2. Humoral Immunity (B-Cells "the antibody producing cells)
Specific antibodies are important in and may protect against viral infections. The most effective type of antiviral antibody is "neutralizing" antibody - Each B cell is programmed to make one specific antibody. For example, one B cell will make an antibody that blocks a virus that causes the common cold, while another produces antibody that zeros in on a bacterium that causes pneumonia.
When a B cell encounters its triggering antigen (along with collaborating T cells and accessory cells), it gives rise to many large cells called plasma cells. Every plasma cell is essentially a factory for producing antibody. They manufacture millions of identical antibody molecules and pour them into the bloodstream.
A given antibody matches an antigen much as a key matches a lock. To some degree, however, the antibody interlocks with the antigen and thereby marks it for destruction.
The activated B-cells give rise to the plasma cells which secrets the antibodies
Antibodies belong to a family of large molecules known as immunoglobulins. Immunoglobulins are shaped to form a Y.
Scientists have identified nine chemically distinct classes of human immunoglobulins (Ig)-four kinds of IgG and two kinds of IgA, plus IgM, IgE, and IgD. Each type plays a different role in the immune defense strategy.
|It the major immunoglobulin in the blood, is also able to enter tissue spaces; it works efficiently to coat microorganisms, speeding their uptake by other cells in the immune system.|
|It usually combines in star-shaped clusters, tends to remain in the bloodstream, where it is very effective in killing bacteria.|
|It concentrates in body fluids-tears, saliva, and the secretions of the respiratory and gastrointestinal tracts-guarding the entrances to the body.|
|Under normal circumstances, it occurs only in trace amounts, probably evolved as a defense against parasites, but it is more familiar as the immunoglobulin responsible for allergic reactions (Allergy).|
|It is almost exclusively found inserted into the membranes of B cells, where it somehow regulates the cell's activation.|
The immune system responds to viral proteins encountered within most tissues of the body by generating helper T cells, which release inflammatory cytokines such as IL-2 and IFN-g. The response to viral proteins in mucosal tissue also stimulates the induction of TGF-ß secreting cells and regulatory T cells which secrete IL-4 and IL-10. This cascade of events results in a suppressive regulatory response as well as stimulation of B cells that secrete IgA, which may be protective against infection at these surfaces. Virus specific antibody binds to the virus, usually to the viral envelope or capsid proteins, and blocks the virus from binding and gaining entry to the host cell. Virus specific antibodies may also act as opsonins in enhancing phagocytosis of virus particles - this effect may be further enhanced by complement activation by antibody-coated virus particles and may lead to complement-mediated lysis of the infected cell, or may direct a subset of natural killer cells to lyse the infected cell through a process known as antibody-directed cellular cytotoxicity (ADCC).
During the course of a viral infection, antibody is most effective at an early stage, before the virus has gained entry to its target cell. In this respect, antibody is relatively ineffective in primary viral infections, due mainly to the lag phase in antibody production.
Phagocytes, Granulocytes, and Their Relatives
Phagocytes (literally, "cell eaters") are large white cells that can engulf and digest microorganisms and other antigenic particles. Some phagocytes also have the ability to present antigen to lymphocytes.
Important phagocytes are monocytes and macrophages. Monocytes circulate in the blood, and then migrate into tissues where they develop into macrophages ("big eaters"). Macrophages are seeded throughout body tissues. Specialized macrophages include alveolar macrophages in the lungs, mesangial phagocytes in the kidneys, microglial cells in the brain, and Kupffer cells in the liver.
They are versatile cells that play many roles.
|•||As scavengers, they rid the body of worn-out cells, digested microorganisms and other debris.|
|•||It is foremost among the cells that "present" antigen to T cells, having first digested and processed it; macrophages in such way play a crucial role in initiating the immune response.|
|•||As secretory cells, monocytes and macrophages are vital to the regulation of immune responses and the development of inflammation; they churn out an amazing array of powerful chemical substances (monokines) including enzymes, complement proteins, and regulatory factors such as interleukin-1.|
Another critical phagocyte is the neutrophils, also known as polymorphonuclear leukocytes or polymorphs. Neutrophils are not only phagocytes but also granulocytes: they contain granules filled with potent chemicals. These chemicals, in addition to destroying microorganisms, play a key role in acute inflammatory reactions.
Granulocytes include also eosinophils and basophils. They typically "degranulate," releasing their chemicals to work on cells or microbes in their surroundings.
