The immune system is responsible not only for defending the body against infection, but also for fighting cancer. Unfortunately, an active immune system also increases the risk of rejection after organ transplantation, and therefore immunosuppressive drugs must often be given to prevent rejection.
Types of body defense mechanisms
The function of the immune system is to protect the body from invasion and damage by various antigens, which can be microorganisms (bacteria, viruses, or fungi), toxins, and malignant cells. There are three main pathways of defense mechanisms:
Surface protection mechanism
In humans, it provides the first line of defense. They include:
- The skin is a relatively impenetrable barrier for most microorganisms.
- The mucous surfaces of the body as the conjunctiva and oral cavity are protected by antibacterial substances including the enzyme lysozyme which is secreted in tears and saliva.
- The ciliated respiratory epithelium is protected by a surface mucus layer which is continuously removed with trapped particles.
- Maintenance of an acidic environment in the stomach and mis-V inhibits the growth of pathogens at this site.
When such a defense fails, two other types of defense mechanisms are activated.
Non-specific immune response (innate immune system)
Invasion of tissue by microorganisms usually triggers a non-specific response called acute inflammation to remove dead tissue or foreign bodies. These types of immune responses include the complement system that mediates various inflammatory processes, phagocytic cells (tissue macrophage system), and natural killer (NK) cells.
Specific immune response
It depends on the recognition of the specific antigen. Normally, cells of the immune system have the ability to differentiate self from non-self. There are two distinct but related types of specific immune response, cell-mediated immune response and humoral immune response.
Immune system cells
The cells of the immune system are Lymphocytes, Macrophages, and antigen-presenting cells, Mast cells, and Granulocytes (neutrophils, eosinophils, basophils).
Morphologically, all lymphocytes are similar in light or electron microscopy. They can be differentiated into 3 types by immunohistochemical method because each type exhibits specific surface markers or surface receptors.
T . Lymphocytes
These originate from the bone marrow and migrate to the thymus where they proliferate, mature, and acquire T cell receptors (TCRs) on their surfaces specialized for the recognition of specific antigens. T cells then migrate to peripheral lymphoid tissues (lymph nodes, spleen, and Peyer’s patch in the ileum) where they come into contact with antigens.
When they are activated by a specific antigen, they proliferate and differentiate into four functional subtypes of T cells (cell-mediated immune response), these are:
- Cytotoxic T cells are known as killer cells. They specifically recognize foreign cells and destroy them by releasing perforins and granzymes. Perforins punch holes in the target cell membrane with subsequent cell lysis, while granzyme induces apoptosis and target cell death.
- Helper T cells produce lymphokines that are able to induce the proliferation and differentiation of B and T lymphocytes.
- Regulatory T (suppressor cells) reduce the activity of other T and B lymphocytes.
- Memory T cells: long-lived cells respond more quickly and vigorously to subsequent exposure to the same antigen.
These originate from the bone marrow where they proliferate, mature, and acquire specialized membrane surface immunoglobulin receptors (SLGs) for the recognition of specific antigens. The B cells then migrate to the peripheral lymphoid tissue where they come into contact with the antigen.
When they are activated by a specific antigen, they multiply and differentiate into:
- Plasma cells: secrete a lot of antibodies (humoral immune response).
- Memory B cells: long-lived cells respond more quickly and vigorously on subsequent exposure to the same antigen.
Natural killer cells (NK lymphocytes)
It lacks the characteristic surface markers of B and T cells. They act nonspecifically to kill virus-infected cells and malignant cells. Antigen-presenting cells (APCs) originate in the bone marrow and are found in most tissues. They interact with T lymphocytes to stimulate an immune response. They include macrophages, Langerhans cells of the skin and oral cavity, B lymphocytes, thymic epithelial reticular cells.
Monocyte neutrophils and macrophages
Neutrophils are mature cells that can attack and destroy foreign agents even in circulating blood (microphages). In contrast, blood monocytes are immature cells that have very little ability to fight off infectious agents. However, once monocytes enter the tissue, they begin to swell and many lysosomes develop in the cytoplasm, giving them the appearance of a bag filled with granules. These cells are now called macrophages, and are highly capable of fighting disease agents within tissues.
Defensive properties of neutrophils and monocyte macrophages
Monocyte neutrophils and macrophages have special properties that help them carry out their defensive function. These properties include:
Invasion of the body by bacteria triggers an inflammatory response. Many different chemicals in tissues cause neutrophils and monocytes to move toward the chemical source. This phenomenon is known as chemotaxis. Chemotactic agents include some bacterial toxins, degenerative products of inflamed tissue, and some reaction products of the complement system.
