Biotechnology - Immunology Basics

Description

Our immune system gives us protection from infectious diseases.  Immunity is a state of protection from harmful bacteria, viruses, parasites etc. The immune system is spread throughout the body and involves many types of cells, organs, proteins, and tissues. It helps to distinguish our own tissue from foreign tissues. Immune system recognizes dead and unnecessary cells and cleared them out. If our immune system encounters a pathogen ( a bacterium, virus, or parasite), it mounts an immune response.

The immune system is made up of two parts: the innate, (general) immune system and the adaptive (specialized) immune system. These two systems work closely together and take on different tasks.

Innate and adaptive immunity

Innate immunity is the first line of defense against infection. Innate immunity acts very quickly. Phagocytic cells such as macrophages, neutrophils, barriers such as skin and a variety of antimicrobial compounds synthesized by the host all play significant roles in innate immunity. The closed surface of the skin and of all mucous membranes already forms a physical barrier against germs, which protects them from entering. The innate immune system activates special immune system cells and proteins if germs get past the skin and mucous membranes and enter the body.

Adaptive immunity is the specific component of the immune system unlike the uniformity in all members of a species of the innate immunity. It specifically targets the type of germ that is causing the infection. Adaptive immunity has a high degree of specificity with the remarkable property of memory.

It may take a few days for the adaptive immune system to respond the first time it comes into contact with the germ, but the next time the body can react immediately. The adaptive immune system is made up of T lymphocytes, B lymphocytes, and antibodies.

T and B lymphocytes

T lymphocytes (T cells) are the white blood cells produced in the bone marrow by the process of hematopoiesis. T cells mature in the thymus and during its maturation they express a unique antigen binding molecule called T-cell receptor, on their membrane.

There are two well-defined subpopulations of T cells i.e., T helper cells (TH) cells and T cytotoxic (TC) cells. TH cells and TC cells can be distinguished from each other by the presence of either CD4 or CD8 membrane glycoproteins on their surface. T cells displaying CD4 function as TH  cell and T cells displaying CD8 function as TC  cells. T cell receptors can only recognize antigen that is bound to cell-membrane proteins called major histocompatibility complex (MHC) molecules. When a naive T  cell recognizes and interacts with an antigen-MHC molecule complex, It is proliferated and differentiaites into memory T cells and effector T cells.

There are two types of MHC (major histocompatibility complex) molecules: class I MHC molecules which are expressed by nearly all nucleated cells and class II MHC molecules which are expressed by only antigen presenting cells. When a T-helper cell (TH cell) encounters an antigen-MHC class II molecule complex, it gets activated and becomes an effector cell which secrets various growth factors known as cytokines. The secreted cytokines activate B cells, TC cells, macrophages and other cells that take part in immune response. 

B lymphocytes mature within the bone marrow and they express a unique antigen-binding receptor on their membrane. B-cell receptor is a membrane-bound antibody molecule. When a naive B cell first encounters the antigen that matches its membrane bound antibody, the antigen-antibody binding happens which causes the cell to divide rapidly into plasma B cells and memory B cells. Memory B cells have longer life span than plasma B cells. Plasma cells live for only few days and secret enormous amount of antibody during this short life span. Secreted antibodies are the major effectors of humoral immunity.

Antibodies

Antibodies are compounds of protein and sugar that circulate in the bloodstream. They are created by the immune system to fight germs and foreign substances. Antibodies are produced by B lymphocytes. Antibodies can quickly detect germs and other potentially harmful substances, and then attach to them.

Antibodies can neutralize germs,  activate other immune system cells by attaching to their surfaces and activate proteins that help in the immune system response.

Antibodies are glycoproteins that consist of twi identical heavy polypeptide chains and two identical light polypeptide chains. Each heavy chain is joined with the light chain by disulphide bonds.

Humoral and cell mediated immunity

Immune responses can be of two types i.e., humoral immunity and cell-mediated  responses. Humoral immunity is mediated by macromolecules found in extracellular fluids such as secreted antibodies, complement proteins, and certain antimicrobial peptides. Humoral immunity is also referred to as antibody-mediated immunity. Antibodies are synthesized and secreted by plasma cells that are derived from the B cells of the immune system. An antibody is used by the acquired immune system to identify and neutralize foreign objects like bacteria and viruses. Each antibody recognizes a specific antigen unique to its target. By binding their specific antigens, antibodies can cause agglutination and precipitation of antibody-antigen products. Binding of antibody to antigen on a microorganism can also activate the complement system, resulting in lysis of the pathogen. Antibody can neutralize toxins or viral particles by coating them so that they can not bind to host cells. Humoral immune responses to antigens begin by exposing the host to an antigen for the first time. Here, the immune system begins to make low levels of antibodies, approximately within a week. During the second exposure to the same antigen, the human immune system produces a much faster response and the ability of these antibodies to bind.

