Chapter 18

How would you recognize a severe allergic reaction?

A severe allergic contact dermatitis reaction for type IV hypersensitivity is much worse than what the boy experienced. While the rash would have still been itchy in the affected area, if it had been worse, the cytotoxic T lymphocytes would have destroyed so many skin cells that the blisters would have become filled with fluid and started to leak. This leakage would then have to be drained, and an alternate method of medication would have to be taken in order to avoid infection. Thus the boy is luck that he went to the doctor when he did, before the area got any more severe.

What types of illnesses cause death in patients with combined immunodeficiencies or AIDS?

AIDeS is a syndrome with several opportunistic or rare infections, associated with several decrease in the number of CD4 cells. AIDS (acquired immunodeficiency syndrom) causes skin infections like shingles and herpes. Moreover, diseases of nervous system include meningitis, toxoplasmosis, and disease of the respiratory system, includes tuberculosis, pneumonia, histoplasmosis, and coccidoidomycosis. Futhermore, disease of digestive system includes diearrhea, thrush, and oral hairy leukoplankia, besudes final stages results in dementia. In AIDS patients, a rare cancer is found in blood vessels called Kaposi's sarcoma. Hence, persons with AIDS or combined immunodeficiency die due to opportunistic infections.

Why is a child born to an RH+ mother not susceptible to Rh-related hemolytic disease of the newborn?

An Rh+ blood group woman is carrying an Rh- fetus, the fetus doesn't have the risk of new born hemolytic disease, in which no antibodies are produced to destroy the fetus's red blood cells

Identify four types of grafts

Autografts (the graft comes from a different part of the patient in question), isografts (grafts between two identical individuals, such as clones or identical siblings), allografts (grafts between genetically distinct members of the same species), and xenografts (grafts between individuals of different species).

Table that showcases the differences between the different blood group types

Blood group: A / Antigens present: A / Antibodies present: Anti-B / Can donate to: A and AB / Can receive form: A and O Blood group: B / Antigens present: B / Antibodies present: Anti-A / Can donate to: B and BA / Can receive form: B and O Blood group: AB / Antigens present: A and B / Antibodies present: none / Can donate to: AB / Can receive form: all groups Blood group: O / Antigens present: none / Antibodies present: Anti-A and Anti-B / Can donate to: All groups / Can receive form: O

In general, people with B cell defects acquire numerous bacterial infections, whereas those with T cell defects get viral diseases. Explain why this is so?

Defects in B-cells produce bacterial infections, while defects in T-cells produce viral disease: Antibody-mediated responses with extracellular bacteria are effective in fighting against bacterial infections. Moreover, some people suffer from bacterial diseases that lack B-cells. Additionally, immune responses of cell mediated fights effectively with pathogens like intracellular viruses. Thus, people who are devoid of T-cells will produce viral infections.

ABO blood group antigens are found on NUCLEATED cells.

False, ABO blood group antigens are present on the surface of red blood cells. The most important of the blood group antigens is the ABO group, which is largely responsible for transfusion reactions. ABO blood groups antigens are not found in nucleated cells.

CYCLOSPORINE is released by degranulating mast cells.

False, Histamines, proteases, and kinins are released by degranulating mast cells.

Graft-versus-host disease can follow a bone marrow ISOGRAFT?

False, Surgical organ or tissue grafting can be made between genetically dissimilar individuals called as ALLOGRAFT. If it is not treated with immunosuppressive drugs, an organ donor's cells attact the recipient's body. Isograft is an organ or tissue graft made between genetically identical individuals. Hence, the correct statement is "Graft-versus-host disease can follow a bone marrow allograft."

The tuberculin reaction is a TYPE I hypersensitivity?

False, The tuberculin reaction is a good example of type IV or delayed type hypersensitive reaction, in which T cell-mediated inflammatory reaction takes 24-72 hours to occur. Protein extract of Mycobacterium tuberculosis is injected into the skin of an individual who has been infected with Mycobacterium tuberculosis. A positive tuberculin test shows hard, red swelling of 10nm in diameter. Tuberculin reaction is not an allergic reaction or type I anaphylactic hypersensitivity reaction.

