The body has two principal acquired immune defence systems Both react to antigens i.e. protein or polysaccharides substances which are able to induce the synthesis of antibodies.
1. Humoral Immunity-- is due to circulating antibodies in the y-globulin fraction of plasma protein. It is mediated by B-lymphocytes, and they activate the complement system to neutralize antigens It is a major defence against bacterial infections.
2. Cellular Immunity-- is responsible for delayed allergic reactions, rejection of transplants of foreign tissue and lysis of tumour cells. It is mediated by T-lymphocytes and constitutes a major defence against infections due to viruses, fungi and few bacteria e.g. tubercle bacillus.
It also helps defend against tumor.
Development of the Acquired Immune System
1. During the foetal development and neonatal life, lymphocyte precursors from the bone marrow enter the thymus gland and become transformed into the lymphocytes responsible for cellular immunity (T-lymphocytes).
Simultaneously these lymphocyte precursors that enter the liver and spleen get transformed into lymphocytes responsible for Humoral immunity (B-lymphocytes).
Afterwards many of T and B lymphocytes migrate to the lymph nodes and bone marrow, where they are morphologically indistinguishable but can beidentified by special techniques. Both types are present throughout life.
2. There is also a slow continuous production of new lymphocytes from stem cells with processing in the bone marrow in adults.
When appropriate contact with an antigen occurs, both types of lymphocytes become activated and differentiate further. This takes place in the organs of the immune system such as the lymph nodes and spleen
3. B-lymphocytes differentiate into Plasma Cells and Memory B Cells. Plasma cells form and secrete protein immunoglobulin (IgG, IgA, IgM, IgD and IgE).
Similarly, T-lymphocytes differentiate into 4 different varieties of T-cells:
(i) helper/inducer T cells; \
(ii) suppressor T cells;
(iii) cytotoxic (effector) T cells or killer cells; and
(iv) memory T cells
4. Cytotoxic and suppressor T cells have on their surface the glycoprotein CD8 (cluster of differentiation) and are, therefore, called T cells. 'Helper"/"Inducer' T cells have on their surface the glycoprotein CD4 and are, therefore, called T cells. CD8 and CD4 are co-receptors (i.e. T-cell receptor) for major histocompatibility complex (MHC) class I and II molecules respectively. (MHCs are a family of membrane protein complexes encoded by a specific set of genes. Every nucleated cell of the body has MHC on its membrane)
Important Note
There are three types of cytotoxic lymphocytes in the body:aß T cells, yo T cells and natural killer cells . These T-cells are prominent in the mucosa of the GIT
5. The Helper and Suppressor T cells are involved in the regulation (neither excess nor deficient) of antibodies production by B-lymphocytes. There are two types of helper T cells:
(i) T helper 1 (Th1) cells secrete IL-2 and y-interferon (concerned with cellular immunity).
(ii) T helper 2 (T 2) cells secrete IL-4 and IL-5 (concerned with humoral immunity) (also refer to Table 15.3, page 127).
6. The Cytotoxic T-cells are responsible for delayed allergic reactions, rejection of transplant of foreign tissues and lysis of tumour cells. They combine directly with target cells that have the antigen which initially stimulated them to bring about their destruction by inserting perforins and by initiating apoptosis.
7. Memory B and T Cells are cells that have been exposed to an antigen and are readily converted to effector cells by a later encounter with the same antigen. Unlike other lymphocytes, they persist in the body for months or even years/life long, such as immunity to measles.
Body is protected against invading organisms by physical barriers like skin and other epithelial linings which constitute the first line of defence. If these mechanisms fail to control the invading organisms, then the second line of defence, the immune system is activated.
Lymphoid tissues are fundamentally involved in the process of immunity i.e. body protection power against invasion by undesirable agents like microorganisms,viruses, tumour cells and parasites.
THE NATURAL (OR INNATE) IMMUNE SYSTEM ----
A. Natural Humoral Responses These are effected by soluble factors in the serum and body fluids, e.g.
1. The complement system
2. C-reactive protein
3. Interferons
4. Natural killer cells
1. The Complement System
The cell-killing effect of circulating antibodies and cellular immunity are mediated by a system of plasma enzymes, called the Complement System.
The enzymes are identified by the numbers C1 to C9.
Cl is made up of 3 subunits, Clq, Clr and Is, therefore, there are 11 proteins in the system. Activation of this system triggers a sequence of 'cascade reactions that activates other components of the system.
The system gets activated by three pathways:
(i) Classical pathway -
initiated by antibody binding to antigen. C1 binds to the antibody-antigen complex (i.e. immune complex) and thus triggers a sequence of events that activates C3.
(ii) Mannose binding lectin pathway initiated when lectin binds mannose groups in bacteria; and
(iii) Alternative or properdin pathway -
initiated by polysaccharides in bacterial cell wall (endotoxin), yeast cell wall ( zymosan ) and tumour cells.
Interaction of factor I with polysaccharides in cell membrane of invading cells triggers reactions that activate C3 and C5. Properdin (a circulating protein) stabilizes the activating enzyme complex.
Once activated, the complement system helps in lysing foreign invaders by the following mechanisms:
(i) Insertion of pore-forming molecules (perforins) in the cell membranes of foreign invaders. Ions move through these pores and the cells become lysed by osmosis.
(ii) Formation of the activated fragments C3a and C5a from C3 and C5 respectively. These fragments release histamine from granulocytes, mast cells and platelets. Histamine dilates the blood vessels and increased capillary permeability
(a) C5b, C6 and C7 are chemotactic and attract leucocytes to the site of the antigen-antibody reaction.