Cell mediated immunity is provided by the effector T cells generated in response to antigen. Activated TH cells and cytotoxic T lymphocytes (CTLs) serve as effector cells in cell-mediated responses. Cytokines secreted by TH cells activate various phagocytic cells which phagocytose and kill microorganisms more effectively.

Cells of the immune system

Hematopoietic stem cell gives rise to all blood cells. In humans, hematopoiesis is the process which involves the formation and development of red and white blood cells. It is a continuous process that generally maintain a steady state in which the production of mature blood cells equals their loss.

The cells of the immune system can be categorized as lymphocytes (T-cells, B-cells and NK cells), neutrophils, and monocytes/macrophages. Lymphocytes are the core cells of the immune system responsible for adaptive immunity and the immunologic attributes of diversity, specificity, memory and self/nonself recognition. Lymphocytes constitute 20-40% of the body's white blood cells and 99% cells in the lymph. B cells, T cells and natural killer (NK) cells are the three types of lymphocytes on the basis of function and cell membrane components. Lymphocytes progress through the cell cycle and enlarge into lymphoblasts. Lymphoblasts differentiate into effector cells or into memory cells. Different maturational stages of lymphocytes can be distinguished by their expression of membrane molecules recognized by particular monoclonal antibodies. 

Natural killer cells (NK cells)

NK cells are large granular lymphocytes that do not express the set of surface markers like B cells and T cells. NK cells play an important role in providing immunity against tumor cells and in virus infected cells. NK cells do not have T-cell receptors or immunoglobulin incorporated in their plasma membranes.  NK cells express a membrane receptor CD16, for the Fc region of antibody, which can attach with the antibody and subsequently destroy the targeted cells. This process is known as antibody-dependent cell-mediated cytotoxicity.

Macrophages

During hematopoiesis in the bone marrow, granulocyte-monocyte progenitor cells differentiate into promonocytes, which exit the bone marrow and enter the blood, where they further differentiate into mature monocytes. Monocytes circulate in the blood for 8 hours, during which they enlarge and then they migrate into the tissues and differentiate into specific tissue macrophages. Macrophages activated by cytokines secreted by T helper cells. Activated macrophages eliminate potentia pathogens more effectively than resting macrophages. Activated macrophages exhibit more phagocytic activity than the resting ones and they secret various cytotoxic proteins that help them eliminate broad range of pathogens.

Phagocytosis

Phagocytosis is the process by which the living cells called phagocytes engulf other cell particles. In higher animals phagocytosis is chiefly a defensive reaction against infection and invasion of the body by antigens. In humans, and in vertebrates generally, the most-effective phagocytic cells are two kinds of white blood cells: the macrophages (large phagocytic cells) and the neutrophils (a type of granulocyte). Macrophages are capable of ingesting and digesting exogenous antigens and endogenous matter. The process of phagocytosis is completed in more than one steps. In the first step, which is known as chemotaxis, macrophages are attracted and move towards a variety of substances. In the next step, the antigen adheres to the macrophage cell membrane and the adhereance induces membrane protrusions called pseudopodia which extend around the attached material. The fusion of pseudopodia encloses the material within a membrane bounded structure called a phagosome, which then enters the endocytic processing pathway. Phagosome fuses with a lysosome to form a phagolysosome. The hydrolytic enzymes present in lysosome digest the ingested material.  Macrophages employ both oxygen dependent and oxygen independent killing mechanisms to generate antimicrobial substances.

Phagocytosed antigen is digested within the endocytic processing pathway into peptides that associate with class II MHC molecules and these peptide-class II MHC complexes then move to the macrophage membrane.

Granulocytes

Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. They are a type of white blood cell that has small granules. There are three types of granulocytes: neutrophils, eosinophils and basophils.