Contrast autografts, isografts, allografts, and xenografts.

Graft types are named according to the relation between donor and the recipient. A graft is called an autograft when tissues are moved to a different location within the same individual. Foreign antigens are not expressed in autograft; hence they do not trigger immune response. A best example for autograft includes, grafting of skin from one area of the body to another to cover a burn area, (or) use of a leg vein to bypass blocked coronary arteries. Isografts are grafts transplanted between genetically identical individuals like siblings or clones. The MHC proteins are identical in these individuals; hence the immune system of the recipient cannot differentiate, between the grafted cells and its own normal body cells. Thus Isografts are not rejected since they do not trigger immune response. Allografts are grafts transplanted between genetically distinct members of the same species. In humans, most of the grafting performed is allograft. Since, the MHC proteins are not same in donor and recipient, it triggers strong type IV hypersensitivity reaction which results in graft rejection. Rejection of graft is suppressed, with immunosuppressive drugs. Xenografts are grafts transplanted between individuals of different species. Since, the tissues of donor and recipient are extremely different, they trigger a rapid and intense rejection of graft, which is very difficult to suppress. Xenografts from matured animals are not commonly used in therapy. Transplanting a baboon's heart into a human is an example of xenograft.

Describe the mechanisms and treatment of haemolytic disease of the newborn.

Hemolytic disease of the newborn is when an incompatible Rh antigen can pose a problem. If an Rh- mother is pregnant with an Rh+ baby, the blood cells that escape towards the later weeks of the pregnancy or childbirth can cause an immune reaction from the mother's immune system. This would cause the mother's body to fight off what it considers to be a foreign antigen. Since this reaction is caused by IgG antibodies, reduction of hemolytic disease of the newborn has been seen by administering anti-Rh IgG to Rh- women. This has resulted in safer and healthier pregnancies and deliveries.

A patient arrives at the doctor's office with a rash covering her legs. How could you determine whether the rash is a type I or a type IV hypersensitivity?

Hypersensitivity refers to the response to immune system's response to foreign antigens or particles. Type I hypersensitivity is also called as immediate hypersensitivity, is an allergic reaction. Type IV hypersensitivity is also know as delayed type hypersensitivity, as the reaction takes two to three days to develop.

The immunoglobulin class that mediates type I hypersensitivity is

IgE

Why is a person who produces a large amount of IgE more likely to experience anaphylactic shock than a person who instead produces a large amount of IgG?

In allergic individuals plasma cells produce IgE in response to allergens. High levels of IgE are produced in only some allergic individuals. The main reason is exposure to environmental factors during infancy and childhood to high levels of indoor antigens such as cigarette smoke, dust mites, and molds. Hence, the sensitized individuals become hypersensitive. Everyone is exposed is exposed to antigens in the environment, which triggers an immune response resulting in the production of IgG. But when cytokines from type II helper T lymphocytes activate the B lymphocytes in allergic persons, the B lymphocytes become turned into plasma cells, switches to IgE instead of producing IgG. Following a sensitized individual's contact with an allergen, many mast cells may degranulate simultaneously, releasing massive amounts of histamine and other inflammatory mediators into the bloodstream. The release of chemicals may exceed the body's ability to adjust, resulting in anaphylactic shock.

Why is AIDS more accurately termed a "syndrome" rather than a mere disease?

It is not a single disease. Syndrome is defined as a group of signs, symptoms, and diseases associated with a common pathology. (skin diseases [shingles & herpes], nervous system [meningitis, toxoplasmosis, cytomegalovirus], respiratory disease [tuberculosis, pneumocystis, histoplasmosis, & coccidioidomycosis], and digestive systems [chronic diarrhea, thrust & oral hairy leukoplakia], blood vessels [kapsoi's sarcoma] and dementia

Compare and contrast the functions of four classes of immunosuppressive drugs.

