Diseases Associated With The Immune System
(such as insect venom or plant pollen) bind to the
Hypersensitivity
● Hypersensitivity refers to an antigenic response that
results in undesirable effects.
● This response occurs in individuals who have been
sensitized by previous exposure to an antigen.
● When a sensitized individual is exposed to that antigen
again, the body’s immune system reacts to it in a
damaging manner.
● The study of hypersensitivity reactions is called
immunopathology.
Allergies & Microbiome
● The “hygiene hypothesis” suggests that limiting
childhood exposure to bacteria and parasites may lower
immune tolerance and limit the body’s ability to cope with
harmless antigens, such as food or pollen.
● Studies show that mammals lacking early exposure to
microorganisms are more susceptible to asthma and
allergies
Types Of Hypersensitivity
Type I (Anaphylactic) Reactions
● Anaphylaxis means “the opposite of protected,” from the
prefix ana-, meaning against, and the Greek phylaxis,
meaning protection.
● Occurs 2 to 30 minutes after a sensitized person is
reexposed to an antigen.
● Anaphylaxis is an inclusive term for the reactions caused
when antigens combine with IgE antibodies.
● Anaphylactic responses can be systemic reactions or
localized reactions
● The IgE antibodies produced in response to an antigen
surfaces of mast cells and basophils.
● Mast cells are especially prevalent in the mucosal and
connective tissue of the skin and respiratory tract and in
surrounding blood vessels.
● Basophils in the bloodstream are recruited to the site of
an infection. Mast cells and basophils contain granules of
histamine and other chemical mediators
● Systemic Anaphylaxis
○ Systemic anaphylaxis (or anaphylactic shock)
results when the release of mediators causes
peripheral blood vessels throughout the body to
dilate, resulting in a drop in blood pressure (shock).
○ Symptoms include narrowing of airway passages
causing respiratory distress, flush or skin rash,
tingling sensations, and nausea.
○ Treatment usually involves self-administration with a
preloaded syringe of epinephrine.
○ Injected antigens are more likely to cause a
dramatic response than antigens introduced via
other portals of entry. People who are allergic to the
venom of stinging insects such as bees and wasps
are at risk for a systemic reaction.
● Localized Anaphylaxis
○ Localized anaphylaxis is usually immediate,
temporary, and less severe than systemic
anaphylaxis.
○ It is associated with ingested or inhaled antigens
(foods) (pollen).
○ In allergies involving the upper respiratory system
(such as hay fever), sensitization and production of
IgE subsequently involve mast cells that release
histamine in the mucous membrane of the upper
respiratory tract
○ Antigens that enter the body via the gastrointestinal
tract can also sensitize an individual. Frequently, food
allergies may not be related to hypersensitivity at all
and are more accurately described as food
intolerances.
○ Hives are more characteristic of a true food allergy,
and ingestion of the antigen may result in systemic
anaphylaxis.
○ Only eight foods are responsible for 97% of food-
related allergies: eggs, peanuts, tree-grown nuts,
milk, soy, fish, wheat, and peas.
○ The typical symptoms are itchy and teary eyes,
congested nasal passages, coughing, and sneezing.
○ Antihistamine drugs, which compete for histamine
receptor sites, are often used to treat these
symptoms.
○ The airborne antigen might be a common
environmental material such as plant pollen, fungal
spores, feces of house dust mites, or animal dander
○ Asthma is an allergic reaction that mainly affects the
lower respiratory system.
○ Symptoms such as wheezing and shortness of
breath are caused by the constriction of smooth
 muscles in the bronchial tubes. These symptoms are Type II (Cytotoxic) Reactions
usually controlled by aerosol inhalants such as
● Type II (cytotoxic) reactions generally involve the
albuterol that relax smooth muscles.
activation of complement by the combination of IgG or
○ Another drug, omalizumab (Xolair®), a humanized
IgM antibodies with an antigenic cell.
monoclonal antibody, blocks IgE for people with
● Activation stimulates complement to lyse the affected
moderate to severe allergic asthma or hives not
cell, which might be either a foreign cell or a host cell that
controlled by antihistamines or leukotriene-blockers
carries a foreign antigenic determinant on its surface.
such as montelukast (Singulair®).
● The most familiar cytotoxic hypersensitivity reactions are
● Preventing Anaphylactic Reaction transfusion reactions, in which red blood cells are
destroyed as a result of reacting with circulating
○ Skin tests are used for a variety of allergies and
antibodies.
involve inoculating small amounts of the suspected
antigen just beneath the epidermis.
○ Sensitivity to the antigen is indicated by a rapid
inflammatory skin reaction that produces redness,
swelling, and itching at the inoculation site called
wheal.
○ Once the responsible antigen has been identified,
the person can either try to avoid contact with it or
undergo desensitization, or subcutaneous allergen-
specific immunotherapy.

