Introduction to Immunology PDF

# Introduction to Immunology ## Host Defense Mechanisms - Humans are in continuous association with micro-organisms, including those that readily colonize the body surfaces. - It is relatively rare that these micro-organisms cause damage to their host. This is due to the effectiveness of the host...

# Introduction to Immunology ## Host Defense Mechanisms - Humans are in continuous association with micro-organisms, including those that readily colonize the body surfaces. - It is relatively rare that these micro-organisms cause damage to their host. This is due to the effectiveness of the host defense mechanisms, which restrict invasion by normal flora and defend against non-indigenous micro-organisms. - Sometimes, the host tolerates colonization by a parasite but restricts it to regions of the body where it can do no harm. - If the parasite invades, an infection is said to have occurred. - If, as a result of infection, pathological harm to the host becomes evident, this is called an infectious disease. - The host defense mechanisms are mediated by the immune system. - For our purposes, the term immunity refers to the relative state of resistance of the host to infectious disease. ## The Immune System - The immune system composed of two major subdivisions: - The **innate** or **non-specific immune system**, which is a primary defense mechanism against invading organisms. - The **adaptive** or **specific immune system**, which acts as a second line of defense. - Both aspects of the immune system have cellular and humoral components. - There is interplay between these two systems, i.e. cells or components of the innate immune system influence the adaptive immune system and vice versa. A diagram illustrates the comparison between **innate** and **adaptive immunity**. * **Innate Immunity** - **Rapid Responses to a broad range of microbes** - **External defenses** - Skin - Mucous membranes - Secretions - **Internal defenses** - Phagocytic cells - Antimicrobial proteins - Inflammatory response - Natural killer cells * **Acquired Immunity** - **Slower responses to specific microbes** - **Humoral response (antibodies)** - **Cell-mediated response (cytotoxic lymphocytes)** ## Differences in Susceptibility of Animal Hosts to Microbial Pathogens (Natural Immunity) - Natural immunity or resistance is based on the genetics of the host. There are two aspects: - **Species resistance**: resistance among all members of a species. - **Individual resistance**: resistance within members of the same animal species. - Certain animals are naturally resistant to certain pathogens. Certain pathogens infect only humans, not lower animals (e.g. syphilis, gonorrhea, measles, poliomyelitis). - Absence of specific tissue or cellular receptors for attachment (colonization) by the pathogen. ## Individual Resistance - There are many reasons why individuals of the same animal species may exhibit greater or lesser susceptibility to the same ineffective agent. - **Age**: related to the development of the immunological system. - **Sex**: related to the presence of the sex organs and anatomical structure related to sex. - **Stress**: complex of factors that influence health. - **Diet, Malnutrition**: infections may be linked with vitamin and protein deficiencies. - **Current Disease or Trauma**: the normal defenses of an animal are impaired by organic diseases. ## Therapy Against Other Diseases - Modern therapeutic procedures used in some diseases can render an individual more susceptible to infection. - Examples of therapeutic procedures that reduce the efficiency of the host's defenses are treatment with corticosteroids, cyto-toxic drugs, antibiotics, or irradiation. A diagram illustrates a human body with labelled areas where the different defense mechanisms operate. ## Antimicrobial Substances in Host Tissues - The body fluids and organized tissues of animals naturally contain a variety of antimicrobial agents that kill or inhibit the growth of microbes. A table presents antimicrobial substances of host origin present in body fluids and organized tissues. - **Lysozyme**: Sources: serum, saliva, sweat, tears. Activity: bacterial cell lysis. - **Complement**: Source: serum. Activity: cell death or lysis of bacteria; participates in inflammation. - **Polypeptides (histones, ß-lysins, and other cationic proteins, tissue polypeptides)**: Sources: serum or organized tissues. Activity: disruption of bacterial plasma membrane. - **Lactoferrin and transferrin**: Sources: body secretions, serum, organized tissue spaces. Activity: inhibit microbial growth. - **Interferons**: Sources: virus-infected cells, lymphocytes. Activity: resistance to virus infections. - **Interleukins**: Sources: macrophages, lymphocytes. Activity: cause fever; promote