ALTERED

IMMUNITY
Hypersensitivity – adaptive immune
response inappropriately exaggerated

Hypersensitivity reaction –
exaggerated response of the immune
response to an antigen
Classification of Hypersensitivity States
Type I: Immediate Hypersensitivity
• characterized by allergic reactions
• occurs immediately following contact with the antigen (allergen)
• mediated by immunoglobulin E (IgE)
• antibodies bound to the mast cells
• Common antigens
• Pollens
• Food (nuts, eggs, seafoods)
• Drugs (penicillin, salicylates)
• Insect Products (bee venom, house dust mites)
• Animal Hair (cat hair and dander)
• Pathophysiology
specific antigen binds to IgE attached to a mast cell

mast cell degranulation is induced

mediators such as histamine are released

allergic reactions are produced

Disease States
1. Hay Fever (Allergic Rhinitis)
Pathophysiology
– atopic reactions to inhaled allergens (pollens, dust, animal
danders)
Characteristic
– localized in the nasal mucosa and conjunctiva of the eye
Clinical manifestations
– paroxysmal sneezing
• watery drainage from the nose
• drainage to the back of the throat
• cough
• itching of the nose and conjunctiva
– fever is NOT present (unless secondary bacterial infection is
present)
2. Bronchial Asthma
Pathophysiology
inhalation of environmental antigen

antigen interacts with specific IgE antibodies

inflammation

mucosal edema
increased mucus secretion
bronchospasm

narrowing of airways
increased airway resistance
Clinical manifestations
– dyspnea
– wheezing
3. Atopic Eczema (dermatitis)
Pathophysiology
• contact with irritants to which a person has specific sensitivity
Characteristic
• acute or chronic
• noncontagious inflammatory condition
• causes the typical wheal-and-flare reaction
Clinical manifestations
• Urticaria
• involves the superficial capillaries
• the wheals have well-defined margins, erythema, vesicles filled with clear
fluid
• pruritus is severe
• Angioedema
• involves capillaries of the deeper skin layers
• nonpitting swelling of localized area of the skin
4. Anaphylaxis and Anaphylactic Shock
Anaphylaxis
• antigen-specific allergic hypersensitivity reaction of the body to a foreign protein or drug
• mediated primarily by IgE interaction with mast cells
• non-IgE reactions may occur
Anaphylactic Shock
• occurs when the reaction becomes systemic
• life-threatening event
• results when a person has been previously sensitized to the antigen
• may occur in a matter of minutes
Clinical manifestations
Respiratory
• bronchospasm
• laryngeal edema
• inspiratory stridor
• wheezing
Cardiovascular
• hypotension/ circulatory shock
• dysrhythmias
• syncope
Dermatologic
• urticaria
• angioedema
• flushing
• pruritus
Gastrointestinal
• nausea, vomiting
• diarrhea
• abdominal cramping
 Type Cause Responsible Cell or Pathophysiology Examples of
Antibody (Immune Mechanism) Disease States

IgE attaches to surface

of mast cell and specific
antigen, triggers release of
intracellular granules from
mast cells

I Foreign protein IgE Hay fever (allergic

Immediate (antigen) rhinitis)
Hypersensitivity Examples: Asthma
(anaphylaxis, atopy) Pollens Allergies
characterized by Food (nuts, eggs, Hives
allergic reactions seafoods) Anaphylactic shock
occurs immediately Drugs (penicillin,
following contact with salicylates)
the antigen (allergen) Insect Products
(bee venom,
house dust
mites)
Animal Hair (cat
hair and dander)
II. Type II: Cytotoxic Hypersensitivity
• In these immune reactions:
• the antibodies are free in the serum
• the antigen is bound to the surface of certain cells or is a component of the
cell membrane
• involves small molecules called haptens
• haptens are fixed to the cell surface, thus resulting in the formation of the
antigen
Pathophysiology
antibodies (IgG or IgM ) react with the antigen
attached to cells

complement is activated

cytolysis or phagocytosis

cell is damaged or destroyed

Disease States
1. Transfusion Reactions
Pathophysiology
antibodies in a recipient’s serum react against antigens in a donor’s
RBCs

hemolysis of donor RBCs

liberation of large quantities of hemoglobin into plasma

excess hemoglobin diffuses into tissues

and precipitates

tissue damage
Characteristic
• antigenic nature of mismatched blood
transfusions depends on the blood type and Rh
factor of the donor
Clinical manifestations
chills fever low back pain

hypotension tachycardia
anxiety
hyperkalemia nausea/ vomiting
urticaria
red or port wine-colored urine
shock irreversible renal failure
2. Erythroblastosis Fetalis
• A severe hemolytic disease of a fetus or newborn
caused by production of maternal antibodies for
fetal red blood cells
• two types of incompatibility diseases:
• Rh incompatibility disease
• ABO incompatibility disease
– both diseases have similar symptoms
– but Rh disease is much more severe because anti-Rh antibodies
cross over the placenta more readily than anti-A or anti-B
antibodies
– a greater percentage of the baby's blood cells are destroyed
by Rh disease.
Pathophysiology
Rh-negative mother and an Rh-positive fetus