ABO Blood Group System

• In 1901, Karl Landsteiner discovered that human blood

could be grouped into four principal types, which were
designated A, B, AB, and O.
• A person’s ABO blood type depends on the presence or
absence of carbohydrate antigens located on the cell
membranes of red blood cells (RBCs).
• The ABO antigens are unique among the antigens on
human cells because antibodies called isoantibodies are
produced in people with different ABO antigens.
• Antigen–antibody reaction causes agglutination and
activates antibodies, which causes lysis of the donor’s
RBCs as they enter the recipient’s system.
RH Blood Group System ● Blood transfusions are not the only way in which an Rh-
person can become sensitized to Rh+ blood. When an Rh-
● In the 1930s, researchers Karl Landsteiner and Alexander
woman and an Rh+ man produce a child, there is at least
Wiener discovered the presence of a different surface
a 50% chance that the child will be Rh+
antigen on human red blood cells that also existed on
● If the child is Rh+, the Rh-mother can become sensitized
rhesus monkeys.
to this antigen during birth when the placental
● The antigen was named Rh factor (Rh for rhesus monkey).
membranes tear and the fetal Rh+ RBCs enter the
● The roughly 85% of the population whose cells possess
maternal circulation, causing the mother’s body to
this antigen are called Rh+; those lacking this antigen
produce anti-Rh antibodies of the IgG type.
(about 15%) are Rh-.
● If the fetus in a subsequent pregnancy is Rh+, the mother’s
● Antibodies that react with the Rh antigen do not occur
anti-Rh antibodies will cross the placenta and destroy the
naturally in the serum of Rh- individuals, but exposure to
fetal RBCs.
this antigen can sensitize their immune systems to
● The fetal body responds to this immune attack by
produce anti-Rh antibodies.
producing large numbers of immature RBCs called
● If blood from an Rh+ donor is given to an Rh- recipient, the
erythroblasts.
donor’s RBCs stimulate the production of anti-Rh
● The term erythroblastosis fetalis was once used to
antibodies in the recipient. If the recipient then receives
describe what is now called hemolytic disease of the
Rh+ red blood cells in a subsequent transfusion, a rapid,
newborn (HDNB).
serious hemolytic reaction will develop.
Type III (Immune Complex) Reactions
○ Type III reactions involve antibodies against
soluble antigens circulating in the serum. In
contrast, type II immune reactions are directed
against antigens located on cell or tissue
surfaces.
○ The antigen–antibody complexes are deposited
in organs and cause inflammatory damage.
○ Immune complexes form only when certain ratios
of antigen and antibody occur. The antibodies
involved are usually IgG.
○ A significant excess of antibody leads to the
formation of complement-fixing complexes that are
rapidly removed from the body by phagocytosis.
When there is a certain antigen–antibody ratio exists, usually
with a slight excess of antigen, the soluble complexes that
form are small and escape phagocytosis
● Type IV (Delayed Cell-Mediated or Delayed
Hypersensitivity) Reactions
○ Type IV reactions involve cell-mediated immune
responses and are caused mainly by T cells.
○ Delayed cell-mediated reactions (or delayed
hypersensitivity) are not apparent for a day or more
○ A major factor in the delay is the time required for
the participating T cells and macrophages to
migrate to and accumulate near the foreign
antigens.
Causes Of Delayed-Cell Mediated Reactions
● Sensitization for delayed hypersensitivity reactions occurs
when certain foreign antigens, particularly those that bind
to tissue cells, are phagocytized by macrophages and
then presented to receptors on the T cell surface.
● Contact between the antigenic determinant sites and the
appropriate T cell causes the T cell to proliferate into
mature differentiated T cells and memory cells
● When a sensitized person is re-exposed to the same
antigen, a delayed hypersensitivity reaction might result.
Memory cells from the initial exposure activate T cells,
which release destructive cytokines in their interaction
with the target antigen.
● In addition, some cytokines contribute to the inflammatory
reaction to the foreign antigen by attracting
macrophages to the site and activating them.
Delayed Cell-Mediated Hypersensitvity Reactions Of The Skin
● One delayed hypersensitivity reaction that involves the
skin is the familiar skin test for tuberculosis. Because
Mycobacterium tuberculosis is often located within
macrophages, this organism can stimulate a delayed
cell-mediated immune response. As a screening test,
protein components of the bacteria are injected into the
