CHAPTER 14: DISORDERS IN IMMUNITY

Some allergies last for a lifetime, some are _______________________________others develop later in life.

"outgrown"

What is epinephrine?

(adrenaline) reverses constriction of airways and slows the release of allergic mediators

What are the three other type III hypersensitivities ?

-Systemic lupus erythematosus (SLE) -Rheumatoid arthritis and ankylosing spondylitis (involves other types of hypersensitivity ) -Myasthenia gravis (case file!!)

T Cells and Their Role in Organ Transplantation

-Transplantation or grafting of organs is a COMMON medical procedure -Although it is life-GIVING, it is PLAGUED with the NATURAL tendency of lymphocytes to seek out and DESTROY FOREIGN antigens -The bulk of the DAMAGE that occurs in graft rejections are attributed to CYTOTOXIC T-cell ACTION*

Type I hypersensitivities and their portals of entry?

-inhalants, ingestants, injectants, and contactants, -skin, respiratory tract, GI tract, and genitourinary tract.

anaphlaxis is characterized by what symptoms?

. Circulatory disruption (tachycardia, low BP) Swelling of the lips, tongue, or throat Generalized hives Loss of consciousness

Thymus gland tumors

:cause severe T-cell deficiencies

Severe Combined Immunodeficiencies (SCIDs)

A collection of syndromes occurring in newborns caused by a genetic defect that knocks out both B and T cell types of immunity. Involve dysfunction in both lymphocyte systems Most serious form of immunodeficiency:

Type II Hypersensitivities: Reactions That Lyse Cells

A complex group of syndromes that involve complement-assisted destruction (lysis) of cells by antibodies (IgG and IgM) directed against those cells' surface antigens: Transfusion reactions Some types of autoimmunities

What is an autoimmune disease?

A disease in which the body's immune system attacks healthy cells. individuals actually develop hypersensitivity to themselves Autoantibodies, T cells, or both mount an abnormal attack against self antigens.

IgE and Mast-Cell-Mediated Allergic Conditions: Atopic Diseases Hay Fever?

A generic term for allergic rhinitis Seasonal reaction to inhaled plant pollen or molds Year-round reaction to airborne allergens or inhalants Targets: respiratory membranes Symptoms: nasal congestion, sneezing, coughing, profuse mucus secretion, itchy, red, and teary eyes, mild bronchoconstriction

Most recognized infection-induced immunodeficiency is ?

AIDS

type 2 hypersensitivity STATE?

ANTIBODY-MEDIATED IgG, IgM antibodies act upon cells with complement and cause cell lysis, include some autoimmune diseases

What is a tuberculin reaction?

Acute skin inflammation at the injection site following an extract of Mycobacterium tuberculosis. Similar skin reactions occur with leprosy, syphilis, histoplasmosis, toxoplasmosis, and candidiasis. TH cells release cytokines and recruit macrophages, neutrophils and eosinophils to the site, causing a red bump.

science behind contact dermatitis?

Allergen penetrates the outer skin layers: Processed by skin dendritic cells and presented to T cells Subsequent exposures attract lymphocytes and macrophages. Cells release enzymes and cytokines that damage the epidermis and vicinity.

Contactants

Allergies that enter through the skin Many are type IV (delayed) hypersensitivities

Hypersensitivity

Allergy and autoimmunity Tissues are attacked by immunologic functions that can't distinguish between self and nonself.

Potentially fatal hemolytic disease of the newborn (HDN)?

Also called erythroblastosis fetalis Characterized by severe anemia and jaundice

chronic, local allergy, whereas anaphylaxis is a systemic, potentially fatal allergic response. Both results from excessive igE production in response to exogenous antigens.

Atopy

Autoimmunities of the Endocrine Glands Graves' disease?

Attachment of autoantibodies to receptors on thyroxin-secreting follicle cells of the thyroid gland Abnormal stimulation of these cells causes over- production of the thyroid hormone and the symptoms of hyperthyroidism.

Neuromuscular Autoimmunities Myasthenia gravis?

Autoantibodies bind to receptors for acetylcholine, a neurotransmitter required for muscle stimulation. First effects felt in the muscles of the eyes and throat, but eventually progresses to complete loss of skeletal muscle function and death. Current treatment includes immunosuppressive drugs and therapy to remove autoantibodies from circulation.

Treatment and Prevention of Allergy?

Avoid the allergen, although this may be difficult in many instances. Take drugs that block the action of lymphocytes, mast cells, or chemical mediators. Use injections that short-circuit the allergic reaction.

Primary immune diseases are genetically induced deficiencies of?

