Download 6.1 Chapter 8-Pt 1 Infection and Immune Deficiencies

Infections and Immune
Deficiencies
Chapter 8 – Part 1
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Normal Bacterial Flora
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All body surfaces have bacteria that live in
relationship with the human body.
Symbiosis - benefits only the human; no harm
to the microorganism
Mutualism - benefits the human and the
microorganism
Commensalism - benefits only the
microorganism; no harm to the human
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Normal Bacterial Flora
Benefits of normal bacterial flora (commensal).
 Produce enzymes that aid digestion of many
molecules in the diet
 Produce antibacterial factors that prevent
attachment and multiplication by pathogens
 Produce B vitamins and vitamin K
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Normal Bacterial Flora
Even normal flora can become pathogenic if the
body’s defenses are breached.
 Pathogenicity – situation in which the
microorganism benefits at the expense of the
human.
 Opportunism – situation that occurs when
benign microorganisms become pathogenic
because of decreased human host
resistance.
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Factors for Infection
1. Mechanism of action – pathogens cause
damage by:
 Direct
damage to cells
 Interference with cellular metabolism
 Release of pathogenic substances and toxins
2. Infectivity - ability of the pathogen to invade
and multiply in the individual.
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Factors for Infection
3. Pathogenicity - ability of an agent to produce
disease—success depends on its speed of
reproduction, extent of tissue damage, and
production of toxins.
4. Virulence - potency of a pathogen measured
in terms of the number of microorganisms or
micrograms of toxin required to kill a host—
for example, measles is of low virulence; the
rabies virus is highly virulent.
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Factors for Infection
5. Immunogenicity - ability of pathogens to
induce an immune response.
6. Toxigenicity - a factor important in
determining a pathogen's virulence, such as
production of soluble toxins or endotoxin.
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Classes of Infectious
Microorganisms
1. Viruses
 Intracellular
parasites much smaller than bacteria
(most are not visible with light microscope).
 Take over the metabolic machinery of host cells
and use it for their own survival and replication.
 Frequently cause destruction of the infected cell.
 Some contain viral DNA; others contain only RNA.
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Bacteriophage
Viruses
Bacterium
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Rotaviruses
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Classes of Infectious
Microorganisms
2. Bacteria
 Prokaryocytes
(lack a nucleus)
 Can be aerobic (require oxygen) or anaerobic (do
not require oxygen), motile or immotile.
 Can take many forms; the most common bacterial
forms are spherical (cocci), rodlike (bacilli), or
spiral (spirochetes).
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Classes of Infectious
Microorganisms
2. Bacteria (cont.)
 Bacteria take up common stains differently,
depending on the structure of their cell walls.
 Gram-positive - stain dark purple when
exposed to Gram stain; lack outer membrane.
 Gram-negative - stain light pink when
exposed to Gram stain; have an outer
membrane.
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Gram-positive
Gram-negative
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Classes of Infectious
Microorganisms
2. Bacteria (cont.)
 There
are many subclasses of bacteria that have
specialized structures and mechanisms of disease
including:
•
•
•
•
Chlamydia
Rickettsiae
Mycoplasma
Mycobacteria.
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Classes of Infectious
Microorganisms
3. Fungi
 Eukaryoctes
(have a nucleus)
 May take the form of yeasts (single-celled
spheres) or molds (multicelled filaments or
hyphae), or both (dimorphic).
 Not motile
 Have thick polysaccharide cell walls that render
them resistant to most antibiotics.
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Classes of Infectious
Microorganisms
4. Protozoa
 Eukaryoctes
(have a nucleus)
 Frequently motile single-celled intracellular
parasites that are larger than bacteria.
 Often infect the gastrointestinal tract, although
infection of the liver, lungs, and central nervous
system is possible.
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Entamoeba histolytica with
Ingested Erythrocytes
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Classes of Infectious
Microorganisms
4. Protozoa (cont.)
 Protozoal infections usually occur in the presence
of infected water (e.g., amebas), venereal
transmission (e.g., Trichomonas vaginalis),
ingestion (e.g., Toxoplasmosis gondii), or insect
vectors (e.g., malaria).
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Classes of Infectious
Microorganisms
5. Helminths
 Large
parasites that can infect the gut, skin, eyes,
and lymphatics.
 Acquired through ingestion (e.g., pinworms or
tapeworms) or through skin penetration
(hookworms, flukes).
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Hookworms
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Pathogenic Defense Mechanisms
Pathogens avoid the host’s defenses (like the
inflammatory and immune responses) in a
number of ways:
1. Develop thick capsules that prevent
phagocytosis (pneumococcus, tuberculosis
bacillus, streptococcus).
2. Produce toxins that kill neutrophils.
3. Proliferate rapidly before a primary immune
response can develop.