skin. If the recipient has (or has had) a previous infection
by tuberculosis bacteria, an inflammatory reaction to the
injection of these antigens will appear in 1 to 2 day.
● Allergic contact dermatitis, another common
manifestation of delayed cell-mediated hypersensitivity, is
usually caused by haptens that combine with proteins
(particularly the amino acid lysine) in the skin of some
people to produce an immune response.
● Reactions to poison ivy, cosmetics, and the metals in
jewelry (especially nickel) are familiar examples of these
allergies.
Autoimmune Diseases
● When the immune system acts in response to self-
antigens and causes damage to one’s own organs, the
result is an autoimmune disease.
● About 75% of the cases of autoimmune disease selectively
affect women. Reasons for this are still being explored, but
hormone differences, genetic susceptibility (females have
two X chromosomal genes and undergo X chromosome
inactivation, whereas males have one), previous
infections, and vitamin D deficiency have been explored
as possibilities.
● Autoimmune diseases occur when there is a loss of self-
tolerance, the immune system’s ability to discriminate self
from non-self.
● Loss of self-tolerance leads to the production of
antibodies against self (autoantibodies) or a response by
sensitized T cells against a person’s own tissue antigens.
Autoimmune reactions, and the diseases they cause, can
be cytotoxic, immune complex, or cellmediated in nature
Cytotoxic Autoimmune Reactions
● Multiple sclerosis is one of the more common
autoimmune diseases, affecting mostly younger adult
women in temperate areas.
● It is a neurological disease in which autoantibodies, T cells,
and macrophages attack the myelin sheath of nerves.
This compromises nerve impulse conduction and leads to
scarring.
● Symptoms range from fatigue and weakness to, in some
cases, eventual severe paralysis. There is considerable
evidence of genetic susceptibility from several genes that
interact.
● The etiology of multiple sclerosis is unknown, but
epidemiological evidence indicates that it probably
 involves some infective agent or agents acquired during
early adolescence.
● The Epstein-Barr virus is frequently mentioned as a prime
suspect. No cure exists, but treatments with interferons,
monoclonal antibodies, and several drugs that interfere
with immune processes can significantly slow progression
of symptoms.
Immune Complex Autoimmune Reaction
• Graves’ disease is a condition in which the thyroid gland
is stimulated to produce increased amounts of thyroid
hormones.
• Normally, the pituitary gland in the brain releases a
hormone called thyroid-stimulating hormone (TSH), which
induces the thyroid gland to produce its hormones.
However, in Graves’ disease there is a malfunction of the
immune system, and abnormal antibodies are released
that mimic TSH.
• These abnormal antibodies cause the thyroid to produce
excessive amounts of hormones, causing pounding of the
heart, trembling, and sweating.
● Myasthenia gravis is a disease in which muscles become
progressively weaker.
● It is caused by antibodies that coat the acetylcholine
receptors at the junctions at which nerve impulses reach
the muscles.
● Eventually, the muscles controlling the diaphragm and the
rib cage may fail to receive the necessary nerve signals.
● Systemic lupus erythematosus is a systemic
autoimmune disease involving immune complex
reactions, which mainly affects women.
● The etiology of the disease is not completely understood,
but afflicted individuals produce antibodies directed at
components of their own cells, including DNA, which is
probably released during the normal breakdown of
tissues, especially the skin.
● The most damaging effects of the disease result from
deposits of immune complexes in the kidney glomeruli.
● Crippling rheumatoid arthritis is a disease in which
immune complexes of IgM, IgG, and complement are
deposited in the joints.
● The chronic inflammation caused by this deposition
eventually leads to severe damage to the cartilage and
bone of the joints.
Cell-Mediated Autoimmune Reactions
● Insulin-dependent diabetes mellitus is a common
condition caused by immunological destruction of insulin-
secreting cells of the pancreas.
● T cells are clearly implicated in this disease; animals that
are genetically likely to develop diabetes fail to do so
when their thymus is removed in infancy
● The fairly common skin condition psoriasis is an
autoimmune disorder characterized by itchy, red patches
of thickened skin.
● Several topical and systemic therapies such as
corticosteroids and methotrexate are available to help
control psoriasis of the skin

