Pathophysiology lecture By Dr. Raja’a Ali H. Al- Husseini

Pathophysiology lecture By Dr. Raja’a Ali H. Al-Husseini College of pharmacy- Kufa University Disorders of the Immune System

General introduction Introduced by Dr. Nawzat M. M.

Immunity:- Is the resistance to a disease, that is provided by the immune system. It can be acquired actively through immunization or by having a disease, or passively by receiving antibodies or immune cells from another source.

Immune mechanisms can be classified into two types:- 1-Speciﬁc or acquired immunity which involves: Humoral and Cellular mechanisms whereby the immune cells differentiate self from nonself and recognize and respond to a unique antigen.Thehumoral immune response involves antibodies produced by activated B lymphocytes. Cell-mediated immunity depends on T-cell responses to cellular antigens. 2-Non speciﬁc immune mechanisms which involve complement system, cytokines, and the phagocytic activities of neutrophils and macrophages.It can distinguish between self and non-self but cannot differentiate among antigens.

THE COMPONENTS OF THE IMMUNE SYSTEM ■ The immune system consists of 1-immune cells, 2-the central immunestructures (the bone marrow and thymus), where immune cells are produced and mature; and 3-the peripheral immune structures (lymph nodes, spleen, and other accessory structures), where the immune cells interact with antigen. ■ The system's principal cells include lymphocytes that recognize antigens and related accessory cells (such as phagocytic macrophages, which engulf and destroy foreign material). Lymphocytes arise in the bone marrow from stem cells, with T lymphocytes ( T cells) migrating to the thymus to mature and B lymphocytes ( B cells) maturing in the bone marrow.

■ Cytokines are molecules that form a communication link between immune cells and other tissues and organs of the body. ■ Recognition of self from nonself by the immune cells depends on a system of MHC membrane molecules that differentiate viral-infected and abnormal cells from normal cells (MHC I) and identify immune cells from other types of cells (MHC II).

The Immune Response ■ The immune response involves a complex series of interactions between components of the immune system and the antigens of a foreign pathogen. ■ Passive immunity represents a temporary type of immunity that is transferred from another source (in utero transfer of antibodies from mother to infant). ■ Active immunity depends on a response by the person’s immune system and is acquired through immunization or actually having a disease. ■ Humoral immunity consists of protection provided by the B lymphocyte-derived plasma cells, which produce antibodies that travel in the blood. ■ Cell-mediated immunity consists of protection provided by cytotoxic T lymphocytes, which protect against virus-infected or cancer cells.

Disorders in the Immune Response A- ALLERGIC AND HYPERSENSITIVITY DISORDERS Introduced by: Dr. AreegWahab A.

Hypersensitivityis an immune response that damages the body's own tissues. They are divided into four classes (Type I – IV) based on the mechanisms involved and the time course of the hypersensitive reaction [ Table 10-1]. Type I hypersensitivity is an immediate or anaphylactic reaction, often associated with allergy. Symptoms can range from mild discomfort to death. Type I hypersensitivity is mediated by IgE, which triggers degranulation of mast cells and basophils when cross-linked by antigen. Type II hypersensitivity occurs when antibodies bind to antigens on the patient's own cells, marking them for destruction. This is also called antibody-dependent (or cytotoxic) hypersensitivity, and is mediated by IgG and IgM antibodies. Immune complexes (aggregations of antigens, complement proteins, and IgG and IgM antibodies) deposited in various tissues trigger Type III hypersensitivity reactions. Type IV hypersensitivity (also known as cell-mediated or delayed type hypersensitivity) usually takes between two and three days to develop.

Allergies also known as hypersensitivity, is a reaction by your immune system to something that doesn't bother other people. People who have allergies usually have sensitivities to more than one thing. Types of substances that commonly cause allergic reactions are; pollen, dust and dust mites, mold spores, pet dander foods, insect stings, medicines. Allergic reactions include runny nose, itching, rashes and swelling. Deficiencies in the immune system cause allergies. These deficiencies have a genetic and and environmental component. Asthma is another type of allergic reaction. The inside of the airway becomes inflamed and react strongly to allergens to which you're sensitive. The reaction causes the airway to constrict, reducing airflow to the lungs. This precipitates wheezing, coughing, and trouble breathing. An asthma attack is an acute allergic reaction of the airway. Severe asthma attacks can be serious and can cause death.