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Pathogenic Defense Mechanisms
4. Hide within cells where the inflammatory and
immune responses cannot reach them.
5. Cross placenta to infect fetus, whose immune
system is still immature.
6. Undergo antigenic variation – change their
surface proteins to evade immune response.
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Pathogenic Defense Mechanisms
Antigenic drift – flu viruses undergo mutation
of surface antigens H and N, allowing
emergence of a new flu strain each year.
Antigenic shifts – major changes in
antigenicity resulting from recombination of H
and N genes from different strains of viruses.
Can result in major worldwide pandemics.
Gene switching – some parasites carry genes
for many different surface antigens that they
switch on and off at frequent intervals.
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Infection and Injury
1. Bacterial disease – most of the injury caused
by bacteria is due to toxins.
 Exotoxins – proteins from gram-positive
bacteria that are released during cell growth.
 Exotoxins
are frequently directly cytotoxic and
act as enzymes that affect host cells.
 Exotoxins are immunogenic, so some
vaccines (tetanus, diphtheria, and pertussis)
are directed against the toxin to protect the
body from cellular damage.
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Infection and Injury
1. Bacterial disease

Endotoxins – lipopolysaccharides (lipid A
and lipid O) that are released from the cell
walls of gram-negative bacteria when the
cell wall is injured during lysis or exposure to
antibiotics.
 Endotoxins
set off a severe inflammatory
response that can result in fever, endotoxic
shock, and dysfunction in many organs.
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Viral Disease
Viral replication
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Viral replication depends on their ability to penetrate
a permissive host cell.
Adsorption - the virus must be able to bind to the
surface of the host cell.
Penetration into the cytoplasm - can occur by
endocytosis (the host cell envelops the virus), viral
envelope fusion with the host cell wall, or direct
penetration of the cell membranes. The virus then
sheds its protective coating (uncoating).
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Viral Disease
Viral replication (cont.)
 Replication - most RNA viruses and a few DNA
viruses can replicate in the cytoplasm. A few
RNA viruses (influenza and retroviruses) and
most DNA viruses replicate in the nucleus. They
use the cell’s enzymes to duplicate viral DNA or
RNA and produce viral proteins.
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Viral Disease
Viral replication (cont.)
 Assembly and release - new viruses are
assembled in the cytoplasm and released from
the cell so that they can infect other cells.
Release of viruses may result from lysis of the
host cell or may occur through budding of the
virus from the host cell surface. This may spare
the cell from death but also renders it a
persistent “factory” for viral replication.
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Viral Disease
Viral replication (cont.)
 Latency - some viruses remain integrated into
the cell for many years, but may cause active
disease in the future in response to stimuli such
as stress, hormonal changes, or
immunodeficiency (e.g. herpes zoster virus →
shingles).
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ACTIVITY