Immune System & Cancer
● Like an infectious disease, cancer represents a failure of
the body’s defenses, including the immune system
● It has long been recognized that cancer cells arise
frequently in the body and that they are usually
eliminated by the immune system much like any other
invading cell—the concept of immune surveillance.
● It was postulated that the cell-mediated immune system
probably arose to combat cancer cells and that the
appearance of a cancerous growth represented a failure
of the immune system.
● This concept has been supported by the observation that
cancers occur most often in older adults, whose immune
systems are becoming less efficient (called
immunosenescence), or in the very young, whose immune
systems may not have developed fully or properly. Also,
individuals who are immunosuppressed by either natural
or artificial means are more susceptible to certain
cancers.
● Taking advantage of the immune system to prevent or
cure cancer led to immunotherapy.
● Cancer vaccines might be either therapeutic (used to
treat existing cancers) or prophylactic (to prevent
development of cancers).
● Monoclonal antibodies are a promising tool for delivering
cancer treatment. Monoclonal antibodies may also be
used to boost immune response by flagging cancer cells
as something to attack
● Another approach is to combine a monoclonal antibody
with a toxic agent, forming an immunotoxin.
● Theoretically, an immunotoxin might be used to
specifically target and kill cells of a tumor with little
damage to healthy cells.
● There are also radioactively labeled antibodies that
attach to cancer cells (called radioimmunotherapy).
Immunodeficiencies
Congenital Immunodeficiencies
● Immunodeficiency: The absence of a sufficient immune
response is called an immunodeficiency, which can be
either congenital or acquired.
● Some people are born with an abnormal immune system.
Defects in, or absence of, a number of genes can result in
congenital immunodeficiency (also known as primary
immunodeficiency).
● Genetic immune deficiencies can affect complement,
phagocytes, B cells, T cells, or a combination of the various
immune system factors
Acquired Immunodeficiencies:
● A variety of drugs, cancers, or infectious agents can result
in acquired immunodeficiency (secondary
immunodeficiency).
● Many viruses infect and kill lymphocytes, lowering the
immune response.
● Removal of the spleen decreases humoral immunity
Acquired Immunodeficiency Syndrome (AIDS)
● Studies show that HIV-1 (the primary HIV found worldwide
in humans) is genetically related to another Lentivirus,
simian immunodeficiency virus (SIV), which is carried by
monkeys, mangabeys, and chimpanzees in central Africa.
● The most commonly accepted theory is that humans in
this part of Africa ate SIVinfected bushmeat (wild game),
allowing the virus to cross over into people. • The earliest
known sample of HIV comes from Kinshasa, Democratic
Republic of the Congo, in 1920.
● Approximately 36 million people are infected with, and
living with, HIV today.
● An estimated 70% of these are in Africa, including the
majority of the world’s HIVinfected children. South and
southeast Asia, with their dense populations, also have a
high number of cases, an estimated 3.5 million.
● In Western Europe and the United States, the mortality
from AIDS has decreased because of the availability of
effective antiviral drug.
● The transmission of HIV requires the transfer of, or direct
contact with, infected body fluids.
• Routes of HIV transmission include sexual contact, breast
milk, transplacental infection of a fetus, blood-
contaminated needles, organ transplants, artificial
insemination, and blood transfusion.
● The two most important fluids in terms of infection risk are
blood, which contains 1000 to 100,000 infective viruses per
milliliter, and semen, which contains about 10 to 50 viruses
per milliliter
● The virus can survive more than 1.5 days inside a cell but
only about 6 hours outside a cell.
● The most high-risk form of sexual contact for HIV infection
is anal-receptive intercourse. These tissues are much
more vulnerable to transmission of disease organisms.
● Vaginal intercourse is much more likely to transmit HIV
from man to woman than vice versa, and transmission
either way is much greater when genital lesions are
present.
● At present, for most of the world the only practical means
of controlling AIDS is to minimize transmission.
● Biomedical interventions include condoms, health
services, HIV testing, and needle programs (sex education,
safe infant feeding programs, and counseling).
● Structural interventions focus on making change in
social, economic, political, and environmental factors that
make individuals or groups vulnerable to HIV.
● Preexposure prophylaxis (PrEP) and postexposure
prophylaxis (PEP) for HIV are used to prevent infection
after a recent exposure.
● The treatment requires strict adherence to daily HIV
dosages to lower the chance of getting infected.
● HIV, of the genus Lentivirus, is a retrovirus.
● It has two identical stranded RNA molecules, the enzymes
reverse transcriptase and integrase, and an envelope of
phospholipid.
● The envelope has glycoprotein spikes termed gp120 (the
notation for a glycoprotein with a molecular mass of 120,000
da) and gp41.
● HIV is often spread by dendritic cells that reside in
mucosal linings, which pick up the virus and carry it to the
lymphoid organs. There it contacts cells of the immune
system, most notably activated T cells, and stimulates an
initial strong immune response.
● Attachment depends on the virus’s glycoprotein spike
(gp120) combining with the CD4 receptor of the virus’s
preferred target—a T helper cell.
● Approximately 65,000 of these receptors are found on
each T helper cell. Certain coreceptors may also be
required for attachment. The two best-known chemokine
coreceptors are named CCR5 and CXCR4.
● Once inside the host cell, viral RNA is released and
transcribed into DNA by the enzyme reverse transcriptase.
● The viral DNA then becomes integrated with the host’s
