Dental Microbiology #211
IMMUNOLOGY
Lecture 1
Tuesday September 20, 2005
Elements of the Immune System.
Immunology is the study of the tissues, cells and molecules involved in the defense of the body against invasion by other organisms such as bacteria, viruses, parasites and fungi.
It is a very old and well established observation that individuals who survive an infectious disease become resistant (immune) when re-exposed to the same infectious agent later, but the same individual is fully susceptible to other infectious agents. In addition to dealing with pathogenic organisms, the function of the immune system is to remove also foreign non-invasive cells and molecules such as foreign red blood cells, pollens, foreign proteins etc.
The cells and tissues involved in the defense against foreign organisms constitute the Immune System. In immune-deficient individuals even minor infections may become fatal. The main function of the vertebrate immune system is to recognize the invading foreign organisms, to prevent their spread and to clear them from the body.
The Cells of the Immune System.
The Immune system is made up of a group of tissues and cells disseminated over the entire organism.
All cells of the immune system originate in the bone marrow from a common precursor called PluripotentHematopoietic Stem Cell (HSC) (Fig.1). This stem cell gives rise to several lineages that will disseminate into the blood stream and to a number of specialized tissues called lymphoid tissues. The following lineages are originally derived from the HSC:
The granulocyte-macrophage lineage consists of the three types of polymorphonuclear leukocytes(granulocytes): the neutrophils, the eosinophils and the basophils, and ofthe macrophages (in tissues)and monocytes in the blood.
The lymphoid lineage is composed of the B (bone marrow-derived) and T (thymus-derived) lymphocytes.
The platelets and the erythrocytes also originate in the bone marrow from a common Megakaryocyte-Erythrocyte progenitor but these cells are not directly involved in immune functions.
The lymphoid tissue and lymphatic circulation.
There are two types of lymphoid tissues: Central and Peripheral. The central lymphoid tissues are the Thymus and the Bone marrow, while the peripheral lymphoid tissues are the spleen, the lymph nodes, and the Mucosal-associated Lymphoid Tissue (MALT) of the intestine and bronchi. The bone marrow and thymus are called central lymphoid tissues because they represent the site of lymphocyte development and maturation. Although it is widely used, the term central lymphoid tissue is not appropriate to apply to the bone marrow because the bone marrow is the site of maturation for all hematopoietic cell lineages, and thus does not fit the definition of a typical lymphoid organ. The peripheral lymphoid tissues become colonized with mature lymphocytes ready to perform their immune functions.
The lymphocytes recirculate continuously between the blood, the peripheral lymphoid organs and the lymphatic circulation. The lymphatic circulation is made up of an extensive system of vessels that collects extracellular fluid from the tissues and returns it to the blood. The extracellular fluid is called the lymph, and the vessels are called lymphatic vessels (Fig 2). The lymphatics collect the lymph into a central lymphatic vessel called the thoracic duct which releases the lymph into the blood stream via the left subclavian vein.
The immune response operates along two arms:
Innate and Adaptive Immunity.
Innate immunity is immediate, does not require previous experience with, or exposure to the pathogenic organism, and is non-specific.
Adaptive immunity starts to function later because it requires time for induction, and is specific. Exposure to an infectious agent will render the host resistant to that agent but not to other unrelated organisms.
The innate immune system is made up of:
I,Mechanical and chemical barriers
- the skin
- the mucosal surfaces
- mucus secretion which exhibit protective and antibacterial properties,
- enzymes: lysozyme in tears and saliva has powerful antibacterial properties
- the acidic environment of the stomach, skin, urine, seminal fluid, vagina
II. The phagocytic cells
III. The Compelement system
II. The phagocytic cells:
When the integrity of the skin or of the mucous membranes is broken, (cuts abrasions, wounds) the invading pathogenic microorganisms are usually prevented from spreading by the phagocytic cells which recognize certain common patterns on the surface of the pathogen, ingest and destroy it. As this process takes place, a local inflammatory response ensues with the associated recruitment of additional phagocytic cells from the circulation. The phagocytic cells are the polymorphonuclear cells, the monocytes/macrophages and the dendritic cells. Dendritic cells are specialized tissue-resident large phagocytic cells that play a crucial role in the induction of the adaptive immune response.
Inflammation
Injured or infected tissues become inflamed through the release of pharmacologic mediators by the phagocytic cells. The initial inflammatory response becomes amplified through the recruitment to the affected area of more phagocytic (inflammatory) cells from the circulation. The classical description of the inflammatory response is by the recognition of four constant elements: pain, redness, swelling and heat (or in latin “dolor, rubor, tumor, calor”). The migration of inflammatory cells is usually associated with accumulation of fluid (edema) to the affected area and is due to increase in capillary permeability thus allowing cells and fluid to cross the vascular endothelium into the tissues. The process whereby inflammatory cells cross the vascular endothelium is called diapedesis (Fig 3).
III. Complement
A group of naturally-occurring plasma proteins produced by the liver that play a major role in the killing and removal of pathogens. (To be discussed later).
Adaptive Immunity.
If the infectious process cannot be stopped by the innate immune response, the immune system provides a second, more powerful line of defense called adaptive immunity.
The adaptive immune system is composed of:
T and B lymphocytes and a group of specialized phagocytic cells called Antigen-presenting cells (APC). Because the phagocytic cells function as both innate and adaptive immune response components, they form a connective link between the two types of immunity. The T lymphocytes are involved in defense against intracellular bacteria such as Mycobacterium tuberculosisand viruses, and in the rejection of foreign tissue and organ grafts (To be discussed later). The B lymphocytes are the cells that produce the antibodies. The adaptive immune response requires time to be induced, is specific and has memory.
Antigens.
An adaptive immune response takes place as a result of exposure to subtances such as peptides and proteins, complex polysaccharides, glycoproteins, nucleoproteins, etc, that are foreign to the individual that is exposed to them. A substance capable of inducing an adaptive immune response is called an Antigen. Microorganisms, whether pathogenic or not are made up of many different protein and carbohydrate molecules each of which can act as antigens and can trigger an adaptive immune response. Tissues and cells foreign to the host can also trigger an adaptive immune response since they express many different antigens. A typical example is the response to red blood cells of a different blood group than that of the host, or the production of antibodies to grass or tree pollens with the consequent development of allergies.
Antibodies are glycoproteins produced by B lymphocytes after exposure of the host to an antigen. Antibodies are specific i.e. they react with, and bind to the antigen molecule that induced their production. Interaction between the antigen and antibody occurs both in vitro and in vivo. (To be discussed later)..
The notion of specificity can be explained in both chemical and geometric terms. A defined portion of an antigen molecule called epitope “docks” and binds to a dedicated region of the antibody, in the shape of a groove or patch called an antibody binding site.
Each antibody (Ab) molecule is specific for, and can interact with only one antigen (Ag) specificity. For instance, Ab produced in response to an Ag expressed by influenza virus will interact only with that Ag and therefore will protect the host against the influenza virus expressing that specific Ag, but not against any other virus or bacterium. Since the influenza virus exists as many different strains, Ab produced during an epidemic with strain A will not necessarily protect the host against a later infection with an influenza virus of strain B, simply because strain A and strain B express distinct Ag specificities. If strain A and B of the influenza virus share some of the same antigens in common, strain A and B are said to express cross-reactive Ag, and exposure to strain A will confer partial, but not full protection against an infection with strain B.
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