activation of immune system. ## Complement - Complement is considered as part of the innate immunity because of its role in inflammation, phagocytosis, and bacterial killing. - Complement can also be activated by reactions between antigens and antibodies, therefore, it may play a role in adaptive immunity. - Complement is an enzymatic system of serum proteins made up of nine major components (C1- C9) that are activated during two pathways: - The **classical pathway**: reactions between antibodies and antigens on the surface of a microbe. - The **alternative pathway**: pathogen surface creates local environment conducive to complement activation. A diagram illustrates the classical pathway, lectin pathway and alternative pathway of complement activation. - **Complement components play a part in phagocytic chemotaxis, opsonization, and the inflammatory response.** - **Some Immunoglobulins (IgG and IgM) can "fix complement" because they have a complement binding site on the Fc portion of the molecule.** - **Complement activation initiates a "cascade reaction" resulting in the following effects:** 1. Generation of inflammatory factors, C3a and C5a, which focus antimicrobial serum factors and leukocytes into the site of infection. 2. Attraction of phagocytes. Chemotactic factors C3a and C5a attract phagocytes to the site. 3. Enhancement of phagocytic engulfment. C3b component on Ag-Ab complex attaches to C3b receptors on phagocytes and promotes opsonization of Ab-coated cells. 4. Lysis of bacterial cells (lysozyme-mediated) or virus-infected cells. When C8 and C9 are bound to the complex, a phospholipase is formed that destroys the membrane of Ag-bearing host cells or the outer membrane of Gram-negative bacteria. ## Inflammation - Of all the defense mechanisms in the animal host, the **inflammatory response** may be the most important for dealing with microbial infection. - Inflammation is necessary for the proper functioning of all the host defenses because it focuses circulating antimicrobial factors on the site of infection. - These include **phagocytes, lymphocytes, antibodies, complement** and other antimicrobial components of plasma. - Inflammation is also an important aspect of bacterial pathogenesis since the inflammatory response induced by a microbe can result in considerable damage to the host. - Inflammation is a tissue reaction to infection or injury, the characteristic symptoms of which are: - **Redness**: The redness is due to increased blood flow to the area of injury. - **Swelling**: The swelling (edema) is due to increased extravascular fluid and phagocyte infiltration to the damaged area. - **Heat**: The heat is due to the increased blood flow and the action of pyrogens (fever-inducing agents). - **Pain**: The pain is caused by local tissue destruction and irritation of sensory nerve receptors. If a whole organ or tissue is involved, loss of function may occur. - **Inflammation can be induced by certain immunological reactions, tissue damage, or the entry of an injurious agent.** - **Certain bacterial cells and/or their products (e.g. structural components or toxins) can induce an inflammatory response.** - **Inflammation is mediated by mast cells in fixed tissues and by basophils in the blood.** - The response may be initiated in a variety of ways: 1. The inflammatory response is triggered by pathogen invasion or tissue injury. Injured and dyeing cells release cytoplasmic constituents that lower the pH in the surrounding extracellular environment. 2. The increased acidity activates an extracellular enzyme, kallikrein, which in turn activates bradykinin. 3. Bradykinin binds to receptors on the capillary walls, opening junctions between cells to allow leakage of plasma components collectively referred to as inflammatory exudate. - The first cells to appear are **neutrophils**, which are actively phagocytic. - Bradykinin also binds to **mast cells** of the connective tissue, initiating other events that are associated with the process of inflammation. - Initially, in the mast cell, there is a rapid influx of Ca++, intracellular cAMP levels drop, and mediator-rich lysosomal granules migrate to the cell surface. They then fuse with the cell membrane and discharge their contents to the exterior by exocytosis. Included in these contents are **histamine and heparin**. A diagram illustrates the steps in the inflammatory response. ## Phagocytic Defenses - Part of the inflammatory response leads to the recruitment of phagocytes to the site of inflammation. - Phagocytes are a class of cells which are capable of ingestion and destruction of micro-organisms that are responsible for inciting the inflammatory response. - **The first to accumulate around the invaders are neutrophils.** - **Later, local and blood-borne macrophages also migrate to the tissue site.