Person producing large amount of IgE experience anaphylactic shock, instead of IgG: Immunosuppressive drugs include glucocorticoids, cytotoxic drugs, cyclosporine, and lymphocyte-depleting therapies. 1. Glucocorticoids are corticosteroids, used as immunosuppressive agents for many years. Presnisone and methyl prednisolone are examples of glucocorticods. The drugs suppressed the response of T cells to antigen and inhibit T cell cytotoxicity and mechanism of cytokine production. Cytotoxic drugs inhibit cell division nonspecifically. Cyclophosphamide, azathiprine, mycophenolate mofetil, brequinar sodium, and leflunomide are examples of cytotoxic drugs. Cyclosphosphamides cross-link daughter DNA molecules in mitotic cells, preventing their separation and blocking mitosis. It impairs both B cell and T cell responses. Azathioprine is a purine analog, which competes with purines during the synthesis of nucleic acids. Thus, blocks DNA replication and suppressing both primary and secondary antibody responses. Mycophenolate mofetil is a cytotoxic drug, which inhibits purine synthesis. Brequinar sodium and leflunomide inhibits pyrimidine synthesis to inhibit cellular replication. Cyclosporine drug is a plypeptide derived from fungi, preventing interleukins and interferon produced by T cells, thereby blocking TH1 responses. Cyclosporine acts on activated T cells. It is less toxic than the other nonspecific drugs. When the drug is given to prevent allograft rejection, only activated T cells attack the graft are suppressed. Lymphocyte-depleting therapies are used to reduce the adverse side effects of less specific immunosuppressive drugs. One of the techniques includes administering an antiserum called antilympocyte globulin, which is specifically, kills activated T cells, and IL-2 receptors are inhibited.

List the signs and symptoms of rheumatoid arthritis

Rheumatoid arthritis is a systematic disorder caused by type III hypersensitivity. When B cells secrete IgM that bind to IgG molecules, the IgM-IgG complexes become deposited in the joints. There they actively complement, cause mast cells to release inflammatory chemicals, and the tissues in which this occurs swells and thickens, causing extreme pain. The inflammation erodes the joint cartilage and boy structure, causing the joints to become distorted and loose. And while the effects wax and wane, the condition becomes progressively worse with time. Thus understanding and researching this condition is vital to patients and their livelihoods.

Discuss the cause and signs of systemic lupus erythematosus

Systematic lupus erythatosus, or lupus for short, is another systematic type III hypersensitivity condition. In patients with lupus, antibodies fight against a number of different self antigens. This causes a number of different conditions and lesions. One consistent feature of lupus is self-reactive antibodies against DNA, which can cause glumerulonephritis or rheumatoid arthritis. Autoantibodies of different kinds in lupus can cause hemolytic anemia, bleeding disorders, altered immune reactivity, muscle inflammation, and even heart damage. Lupus is difficult to diagnose because of the vast scope of signs and symptoms associated with the disease, thus it is believed to have many causes. However, its damage is apparent, thus it needs to be understood and studied more.

In both Graves' disease and juvenile-onset diabetes mellitus, autoantibodies are directed against cytoplasmic membrane receptors. Speculate on the clinical consequences of an autoimmune response to estrogen receptors.

Systemic consequences are resulted when an autoimmune response is bound to estrogen. This is due to the presence of different cells producing estrogen receptors. There is reduction in fertility when any damage occurs to ovaries. Moreover, there is alteration in menstrual cycle in damaging the cells of endometrial. Since, the cells are involved in the growth of bone, which consists of receptors for estrogen there is impairment in remodeling.. Furthermore, the estrogen receptors in hypothalamus are targeted with high diversity and are not protected by blood-brain barrier. However, hypothalamus are controls the regulation of endocrine functions. Thus, the estrogen receptors are targeted by an immune response that supports in fighting against estrogen-responsive cancers.

Which of the following is an autoimmune disease?

Systemic lupus erythematosus

What mechanism is causing the signs and symptoms you are seeing?

The mechanism of type IV hypersensitivity is what is causing this boy's signs and symptoms of a re, itchy, tender area where the bee stung him. Upon the stinging, the boy's skin proteins were modified, which registered as a foreign agent in the body. This caused the body to send cell-mediated immune responses to the area, which in turn caused the irritating rash.

