Chapter 16: Disorders of the Immune Response Porth

Put the normal sequence of actions of a polymorphonuclear phagocyte in order. a. Phagocytosis b. Kill the ingested pathogens c. Chemotaxis d. Generate microbidcidal substances e. Adherence

1. Chemotaxis 2. Adherence 3. Phagocytosis 4. Generate microbidcidal substances 5. Kill the ingested pathogens

It has been postulated that an autoimmune disease needs a "trigger event" for it to clinically manifest itself in a body. What are these "trigger events" thought to be?

A microorganism or virus, A self-antigen from a previously sequestered body tissue, or a chemical substance. Because autoimmunity does not develop in all persons with genetic predisposition, it appears that other factors such as a "trigger event" interact to precipitate the altered immune state. The event or events that trigger the development of an autoimmune response are unknown. It has been suggested that the trigger may be a virus or other microorganisms, a chemical substance, or a self-antigen from a body tissue that has been hidden from the immune system during development.

What is the difference between a primary and a secondary immunodeficiency?

A primary deficiency or immunodeficiency is congenital or inherited. A secondary immunodeficiency is acquired.

Combine immunodeficiency syndrome is a disorder in which both B and T lymphocytes are affected. This results in defects in both humoral and cell-mediated immunity. What could be the cause of this disorder?

A single mutation in any gene that influences major histocompatibility antigens. Disorders that affect both B and T lymphocytes with resultant defects in both humoral and cell-mediated immunity fall under the broad classification of combined immunodeficiency syndrome. A single mutation in any one of the many genes that influence lymphocyte development or response, including lymphocyte receptors, cytokines, or major histocompatibility antigens, could lead to combined immunodeficiency.

A transplant reaction that occurs immediately after transplantation is caused by ____ antibodies that are present.

A transplant reaction that occurs immediately after transplantation is caused by antidonor antibodies that are present. When preformed antidonor antibodies are present, rejection occurs immediate after transplantation.

Secondary immunodeficiency

Acquired later in life

Some people are so sensitive to certain antigens that they react within minutes by developing itching, hives, and skin erythema, followed shortly thereafter by bronchospasm and respiratory distress. What is this commonly known as?

Anaphylactic reaction. Anaphylaxis is a systemic life-threatening hypersensitivity characterized by widespread edema, vascular shock secondary to vasodilation and difficulty breathing. It is not called an antigen reaction, neither is it called an Arthus reaction.

____ is a systemic life-threatening hypersensitivity reaction characterized by widespread edema, vascular shock secondary to vasodilation, and difficulty breathing.

Anaphylaxis

____ mediated destruction of cells that are coated with low levels of IgG antibody and are killed by a variety of effector cells, which bind to their target by their receptors for IgG and cell lysis occurs without phagocytosis.

Antibody-dependent cellular cytotoxicity

A term used by pathologists and immunologists to describe localized tissue necrosis caused by immune complexes is the ______.

Arthus reaction

Combined immunodeficiency (CID) is distinguished by low, not absent, T-cell function. These diseases are usually associated with other disorders and arise from diverse genetic causes. What disease is considered a CID?

Ataxia-telangiectasia. Ataxia-telangiectasia is a complex syndrome of neurologic, immunologic, endorocinologic, hepatic, and cutaneous abnormalities. Pierre-Robin syndrome, Angelman syndrome, and Adair-Dighton syndrome are not immunologic deficiencies.

T cells can be functionally divided into two subtypes: ____ and ____ T cells.

CD4+ helper, CD8+ cytotoxic

Adenosine deaminase deficiencies and T-cell cytokine receptor mutations

Cause of SCID

Type III hypersensitivity reaction

Complement-mediated immune disorders

The incidence of latex allergy is skyrocketing because of diseases such as HIV. It is known that the use of latex examining gloves has played a major role in the increasing incidence of latex allergy. What plays a significant role in the allergic response to latex gloves?

Cornstarch powder used inside the gloves. Cornstarch powder is applied to the gloves during the manufacturing process to prevent stickiness and give the gloves a smooth feel. The cornstarch glove powder has an important role in the allergic response. Latex proteins are readily absorbed by glove powder and become airborne during removal of the gloves. Baking powder is not used inside the gloves. Pieces of latex that become airborne and latex proteins that attach to clothing are not significant contributors to the incidence of latex allergy.

Primary cell-mediated disorders of the immune system cause severe problems with infections. Children with these disorders rarely survive beyond childhood without a bone marrow transplant. What is a disease that involves primary cell-mediated disorders of the immune system?

DiGeorge Syndrome. In general, persons with cell-mediated immunodeficiency disorders have infections or other clinical problems that are more severe than antibody disorders. Children with defects in this branch of the immune response rarely survive beyond infancy or childhood, unless immunologic reconstitution is achieved through bone marrow transplantation. In DiGeorge syndrome children who survive the immediate neonatal period may have recurrent or chronic infections because of impaired T-cell immunity. Children also may have an absence of immunoglobulin production, caused by a lack of helper T-cell function. The X-linked immunodeficiency of hyper-IgM, also known as hyper-IgM syndrome, is characterized by low IgG and IgA levels with normal, or more frequently, high IgM concentrations. X-linked agammaglobulinemia is a primary humeral immunodeficiency disorder. Y-linked agammaglobulinemia does not exist.