** - Neutrophils and macrophages are sometimes referred to as professional phagocytes. ## Properties of Neutrophils - Neutrophils have their origin in multi-potential stem cells in the bone marrow. They are short-lived cells which constitute 30-70% of the circulating white blood cells. - During differentiation in the marrow, the nucleus of the cell becomes multilobed (hence the name polymorphonuclear leukocyte). Cell division ceases, and mitochondria and endoplasm reticule disappear from the cytoplasm. At the same time, the cell becomes motile and actively phagocytic.. - Properties of neutrophils include: - Only half of the neutrophils in human circulation are detectable in the blood. - There are approximately 100 near-mature cells in the bone marrow pool. - Neutrophils never return to the circulation once they enter the tissues, intestinal tract, or respiratory tract. ## Properties of Macrophages - Macrophages (also called mononuclear phagocytes) also arise from bone marrow stem cells which gives rise to monocytes which develop into monocytes that are released into the blood stream. - Monocytes typically circulate in blood for 1 to 3 days before migrating into tissues where they become macrophages or dendritic cells. - Monocytes are actively phagocytic and bactericidal. Within 2 days or so, the blood stream monocytes emigrate into the tissues where they settle, enlarge and become fixed macrophages. - Macrophages are more active in phagocytosis than monocytes and develop many more granules containing hydrolytic enzymes. - New macrophages can develop by cell division under inflammatory stimuli. - The total pool of macrophages is referred to as the system of **mononuclear phagocytes.** - In the lymph nodes, macrophages function as scavengers to remove foreign material from the circulation. - Compared to neutrophils, macrophages are long-lived cells. - As phagocytes, neutrophils play a more important role in the acute stages of an infection, while macrophages are principally involved in chronic types of infections. - Macrophages and related dendritic cells are among an elite corps of **antigen-presenting cells** or **APC's**. ## The Phagocytic Process - **Phagocytosis and destruction of engulfed bacteria involves the following sequence of events**: - **Delivery of phagocytic cells to the site of infection** - **Phagocytic adherence to the target** - **Ingestion or engulfment of the target particle** - **Phagolysosome formation** - **Intracellular killing** - **Intracellular digestion** A diagram illustrates these steps in the phagocytic process in macrophages. ## Adaptive Immunity - Innate immunity, by itself, may not be sufficient to protect a host against an invading pathogen or to prevent disease from occurring. - However, if innate immunity fails, the organism may yet be detected and attacked by the mechanisms of adaptive immunity. - The innate and adaptive immune responses both function to protect against invading organisms. - The two systems differ in the following ways: - **The innate immune system is constitutively present and reacts immediately to infection**. The adaptive immune response takes some time to develop. - **The innate immune system is not specific in its response**. The adaptive immune system is antigen-specific and reacts only with the organism that induced the response. - **The adaptive immune system exhibits immunological memory.** It "remembers" an invading organism and reacts more rapidly on subsequent exposure to the same organism. A table outlines the main differences between innate and adaptive immunity. ## Antigens - An antigen (Ag) is a foreign substance (i.e., not part of the animal's tissues) of relatively high molecular weight (>12,000 daltons) that induces a specific immunological response in the form of AMI or CMI or both. - Because of their complex macromolecular structure, a single micro-organism consists of multiple antigens (e.g. surface structures such as cell wall components, fimbriae, flagella, etc., or extracellular proteins, such as toxins and extracellular enzymes). - The coat proteins and some of the envelope proteins of animal viruses are also antigenic. - The animal host respond specifically to every antigen to come into contact with the components of the immunological system. ## Active vs Passive Immunity - Although adaptive immunity develops in an animal which is undergoing a specific immunological response to an antigen, the immune cells and factors generated can be shared among two or more animals. - Hence, adaptive immunity can be acquired by an animal in two ways: - **Active immunity**: individual is exposed to an antigen and develops its own response. - **Passive immunity**: individual is given pre-formed antibody from another source.