fetal RBCs enter maternal circulation

immunologic reaction occurs

mother develops antibodies against the Rh factor in fetal RBCs

the maternal antibodies pass through the placenta

into the fetus

excessive destruction of fetal RBCs occurs

fetal anemia, hyperbilirubinemia

Clinical manifestations (fetus)

anemia jaundice kernicterus
high levels of insulin and hypoglycemia
hydrops fetalis
accumulation of fluids within the baby's body, giving it a swollen appearance
 Type Cause Responsible Cell Pathophysiology Examples of
or Antibody (Immune Mechanism) Disease States

Antibody reacts with antigen,

II Foreign protein IgG or IgM activates complement, causes Transfusion reactions
Cytotoxic Hypersensitivity (antigen) cytolysis or phagocytosis Hemolytic drug reactions
In these immune reactions: Erythroblastosis fetalis
> the antibodies are free in the Hemolytic anemia
serum Vscular purpura
> the antigen is bound to the Goodpasture’s syndrome
surface of certain cells or is a
component of the cell membrane
involves small molecules called
haptens
haptens are fixed to the cell
surface, thus resulting in the
formation of the antigen
 III. Type III: Immune Complex
Disease
Pathophysiology

antigen-antibody (immune) complex formation

precipitation of immune complexes in tissues

IgG or IgM activation of complement

chemotactic factors enhanced opsonization cell lysis

membrane permeability phagocytosis

destruction of
inflammation and edema target cells
 Disease States
1. Serum Sickness
 very similar to an allergic reaction
Pathophysiology
injection of large doses of drug or antiserum

patient's immune system recognizes the proteins in the drug

or antiserum as foreign

produces antibodies against the foreign proteins

the newly formed antibodies bind with the foreign protein

to form immune complexes

immune complexes enter the walls of blood vessels

setting off an inflammatory reaction

 While other types of allergic reactions may produce a rapid
response, the serum sickness reaction is delayed because
it takes time for the body to produce antibodies against the
new protein
Clinical manifestations
 severe skin reactions (often on palms and soles)
 fever
 joint pain and arthritis (usually in larger joints)
 vasculitis
 lymphadenopathy (especially around site of injection)
 glomerulonephritis
some drugs associated with this type of reaction:
allopurinol captopril (Capoten)
cephalosporin penicillins
2. Arthus Reaction
 inflammation and cellular death at the site
of injection of antigen
 person injected has been previously
sensitized
 causes acute, localized edema with tissue
inflammation and little vasculitis
3. Systemic Lupus Erythematosus (SLE)
 multisystem, chronic, remitting and
relapsing, rheumatic disease
 may assume several forms
 common: women 20-40 years of age
 more common and more severe in African-
American women
 involve antinuclear antibodies (ANAs)
 antibodies to DNA, nucleoproteins, or other nuclear
components
 antibodies against double-stranded DNA  highly
specific for SLE
Pathophysiology
immune complexes are formed between ANAs and
nuclear antigens in the serum, small blood vessels,
skin and glomerular basement membrane

complement activation

widespread degeneration of connective tissue

especially in the heart, glomeruli, blood vessels,
skin, spleen, retroperitoneal tissues
Clinical manifestations
 stiffness and pain in the hands, feet or large joints
 joints are red, warm and tender
 patchy atrophy of the skin
 erythematous rash (butterfly pattern over the nose and
cheeks)
 discoid lesions on face, neck and scalp
 renal S/Sx (proteinuria, hematuria, renal failure)
 systemic S/Sx (fever, fatigue, weight loss, anorexia)
 cardiopulmonary S/Sx (pericarditis, pleural effusions,
pneumonitis)
 neurologic S/Sx (headache, seizures)
 hematologic S/Sx (hemolytic anemia, thrombocytopenia,
leukopenia)
4. Rheumatoid Arthritis (RA)
 chronic, systemic, inflammatory disease
 specifically affects the small joints of the
hands and feet in the early stages
 involves the larger joints in later stages
 common: women
Pathophysiology
 T lymphocytes react with specific antigens in the joints
 Rheumatoid factor (RF) -- an IgM anti-IgG
a self-antigen
an antigen in the synovial cavity
or an infectious antigen
stimulate RF production

RF-IgG complexes form

precipitate in the synovial fluid

complement activation occurs and attracts

polymorphonuclear leukocytes

inflammation and destruction of articular cartilage occurs

granulation tissue and inflammatory cells form

a mass called pannus
Clinical manifestations
 fatigue, weakness, joint stiffness, vague
arthralgias (early Sx)
 morning stiffness that gradually improves
after rising
 symmetrical inflammation and swelling of
joints
 in the hands and feet
 Type Cause Responsible Cell Pathophysiology Examples of
or Antibody (Immune Mechanism) Disease States
III Foreign IgG, IgM, IgA Antigen-antibody Rheumatoid arthritis
Immune Complex protein complexes precipitate in
Disease (antigen) Systemic lupus
tissue, activate
Endogenous erythematosus
antigens complement, cause
inflammatory reaction Serum sickness

