ZO 211 Week 5 chapter 14

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Chapter 14
Lecture

2. The Immune Response:
A Two-Sided Coin
• The human immune system is powerful and
intricate, having the potential to cause injury and
disease.
• Defects in the immune system can range from
hay fever to dermatitis.
• Abnormal or undesirable immune functions can
result in:
- Asthma
- Anaphylaxis
- Diabetes
- Rheumatoid arthritis
- Graft rejection

3. The Immune Response (cont’d)
• Immunopathology: the study of disease
associated with the overreactivity or
underreactivity of the immune response
• Hypersensitivity:
- Allergy and autoimmunity
- Tissues are attacked by immunologic functions that
can’t distinguish between self and nonself.
• Hyposensitivity or immunodeficiency: immune
system is incompletely developed, suppressed,
or destroyed

5. Hypersensitivity: Four Types
• Type I: anaphylaxis, allergies such as hay
fever, asthma
• Type II: blood group incompatibility,
pernicious anemia, myasthenia gravis
• Type III: systemic lupus erythematosus,
rheumatoid arthritis, serum sickness,
rheumatic fever
• Type IV: Infection reactions, contact
dermatitis, graft rejection

7. Concept Check
Which of the following is not a result of an
abnormal or undesirable immune function?
A. Asthma
B. Anaphylaxis
C. Contact dermatitis
D. Fever
E. Lupus

8. Type I Allergic Reactions:
Atopy and Anaphylaxis
• Allergy vs. Hypersensitivity:
- Allergy: exaggerated immune response that is
manifested by inflammation
- Hypersensitivity: delayed reactions
• Allergens: innocuous substances that induce
allergy in sensitive individuals
• Atopy: chronic local allergy such as hay fever
or asthma
• Anaphylaxis: systemic, sometimes fatal reaction
that involves airway obstruction and circulatory
collapse

9. Who Is Affected?
• Allergists estimate that 10 – 30% of the
population is prone to atopic allergy. Self-
treatment with over-the-counter medications
makes this a low estimate.
• Type I allergies:
- Relatively mild
- Asthma and anaphylaxis may require hospitalization
and can cause death.
- Some allergies last for a lifetime, some are
“outgrown,” others develop later in life.

10. Who Is Affected (cont’d)
• Generalized susceptibility to allergens is
inherited, not the allergy to a specific substance.
• Genetic basis for atopy:
- Increased IgE production
- Increased reactivity of mast cells
- Increased susceptibility of target tissue to allergic
mediators
• The prospect of a child’s developing atopic
allergy is 25% if parents are afflicted and 50% if
siblings or grandparents are afflicted.

11. Who Is Affected? (cont’d)
• Hygiene hypothesis:
- The industrialized world has created a hygienic
environment: antimicrobial substances, insulated
homes, etc.
- Immune systems need to be “trained” by interaction
with microbes as they develop.
- It has been shown that children who grow up on
farms have lower incidences of several types of
allergies.
- Delivery by caesarian section and maternal history of
allergy elevates childhood risk of allergy by a factor of
eight.

12. Who Is Affected? (cont’d)
• Effect of breastfeeding:
– Newborns breastfed for the first 4 months
have a lower risk of asthma and eczema.
– Cytokines and growth factors in human milk
act on the baby’s gut mucosa to induce
tolerance to antigens.
– Human Microbiome Project: 600 species of
bacteria can be transferred to infants through
breast milk.

13. The Nature of Allergens and
Their Portals of Entry
• Allergens have certain immunogenic
characteristics:
- Proteins are more allergenic than
carbohydrates, fats, or nucleic acids
- Haptens: nonproteinaceous substances with
a molecular weight of less than 1,000 that
can form complexes with carrier molecules in
the body
- Organic and inorganic chemicals found in
industrial and household products, cosmetics,
food, and drugs are haptens.

14. The Nature of Allergens and
Their Portals of Entry (cont’d)
• Mucosa of the gut and respiratory tract:
– Thin, moist surface that is normally quite
penetrable
• Skin:
– Dry, tough keratin is generally less permeable
– Access occurs through tiny breaks, glands,
and hair follicles.

15. The Nature of Allergens and
Their Portals of Entry (cont’d)
• 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
• Contactants:
- Allergies that enter through the skin
- Many are type IV (delayed) hypersensitivities

17. Mechanisms of Type I Allergy:
Sensitization and Provocation
• The Role of Mast Cells and Basophils:
- Mast cells are located in all connective tissues, but in
particularly high concentrations in the lungs, skin,
gastrointestinal tract, and genitourinary tract.
- Each cell carries 30,000 to 100,000 cell receptors that
bind IgE and degranulate, releasing inflammatory
cytokines.
• 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.