Antiviral drugs are designed to interfere with
various steps in the virus’s life cycle. Identify
the steps in this process that you think would
be easiest to disrupt and explain your
reasoning.
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Cellular Effects of Viruses
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Dysfunction - DNA, RNA, or protein synthesis
may be impaired.
Lysis - some viruses disrupt lysosomal
membranes triggering apoptosis and
autodigestion of the cell.
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Cellular Effects of Viruses
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Fusion - virally infected cells may fuse with
healthy cells into structures called
multinucleated giant cells, or syncytia.
Antigenicity - may cause the host cell to
present foreign antigen on its surface,
triggering an immune response against
infected cell.
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Cellular Effects of Viruses
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Cancerous transformation –
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Viruses may integrate themselves into the host DNA,
causing the cell to becomes cancerous.
Uncontrolled growth of the cell may be caused by
disruption of its normal regulatory gene sequencing or
because the virus itself contains a cancer-causing
gene (viral oncogenesis).
Examples: Hepatitis B virus, human papilloma virus.
Secondary infection - viral infection can make
tissues more susceptible to bacterial infection.
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Immune Response to Viral
Infections
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Viruses can often hide from the host defenses
because they reproduce intracellularly.
Infected cells release interferon to help
neighboring cells protect themselves.
Because viruses must spread from cell to cell,
an immune response develops which
eventually cures the infection.
Viral infections are usually self-limiting.
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Fungal Disease
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Fungi can live anywhere in the body (most
commonly on the skin).
Fungi can adapt to the host environment and
can survive in a wide variety of conditions.
Spread rapidly whenever host defenses are
compromised, such as when commensal
bacterial are lost (widespread use of
antibiotics).
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Fungal Disease
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Cause serious systemic infection, especially
in immunocompromised individuals who have
decreased phagocytic and T lymphocyte
function (opportunistic infection).
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Do not respond to most antibiotics
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Examples: Candida albicans (thrush, vaginal and
systemic infections)
Pneumocystis carinii (pneumonia)
Thick polysaccharide walls
Vaccines are not effective.
Antifungal drugs are toxic to host cells.
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Candida albicans
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Clinical Manifestations of
Infectious Disease
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Variable, depending on the pathogen.
May be directly caused by the pathogen or
indirectly caused by its products.
Fever –
 Occurs
when the set point for body
temperature is raised in the hypothalamus
(involves prostaglandins).
 This can be due to either exogenous pyrogens
(from pathogens) or endogenous pyrogens
(like IL-1, interferon, and tumor necrosis
factor-alpha).
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Countermeasures against
Pathogenic Disease
Vaccines - induce a primary immune response, thus
priming the immune system so that exposure to
the actual organism in the future is met with a
vigorous and effective defense.
 Inactivated or weakened, but antigenically similar
material is used to make vaccine.
 This could be an attenuated organism (live but
weakened), dead organisms, a recombinant viral
protein, bacterial antigens, or toxins.
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Countermeasures against
Pathogenic Disease
Vaccines (cont.)
 Attenuated viruses can cause life-threatening
infections in immunocompromised individuals.
 Some individuals fail to mount an adequate
immune response to certain vaccines, either for
genetic reasons or because they are taking drugs
that suppress their immune system.
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Countermeasures against
Pathogenic Disease
Antimicrobials – substances that kill or inhibit the
growth of bacteria, viruses, fungi, or parasites.
 Antibiotics - used in the management of
bacterial infections.
 Different
antibiotics are effective against different
bacteria.
 Modes of action - inhibit synthesis of cell wall,
damage cytoplasmic membrane, alter metabolism
of nucleic acid, inhibit protein synthesis, or modify
energy metabolism.
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Modes of Antibiotic Action
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Countermeasures against
Pathogenic Disease
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Antivirals - because viruses reproduce inside the
host cell, it has been more difficult to develop
safe and effective antivirals.
 Research into HIV has lead to new antivirals
that can also treat other types of viruses.
Antifungals are frequently highly toxic and have
many side effects.
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ACTIVITY

Why is it easier to develop effective drugs
against bacteria than to develop effective
antiviral or antifungal agents?
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Pathogenic Adaptations
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Development of drug resistance - one of the
most serious challenges to effective
management of infectious disease.
 Occurs when microorganisms undergo a
mutation of genes that renders them
resistant to available antimicrobials.
Antigenic changes (see above)
Suppression of immune response (see
below)
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Deficiencies in Immunity
Overview:
 Immunodeficiency is the failure of
mechanisms of self-defense to function in
their normal capacity.
 Primary (congenital) immunodeficiencies are
caused by genetic defects that disrupt
lymphocyte development.
 Secondary (acquired) immunodeficiencies
are caused by disease or other physiologic
alterations.
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Deficiencies in Immunity
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
The clinical hallmark of immunodeficiency is
recurrent infections, both by common pathogens
and by microorganisms that do not normally
cause disease (opportunistic infections).
The type of infection usually reflects the immune
system defect:
 T cell defects result in more fungal and viral
infections.
 B cell or complement defects result in
primarily bacterial infections.
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Deficiencies in Immunity

