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Infection and Altered Immunity
Chapter 8
Hypersensitivity
 “Heightened state of immune responsiveness”
 Excessive reaction to an antigen that results in a
pathologic response when re-exposed to the same
antigen.
 In other words, the immune system has responded
in such a way that it is not beneficial to the host.
 Examples: allergy, autoimmunity, and alloimmunity

Examples: tissue damage, allergies, rashes, breathing
problems, etc.
Hypersensitivity
 The different types of hypersensitivity are
classified in “Types”.
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Type I
Type II
Type III
Type IV
 Some of the types will overlap in certain
diseases.
Type I Hypersensitivity
 Mast cell-bound IgE antibody reacts with antigen
to release physically active substances (histamine,
chemotactic factors, etc.).
 Individuals have an inherited tendency to respond
to naturally occurring inhaled and ingested
allergens with continual production of IgE.
 Symptoms: allergic rhinitis, asthma, urticaria, food
allergies, anaphylactic shock, diarrhea, and/or
vomiting
Type I Hypersensitivity
Type I Hypersensitivity
Type I Hypersensitivity
Type I Hypersensitivity
 Treatment

Depends on severity
Antihistamines (Benedryl, Sudafed)
 Bronchodilators (Albuterol)
 Corticosteroids
 Epinephrine

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Hyposensitization (Building up of IgG
“blocking” antibodies)
Type II Hypersensitivity
 “Cytotoxic, Tissue-specific
Hypersensitivity”
 Free antibody (IgG or IgM) reacts with
antigenic determinants on cell membranes

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Phagocytosis
Complement Activation (Which pathway?)
 Examples: Immediate drug reactions,
autoimmunity, alloimmunity
Type II Hypersensitivity
 Types of Type II Hypersensitivity
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Transfusion Reactions
Hemolytic Disease of the Newborn
Autoimmune Hemolytic Anemia
Type II Hypersensitivity
Type III Hypersensitivity
 Antibody reacts with soluble antigen to form
complexes that precipitate in the tissues.
 When soluble antigen combines with
antibody, complexes precipitate out of the
serum and deposit in tissues, bind/activate
complement, and cause tissue damage.
Type III Hypersensitivity
 Examples:
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Serum Sickness (Result of passive immunization with
animal serum to treat disease)
Autoimmune diseases (Lupus and RA)
Glomerulonephritis
Type IV Hypersensitivity
 “Delayed Hypersensitivity”
 Sensitized T cells release lymphokines that recruit
macrophages, neutrophils, produce edema, and
enhance the inflammatory response
 Antibody and Complement are not directly
involved
 Symptoms take several hours to develop
Type IV Hypersensitivity
 Contact Dermatitis

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Poison Ivy, Poison Oak, topical anesthetics, antiseptics,
and antibiotics
Process takes days but effects last for years (blisters,
peeling, weeping)
 TB Test and Graft Rejection
Type IV Hypersensitivity
Autoimmunity
 Autoimmunity is a breakdown of tolerance in
which the body’s immune system begins to
recognize self-antigens as foreign.
 Theories

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Exposure to a previously sequestered antigen
Development of a neoantigen (tumor antigen)
Complications of an infectious disease
Alteration of suppressor T cells
Autoimmunity
 Previously sequestered antigen

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Some antigens are hidden from the immune
system and never come into contact with
antigen-presenting cells, lymphoid organs, etc.
These sequestered antigens can be released
from damaged tissue and enter the lymphatics.
 Neoantigen

Usually haptens that become immunogenic
after binding to host proteins
Autoimmunity
 Antigens from infectious diseases

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Closely resemble host antigens
Form antigen-antibody complexes that initiate the
immune response (hypersensitivity type III)
 Alterations of suppressor T cells
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If a specific cell-line of T suppressor cells is affected, a
tissue specific autoimmune disease could result
A general autoimmune reaction could occur if many
cell populations were dysfunctional
Autoimmunity
 Autoimmune diseases will commonly
follow family lines (HLA antigens)
 Common autoimmune diseases

Lupus

Photosensitive facial rash
 Worsens with sun exposure
 “Lupus” (wolf-like)
Common Laboratory Tests
 Fluorescent
Antinuclear
Antibody Test