18. Cytokines, Target Organs,
and Allergic Symptoms
• Histamine:
- 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

19. Cytokines, Target Organs,
and Allergic Symptoms (cont’d)
• Bradykinin:
- Prolonged smooth muscle contraction of the
bronchioles
- Dilation of peripheral arterioles
- Increased capillary permeability
- Increased mucus secretion
• Serotonin: effects appear to complement those
of histamine and bradykinin

20. Cytokines, Target Organs,
and Allergic Symptoms (cont’d)
• Leukotriene:
- “Slow-reacting substance of anaphylaxis”
- Induces gradual contraction of smooth muscle
- Prolonged bronchospasm
- Vascular permeability
- Mucus secretion
- Stimulates polymorphonuclear leukocytes

21. Cytokines, Target Organs,
and Allergic Symptoms (cont’d)
• 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
prostaglandins.

24. 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

25. Atopic Diseases (cont’d)
• 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.

26. Atopic Diseases (cont’d)
• 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.

27. 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.

28. 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
• Allergen is not the intact drug itself, but a hapten given
off when the liver processes the drug.

29. Anaphylaxis: An Overpowering
IgE-Mediated Allergic Reaction
• Anaphylaxis/anaphylactic shock:
- Cutaneous anaphylaxis: wheal-and-flare
inflammatory reaction to the local injection of
allergen
- 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

30. Diagnosis of Allergy:
In Vitro Methods
• Radioallergosorbent (RAST) test: measures
levels of IgE to specific antigens
• Tryptase test: measures tryptase, an
enzyme released by mast cells that increases
during an allergic response
• Differential blood cell count can reveal high
levels of basophils and eosinophils.
• Leukocyte histamine-release test: measures
the amount of histamine released from the
patient’s basophils when exposed to a
specific allergen.

31. Diagnosis of Allergy:
In Vivo Methods
• Skin Testing: In vivo 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).

33. 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.

34. Taking Drugs to Block Allergy
• 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.
• Omalizumab (Xolair): monoclonal antibody that
inactivates IgE

35. Taking Drugs to Block Allergy
(cont’d)
• Antihistamines:
- Most widely used medications for preventing
symptoms of atopic allergy
- Bind to histamine receptors on target organs
• Aspirin and acetaminophen: reduce pain by
interfering with prostaglandins
• Theophylline: bronchodilator that reverses
spasms in respiratory smooth muscles
• Epinephrine (adrenaline): reverses constriction
of airways and slows the release of allergic
mediators

36. Allergy “Vaccines”
• Desensitization or hyposensitization:
- Therapeutic way to prevent reactions
between allergen, IgE, and mast cells
- Allergen preparations include pure, preserved
suspensions of plant antigens, venoms, dust
mites, dander, and molds.
- Blocking antibodies: one hypothesis is that
injected allergens stimulate formation of these
allergen-specific IgG antibodies
- Also hypothesized that allergen delivered in
this fashion combines with IgE itself, taking it
out of circulation

37. Allergy “Vaccines” (cont’d)
• “Decoy” allergy vaccines
- Allergy shot contains an innocuous molecule
that resembles a bacterium.
- Engages components of the immune system
that are active in allergy, causing them to stop
reacting inappropriately to specific allergens.
- A vaccine has been developed to aid those
suffering from cat allergies.
- Other vaccines are under development to
alleviate allergies and protect against viral
infection at the same time.

39. Concept Check
Which of the following is not an IgE and/or
mast-cell-mediated allergic condition?
A. Asthma
B. Food allergy
C. Systemic lupus erythematosus
D. Allergy to penicillin
E. Eczema

40. Learning Outcomes Section 14.3
• List the three immune components
causing cell lysis in type II hypersensitivity
reactions.
• Explain the role of Rh factor in hemolytic
disease development and how it is
prevented in newborns.

41. Type II Hypersensitivities: Reactions
That Lyse Foreign 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
• 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

42. The Rh Factor
and Its Clinical Importance
• First discovered in experiments exploring
genetic relationships among animals:
- Rabbits injected with the RBCs of rhesus
monkeys produced an antibody that also reacted
with human RBCs.
- This monkey antigen (Rh for rhesus) was
present in about 85% of humans and absent in
about 15%.
- Rh+
is a dominant gene, Rh-
is recessive.
- The only way to develop antibodies against this
factor is through placental sensitization or
transfusion.