Glomerulonephritis
 IV. Type IV: Cell-Mediated
Hypersensitivity
• differs from the other three types of reactions in
that it is not caused by antibodies
• results from specifically sensitized T
lymphocytes without the participation of
antibodies
• typically occur 24 to 72 hours after exposure to
an antigen
• delayed reactions
Pathophysiology
T cells react with an antigen (foreign material)

release lymphokines
that draw macrophages into the area

macrophages release monokines

that enhance inflammatory response

destruction of tissues and foreign material

 Disease States
1. Contact Dermatitis
• common allergic skin reaction
• occurs on contact with certain household chemicals,
cosmetics, and plant toxins
common antigens:
leather drugs dyes in clothing
poison ivy poison oak
• area of contact becomes red and indurated with well-
circumscribed lesions
• vesicles appear in the epidermis
• lymphocytes and macrophages infiltrate the area and
react with epidermal cells  forming blebs that contain
sterile, protein-rich fluid are formed
2. Infections
• mycobacteria, protozoa, fungi
• these organisms present a chronic antigenic stimulus
• T lymphocytes and macrophages react
• best example: tuberculin test response
• test is used to determine whether the person has been sensitized to the
disease
• reddening and induration of site
– begin within 12 hours of injection of tuberculin
– peak in 24 to 72 hours
• mainly a dermal reaction
• positive response
– due to presence of antigen-specific T cells
– T cells react due to presence of mycobacterium organisms that the
macrophages are unable to destroy
3. Granulomatous Hypersensitivity Response
• most important form of delayed hypersensitivity
• results in the formation of granulomas in
different areas of the body
• results from microorganisms being present
within macrophages or other substances that the
cell is unable to destroy
• characteristic morphologic feature: epithelioid
cell
• large, flattened cell
• may be derived from activated macrophages
4. Transplant or Graft Rejection
• when tissues containing nucleated cells are transplanted from one
person to another, T-cell responses almost always trigger a
response against the transplanted organ
• targeting of transplanted organs depends on whether the
histocompatibility antigens are similar enough between the donor
and the recipient to prevent the activation of the rejection
phenomenon
• each individual has surface antigens (self-proteins) on his cells
that distinguish these cells from other people and from other organs
Major types of grafts
– Autografts – tissue transplanted from one site to another on the same person
– Isografts – tissue grafts from an identical person (identical twin)
– Allografts – tissue taken from an unrelated person
– Xenografts – tissue taken from a different animal species
• Autografts and isografts are ideal donors
• Xenografts are never successful
• Allografts are more successful with a closer tissue match
 Types of Rejections
a. First-Set, Second-Set, and Hyperacute Rejection
First-Set rejection
– usually occurs 11 to 15 days after grafting
– the initial graft is accepted but is rejected due to a T-cell response
– delayed response reflects the time necessary for the T lymphocyte to
become sensitized to the transplanted antigens
Second-Set rejection
– if the same recipient is regrafted with tissue from the previous donor,
there will be a much more rapid rejection process
– does not occur if the recipient is regrafted with tissue from another donor
Hyperacute rejection
– fulminant reaction that occurs within minutes after transplantation
– characterized by severe necrotizing vasculitis
– due to the presence in the recipient’s blood of high levels of preformed
antibodies against antigens on the transplanted cells
b. Acute Rejection
• complex reaction involving both cell-mediated
and humoral responses
• may occur days or months after
transplantation
• called acute because it progresses rapidly once
it has begun
• immune system of host recognizes, develops
sensitivity to, and attempts to eliminate the
antigenic differences of the donor organ
 After transplantation

lymphocytes become sensitized antibody response

as they pass through (humoral component) causes
the donor site deposition of
immune complexes
in the small vessels of the graft

parenchymal cell necrosis acute vasculitis

lymphocyte infiltration of tissues ischemic changes
Chronic Rejection
• slow deterioration of organ function over a
period of time
• usually months to years
• T lymphocyte (Type IV reaction) causes a
relentless destruction of parenchymal cells
• cardinal features:
• obliteration of the lumen of blood vessels by
proliferating smooth muscle cells and
interstitial fibrosis
 Type Cause Responsible Cell or Pathophysiology Examples of
Antibody (Immune Mechanism) Disease States
IV Foreign protein, T lymphocytes Sensitized T cell reacts with Contact dermatitis
Delayed/Cell- cell or specific antigen to induce Transplant graft
mediated tissue inflammatory process by direct reaction
differs from the other cell action or by activity of Granulomatous diseases
three types of lymphokines
reactions in that it
is not caused by
antibodies
results from specifically
sensitized T
lymphocytes
without the
participation of
antibodies
typically occur 24 to 72
hours after
exposure to an
antigen
delayed reactions