DNA with the help of viral integrase. The DNA may control
the production of an active infection in which new viruses
bud from the host cell.
● Alternatively, this integrated DNA may not produce new
HIV, but hide in the host cell’s chromosome as a provirus.
● HIV produced by a host cell is not necessarily released
from the cell but may remain as latent virions in vacuoles
within the cell.
● A subset of the HIV-infected cells, instead of being killed,
become long-lived memory T cells in which the reservoir
of latent HIV can persist for decades.
● There are two major subtypes of HIV: HIV-1 and HIV-2.
● HIV-1 accounts for about 99% of cases worldwide. HIV-1
viruses are further subdivided into groups that are
assigned letter combinations. Group M (for “majority”)
accounts for about 90% of cases.
● Subtype B is the dominant HIV found in Europe, Australia,
Japan, and the Americas, and almost half of people
diagnosed with HIV-1 have subtype C.
● HIV-2 is endemic in West Africa, but its spread throughout
the world has been limited. HIV-2 is generally
characterized by having a longer asymptomatic period
with lower viral load and mortality rate.
The Stages Of HIV Infection
PHASE 1: The number of viral RNA molecules per milliliter of
blood plasma may reach more than 10 million in the first week
or so, during the acute infection stage. Billions of CD4+ T cells
may be infected within a few weeks, lowering their numbers.
Immune responses, and fewer uninfected cells to target,
deplete the viral numbers in blood plasma sharply within a few
weeks. The infection may be asymptomatic or cause
lymphadenopathy (swollen lymph nodes.
PHASE 2: The numbers of CD4+ T cells decline steadily. HIV
replication continues but at a relatively low level, probably
controlled by CD8+ T cells and occurs mainly in lymphatic
tissue. There are few disease symptoms, persistent infections
by the yeast Candida albicans, which can appear in the
mouth, throat, or vagina, may signal a decline in immune
response. Other conditions may include fever and persistent
diarrhea. Oral leukoplakia (whitish patches on oral mucosa),
which results from reactivation of latent Epstein-Barr viruses,
as well as other indications of declining immunity, such as
shingles.
PHASE 3: In clinical AIDS, CD4+ T cell counts fall below 200
cells/μl, and susceptibility to opportunistic infections is high.
(The normal population in a healthy individual is 500 to 1500
CD4+ T cells/μl.) Important AIDS indicator conditions appear,
such as C. albicans infections of bronchi, trachea, or lungs;
cytomegalovirus eye infections; tuberculosis; Pneumocystis
pneumonia; toxoplasmosis of the brain; and Kaposi’s sarcoma.
Success in treating these conditions has extended the lives of
many HIV infected people.
HIV Positive vs. AIDS Disease Status
• During phases 1 and 2 of the infection, patients are
classified as HIV-positive. During phase 3, patients are
classified as having AIDS.
• The purpose of dividing patients into these categories is
primarily to furnish treatment guidelines on when to
administer certain drugs.
• The progression from initial HIV infection to AIDS usually
takes about 10 years in adults without treatment.
• Untreated, at least 100 billion HIVs are generated every
day, each with a remarkably short half-life of about 6
hours.
• These viruses must be cleared by the body’s defenses,
which include antibodies, cytotoxic T cells, and
macrophages.
• Almost all HIVs are produced by infected CD4+ T cells,
which survive for only about 2 days instead of the normal
life span of several years.
• Every day, about 2 billion CD4+ T cells are produced in an
attempt to compensate for losses. Over time, however,
there is a daily net loss of at least 20 million CD4+ T cells.
Impact Of Age On Survival With HIV Infection
• Older adults are less able to replace CD4+ T cell
populations. Infants and younger children have an
immune system that is not fully developed, leaving them
much more susceptible to opportunistic infections.
• Infants born to HIV-positive mothers are not always
infected—in fact, only about 20% are.
• HIV-positive mothers who are actively undergoing
antiretroviral treatment can reduce the risk of transmitting
the virus to their offspring by 99%
Exposed But Not Infected Population
• Certain high-risk people are repeatedly exposed to HIV
but remain free of infection.
• About 1–3% of the populations of the Western world do not
have a gene for CCR5, a coreceptor typically found on T
helper cells that HIV binds to before entering the cell.
• Long-Term Survivors: Occasionally, certain untreated
individuals who have been infected with HIV for more than
10 years have not progressed to AIDS. These people are
called long-term nonprogressors.
• Other individuals who are repeatedly infected with the
virus never progress to AIDS and have little to no virus in
their blood. They are called elite controllers.
• These long-term survivors make up less than 5% of the
HIV-infected population.
Diagnostic Methods
• The CDC recommends routine screening for HIV infections.
Recommendations for screening vary based on risk of
exposure, from once in a lifetime to every 6 months for
people who engage in highrisk behaviors
• The standard procedure for detecting HIV antibodies has
been blood tests using an ELISA test to detect HIV
antibodies. Positive screening tests for antibodies must be
confirmed by additional testing, usually by the Western
blot test.
• There are now several relatively inexpensive, rapid tests
available for HIV screening that are used in developing,
poor countries. The tests use urine or fingerstick amounts
of blood, and the OraQuick® test can even use an oral
swab to check for HIV antibodies. They return results in 20
to 30 minutes.
Elisa Test
• The enzyme-linked immunosorbent assay (ELISA) is the
most widely used of a group of tests known as enzyme
immunoassay (EIA).
• A microtiter plate with numerous shallow wells is used in
this procedure. ELISA procedures are popular primarily