Why does it take up to 6 months for the symptoms of a primary immunodeficiency to show up?

During the first few months of life, infants are protected from infection by IgG antibodies that have been transferred from the maternal circulation during fetal life. An infant's level of maternal IgG gradually declines over a period of approximately 6 months. Concomitant with the loss of maternal antibody, the infant's immature humoral immune system begins to function, and between the ages of 1 and 2 years, the child's antibody production reaches adult levels. Once the level of maternal antibodies drop, the infant is susceptible to infection.

X-linked agammaglobulinemia

Essentially undetectable levels of all serum immunoglobulins

_____ disorders refer to excessive or inappropriate activation of the immune system.

Hypersensitivity

The immune system typically responds to invaders of all types in our body. However, it can also cause tissue injury and disease. What is this effect called?

Hypersensitivity action. Disorders caused by immune responses are collectively referred to as hypersensitivity reactions. Antigens cause allergic reactions. Mediator response action and allergen stimulating reaction have nothing to do with hypersensitivity reactions.

Type I hypersensitivity reaction

IgE mediated disorders

Infants are born with a passive immunity that occurs when immunoglobulin antibodies cross the placenta from the maternal circulation prior to birth. Which immunoglobulin is capable of crossing the placenta?

IgG. During the first few months of life, infants are protected from infection by IgG antibodies that have been transferred from the maternal circulation during fetal life. IgA, IgM, IgD, and IgE do not normally cross the placenta.

____ can be defined as an abnormality in the immune system that renders a person susceptible to diseases normally prevented by an intact immune system.

Immunodeficiency

Compare the direct cell-mediate cytotoxicity of type IV hypersensitivity reactions with the delayed-type hypersensitivity reactions.

In direct cell-mediated cytotoxicity, CD8+ cytolytic T lymphocytes (CTLs) directly kill the antigen-presenting target cells. In viral infections, CTL responses can lead to tissue injury by killing infected target cells even if the virus itself has no cyotoxic effects. Because CTLs cannot distinguish between cytopathic and noncytopathic viruses, they kill virtually all infected cells, regardless of whether the infection is harmful or not. Delayed-type hypersensitivity reactions occur in response to soluble protein antigens and primarily involve antigen-presenting cells such as macrophages and CD4+ helper T cells of the TH1 type. During the reaction, TH1, cells are activated and secrete an array of cytokines that recruit and activate monocytes, lymphocytes, fibroblasts, and other inflammatory cells. These T-cell mediated responses require the synthesis of effector molecules and take 24 to 72 hours to develop, which is why they are called delayed-type hypersensitivity disorders.

Selective IgA deficiency

In levels of serum and secretory IgA

Hyper-IgM syndrome

Low IgG and IgA levels, high IgM concentrations

Ataxia-telangiectasia

Lymphopenia and a decrease in the ratio of CD4+ helper T cells to CD8+ suppressor T cells

DiGeorge syndrome

Partial or complete failure of development of the thymus and parathyroid glands

Drug-induced secondary hypogammaglobulinemia is considered reversible. Which drugs produce hypogammaglobulinemia?

Phenytoin, Corticosteroids, Carbamazepine, and Disease-modifying antirheumatic drugs. Medications that cause reversible secondary hypogammaglobulinemia include the disease-modifying antirheumatic drugs, corticosteroid agents and the antiepileptic drugs, phenytoin and carbamazepine. Interferon beta-1a drugs are used in the treatment of autoimmune disorders.

Transient hypogammaglobulinemia of infancy

Repeated bouts of upper respiratory and middle ear infections

____ sickness is a systemic immune complex disorder that is triggered by the deposition of insoluble antigen-antibody complexes in blood vessels, joints, heart, and kidney tissue.

Serum

A systemic immune complex disorder that is caused by insoluble antigen-antibody complexes being deposited in blood vessels, the joints, the heart, or kidney tissue is called what?

Serum sickness. Serum sickness is a systemic immune complex disorder that is triggered by the deposition of insoluble antigen-antibody (IgM, IgG, and occasionally IgA) complexes in blood vessels, joints, heart, and kidney tissue. This is not anti-immune disease, SLE or antigen-antibody sickness.

What is SCID?

Severe combined immunodeficiency (SCID) is the result of genetic mutations that lead to absence of all T- and B-cell function and, in some cases, lack of natural killer cells. Affected infants have a disease course that resembles AIDS, with failure to thrive, chronic diarrhea, and opportunistic infections. Survival beyond the first year of life is rare without prompt immune reconstitution through bone marrow or hematopoietic stem cell transplantation. Early diagnosis is critical because the chance of successful treatment is highest in infants who have not experienced severe opportunistic infections. There is also hope that gene therapy will someday be available for some, if not all, forms of SCID.