(b) C3b is responsible for opsonization and phagocytosis of bacteria . It also initiates reactions that activate the rest of the complement enzymes.
2. C-Reactive Protein
Entry of foreign invaders (antigens) activates concentration of many plasma proteins, specially of C-reactive protein (CRP) which coats the invading antigen. CRP-coated organisms activate the complement system which in turn, facilitates phagocytosis.
Normal plasma level: <1 mg/dL
3. Interferons
Virally infected cells release 'interferons' into ECF which:
(i) forms a protective ring of uninfected cells, thus limits the spread of infection; (1) inhibits protein synthesis by promoting degradation of mRNA thereby inhibits replication of viruses.
4. Natural Killer Cells (NK Cells)
These are special type of cytotoxic lymphocytes, also called non-T, non-B lymphocytes. These are large lymphocytes that make up 10-15% of the circulating agranulocytes.
Characteristic features:
(i) They kill cells without any apparent prior sensitization and without the involvement of major histocompatibility antigen.
(ii) They destroy cells that have undergone malignant transformation, thus help prevent the establishment of cancerous tumours.
(iii) They attack viruses and kill antibody-coated viruses.
(iv) Their activity is increased by interleukin-2 (IL-2).
(v) They represent
(a) an important natural first line of defence against viral infections
(b) combating the spread of disease while more specific T and B cell responses are activated.
(vi) They may represent a primitive immune system from which Tand B cell system evolved
B. Natural Cellular Responses
Foreign substances entering the blood stream are dealt win by circulating phagocytes in neutrophils and monocytes Cell mediated 1st and 2nd line of defence respectively
If initial inflammatory response by neutrophils and monocytes does not prevent the spread of the foreign material further than, the 'fixed' macrophages, in the liver spleen, lymph nodes and other body tissues may succeed in eliminating it from the tissue fluid.
THE ACQUIRED IMMUNE SYSTEM
If the invaders overcome the natural immune system, then the acquired immune system comes into play.
The body has two principal acquired immune defence systems Both react to antigens i.e. protein or polysaccharides substances which are able to induce the synthesis of antibodies.
1. Humoral Immunity-- is due to circulating antibodies in the y-globulin fraction of plasma protein. It is mediated by B-lymphocytes, and they activate the complement system to neutralize antigens It is a major defence against bacterial infections.
2. Cellular Immunity-- is responsible for delayed allergic reactions, rejection of transplants of foreign tissue and lysis of tumour cells. It is mediated by T-lymphocytes and constitutes a major defence against infections due to viruses, fungi and few bacteria e.g. tubercle bacillus.
It also helps defend against tumor.
Development of the Acquired Immune System
1. During the foetal development and neonatal life, lymphocyte precursors from the bone marrow enter the thymus gland and become transformed into the lymphocytes responsible for cellular immunity (T-lymphocytes).
Simultaneously these lymphocyte precursors that enter the liver and spleen get transformed into lymphocytes responsible for Humoral immunity (B-lymphocytes).
Afterwards many of T and B lymphocytes migrate to the lymph nodes and bone marrow, where they are morphologically indistinguishable but can beidentified by special techniques. Both types are present throughout life.
2. There is also a slow continuous production of new lymphocytes from stem cells with processing in the bone marrow in adults.
When appropriate contact with an antigen occurs, both types of lymphocytes become activated and differentiate further. This takes place in the organs of the immune system such as the lymph nodes and spleen
3. B-lymphocytes differentiate into Plasma Cells and Memory B Cells. Plasma cells form and secrete protein immunoglobulin (IgG, IgA, IgM, IgD and IgE).
Similarly, T-lymphocytes differentiate into 4 different varieties of T-cells:
(i) helper/inducer T cells; \
(ii) suppressor T cells;
(iii) cytotoxic (effector) T cells or killer cells; and
(iv) memory T cells
4. Cytotoxic and suppressor T cells have on their surface the glycoprotein CD8 (cluster of differentiation) and are, therefore, called T cells. 'Helper"/"Inducer' T cells have on their surface the glycoprotein CD4 and are, therefore, called T cells. CD8 and CD4 are co-receptors (i.e. T-cell receptor) for major histocompatibility complex (MHC) class I and II molecules respectively. (MHCs are a family of membrane protein complexes encoded by a specific set of genes. Every nucleated cell of the body has MHC on its membrane)
Important Note
There are three types of cytotoxic lymphocytes in the body:aß T cells, yo T cells and natural killer cells . These T-cells are prominent in the mucosa of the GIT
5. The Helper and Suppressor T cells are involved in the regulation (neither excess nor deficient) of antibodies production by B-lymphocytes. There are two types of helper T cells:
(i) T helper 1 (Th1) cells secrete IL-2 and y-interferon (concerned with cellular immunity).
(ii) T helper 2 (T 2) cells secrete IL-4 and IL-5 (concerned with humoral immunity) (also refer to Table 15.3, page 127).
6. The Cytotoxic T-cells are responsible for delayed allergic reactions, rejection of transplant of foreign tissues and lysis of tumour cells. They combine directly with target cells that have the antigen which initially stimulated them to bring about their destruction by inserting perforins and by initiating apoptosis.
7. Memory B and T Cells are cells that have been exposed to an antigen and are readily converted to effector cells by a later encounter with the same antigen. Unlike other lymphocytes, they persist in the body for months or even years/life long, such as immunity to measles.
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