because they are sensitive and require little interpretive
skill to read.
Indirect Elisa
• indirect ELISA tests are used to screen blood for antibodies
to HIV.
• For such a purpose, the microtiter wells contain antigens,
such as the inactivated virus that causes the disease.
• A sample of the patient’s serum is added to the well; if it
contains antibodies against the virus, they will bind the
antigen.
• The well is rinsed to remove unbound antibodies. If
antibodies in the serum and the virus in the well have
attached to each other, they will remain in the well—a
positive test
• To make a positive test visible, some anti-HISG (an
immunoglobulin that will attach to any antibody, including
the one in the patient’s serum that has attached to the
virus in the well.
The anti-HISG is linked to an enzyme. A positive test consists of
a “sandwich” of a virus/antibody/enzyme-linked-anti-HISG. At
this point, the substrate for the enzyme is added, and a
positive test is detected by the color change caused by the •
enzyme linked to the anti-HISG.
 Western Blotting (Immunoblotting)
• Western blotting, often simply called immunoblotting, can
identify a specific protein in a mixture (such as proteins
extracted from a blood sample).
• The components of the mixture are separated by
electrophoresis in a gel and then transferred to a protein-
binding sheet (blot).
• There the blot is flooded with an enzyme-linked antibody
specific for the antigen. The location of the antigen and
the enzyme-linked antibody reactant can be visualized,
usually with a color-reacting label similar to an elisa test
reaction.
Diagnostic Methods
• A problem with antibody-type testing is the window of
time between infection and the appearance of detectable
antibodies, or seroconversion.
• This interval, which can be as long as 3 months, where
seroconversion follows the peak number of viruses in
circulation. Because of this delay, the recipient of an organ
transplant or a blood transfusion can become infected
with HIV even though antibody tests did not show the
presence of the virus in the donor
Antiretroviral Therapy
• The rapid reproductive rate and frequent occurrence of
drug resistant mutations dictates that multiple drugs,
given simultaneously, must be used. The current
treatment is termed Highly Active Antiretroviral Therapy
(HAART).
• This therapy consists of administering drug combinations
to minimize survival of resistant strains.
• The number of HIV in circulation is often reduced to fewer
than can be detected, but this is not the same as
eradication
• Major obstacles to treating HIV, as with developing a
vaccine, are the high mutation rate that quickly leads to
resistant strains and the persistence of latent viral
reservoirs.
• If the effective drugs are interrupted or discontinued, the
virus rebounds rapidly. Research into the reproductive.
mechanisms of HIV has increased the number of potential
targets for chemical intervention
Fusion & Entry Inhibitors
• For infection to occur, the virus must attach to the cell’s
CD4 receptors; an interplay between the gp120 spike on
the virus and the coreceptor (such as CCR5) must occur;
and finally, there must be a fusion with the cell to allow
viral entry.
• Drugs to block these steps are grouped as cell entry
inhibitors; some of the drugs of this group target the gp41
region of the viral envelope, which facilitates fusion.
• An example is enfuvirtide, which is expensive and requires
daily injections. Another cell entry inhibitor is maraviroc,
which blocks the chemokine receptor CCR5 to which HIV
must bind.
Reverse Transcriptase Inhibitors
• After virus fusion with the host cell, reverse transcription
from the RNA genome produces a double-stranded cDNA
copy of the HIV genome.
• The first target of anti-HIV drugs was the enzyme reverse
transcriptase, an enzyme not present in human cells.
• The nucleoside reverse transcriptase inhibitors (NRTIs) are
analogs of nucleosides and cause the termination of viral
DNA by competitive inhibition.
• There are other drugs that inhibit reverse transcription
that are not analogs of nucleic acids; these are the so-
called non-nucleoside reverse transcriptase inhibitors
(NNRTIs). Atripla® is a combination of two NRTIs plus
efavirenz (a NNRTI)
Integrase Inhibitors
• After reverse transcription, the cDNA of the HIV enters the
nucleus. There the cDNA must be integrated into the host
chromosome to form the HIV provirus.
• This step requires an enzyme, HIV integrase, which is a
target for drugs called integrase inhibitors. Raltegravir,
dolutegravir, and elvitegravir are examples
Protease Inhibitors
• A third enzyme target is HIV proteases. Proteases perform
the essential process of cleaving lengthy viral precursor
proteins into smaller, mature structural proteins (such as
the capsid proteins) and functional proteins (such as
essential enzymes).
• Most of this occurs as the virus is budding from the cell
membrane. Protease inhibitor drugs such as atazanavir,
indinavir, and saquinavir have proved especially effective
when combined with reverse transcriptase inhibitors.
Antimicrobial Drugs
• CHEMOTHERAPY with ANTIMICROBIAL drugs
• Antimicrobial Drugs - Kills and interferes microorganism
growth
• Selective Toxicity - these drugs are specific
• Paul Ehrlich - Coined the term Selective Toxicity and
chemotherapy.
o It all started from a speculation: “A magic bullet
will destroy the pathogen, but not the host.”
D Selective Toxicity Effectiveness GS
• Type of Pathogen
• Viral Infection (pathogen is within the cell)
• Selective toxicity “works well” if the pathogen is a
prokaryotic cell because prokaryotes are different to
human cells
• Selective toxicity doesn’t “work well” if the pathogen is a
eukaryotic cell (fungus, protozoan, helminthic) because
their structures are similar to ours
• Alexander Fleming - Discovered Penicillium Notatum
• A bacterium, STAPHYLOCOCCUS AUREUS, surrounded a
mold that inhibited or stopped the bacteria from growing.
o That mold was PENICILLIN
o PENICILLIN is an ANTIBIOTIC
 Antibiotic Inhibiting Cell Wall Synthesis