Describe the significance of the tuberculin test

The tuberculin test was born from the tuberculin response, and it is a prominent example of a delayed hypersensitive reaction. In this test, tuberculin is injected into the skin of a person. If they have never had the infection, no response will occur. However, if the injection develops into a red, hard, swollen lump, that indicates a positive reading. This lump is caused by inflammation, which is at its peak within 24-72 hours after injection. This is an important test because it shows the time it takes for the lymphocytes and macrophages present in the positive reading to get there. Thus, it is a prime example of type IV hypersensitivity.

Explain the roles of three inflammatory chemicals (mediators) released from mast cell granules.

There are three main inflammatory chemicals released from mast cell granules during a type I hypersensitivity reaction. These chemicals are: kinins, proteases, and leukotrienes. Kinins are power inflammatory chemicals. They cause smooth muscle to contact, causing inflammation and irritation in the affected areas. Proteases are enzymes that destroy nearby cells. This activates the complement system, which results in more inflammatory chemicals to be released. These damage tissue due to their inflammatory properties. Leukotrienes are lipid molecules that are also powerful inflammatory agents. These cause slow and prolonged smooth muscle contraction, inflammation, and increased vascular permeability. Prostaglandins are also like leukotrienes in that they are lipid molecules that cause smooth muscle contraction.

What special clinical problems might be encountered when these xenografts are used?

Tissues are different in pigs and humans where matching of tissue is not possible in xenografts. This is because different MHC (major histocompatibility) genes and proteins exist in pigs. Moreover, the xenografts have antigens that will be recognized as non-self. In addition, Xenografts provoke rapid and intense rejections that is difficult to suppress. Therefore, xenografts require immunosuppressive therapy that leaves the recipient, deadly infections. Hence, xenografts from mature animals are not commonly used therapeutically.

TYPE III hypersensitivity reactions may lead to the development of glomerulonephritis.

True

Why do the blisters of positive tuberculin reactions resemble the blisters of poison ivy?

Tuberculin skin test and oil of poisonous ivy comes under type IV or delayed type hypersensitivity reaction. They both trigger cell-mediated immune response. Tuberculin is mediated by the response of memory T cells. Additionally, an individual is infected with Mycobacterium tuberculosis, results in cell-mediated immune response to generate memory T cells. In tuberculin test, red, hard swelling, and inflammation reaches greater intensity within 24-72 hours. When the lesions developed are examined microscopically, it reveals infiltration of lymphocytes and macrophages. Futhermore, oil of poisonous ivy is a highly reactive hapten that binds to any protein it contacts. It includes the proteins in the skin when anyone rubs the plant. The chemically modified skin protein is regarded as foreign, triggering a cell-mediated immune response, and resulting in an intensely irritating skin rash called allergic contact dermatitis. Thus, Tc cells destroy skin cells that become acellular, and fluid-filled blisters develop.

Acute anaphylaxis

Type I hypersensitivity

Asthma

Type I hypersensitivity

Hay fever

Type I hypersensitivity

Milk allergy

Type I hypersensitivity

Describe three disease conditions resulting from type I hypersensitivity mechanisms

Type I hypersensitivity is not only uncomfortable for patients with allergies; it can also cause three disease conditions. These conditions are : hay fever, asthma and urticaria. Hay fever occurs when the allergic person inhales allergens, inducing a response in the upper respiratory tract. This results in a runny nose, sneezing, itchy throat and eyes, and watery eyes. If the allergens that are inhaled are particularly small, they can reach the lungs. This causes asthma, which causes severe difficulty with breathing, wheezing, coughing, mucus production, and constriction of the smooth muscle in the bronchi. Asthma is a life threating medical condition, and should be medically treated through proper information and inhaler use. Urticaria is also known as hives. These raised, itchy, red areas on the skin are caused by a release of histamine, causing a leakage of serum from local blood vessels. All of these conditions are medical reasons as t why type I hypersensitivity should be understood and controlled appropriately in all allergy prone patients.