Wiskott-Aldrich syndrome

Susceptible to infections caused by encapsulated microorganisms

Collectively, _____ protect against fungal, protozoan, viral, and intracellular bacterial infections; control malignant cell proliferation; and are responsible for coordinating the overall immune response.

T lymphocytes

Type IV hypersensitivity reaction

T-cell mediated disorders

Explain how a patient can become sensitized to an allergen (antigen) in a type I hypersensitivity reaction.

Type I hypersensitivity reactions begin with mast cell or basophil sensitization. During the sensitization or priming stage, allergen-specific IgE antibodies attach to receptors on the surface of mast cells and basophils. With subsequent exposure, the sensitizing allergen binds to the cell-associated IgE and triggers a series of events that ultimately lead to degranulation of the sensitized mast cells or basophils, causing release of their preformed mediators. Mast cells are also the source of lipid-derived membrane products (e.g. prostaglandins and leukotrienes) and cytokines that participate in the continue response to the allergen.

___ hypersensitivity reactions are responsible for the Vasculitis seen in certain autoimmune diseases, such as systemic lupus erythematosus (SLE), or the kidney damage seen with acute glomerulonephritis.

Type III

A large number of primary immunodeficiency diseases have been mapped to the ____ chromosome.

X

The ____ immune response is composed mainly of T and B cells and responds to infections more slowly, but more specifically, than the innate immune system.

adaptive

Type I hypersensitivity reactions to antigens is referred to as ______.

allergic reactions

Of all the primary immunodeficiency diseases, those affecting _____ production are the most frequent.

antibody

Type II hypersensitivity reaction

antibody-mediated disorders

Persons with ____ allergic conditions tend to have high serum levels of IgE and increased numbers of basophils and mast cells.

atopic

Loss of self-tolerance with development of _____ is characteristic of a number of autoimmune disorders.

autoantibodies

____ 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.

autoimmune

Transplanted tissue can be categorized as an _____ graft if donor and recipient are the same person, _____ graft if the donor and recipient are identical twins, and _____ if the donor and recipient are related or unrelated but share similar HLA types.

autologous, syngeneic, allogeneic

SCID is more commonly found in _____, as it is X linked.

boys

Disorders that affect both B and T lymphocytes, with resultant defects in both humoral and cell-mediated immunity, fall under the broad classification of _____ syndrome.

combined immunodeficiency

Hereditary angioneurotic edema is a form of _____ deficiency.

complement

Allergic _______ denotes an inflammatory response confined to the skin that is initiated by re-exposure to an allergen to which a person had previously become sensitized.

contact dermatitis

Immunoglobulin G subclass deficiency

decreases in one or more of IgG subgroups

Chediak-Higashi syndrome is an abnormality of _____ of phagocytes.

degranulation

_____ occurs when immunologically competent cells or precursors are transplanted into recipients who are immunologically compromised.

graft-versus-host disease

The adaptive immune system is further divided into the ___ and _____ immune systems.

humoral, cellular

Under normal conditions, the ____ response deters or prevents disease.

immune

The ____ immune system is composed of the phagocytic leukocytes, natural killer (NK) cells, and complement proteins.

innate

Abnormal immunoglobulin loss can occur with chronic _____ disease; because of abnormal glomerular filtration, patients lose serum IgA and IgG in their urine.

kidney

Secondary humoral immunodeficiencies can also result from a number of ____ including chronic lymphocytic leukemia, lymphoma, and multiple myeloma that interfere with normal immunoglobulin production.

malignancies

During the first few months of life, infants are protected from infection by IgG antibodies that originate in _____ circulation during fetal life.

maternal

Defects in humoral immunity increase the risk of recurrent _____ infections.

pyogenic

Chronic granulomatous disease is a group of inherited disorders that greatly reduce or inactivate the ability of phagocytic cells to produce the _____.

respiratory burst

Allergic ___ is characterized by symptoms of sneezing, itching, and watery discharge from the nose and eyes.

rhinitis

Chronic cirrhosis of the liver would reduce the production of complement proteins; this type of deficiency would be classified as _____.

secondary

The ability of the immune system to differentiate self from nonself is called _____.

self-tolerance

In _____, genetic mutations lead to absence of all T and B cell function and, in some cases, a lack of NK cells.

severe combined immunodeficiency (SCID)

Common variable immunodeficiency

the terminal differentiation of mature B cells to plasma cells is blocked

A major barrier to ____ is the process of rejection in which the recipient's immune system recognizes the graft as foreign and attacks it.

transplantation

There are three different types of antibody-mediated mechanisms involved in ____ reactions: Opsonization and complement- and antibody receptor-mediated phagocytosis, complement- and antibody receptor-mediated inflammation, and antibody-mediated cellular dysfunction.

type II

Hypersensitivity reactions that are mediated by specifically sensitized T lymphocytes are divided into two basic types: direct cell-mediated cytotoxicity and delayed-type hypersensitivity, and generally classified as ______.

type IV reactions