B cells, T cells, the thymus gland, or combinations of these. SCIDs are the most severe due to the lost of both humoral and cell-mediated immunity.

antihistamines act to

Bind to histamine receptors on target organs.

Examples of Autoimmune Diseases:: Systemic Autoimmunities Rheumatoid arthritis

Causes progressive, debilitating damage to the joints and at times to the lungs, eyes, skin, and nervous system Autoantibodies form immune complexes that bind to the synovial membrane of joints, activating cytokine release by macrophages. Chronic inflammation develops, leading to scar tissue and joint destruction. Cytokines trigger additional type IV delayed hypersensitivity responses.

Taking Drugs to Block Allergies?

Corticosteroids

__________________________- and maternal history of allergy elevates childhood risk of allergy by a factor of eight.

Delivery by caesarian section

Which statement is true with reguard to autoimmune diseases and hypersensitivity reactions?

Diabetes mellitus type I is associated with T-cell dysfunction.

Drug Allergy?

Drugs are foreign compounds capable of stimulating allergic reactions. Drug allergy is one of the most common side effects of treatment, affecting 5 - 10% of hospitalized patients. Reactions range from a mild rash to fatal anaphylaxis. Compounds implicated: Antibiotics: penicillin Synthetic antimicrobials: sulfa drugs Aspirin Opiates Contrast dye used in X rays

Primary Immunodeficiency Diseases

Due to an inherited abnormality In some diseases, the lymphocytes are absent, or present at low levels. In other diseases, the lymphocytes are present, but do not function normally. An individual can lack either B or T cells, or both. Some deficiencies can affect other cell functions as well.

type 1 hypersensitivity STATE?

IMMEDIATE HYPERSENSITIVITY IgE- mediated, involves mast cells, basophils , and allergic mediators

type 3 hypersensitivity STATE

IMMUNE-COMPLEX MEDIATED antibody-mediated inflammation, circulating IgG, complexes deposited in basement membranes of target organs; includes some autoimmune diseases

The primary participants in type I hypersensitivities are?

IgE, basophils, mast cells, and mediators of the inflammatory reponse

study of diseases associated with overactivity and underactivity of the immune response, including allergies, autoimmunity, transplantion and transfusion reactions, immunodeficiency diseases, and cancer.

Immunopathology

Genetic basis for atopy?

Increased IgE production Increased reactivity of mast cells Increased susceptibility of target tissue to allergic mediators

secondary immunodeficiency is caused by what?

Infection Organic disease Chemotherapy Radiation

What is a type IV hypersensitivity reaction?

Infection reactions, contact dermatitis, graft rejection cell mediated, cytotoxic

IgE and Mast-Cell-Mediated Allergic Conditions: Atopic Diseases Atopic dermatitis/ eczema?

Intensely itchy inflammatory condition of the skin Sensitization occurs through ingestion, inhalation, and skin contact with allergens. Usually begins in infancy and is characterized by reddened, weeping, encrusted skin lesions on the face, scalp, neck, and inner surfaces of limbs and trunk. Progresses to a dry, scaly, thickened skin condition in adults Lesions are itchy, painful, and predisposed to secondary bacterial infections.

Type IV Hypersensitivities: Cell-Mediated (Delayed) Reactions

Involves primarily the T-cell !!branch of the immune system. Results when T cells respond to antigens displayed on self tissues or transplanted foreign cells Traditionally known as "delayed hypersensitivity": Symptoms arise one to several days following the second contact with antigen.

Type III Hypersensitivities:: Immune Complex Reactions?

Involves the reaction of soluble antigen with antibody, and deposition of resulting complexes in various tissues in the body Also involves the activation of complement Unlike type II hypersensitivities, antigens are not attached to the surface of a cell.

Which statement is true of autoimmunity? - in involves misshapen antibodies -it refers to "automatic immunity" -it often manifests as types II, III, and IV hypersensitivites - it has an acute course and then usually resolves itself.

It often manifest as types II, III, and IV hypersensitivities

Mechanisms of Immune Complex Disease?

Large quantities of antibodies are produced in response to an exposure to a profuse amount of antigen. Upon second exposure, antigen-antibody complexes are formed. These recruit complement and neutrophils that would normally eliminate these complexes.

The Role of Mast Cells and Basophils

Mast cells are located in the connective tissue of virtually all organs; high concentration in lungs, skin, GI, and genital tract Basophils circulate in blood and migrate into tissues Each cell can bind 10,000-40,000 IgE Cytoplasmic granules contain physiologically active cytokines, histamine, etc. Cells degranulate when stimulated by allergen

Autoimmunities of the Endocrine Glands Type I Diabetes?