This is the process by which neutrophils and monocytes can squeeze through the pores of the blood vessels to reach the inflamed area.
Both neutrophils and monocytes move through the tissue by ameboid motion to reach the site of inflammation.
Phagocytosis and degranulation
Upon reaching the site of inflammation, neutrophils and monocytes perform their most important function which is phagocytosis: this means engulfing the invading organism by endocytosis (phagocytosis).
Neutrophil granules release their contents into the phagocytic vagola containing bacteria and also into the interstitial space (degranulation). The granules contain various proteases plus antimicrobial proteins called defensins, and the cell membrane-bound enzyme NADPH oxidase is activated, with the production of toxic oxygen metabolites.
The combination of toxic oxygen metabolites and proteolytic enzymes from the granules makes neutrophils a very effective killing machine. Activated monocytes engulf and kill bacteria in a process generally similar to that of neutrophils.
Rough surfaces, loss of protective film, and recognition of foreign materials promote phagocytosis. The immune system develops antibodies against infectious agents. These antibodies then attach to the bacterial cell membrane and thus make the bacteria susceptible to phagocytosis. These antibodies are called opsonins and the whole process is called opsonization.
The tissue macrophage system (Reticule-endothelial system) is a common phagocytic system located in all tissues, but especially in tissue areas where large amounts of particles, toxins and other unwanted substances must be destroyed such as the liver and spleen.
The basic structure of immunoglobulins is the same for all classes:
The immunoglobulin molecule is Y-shaped and consists of 4 polypeptide chains: 2 identical light chains (L) and 2 identical heavy chains (H), linked by disulfide bonds. Both the L and H chains have a variable region (VL & VH) an amino-terminal part and a constant region (CL & CH) a carboxy-terminal region. The variable region has a variable amino acid sequence and forms the immunoglobulin antigen binding site.
Each immunoglobulin has two identical antigen-binding sites. The constant region has a nearly constant amino acid sequence in all immunoglobulins of the same class. Immunoglobulins are glycoproteins containing carbohydrate groups attached to constant regions of the heavy chain.
- It has a lower molecular weight (32 kDa) and is about the length of the H-chain.
- The VL region is the amino-terminal while the CL region is the carboxy-terminal L-chain.
- According to the structure of the CL region, there are 2 types of light chains: Kappa (k) and lambda (λ). A given immunoglobulin molecule contains two k or two chains, k chains are more common.
- Has a higher molecular weight (50-70 kDa).
- The VH region is the -amino terminal, while the CH region is the -carboxy-terminal of the H-chain.
- The structure of the CH region determines the immunoglobulin classes and subclasses:
There are 5 types of heavy chains: and , which define the class of immunoglobulins, namely: IgA, IgG, IgD, IgE, and IgM respectively.
There are five classes of immunoglobulins that differ in the amino acid sequence in the constant region of the heavy chain.
Immunoglobulin G (IgG) is elevated in the secondary immune response. It repairs and activates complement (especially the classical pathway). It has antibacterial, antiviral, antiprotozoal and antitoxin activity. Due to its low molecular weight, it can cross the blood vessels to the tissues and can cross the placenta to the fetus providing passive immunity to the newborn in the first 6 months after delivery.
Immunoglobulin A (IgA) provides immunity to newborns (found in colostrum and milk). It repairs and activates complement (alternative pathway). It is responsible for local immunity on the surface of the mucous membrane, which is the main entry site for pathogens.
Immunoglobulin M (IgM) is produced in the primary immune response. IgM provides an agglutination reaction with the antigen. It repairs and activates complement (classical pathway).
Immunoglobulin E (IgE) mediated allergy (type I hypersensitivity reaction): IgE binds to receptors on tissue mast cells or blood basophils with its F c . The antigen binds to this IgE, which causes the release of mediators such as histamine, bradykinin, and serotonin. Histamine and bradykinin cause vasodilation of small blood vessels in the skin causing urticaria. Serotonin can cause vasoconstriction and bronchoconstriction leading to bronchial asthma. IgE protects against parasites by causing the release of enzymes from basophils.
Immunoglobulin D (IgD) is present on the surface of B lymphocytes where it functions as a receptor for antigens. Antibodies to insulin and food toxins are found as IgD.