Animal cells
are fixed to
the slide
Rheumatoid Arthritis
 Systemic autoimmune disorder affecting the
synovial membrane of multiple joints.
Rheumatoid Arthritis
Progression
 Malaise, fever, weight loss, and joint pain
 Joint pain lasting longer into the day
 Progression from small joints to large joints
in a symmetric fashion
 Muscle spasms leading to joint deformity
 Nodules (necrotic areas) on the bones
Other Autoimmune Related
Diseases
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Hashimotos Thyroiditis & Graves Disease (thyroid)
Insulin-dependent Diabetes (pancreas)
Multiple Sclerosis (myelin sheath)
Myasthenia Gravis (muscles in the face)
Goodpasture’s Syndrome (kidney)
Autoimmune thrombocytopenia
Pernicious anemia
Ulcerative colitis
Alloimmune Graft Rejection
 Alloimmunity occurs when an individual’s
immune system reacts against antigen of the
tissue of other members of the same species.
 Transplants are complicated by an
alloimmune response to donor HLA antigens.
 Classified as hyperacute, acute, or chronic
depending on activation time.
Alloimmune Graft Rejection
 Hyperacute
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Patient has preexisting IgG or IgM antibody to
the tissue.
Antibody binds to the tissue and activates an
inflammatory response.
This results in the cessation of blood flow to the
graft.
Alloimmune Graft Rejection
 Acute

The rejection is a cell-mediated immune response
that occurs approximately 2 weeks after the
transplant.
 Chronic

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Can occur after months or years of normal
function
Signs and Symptoms: slow progressive organ
failure and damage to endothelial cells of the
blood vessels
Infectious Agents
 Symbiosis – two organisms living together in
close association
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Commensalism – neither organism is harmed
Mutualism – association is beneficial to both
Parasitism (pathogenicity) – one benefits and the
other is harmed
Infectious Agents
 Pathogens cause cellular injury because they
circumvent defensive barriers.
 Pathogens directly damage cells, interfere with
cellular metabolism, and limit the functionality of
the cell.
 Virulence
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Ability of a pathogen to cause disease
Presence of enzymes, toxins, number, capsules,
intracellular invasion
Modes of Disease Transmission
 Contact Transmission
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Direct (touching, kissing, intercourse, etc.)
Indirect (fomites - shared objects)
Droplet (distance < 1 meter)
 Common Vehicle Transmission
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Contaminated food, water, blood, vector, etc.
 Carrier

People who are carrying the pathogen but do not appear
to be ill.
Size Comparison
Bacteria
 Unicellular
 Aerobic
 Anaerobic
 Bacteria can live as opportunists,
commensals, and intracellular and
extracellular parasites.
Bacterial Shapes
 Bacteria are
characterized by their
shape and size.
 Before specific culture
information is available,
physicians use location
and appearance
characteristics to begin
antibiotic therapy
Bacterial Shapes
 Cocci
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Spherical, nonmotile bacteria
Subcategories
Diplo (pair)
 Strepto (chain)
 Staphylo (irregular
cluster)
 Tetra (group of
four)

Bacterial Shapes
 Bacilli
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Rod-shaped bacteria
 Spirillia
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Rod-shaped, rigid, spiral
organisms
 Spirochetes
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Non-rigid, spiral rods
 Pleomorpic
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Cells that do not fit in any of
the above categories (no
defined shape)
Bacteria
 Cell Wall
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The cell wall is composed of peptidoglycan
Peptidoglycan is a large molecular network of
glucose and amino acids.
Based on cell wall characteristics, bacteria are
classified as gram (+) or gram (-).
Gram Positive
Gram Negative
Identifying a Specific Bacterium
Gram Stain
Bacterial Toxins
 Gram + bacteria produce exotoxins
Exotoxins are released from the bacterium during it’s
life cycle.
 Exotoxins cause symptoms specific to the disease.
 Examples: Botulism, tetanus, staph food poisoning,
Toxic Shock Syndrome
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 Gram – bacteria produce endotoxins
Endotoxins are released from the cell when it dies
 Produce generalized symptoms
 Example: Salmonella food poisoning
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Sporulation
 Sporulation is the formation of
endospores.
 When nutrients become scarce
and conditions are
unfavorable, certain bacteria
(Bacillus, Clostridium, etc.)
will form endospores.
 Endopores help the DNA of
the bacteria survive extreme
temperatures, radiation, and
chemicals.
Viruses
 A virus is not technically
living. It can not perform any
metabolic activity.
 A virus must replicate inside a
host cell.
 The virus provides the RNA
and DNA to replicate, and the
host cells provide the energy
and resources.
 Components

Nucleic acid, capsid, and an
envelope (optional)
Viruses
 Viral replication depends on absorption,
penetration, uncoating, replication, assembly, and
ability to release new virons.
 Effects