Neutrophils are normally found in the bloodstream and are the most abundant type of phagocyte, constituting 60% to 65% of the total circulating white blood cells, Neutrophils are produced by hematopoiesis in the bone marrow. They are released into the peripheral blood and circulate for 7-10 hour before migrating into the tissues. In tissues, they have a few days life span. Neutrophil has a multilobed nucleus and a granulated cytoplasm. For its multilobed nucleus, it is often called a polymorphonuclear leukocyte (PMN). Neutrophils are active phagocytic cells.

Eosinophils are motile phagocytic cells that can migrate from blood into the tissue space. They are less phagocytic than neutrophils. Eosinophils have kidney-shaped lobed nuclei (two to four lobes). The secreted contents of eosinophils granules may damage the parasite membrane.

Basophils are one of the least abundant cells in bone marrow and blood. Like neutrophils and eosinophils, they have lobed nuclei; however, they have only two lobes. Basophils are non-phagocytic granulocytes. When an infection occurs, mature basophils will be released from the bone marrow and travel to the site of infection. When basophils are injured, they will release histamine, which contributes to the inflammatory response that helps fight invading organisms.

Mast cells

Mast cells are a type of granulocyte that are present in tissues. Mast cells can be found in a wide variety of tissues, including the skin, connective tissues of various organs, and mucosal epithelial tissue of the respiratory, genitourinary, and digestive tracts. These cells contain large number of cytoplasmic granules that contain histamine and other pharmacologically active substances. Mast cells are also involved in mediating inflammation and autoimmunity as well as mediating and regulating neuroimmune system responses.

Dendritic cells

Dendritic cells (DCs) are antigen-presenting cells of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems. Dendritic cells are covered with long membrane extensions that resemble the dendrites of nerve cells. Four types of dendritic cells are Langerhans cells, interstitial dendritic cells, myeloid cells, and lymphoid dendritic cells. Follicular dendritic cells are another type which do not arise in bone marrow and has a different function from the antigen presenting dendritic cells.

Organs of the immune system

Primary lymphoid organs

Thymus

The thymus is a primary lymphoid organ. Unlike most other lymphoid structures, the thymus grows rapidly and attains its greatest size relative to the rest of the body during fetal life and the first years after birth. The thymus is a flat, bilobed organ situated above the heart. Each lobe is surrounded by a capsule and is divided into lobules. Each lobule is divided into two compartments, the outer cortex which is packed with immature T cells called thymocytes and the innere medulla. Thymus generate and select a repertoire of T cells that will protect the body from infection.

Bone marrow

Bone marrow is a primary lymphoid organ. In humans and mice, bone marrow is the site of B-cell origin and development. Immature B cells proliferate and differentiate within the bone marrow.  A selection process within the bone marrow eliminates B cells with self reactive antibody receptors. Bone marrow is not the site of B-cell development in all species. In birds, a lymphoid organ called the bursa of Fabricus, a lymphoid tissue associated with the gut, is the primary site of B-cell development.

Secondary lymphoid organs 

Lymph nodes and the spleen are the most highly organized of the secondary lymphoid organs.

Lymph nodes are the sites where immune responses are mounted to antigens in lymph. Lymph nodes are encapsulated bean shaped structures containing a reticular network packed with lymphocytes, macrophages and dendritic cells.

Spleen mounts immune response to antigens in the blood stream. Spleen is a large, ovoid secondary lymphoid organ situated high in the left abdominal cavity. The spleen is surrounded by a capsule that extends into a number of projections internally to form a compartmentalized structure. The two compartments are red pulp and white pulp and are separated by a marginal zone. The red pulp is the site where old and defective red blood cells are destroyed and removed. The white pulp surrounds the branches of splenic artery, forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes.

The mucous membrane lining the digestive, respiratory and urogenital systems are defended by a group of organized lymphoid tissues collectively known as mucosal-associated lymphoid tissue (MALT). MALT inductive sites are secondary immune tissues where antigen sampling occurs and immune responses are initiated. These surfaces protect the body from an enormous quantity and variety of antigens. The tonsils, the Peyer patches within the small intestine, and the vermiform appendix are examples of MALT.

What You Will Learn!

• Immunology Basics - T and B lymphocytes, Antibodies, Humoral and cell mediated immunity
• Cells of the immune system - Natural killer cells, Macrophages, Phagocytosis, Granulocytes, Mast cells, Dendritic cells
• Organs of the immune system - Primary lymphoid organs, Thymus, Bone marrow,
• Organs of the immune system - Secondary lymphoid organs

Who Should Attend!

• Biotechnology students

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