43. Hemolytic Disease of the
Newborn and Rh Incompatibility
• Placental sensitization occurs when the
mother is Rh-
and the unborn child is Rh+:
- Fetal RBCs may leak into the mother’s
circulation during childbirth when the placenta
detaches.
- Mother’s immune system detects the foreign
Rh factors on fetal RBCs and is sensitized to
them by producing antibodies and memory
B cells.
- Does not usually affect the child because the
process occurs so late in pregnancy.

44. Hemolytic Disease of the
Newborn (cont’d)
• In the next pregnancy with an Rh+ fetus:
- Fetal blood cells escape into maternal circulation late
in pregnancy, eliciting a memory response.
- Maternal anti-Rh antibodies cross the placenta, affix
to fetal RBCs, and cause complement-mediated lysis.
• Potentially fatal hemolytic disease of the
newborn (HDN):
- Also called erythroblastosis fetalis
- Characterized by severe anemia and jaundice

45. Preventing Hemolytic Disease
of the Newborn
• Once sensitization has occurred, all other
Rh+
fetuses will be at risk.
• A careful history of the Rh-
pregnant
woman is needed:
- Rh types of children and Rh status of the
father are needed.
- If the father is Rh-
, there is no risk.
- If the father is Rh+
, the fetus may be Rh+.

46. Preventing Hemolytic Disease
of the Newborn (cont’d)
• RhoGAM antiserum:
- Passive immunization for an Rh-
mother with an
Rh+
fetus
- Immunoglobulin fraction of human anti-Rh serum
prepared from pooled human sera
- Injected at 28 – 32 weeks and again immediately
after delivery
- Sequesters fetal RBCs that have escaped into
maternal circulation and prevents sensitization
- Must be given with each pregnancy with an Rh+
fetus

48. Concept Check
When is the RhoGAM shot needed?
A. Rh+
mother, Rh+
fetus
B. Rh+
mother, Rh-
fetus
C. Rh-
mother, Rh-
fetus
D. Rh-
mother, Rh+
fetus
E. All of the choices are correct. The
mother always responds to the fetus as
foreign tissue and mounts an immune
response against it.

49. 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:
- Involves the production of IgG and IgM
antibodies
- Also involves the activation of complement
- Unlike type II hypersensitivities, antigens are
not attached to the surface of a cell.
- Immune complex reaction: produces free
floating complexes that are deposited into
tissues

50. 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.
• In immune complex disease, these complexes are
deposited in the basement membrane of epithelial
tissues:
- Neutrophils release lysosomal granules that digest
tissues and cause a destructive inflammatory condition.

51. Types of
Immune Complex Disease
• Arthus reaction and serum sickness are
associated 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

52. The Arthus Reaction
• Localized dermal injury due to inflamed blood
vessels
• Usually an acute reaction to a second injection
of vaccines (boosters) or drugs at the same site
as the first injection:
- Area becomes 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.

53. Serum Sickness
• Named for a condition in soldiers treated with
horse serum for tetanus:
- Also caused by injections of animal hormones and
drugs
• A systemic injury initiated by antigen-antibody
complexes that circulate in the blood and settle
into membranes at various sites:
- Kidney, heart, skin, and joints
- Condition can become chronic causing enlarged
lymph nodes, rashes, painful joints, swelling, fever,
and renal dysfunction.

55. Concept Check
Which of the following antibody types is not
involved in serum sickness or the Arthus
reaction?
A. IgA
B. IgE
C. IgG
D. IgM
E. All of the choices are involved.

56. Learning Outcomes Section 14.5
• Describe one example of a type IV
delayed hypersensitivity reaction.
• List four classes of grafts, and explain how
host versus graft and graft versus host
diseases develop.

57. 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.

58. Infectious Allergy
• 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.
- TH1 cells release cytokines and recruit
macrophages, neutrophils and eosinophils to
the site, causing a red bump.

59. Contact Dermatitis
• 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.
• 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.

61. 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.

62. The Genetic and Biochemical
Basis for Graft Rejection
• MHC or HLA class I and II markers are
extremely important for recognizing self.
• Although a person can exhibit variability in
the pattern of these markers, the pattern is
identical in different cells in the same person.
• Similarity is seen in related siblings and
parents.
• When a donor tissue (graft) displays surface
molecules of a different MHC class, the
T cells of the recipient will react to it as a
foreign substance.