Molecular mimicry has been implicated in sensitization of cytotoxic T cells to attack and lyse insulin-producing beta cells. A recent study showed permanent reversal of this by re-infusion of stem cells after complete immune suppression.

What is alloantigens?

Molecules that differ in the same species that are recognized by the lymphocytes of the recipient Not an immune dysfunction; the immune system is functioning normally by reacting to foreign cells in an organ or tissue transplant

Food Allergy

Most common food allergens come from peanuts, fish, cow's milk, eggs, shellfish, and soybeans. Mode of entry is intestinal. Symptoms include vomiting, diarrhea, and abdominal pain. Other manifestations include hives, rhinitis, asthma, and occasionally anaphylaxis. Hypersensitivity involves IgE and degranulation of mast cells, but not all reactions involve this mechanism. Care should be taken vaccinating individuals with egg allergies.

Examples of Autoimmune Diseases:: Systemic Autoimmunities Systemic lupus erythematosus (SLE or lupus)

Name originated from the characteristic butterfly-shaped rash that drapes across the nose and cheeks. Manifestations vary, but all patients develop autoantibodies against organs, tissues, or intracellular materials. Viral infection and loss of normal immune response suppression are suspected as causes.

Immunodeficiency Diseases:Hyposensitivity of the Immune System?

Occasionally, an individual is born with or develops weakened immune responses. Predominant consequences of immunodeficiencies are recurrent, overwhelming infections with opportunistic microbes.

Neuromuscular Autoimmunities Multiple sclerosis?

Paralyzing neuromuscular disease associated with lesions on the myelin sheath of nerves and white matter of the nervous system. T

Hemolytic Disease of the Newborn and Rh Incompatibility

Placental sensitization occurs when the mother is Rh- and the unborn child is Rh+:

What are prostaglandins?

Regulate smooth muscle contraction; stimulate uterine contractions during delivery Vasodilation Increased vascular permeability Increased sensitivity to pain Bronchoconstriction Nonsteroidal anti-inflammatory drugs (NSAIDs) prevent the actions of these

IgE and Mast-Cell-Mediated Allergic Conditions: Atopic Diseases Asthma?

Respiratory disease characterized by episodes of impaired breathing due to severe bronchoconstriction Airways of asthmatics are extremely sensitive to minute amounts of inhalants, ingestants, or other stimuli and are chronically inflamed. Symptoms range from labored breathing to fatal suffocation. Rales: clicking, bubbling, or rattling sounds in the lungs Lungs are overreactive to leukotrienes and serotonin. Natural killer cells are also recruited and activated.

Types of Immune Complex Disease: arthus reaction and serum sickness with certain types of passive immunization?

Similar to anaphylaxis in that all require sensitization and preformed antibodies Differences from anaphylaxis: Depend on IgG, IgM, or IgA rather than IgE Require large doses of antigen Symptoms are delayed hours to days

AIDS, an infection-induced immunodeficiency, affects

T helper cells and antigen-presenting cells

What is AIDS?

T helper cells, monocytes, macrophages, and antigen-presenting cells infected by HIV Depletion of T-helper cells and impairment of immune responses account for cancers and opportunistic infections is caused by this acquired immune deficiency syndrome

Type 4 hypersensitivity STATE?

T-CELL MEDIATED delayed hypersensitivity and cytotoxic reactions in tissue, includes some autoimmune diseases

Allergy Vaccines: Desensitization or hyposensitization?

Therapeutic way to prevent reactions between allergen, IgE, and mast cells

What is the Arthus reaction?

Usually an acute reaction to a second injection of vaccines (boosters) or drugs at the same site as the first injection: Area beco Localized dermal injury due to inflamed blood vessels mes red, hot to the touch, swollen, and painful Symptoms are due to the destruction of tissues in and around blood vessels, and the release of histamine from mast cells and basophils. It is self-limiting and usually rapidly cleared, but occasionally intravascular blood clotting, necrosis, and loss of tissue can occur.

Antihistamine?

a drug that blocks the effects of histamine in the body Most widely used medications for preventing symptoms of atopic allergy Bind to histamine receptors on target organs (Benadryl trade name for histamine-blocker diphenhydramine. )

Immunodeficiency Diseases:Hyposensitivity of the Immune System: What is secondary immunodeficiency?

acquired after birth and caused by natural or artificial agents

Inhalants

airborne environmental allergens such as pollen, house dust, dander, or fungal spores

Ingestants

allergens that enter by mouth that cause food allergies

Injectant

allergies triggered by drugs, vaccines, or hymenopteran (bee) venom

What is contact dermatitis?

an inflammation caused by contact with a substance or chemical Caused by exposure to resins in poison ivy and poison oak, haptens in household and personal articles, and drugs Requires a sensitizing dose followed by a provocative dose.