Management of immunodeficient individuals
requires constant vigilance for the early signs of
infection and rapid administration of
antimicrobials.
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Primary (Congenital) Immune
Deficiencies
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
Most are the result of a single gene defect.
Usually become apparent from recurrent or
persistent infections suffered by infants
beyond six months of age.
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ACTIVITY

Why are primary immunodeficiencies not
apparent until a child is about six months old?
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B Lymphocyte Deficiencies
Usually results in decreased levels of antibody, but
does not affect T cell function.
a. Selective IgA deficiency - characterized by a
lack of IgA production and results from an inability
of plasma cells to class-switch to IgA (can still
make other antibody types).
 Secretory
immune system is compromised - results
in infections of the GI tract, lungs & sinuses.
 Often accompanied by chronic intestinal
candidiasis, autoimmune diseases, and allergy.
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B Lymphocyte Deficiencies
b. Bruton agammaglobulinemia - results from
defects in the bursal-equivalent tissue necessary
for B cell development.
 Children with this disorder have absent or very
low levels of all of the immunoglobulin types.
 Highly prone to all types of infection, especially
those by encapsulated microorganisms.
 Frequently experience otitis media, pharyngitis,
pneumonia, and septicemia.
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T Lymphocyte Deficiencies

Because helper T cells are needed for many B
cell responses, antibody levels are often low.
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T Lymphocyte Deficiencies
a. DiGeorge syndrome – results from congenital
thymic aplasia (absence of thymus gland) or
hypoplasia and diminished parathyroid gland
development.
 T-cell
number and function are severely
compromised, resulting in numerous fungal
infections (especially of the GI tract) and bacterial
and viral pneumonias.
 Parathyroid dysfunction leads to hypocalcemia and
tetany.
 Abnormal facial development is also common.
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DiGeorge Syndrome
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Combined Deficiencies
Affect both B and T cells.
a. Severe combined immunodeficiency disease
(SCID) - caused by a failure of stem cell
development into mature lymphocytes.
 Most children with SCID have few or no T and
B lymphocytes, but they do have normal
numbers of neutrophils and macrophages.
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Combined Deficiencies
a. Severe combined immunodeficiency disease
(cont.)
 SCID
can also arise from inherited enzymatic
defects (in adenosine deaminase [ADA]) that
result in the accumulation of toxic purines within
rapidly dividing cells such as lymphocytes.
 Children with this disorder lack both cellular and
humoral immunity and are highly susceptible to
infections from viruses, bacteria, fungi, and
parasites.
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Combined Deficiencies
b. Bare lymphocyte syndrome - characterized by
an inability of macrophages and lymphocytes to
express HLA (MHC) class I or II antigens.
 Very severe form of SCID - immune system
cannot present foreign antigens to
lymphocytes.
 Causes failure of the entire immune system
and results in fatal infections for most children
younger than 5 years of age.
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Combined Deficiencies
c. Wiskott-Aldrich syndrome - X-linked recessive
disorder characterized by decreased IgM
antibody production.
 Impairs ability to defend against encapsulated
bacteria (Streptococcus pneumoniae and
Haemophilus influenza), as well as many
viruses.
 Platelet dysfunction also occurs, leading to
bleeding problems.
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Complement Deficiencies
a. C3 deficiency – most severe. Often results in
life-threatening infections by encapsulated
bacteria.
b. Deficiencies of terminal components (C5 –
C9) – increase risk of Neisseria infections.
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Phagocyte Deficiencies
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
Often associated with inadequate
opsonization of encapsulated bacteria,
resulting in severe infections of these (see
above).
Phagocytosis can also be impaired by
inadequate numbers of phagocytes,
especially neutrophils.
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Phagocyte Deficiencies