• Substance produced by microorganisms that inhibits • targets peptidoglycan wall.

other microorganisms Inhibiting Protein Synthesis
• Sources of Antibiotics:
• targets a pathogen’s ribosomes.
o Streptomyces: filamentous bacteria (produces
more than a half of the antibiotics).
• 80S ribosome – eukaryotic

o Bacillus: endospore-forming bacteria • 70S ribosome – prokaryotic

o Penicillium and Cephalosporium: molds Injuring The Plasma Membrane
• Antibiosis - Mechanism of inhibition.
o ALL antibiotics are antimicrobial drugs, but NOT • changes the permeability of the plasma membrane.
ALL antimicrobial drugs are antibiotics. • Disrupts the inner and outer membranes
o Antibiotics are a type of antimicrobial drugs.
Inhibiting The Nucleic Acid Synthesis
Spectrum of Antimicrobial Activity
• Interferes with DNA replication and transcription.
• Affects SMALL RANGE of microbial types, NARROW
• Block bacterial TOPOISOMERASE or RNA POLYMERASE
Spectrum of Antimicrobial Activity
• Affects WIDE RANGE of microbial types, BROAD Spectrum
Inhibiting The Synthesis Of Essential Metabolites
of Antimicrobial Activity
• Drug with a Narrow Spectrum is BETTER than a Broad • ANTIMETABOLITE - Completely inhibits a particular
Spectrum. enzymatic activity. Example: sulfanilamide and para-
• An Antimicrobial Drug with a Broad Spectrum can kill even aminobenzoic acid.
NORMAL MICROBIOTA • Antimetabolites are chemotherapy drugs that prevent
• If they fail to kill the target, SUPERINFECTION will occur. cancer cells from making more cancer cells (replicating).
• They trick cancer cells into using the drug instead of the
• SUPERINFECTION is the overgrowth of a pathogen that has
molecules it needs to make the genetic material to
developed ANTIBIOTIC RESISTANCE
replicate, or DNA.
Action of Antimicrobial Drugs
• BACTERICIDAL - kill microbes
• BACTERIOSTATIC - prevent microbes from growing
 Different Antimicrobial drugs