What is type I hypersensitivity reaction?

anaphylaxis, allergies such as hay fever, asthma, immediate ( hay, fever, anaphylaxis)

Like type II reactions, type III hypersensitivities involve the production of IgG and IgM and the activation of complement; they differ in that the ?

antigen recognized in these reactions is soluble.

what is leukotriene?

are substances released by mast cells during inflammatory responses. Slow-reacting substance of anaphylaxis!!" Induces gradual contraction of smooth muscle Prolonged bronchospasm Vascular permeability Mucus secretion

Types of Immune Complex Disease?

arthus reaction and serum sickness with certain types of passive immunization

Autoimmune reactions occur when ?

autoantibodies or host T cells mount an abnormal attack against self antigens, due to virus-induced alterations of immunity of failure to remove self-reactive clones.

The four classes of transplants or grafts are determined by the degree of MHC similarity between graft and host. From most the least similar, these are?

autographs, isografts, allografts, and xenografts.

In immune complex disease, these complexes are deposited in the ______________________ of epithelial tissues:

basement membrane

Antihistamines: Acts

bind to histamine receptors on target organs

What is type II hypersensitivity reaction?

blood group incompatibility, myasthenia gravis (Case file) antibody-mediated (blood type incompatibilities)

Radiation and anticancer drugs are damaging to the ?

bone marrow and other body cells

What is theophylline?

bronchodilator that reverses spasms in respiratory smooth muscles

Leukemia

cancer cells outnumber normal cells, displacing them from bone marrow and blood

Patho of MS?

cell and autoantibody-induced damage compromises the capacity of neurons to send impulses. Symptoms include muscle weakness, tremors, difficulties in speech and vision, and paralysis. Possible association between infection with human herpesvirus 6 Treatments include immunosuppresants and interferon beta.

What is systemic anaphylaxis?

characterized by sudden respiratory and circulatory disruption that can be fatal within minutes due to airway blockage Bee stings and injection of antibiotics or serum are most commonly implicated Result of the sudden, massive release of chemicals into the tissues and blood, which act rapidly on target organs!!!

Atopy

chronic local allergy such as hay fever or asthma

Anaphlaxis is characterized by what symptoms?

circulatory disruption, swelling of the lips, tongue, and throat, generalized hives, loss of conciousness

which of the following plays a role in the Arthus reaction?

complement

Type II hypersensitivites are due to

complement induced lysis of cells in the presence of antibodies

Mechanisms of Type I Allergy: Sensitization and Provocation Each cell carries 30,000 to 100,000 cell receptors that bind IgE and degranulate, releasing inflammatory _________________

cytokines

Type IV or delayed hypersensitivity reactions, like the tuberculin reaction and transplant reactions (host rejection and GVHD), occur when?

cytotoxic T cells attack either self tissue or transplanted foreign cells.

Antigens that trigger hypersensitivity reactions are allergens, which are either ?

exogenous (originate outside the host) or endogenous (involve's the host's tissue)

Which of the following is not a result of an abnormal or undesirable immune function? Asthma Anaphylaxis Contact dermatitis Fever Lupus

fever

Select the correct pairing of the inflammatory cytokine and its function

histamine/constricted bronchioles

Cytokines and growth factors in __________________________________ act on the baby's gut mucosa to induce tolerance to antigens.

human milk

Cancers that target the bone marrow can be responsible for malfunction of ?

humoral and cellular immunity

Drugs that prevent graft rejection can also suppress beneficial ?

immune responses

Hyposensitivity or immunodeficiency

immune system is incompletely developed, suppressed, or destroyed

Second immune diseases are caused by

infection (i.e., AIDS) organic disease, chemotherapy, or radiation.

The Tuberculin reaction is an

infectious allergy

Neutrophils release lysosomal granules that digest tissues and cause a destructive ?

inflammatory condition.

Generalized susceptibility to allergens is _______________________________________, not the allergy to a specific substance.

inherited

What are corticosteroids?

inhibit the activity of lymphocytes and reduce the production of IgE Have dangerous side effects and should not be taken for long periods Some drugs block the degranulation of mast cells and reduce the levels of inflammatory cytokines. Other drugs block synthesis of leukotriene.

Allergens:

innocuous substances that induce allergy in sensitive individuals

autoimmune disease specific?

involves only one organ or tissue

autoimmune disease systemic?

involves several major organs

Type III hypersensitivity reactions occur when?

large quantities of antigen react with host antibody to form insoluble immune complexes that settle in tissue cell membranes, causing chronic destructive inflammation.