The mast cell is a non-circulating counterpart of the basophil. Located in the lungs, skin, tongue, and linings of the nose and intestinal tract, the mast cell is responsible for the symptoms of allergy.
Another related structure is the blood platelet. Platelets, too, contain granules. In addition to promoting blood clotting and wound repair, platelets release substances that activate components of the immune system.
Different types of white cells (phagocytes, granulocytes and their relatives
The complement system is made up of a series of about 25 proteins that work to "complement" the activity of antibodies in destroying bacteria, either by facilitating phagocytosis or by puncturing the bacterial cell membrane. Complement also helps to rid the body of antigen-antibody complexes. In carrying out these tasks, it induces an inflammatory response.
Complement proteins circulate in the blood in an inactive form. When the first of the complement substances is triggered-usually by antibody interlocked with an antigen-it sets in motion ripple effect. As each component is activated in turn, it acts upon the next in a precise sequence of carefully regulated steps known as the "complement cascade" which ends in creation of a unit known as the membrane attack complex. Inserted in the wall of the target cell, the membrane attack complex constitutes a channel that allows fluids and molecules to flow in and out. The target cell rapidly swells and bursts. One byproduct causes mast cells and basophils to release their contents, producing the redness, warmth, and swelling of the inflammatory response. Another stimulates and attracts neutrophils. Another opsonizes or coats target cells so as to make them more palatable to phagocytes.
Antibodies and complement thus affect viruses at two points in their replication cycles: during their extracellular phase antibodies can bind and neutralize the virus directly, and during the viral intracellular phase antibody and complement can interact with exposed (membrane-associated) viral proteins, leading to antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-mediated cytolysis.
Viral Immune Evasion
Why we ever get infected even in the absence of immune suppression?
Every virus capable of infecting vertebrates has some means of dealing with the immune response. These methods range from the very rapid replication that may allow some viruses to complete a replication cycle before the specific immune response has a chance to develop - to the profound, such as the near-total ablation of the immune system in late-stage HIV infection. In several instances, viruses block the responses by interfering with any of the components of the immune system.
Cytokines, mostly produced by T helper cells, are most critical in the acute phase of the immune response; interleukin-1 (IL-1), interleukin-2 (IL-2), interferon-g (IFN-g), and tumor necrosis factor (TNF) induce inflammation, recruit and stimulate other immune components, and generally induce an inhospitable environment for any kind of microbes. (11). The cytokines, IL-6 and TNF- play an important role in the pathogenesis of symptom production in influenza, while 2 other cytokines, IL-10 and IFN- , involved in the counter-regulation of the immune response to stop any fulmination of the inflammatory response. Experimental studies showed that a number of viruses secrete potent chemokine inhibitors in order to stop the protective reaction of the immune system against the virus (12,13).
Since NK cells are also very important in the early phase of clearing infections (14) one would also expect that some viruses target these cells. Some NK effects are also mediated by cytokines, and in particular IFN-g (15).
The Role of The Immune System In Allergic Reactions
The most common types of allergic reactions-hay fever, some kinds of asthma, and hives-are produced when the immune system respond to a false alarm. In a susceptible person, a normally harmless substance-grass pollen or house dust, for example-is perceived as a threat and is attacked. Such allergic reactions are related to the antibody known as immunoglobulin E. Like other antibodies, each IgE antibody is specific; one reacts against oak pollen, another against ragweed.
The first time an allergy-prone person is exposed to an allergen, he or she makes large amounts of the corresponding IgE antibody. These IgE molecules attach to the surfaces of mast cells (in tissue) or basophils (in the circulation). Mast cells are plentiful in the lungs, skin, tongue, and linings of the nose and When an IgE antibody sitting on a mast cell or basophil encounters its specific allergen, the IgE antibody signals the mast cell or basophil to release the powerful chemicals stored within its granules. These chemicals include histamine, heparin, and substances that activate blood platelets and attract secondary cells such as eosinophils and neutrophils. The activated mast cell or basophil also synthesizes new mediators, including prostaglandins and leukotrienes, on the spot.
It is such chemical mediators that cause the symptoms of allergy, including wheezing, sneezing, runny eyes, rhinorrhea and itching. They can also produce anaphylactic shock, a life-threatening allergic reaction characterized by swelling of body tissues, including the throat, and a sudden fall in blood pressure.