B- TRANSPLANTATION IMMUNOPATHOLOGY Introduced by: Dr. Hussein S. Mohammed

B- TRANSPLANTATION IMMUNOPATHOLOGY Not long ago, transplantation of solid organs (e.g., liver, kidney, heart) and bone marrow was considered experimental and used only for patients who have no other options. However organ and bone marrow transplantation has been enhanced by a greater understanding of humoral and cellular immune regulation, the development of immunosuppressive drugs and an appreciation of the role of the MHC antigens in transplant rejection. The likelihood of rejection varies with the degree of HLA (Human Leukocytes Antigens) or MHC (Major Histo-compatibility Complex) relatedness between donor and recipien

A rejection can involve:- an attempt by the recipient’s immune system to eliminate the donor cells, as in HVGD( Host-Versus-Graft Disease which is usually limited to allogeneic organ transplants), an attack by the cellular immunity of the transplanted tissue on the unrelated recipient tissue, as in GVHD (Graft-Versus-Host Disease occurs mainly in patients who undergo bone marrow transplant, sometimes may also occur after transplantation of solid organs rich in lymphoid cells (e.g., the liver)).

Three basic requirements are necessary for GVHD to develop: • [1] The donor bone marrow must have a functional cellular immune component. • [2] The recipient’s tissue must bear antigens foreign to the donor tissue. • [3] The recipient’s immunity must be compromised to the point that it cannot destroy the transplanted cells.

C –AUTOIMMUNE DISORDERS Introduced by : Dr. GhadeerMalik A.

C –AUTOIMMUNE DISORDERS Autoimmune diseases represent a group of disorders that are caused by a breakdown in the ability of the immune system to differentiate between self- and non self antigens. Normally, there is a high degree of immunologic tolerance to self-antigens, which prevents the immune system from destroying the host. Autoimmune diseases can affect almost any cell or tissue in the body. Some autoimmune disorders are tissue speciﬁc such as Autoimmune Adrinalitis; others, such as Rheumatoid Arthritis affect multiple organs and systems,scleroderma, autoimmune haemolyticanemia , autoimmune adrenalitis, insulin- dependent diabetes mellitus.

■ Immunologic tolerance is the ability of the immunesystem to differentiate self from nonself. ■ Central tolerance involves the elimination of self-reactive T and B cells in the central lymphoid organs. Self-reactive T cells are deleted in the thymus and self-reactive B cells in the bone marrow. ■ Peripheral tolerance derives from the deletion or inactivation of self-reactive T and B cells that escaped deletion in the central lymphoid organs. ■ Autoimmune disorders result from the breakdown in the integrity of immune tolerance such that a humoral or cellular immune response can be mounted against host tissue or antigens, leading to localized or systemic injury.

C –AUTOIMMUNE DISORDERS Introduced by: Dr. Hawraa Ali Naser

Some people are allergic to a wide range of substances, while others are affected by only a few or none. Why the difference? The reasons can be found in the makeup of an individual's immune system, which may produce several chemical agents that cause allergic reactions. The main immune system substances responsible for the symptoms of allergy are the histamines that are produced after exposure to an allergen. When an allergen first enters the body, the lymphocytes make what are known as E antibodies. These antibodies attach to mast cells, large cells that are found in connective tissue and contain histamines. The histamines are chemicals released by basophils, a type of lymphocyte, during the inflammatory response.

There are many treatments for allergy, including (obviously) avoidance of the substance to which the patient is allergic. Among these treatments are the administration of antihistamines, which either inhibit the production of histamine or block histamines at receptor sites.