Cell protein synthesis cessation, release the cell’s own
lysosomal enzymes causing cell death, fusion of host
cells, alteration of antigenic properties causing the
immune system to attack the host cell, and
transformation of host cells into cancerous cells.
Fungi
 Fungi are important for
the decomposition and
recycling of organic
material.
 Fungi are divided into
two groups, yeasts and
molds
 Examples: Candida
Albicans (yeast
infection) and Tenia
Corporis (ringworm)
Fungi
 Fungi release mycotoxins and enzymes
that damage connective tissues
 Diseased caused by fungi are called
mycoses.
 Fungi can cause superficial and deep
infections
 Some fungi are part of the normal body
flora and act as opportunists
Ascaris
 Ascaris lumbricoides
Pinworms
 Life cycle
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Fecal/oral
 Diagnosis:
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Use of
pinworm
paddles
Immunodeficiencies
 Immune deficiencies occur because of the
impairment of one or more components of the
immune or inflammatory response.
 Usually manifested by the tendency to develop
unusual or recurrent infections.
 Can be unsafe to administer immunizing agents.
 At risk for graft-versus-host disease

White cells in transfused blood can are immunologically
active, but the host cells aren’t.
Graft-Versus-Host Disease
Immunodeficiencies
 Primary Immune Deficiency (Congenital)
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Occurs during leukocyte development in the
fetus or embryo.
Can affect one or more white cell lines
If the T and B cell lines are affect, the patient
will have normal number of the other leukocytes,
but they will have low number of T cells, and
diminished levels of antibodies.
Immunodeficiencies
 Di George Syndrome
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Lack or partial lack of the thymus
Lymphopenia and decreased T cell function
 Bruton agammaglobulinemia syndrome
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Failure of B cell precursors to become mature B
cells.
Immunodeficiencies
 Wiskott-Aldrich Syndrome
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X-linked recessive disorder
IgM production is depressed
 Selective IgA deficiency
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Produce other types of antibody but not IgA
Can cause chronic intestinal candidiasis and
increased allergen uptake, and more severe
allergen responses
Acquired or Secondary Immune
Deficiencies
 Develop after birth and not related to genetic
defects
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Nutritional deficits
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T cell number and function
Enzyme cofactor deficiency
Chemotherapeutic agents
Corticosteroids
Burn victims
Emotional stress
HIV
 In 1981, a cluster of young men, with no known
immune dysfunction, developed opportunistic
infections with Pneumocystis carinii.
 The only link was that they were homosexual.
 In 1982, it was discovered in hemophiliacs.
 The virus HIV-1 was identified in 1983
 HIV-2 was discovered in 1986
HIV
 HIV is a retrovirus
 Retroviruses infect cells by binding to a surface
receptor and inserting their RNA into the target cell
 A viral enzyme reverse transcriptase converts the
RNA to DNA and inserts the viral genetic material
into the host cell.
 The genetic material can begin replicating
immediately or remain latent for a period of time
(up to 10 years).
HIV
HIV
 HIV is of course spread primarily through contact
with blood or body fluids containing the virus. It is
also speculated that ulcerations from other sexually
transmitted diseases provide opportunities for the
virus to enter the host.
 Concentrations of HIV
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High: blood and semen
Low: vaginal fluid, tears, sweat, breast milk
 Has also been transmitted through infected tissue
HIV
 Pathology
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Latent period may last up to 10 years
Virus infects cells utilizing the CD4 antigen receptor
The virus replicates in the T4 cell until the cell dies.
Other cells have CD4 receptors (monocytes,
macrophages, and some brain and skin cells)
The number of T4 cells continues to diminish until the
patient is prone to opportunistic infections.
Testing for HIV
 Presentation at time of diagnosis
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Serologically negative, serologically positive
but asymptomatic, early stages of HIV, or
AIDS
 Window Period
 Laboratory Tests
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Antigen Tests
Antibody Tests (most common)
Testing for HIV
 FYI
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Western Blot
Confirmation
 Antigen must
be pure

Testing for HIV
 Treatment (antiviral agents)
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Interferons
Azidothymidine (AZT), Dideoxycytidine (ddC),
and Dideoxyinosine (ddI)
“HIV Cocktail”
 Reverse transcriptase and protease inhibitors
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New AIDS vaccine
How to test?
 Genetic variants
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Treatment of Immune
Deficiencies
 Administration of gamma globulin
 Administration of fresh-frozen plasma
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Antibodies and complement
 Bone marrow transplants
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Graft-versus-host, and HLA antigens
 Gene therapy