Discuss the mechanisms underlying transfusion reactions

Type II hypersensitivity is known as cytotoxic hypersensitivty. This causes the destruction of donor red blood cells if a blood transfusion occurs between incompatible blood types. Red blood cells have many different glycoproteins on their cell surfaces. Blood group antigens are specific to each blood group type. If a donor's blood is incompatible with the recipient's blood type, the donor's blood group antigens may stimulate the production of antibodies against that blood in the recipient. This can result in a life threatening reaction, thus it is unsafe and should be avoided by identifying both the donor's and recipient's blood types to ensure compatibility

Farmer's lung

Type III hypersensitivity

Describe hypersensitivity pneumonitis and glumerulonephritis

Type III hypersensitivity at the localized level comes in two types: hypersensitivity pneumonitis, and glomerulonephritis. Hypersensitivity pnemonitis can affect the lungs when a patient inhales the antigen deep into their lungs. This causes a reaction, forming immune complexes that then actively complement in the lungs. This causes the patient to have difficulty breathing, which is always considered a life threatening condition. Glomerulonephritis is when the immune complexes that are circulating deposit it the kidney's glomeruli. This causes the kidney to become damaged, hindering blood filtration. This could ultimately lead to kidney failure, thus it is a very serious condition. Both of these types of localized type III hypersensitivity are serious conditions, thus they need to be understood appropriately, so as to combat their negative effects.

Outline the basic mechanism of type III hypersensitivity

Type III hypersensitivity is also called immune complex-mediated hypersensitivity. In this type of hypersensitivity, the immune complexes formed by antigens bound to antibodies circulate in the blood until they lodge into organs, joints or tissues. This triggers mast cell degranulation, releasing tissues damaging inflammation. This can occur locally or throughout the body, and there is currently no known cure. Thus, learning about and researching these immune responses are the key to unlocking the secret of why patients suffer from this kind of hypersensitivity.

Allergic contact dermatitis

Type IV hypersensitivity

Allograft rejection

Type IV hypersensitivity

Graft-versus-host disease

Type IV hypersensitivity

Outline the mechanism of type IV hypersensitivity

Type IV hypersensitivity is also know as delayed or cell-mediated hypersensitivity. The antigens that cause the reaction do not provoke inflammation until 12-24 hours after contact. This is because the action responsible for the inflammation comes from interactions between antigens, antigen-presenting cells, and T cells. When contact first occurs, the macrophages and T cells that are responsible for the reaction need time to migrate to and divide at the site of contact. Thus, there is a delayed response time.

A deficiency of both B cells and T cells is most likely a(n)

a primary immunodeficiency

Infection with HIV causes

acquired immunodeficiency syndrome

What do medical personnel administer to counter various type I hypersensitivities?

all of the above (antihistamine, brochodilator, corticosteroid, epinephrine)

When a surgeon conducts a cardiac bypass operation by transplanting a piece of vein from a patient's leg to the same patient's heart, this is

an autograft

Compare four types of drugs commonly used to prevent graft rejection

glucocorticoids - have been used the longest. They suppress the response of T cells to antigens, and inhibit T cell cytotoxicity and cytokine production. Cytotoxic drugs inhibit mitosis and cytokinesis, thus inhibiting lymphocyte proliferation. Cyclosporine is a polypeptide drug that prevents the production of interleukins and interferons by T cells, thus blocking the Th1 response. It is much less toxic than nonspecific drugs, and is ususally given in combination with gucocorticoids. Lymphocyte-depleting therapies are specified therapies aimed at targeting a narrow range of cells, so as to reduced any complications seen in the other medications.

A positive tuberculin skin test indicates that a patient not immunized against tuberculosis

has been exposed to tuberculosis antigens

The major infammatory mediator released by degranulating mast cells in type I hypersensitivity is

histamine

Systemic lupus erythematosus

not a hypersensitivity

AIDS

not a hypersensitivty

Hemolytic disease of the newborn is caused by antibodies against which major blood group antigen?

rhesus antigen

Farmer's lung is a hypersensitivity pneumonitis resulting from a

type III hypersensitivity to mold spores