63. Host Rejection of Graft
• Cytotoxic T cells of a host recognize foreign class I
MHC markers.
• Release IL-2 as part of general immune mobilization
• Helper and cytotoxic T cells bind to the grafted
tissue and secrete lymphokines that begin the
rejection process within 2 weeks of transplantation.
• Antibodies are formed against the transplanted
tissue and contribute to damage.
• The result is destruction of the vascular supply and
death of the graft.

64. Graft Rejection of Host
• Some grafted tissues (bone marrow) contain
indigenous populations of passenger
lymphocytes.
• These lymphocytes create an immune response
to the host.
• Graft versus host disease:
- Graft attacks any host tissue bearing MHC markers.
- Effects are systemic and toxic.
- Papular, peeling skin rash is the first symptom; other
organs are affected.
- Occurs within 100 – 300 days of the graft.

66. Classes of Grafts
• Autograft: tissue transplanted from one
site on an individual’s body to another site
• Isograft: tissue from an identical twin is
used
• Allograft: exchanges between genetically
different individuals belonging to the same
species; the most common types of grafts
• Xenograft: a tissue exchange between
individuals of a different species

68. Types of Transplants
• Transplantation has been performed on
every major organ, but most often involves
the skin, liver, heart, kidney, coronary
artery, cornea, and bone marrow.
• Sources of organs:
- Live donors: kidney, skin, bone marrow, and
liver
- Cadavers: heart, kidney, and cornea
- Fetal tissue: stem cells

69. Types of Transplants (cont’d)
• Bone marrow transplantation:
- Used in individuals with immune deficiencies, aplastic
anemia, leukemia, and other cancers
- Patient is treated with chemotherapy and whole-body
irradiation to destroy their own blood cells, preventing
rejection.
- Closely matched donor marrow is infused.
- GVHD can still occur, and antirejection drugs may be
necessary.
- After transplantation, a recipient’s blood type may
change to the blood type of the donor.

70. Concept Check:
Match the class of tissue graft with its description.
1. Allograft
2. Autograft
3. Isograft
4. Xenograft
A. Graft between
identical twins
B. Graft between
different species
C. Graft within an
individual
D. Graft between
non-identical twins

71. Learning Outcomes Section 14.6
• List at least three autoimmune diseases
and the common immunologic features in
them.

72. An Inappropriate Response
to Self: Autoimmunity
• Autoimmune diseases: individuals
actually develop hypersensitivity to
themselves
- Autoantibodies, T cells, or both mount an
abnormal attack against self antigens.
- Systemic: involves several major organs
- Organ specific: involves only one organ or
tissue

74. Genetic and Gender Correlation
in Autoimmune Disease
• Cases cluster in families, and even
unaffected members tend to develop
autoantibodies for the disease.
• Particular genes in class I and II MHC
coincide with certain autoimmune diseases:
– Rheumatoid arthritis and ankylosing spondylitis are
more common in persons with B-27 HLA type.
• X-chromosome inactivation in females may also
play a role in autoimmunity.

75. Genetic and Gender Correlation
in Autoimmune Disease (cont’d)
• Molecular mimicry:
– Microbial antigens bearing molecular
determinants similar to human cells induce
the formation of autoantibodies.
– One explanation for the pathology of
rheumatic fever
– Psoriasis flare-ups after strep throat infections
may also be due to T cells primed to react
with keratin in the skin.
– Type I diabetes and multiple sclerosis may be
triggered by a viral infection.

77. 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.

78. Systemic Autoimmunities
(cont’d)
• 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.
- Epstein-Barr virus has been implicated as a
precipitating cause.

79. 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.
• 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 type 1
diabetes by re-infusion of stem cells after complete
immune suppression.

80. 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.

82. Neuromuscular Autoimmunities
(cont’d)
• Multiple sclerosis:
- Paralyzing neuromuscular disease associated with
lesions on the myelin sheath of nerves and white
matter of the nervous system.
- T 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.

83. Concept Check
Autoimmunities are caused by:
A. Genetic predisposition
B. X-chromosome inactivation in females
C. Molecular mimicry
D. Viral infection
E. All of the choices are correct.

84. Learning Outcomes Section 14.7
• Distinguish between primary and
secondary immunodeficiencies, explaining
how each develops.

85. 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.
• Primary immunodeficiencies: present at birth
(congenital), usually stemming from genetic
errors
• Secondary immunodeficiencies: acquired after
birth and caused by natural or artificial agents

87. 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.