It has been shown that children who grow up on farms have _____________________ incidences of several types of allergies.

lower

In SCID patients, Only serious option for longtime survival is total replacement or correction of ?

lymphoid cells

Allergens are treated by ?

medications that interrupt the allergic response at certain points. Allergic reactions can often be prevented by desensitizing therapy.

Diagnosis of Allergy: In Vivo Methods skin testing?

method to detect precise atopic or anaphylactic sensitivities Skin is injected, scratched, or pricked with a small amount of pure allergen extract. 20 minutes after antigenic challenge, a wheal and flare result shows sensitivity. The diameter of the wheal is measured and rated on a scale from 0 (no reaction) to 4 (greater than 15 mm).

What does histamine do?

most profuse and fast-acting allergic mediator, Constricts smooth muscle in the small bronchi and intestine, causing labored breathing and intestinal motility, Relaxes vascular smooth muscle and dilates arterioles and venules, resulting in wheal-and-flare reactions in the skin,Stimulates eosinophils to release inflammatory cytokines, escalating symptoms

antibodies block or destroy acetylcholine receptors at the neuromuscular junction, preventing muscle contraction from occurring. Normally, nerve impulses travel down the nerve to the nerve ending, where the neurotransmitter acetylcholine binds to its receptors, which are then activated to generate a muscle contraction.

myasthenia gravis

What is serotonin?

neurotransmitter effects appear to complement those of histamine and bradykinin

Mechanisms of Type I Allergy: Sensitization and Provocation Symptoms of allergy are not caused by the direct action of allergen on tissues, but the ____________________________

physiological effects of mast-cell-derived allergic mediators on target organs.

Type II hypersensitivities are complement assisted reactions that occur when?

preformed antibodies (IgG or IgM) react with foreign cell-bound antigens, leading to membrane attack complex, formation and lysis.

Immunodeficiency Diseases:Hyposensitivity of the Immune System: What is primary immunodeficiency?

present at birth (congenital), usually stemming from genetic errors

Plasma cell tumors:

produce large amounts of nonfunctional antibodies

What is the immune complex reaction?

produces free floating complexes that are deposited into tissues

What is aspirin?

reduce pain by interfering with prostaglandins

SCID children require ______________________________ to protect them from opportunistic infections:

rigorous aseptic techniques

The contact with allergen that primes mast cells is the

sensitizing dose

Type I hypersensitivities are set up by ?

sensitizing dose of allergen and expressed when a second provocative dose triggers the allergic response.

The mediators of type III hypersensitivity reactions include ?

soluble IgA, IgG, or IgM, and agents of the inflammation response.

Allergies are diagnosed using in vitro and in vivo test that assay for ?

specific immune cells, IgE production, or local reactions to allergens.

An ironic outcome of lifesaving medical procedures is the ?

suppression of the immune system

Examples of autoimmune diseases include?

systemic lupus erythematosus, reheuma arthritis, diabetes mellitus, myasthenia gravis, and MS

What is a type III hypersensitivity reaction?

systemic lupus erythematosus, rheumatoid arthritis, rheumatic fever (immune complex )

Anaphylaxis:

systemic, sometimes fatal reaction that involves airway obstruction and circulatory collapse

immunodeficiency diseases occur when?

the immune response is reduced or absent.

which of the following statements is most correct regarding SCIDS?

the involve dysfunction of both lymphocycte (B and T cells) systems.

Immunopathology

the study of disease associated with the overreactivity or underreactivity of the immune response

Newborns breastfed for the first 4 months have a lower risk of asthma and eczema.T/F?

true

Localized (arthus) and systemic (serum sickness) reactions are ?

two forms of type III hypersensitivities.

There are four categories of hypersensitivity reactions?

type I: allergy and anaphlaxis type II: complement, IgG and IgM, mediated tissue destruction type III: immune complex reactions type IV: delayed hypersensitivity reactions

Hemolytic disease of the newborn (erythroblastosis) is a ?

type II hypersensitivity that occurs when Rh- negative mothers are initially sensitized to RBC's from a first born Rh+ positive baby. When carrying a second Rh+ fetus, maternal anti-Rh antibodies can cross the placenta, causing hemolysis of the fetal Rh+ RBCs

The T-cell branch of the immune system is primary responsible for which hypersensitivities?

type IV

What is bradykinin?

vasodilator Prolonged smooth muscle contraction of the bronchioles Dilation of peripheral arterioles Increased capillary permeability Increased mucus secretion

the hygiene hypothesis suggests that

we may need more contact with microbes as our immune systems mature

What is cutaneous anaphylaxis?

wheal-and-flare inflammatory reaction to the local injection of allergen