Phagocyte activity can also be defective
because of an inability to kill organisms
intracellularly.
 These
defects most commonly result from
cytoplasmic granule formation (e.g., ChediakHigashi syndrome) or deficiencies in
lysosomal enzymes such as myeloperoxidase
(e.g., chronic granulomatous disease).
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Secondary (Acquired) Immune
Deficiencies
Causes - caused by superimposed conditions, not
genetically encoded.
 Stress, trauma, malnutrition, malignancy, and
infection.
 Many medications can suppress immune
function, especially those drugs used for the
treatment of cancer, inflammation, or transplant
rejection.
 More common than primary immunodeficiencies.
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Acquired Immunodeficiency
Syndrome (AIDS)
Overview



Acquired dysfunction of the immune system
caused by a retrovirus (HIV) that infects and
destroys CD4+ lymphocytes (helper T cells).
HIV (Human Immunodeficiency Virus) - virus
responsible for AIDS
AIDS (Acquired Immune Deficiency Syndrome) term used to refer to the disease syndrome
occurring in individuals who are HIV positive and
who develop opportunistic infections, tumors or
other symptoms of AIDS.
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HIV Virus
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Acquired Immunodeficiency
Syndrome (AIDS)
Transmission - through body fluids via:
 sexual contact
 sharing of needles
 contaminated blood transfusions
 passage from mother to child at birth
 through breast milk
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Acquired Immunodeficiency
Syndrome (AIDS)

HIV Infection of Host Cells – HIV binds to
cells with the CD4 receptor located on Th
cells, macrophages, and a few others.
 Impairs function of these cells, especially
helper T cells.
 Inserts into DNA of these cells and can
remain latent for many years.
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Acquired Immunodeficiency
Syndrome (AIDS)
Clinical Course of HIV Infection
 Early-stage disease – 1-6 weeks after
infection patients may present with mild
symptoms resembling influenza, such as
night sweats, swollen lymph glands, diarrhea,
or fatigue.
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Acquired Immunodeficiency
Syndrome (AIDS)
Clinical Course of HIV Infection
 The
early stage, with or without symptoms,
may last as long as 10 years without
treatment.
 During this period the virus is actively
proliferating in lymph nodes.
 Infected individuals may not test positive for
HIV for many months after infection.
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Progression of HIV to AIDS
Progression of HIV to AIDS – After infection
with HIV the immune system attempts to
control the infection.
Cytotoxic T cells destroy virus infected cells,
including Th cells, keeping the viral load low.
As the Th cell numbers drop, the Tc cells become
less effective.
When the Th level drops below 200/mm3 the Tc
cells are no longer effectively stimulated and the
amount of virus detectable in the blood begins to
rise.

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Progression of HIV to AIDS
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Acquired Immunodeficiency
Syndrome (AIDS)
Clinical Course of HIV Infection
 AIDS – a patient is diagnosed with AIDS if
they have antibodies against HIV (test
seropositive), and have atypical or
opportunistic infections and cancers (like
Kaposi’s sarcoma), as well as indications of
debilitating chronic disease (e.g., wasting
syndrome, recurrent fevers).
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Acquired Immunodeficiency
Syndrome (AIDS)
Clinical Course of HIV Infection
 New cases of AIDS are commonly diagnosed
by decreased CD4+ T cell (Th) numbers.
 Less than 200/mm3; normal = 800-1000/mm3.
 The average time from infection to
development of AIDS is about 10 years
without treatment.
 With treatment this can be extended,
perhaps indefinitely.
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Acquired Immunodeficiency
Syndrome (AIDS)
Clinical Course of HIV Infection
 Death is usually due to overwhelming
infections (without treatment) or side effects
of therapy (with HAART).
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Acquired Immunodeficiency
Syndrome (AIDS)
Treatment
 Highly Active Antiretroviral Therapy (HAART)
– consists of a combination of drugs,
including reverse transcriptase inhibitors and
protease inhibitors to slow viral proliferation in
the body.
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ACTIVITY
1. Which of the primary immunodeficiencies
does AIDS most closely resemble? Why?
2. What are the benefits of giving antiretrovirals
drugs as a combination rather than
individually?
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