89. Clinical Deficiencies in B-Cell
Development or Expression
• Genetic deficiencies in B cells usually result in
abnormal immunoglobulin (Ig) expression:
– In some cases, certain classes of Igs are absent.
– In other cases, all levels of Ig are reduced.
• Agammaglobulinemia: absence of gamma
globulin; it is very rare for Ig to be completely
absent.
• Hypogammaglobulinemia: abnormally low
levels of gamma globulin

90. Clinical Deficiencies in B-Cell
Development or Expression (cont’d)
• Symptoms of hypogammaglobulinemia:
– Recurrent, serious bacterial infections appear
about 6 months after birth.
– Pyogenic cocci, Pseudomonas, and Haemophilus
influenzae are most often implicated; infections
with viruses and protozoa are common as well.
– Most common infection sites: lungs, sinuses,
meninges, and blood
• Current treatment is passive immunotherapy
with immune serum globulin and continuous
antibiotic therapy.

91. Clinical Deficiencies in B-Cell
Development or Expression (cont’d)
• Lack of a particular class of immunoglobulin
is a relatively common condition:
– IgA deficiency is the most prevalent form.
– Individuals have normal quantities of B cells and
other immunoglobulins.
– Lack protection against local microbial invasion of
mucous membranes, suffer recurrent respiratory
and gastrointestinal infections.
– Usual treatments do not work because passive
antibody therapy is high in IgG, not IgA.

92. Clinical Deficiencies in T-Cell
Development or Expression
• Defects in T-cell development result in a
broad spectrum of diseases:
– Severe opportunistic infections
– Cancer
– More devastating than B-cell deficiencies,
because T helper cells are required to assist
in most specific immune functions

93. Abnormal Development
of the Thymus
• DiGeorge syndrome or thymic aplasia:
- Congenital absence or immaturity of the
thymus gland
- High susceptibility to infections by fungi,
protozoa, and viruses
- Vaccinations using attenuated microbes pose
a danger and common childhood infections
can be fatal.
- Reduced antibody production allows for
transplantation of thymic tissue.

94. Severe Combined
Immunodeficiencies (SCIDs)
• Most serious form of immunodeficiency:
- Involve dysfunction in both lymphocyte
systems
- Some SCIDs are due to the lack of
lymphocyte stem cells in the bone marrow;
others due to dysfunction of B and T cells
later in development
- Infants with SCID usually develop candidiasis,
sepsis, pneumonia, or systemic viral
infections within days after birth.

95. Severe Combined
Immunodeficiencies (SCIDs – cont’d)
• Two most common forms: Swiss-type
agammaglobulinemia and thymic alymphoplasia:
- Genetic defects in the development of the lymphocyte
stem cell in the bone marrow
- Extremely low numbers of all lymphocyte types
- Poorly developed humoral and cellular immunity
• Adenosine deaminase deficiency: lymphocytes
develop but a metabolic product builds up and
selectively destroys them

96. Severe Combined
Immunodeficiencies (SCIDs – cont’d)
• SCID children require rigorous aseptic
techniques to protect them from opportunistic
infections:
- David Vetter: lived his life in a sterile plastic bubble
• Only serious option for longtime survival is total
replacement or correction of lymphoid cells:
- Infants can benefit from fetal liver or stem cell grafts
- X-linked and ADA types of SCID can be treated with
gene therapy; insertion of normal genes to replace
the defective genes

97. Secondary Immunodeficiency
Diseases
• Caused by one of four general agents:
- Infection
- Organic disease
- Chemotherapy
- Radiation
• Most recognized infection-induced
immunodeficiency 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 caused by AIDS.

98. Secondary Immunodeficiency
Diseases (cont’d)
• Cancers that target the bone marrow can
be responsible for malfunction of humoral
and cellular immunity:
– Leukemia: cancer cells outnumber normal
cells, displacing them from bone marrow and
blood
– Plasma cell tumors: produce large amounts of
nonfunctional antibodies
– Thymus gland tumors: cause severe T-cell
deficiencies

99. Secondary Immunodeficiency
Diseases (cont’d)
• An ironic outcome of lifesaving medical
procedures is the suppression of the
immune system:
- Drugs that prevent graft rejection can also
suppress beneficial immune responses.
- Radiation and anticancer drugs are damaging
to the bone marrow and other body cells.

100. Concept Check
The most common deficiency in
immunoglobulins is _____ deficiency.
A. IgA
B. IgD
C. IgE
D. IgG
E. IgM