. In cases of extreme allergic reaction leading to anaphylactic shock, the patient may require an injection of epinephrine (also sometimes called adrenaline), a hormone that the body produces for responding to situations of fear and danger In the case of anaphylactic shock, which involves such severe constriction of the breathing passages that the patient runs a risk of suffocation, epinephrine causes the passages to open, making it possible to breathe again.

Rheumatoid arthritis, as its name suggests, is a type of both rheumatism and arthritis, which are general names for diseases associated with inflammation of connective tissue. Rheumatoid arthritis occurs when the immune system attacks and destroys the tissues that line bone joints and cartilage. The disease can affect any part of the body, although some joints may be more susceptible than others are. As it progresses, joint function diminishes sharply, and deformities arise.

Pernicious anemia was so named at a time when it, too, was almost always fatal (pernicious means "deadly"), though treatments developed in the twentieth century have changed that situation. A disorder in which the immune system attacks the lining of the stomach in such a way that the body cannot metabolize vitamin B12 (see Vitamins), pernicious anemia manifests symptoms that include weakness, sore tongue, bleeding gums, and tingling in the extremities.

Autoimmune disorders are diagnosed and monitored through auto-antibody blood tests, blood tests that measure inflammation and organ function, family history, physical examination, and diagnostic tools such as x rays, etc. There is no cure for autoimmune disorders. Sometimes these disorders may disappear on their own, get worse or lessen in intensity over time. Treatment for these diseases must be tailored by the physician to relieve pain, minimize risk to the patient, and preserve organ function.

D-IMMUNODEFICIENCY DISORDERS Introduced by: Dr. Ahmed Adnan G.

D-IMMUNODEFICIENCY DISORDERS IMMUNO-DEFICIENCY (ID)can be defined as an abnormality in one or more branches of the immune system that renders a person susceptible to diseases normally prevented by an intact immune system, resulting from absolute or partial loss of the normal immune response. Abnormalities of the immune system can be classified : 1- Primary Immune deficiency (congenital or inherited)P.I.D. ■ In Primary ID Most primary immunodeﬁciency states are inherited and are either present at birth or become apparent shortly after birth. 2- secondary I.D. (when the immunodeficiency is acquired later in life). These are more common than primary disorders of genetic origin.

AIDS (Acquired Immun-DeficiencySyndrome) is the most common type of secondary immunodeﬁciency. It is an infectious disease of the immune system caused by the retrovirus HIV (human immunodeficiency virus HIV . HIV is transmitted from one person to another through: - 1- sexual contact. 2- through blood exchange. 3- perinatally.

Acquired immune deficiency disorders often are the result of side effects from drugs used to treat serious disorders. Corticosteroids, for example, are immunosuppressants used to suppress inflammation resulting from disorders such as rheumatoid arthritis.Immunosuppressants, however, also suppress the body's ability to fight disease and infections. Some cancer treatments and chemotherapy drugs are also powerful immunosuppressants. Immune deficiency disorders can also result from any prolonged illness. Diabetes for example can cause immune deficiency disorder, because white blood cells don't work well when blood sugar levels are high. Acquired Immune deficiency disorder (AIDS) can result from the infection by the human immunodeficiency virus (HIV).

Malnutrition can cause immune deficiency disorders. Being more than 20% underweight is a risk factor for acquiring a severe impairment of the immune system. There is no cure for AIDS. Treatment largely involves the use of drugs that interrupt the replication of the HIV virus and prevention or treatment of complications such as opportunistic infections. Infected women may transmit the virus to their offspring in utero, during labor and delivery, or through breast milk

Currently available antiretroviral drugs for the treatment of HIV fall into three categories: nucleoside reverse transcriptase inhibitors ,non-nucleoside reverse transcriptase inhibitors And protease inhibitors. Examples: zidovudine (AZT), didanosine Non-nucleoside reverse transcriptase inhibitors Examples: nevirapine, efavirenz

Thanks for listining Dr. Rajaa A. H.

Pathophysiology lecture By Dr. Raja’a Ali H. Al- Husseini