• Antibiotic
• Antifungal
• Antiviral
• AntiProtozoan
• Antihelmintic

Antibiotic

Antifungal
• OPPORTUNISTIC INFECTIONS - “do not cause disease in
healthy people but deadly for immunocompromised
individuals.”
Agents Affecting FUNGAL STEROLS - Polyenes, Azoles, Allylamines,
Griseofulvin
Agents Affecting FUNGAL CELL WALLS- Echinocandins
Agents Inhibiting NUCLEIC ACIDS- Flucytosine
Nucleic acid synthesis: ACYCLOVIR, RIBAVIRIN, ADEFOVIR,
DIPIVOXIL CIDOFOVIR
Nonnucleoside inhibitor: NEVIRAPINE
ASSEMBLY AND EXIT INHIBITORS
Protease inhibitors: ZANAMIVIR (Relenza®), OSELTAMIVIR
(Tamiflu®), and PERAMIVIR (Rapivab®)
INTERFERONS– ALPHA INTERFERON, IMIQUIMOD
ANTIRETROVIRALS– Specifically for HIV and AIDS

Agents Inihibiting FUNGAL REPRODUCTION – Griseofulvin

ANTIPROTOZOAN & ANTIHELMINTHIC

UNKNOWN (but it seems to bind to DNA) – PENTAMIDINE: treats ANTIPROTOZOAN DRUGS

pneumocystis pneumonia (complication of AIDS)
1. QUININE
Antiviral 2. QUINACRINE
The “struggles”… 3. METRONIDAZOLE
4. TINIDAZOLE
60% caused by viruses 15% by bacteria
5. MILTEFOSINE
Development can be CHALLENGING.
Viruses replicate using the HOST’S OWN CELLS, making it ANTIHELMINTHIC DRUGS
difficult to target the virus without damaging the host’s cell. 1. NICLOSAMIDE,
ENTRY AND FUSION INHIBITORS 2. PRAZIQUANTEL
Entry: MARAVIROC
3. MEBENDAZOLE
Fusion: ENFUVIRTIDE 4. ALBENDAZOLE
5. IVERMECTIN
UNCOATING, GENOME INTEGRATION, AND NUCLEIC ACID
SYNTHESIS INHIBITORS

Uncoating: AMANTADINE and RIMANTADINE

Integrase: RALTEGRAVIR and ELVITEGRAVIR ;
 Tests to Guide Chemotherapy
• DISK-DIFFUSION METHOD - PETRI PLATE WITH TEST
ORGANISM IS “SEEDED”
o THE LARGER THE ZONE OF INHIBITION, THE MORE
SENSITIVE
o Determines MINIMAL INHIBITORY CONCENTRATION

Persistence
• WHEN A SMALL POPULATION OF MICROBES SURVIVE FROM
THE DRUG.
• They do not grow when a drug is present. HOWEVER,
population growth can resume when drug is removed

Resistance
• Occurs when an infection responds poorly to an antibiotic
that once could treat it successfully.

Superbug
• BACTERIA THAT ARE RESISTANT TO LARGE NUMBERS OF
ANTIBIOTICS
• BACTERIA becomes resistant. NOT THE PERSON
• Resistance happens due to a change in bacteria DNA.
• A new protein they use as a tool to fight the antibiotic.

Bacterial resistance to Antibiotics

• BLOCKING ENTRY - Prevention of Penetration to the Target
Site within the Microbe. prevent the antibiotic from
entering the microbe.
• INACTIVATION BY ENZYME - Enzymatic Destruction
Inactivation of the Drug. destroy or inactivate the
antibiotic by enzymatic reaction.
• ALTERATION OF TARGET MOLECULE - Alteration of the
Drug’s Target Site. Modification of the antibiotic’s targe
• EFFLUX OF ANTIBIOTIC - .Rapid Efflux (Ejection) of the
Antibiotic. pump the antibiotic out of the cell.
• Resistance can also happen in ANTIBIOTIC MISUSE AND
OVERUSE
• PRESCRIPTION from healthcare professionals is a MUST!

Therapeutic Index: Risk vs. Benefit

• EFFECTS OF COMBINATIONS OF DRUGS
o SYNERGISM drug 1 + drug 2 = GREATER EFFECT
o ANTAGONISM drug 1 + drug 2 = LESS EFFECTIVE

Respiratory Infection (Bacteria)
Streptococcal Infection
• Gram-positive bacteria cause diseases like meningitis,
pneumonia, sore throat, and dental cavities. They secrete
toxins and enzymes, causing lesions that heal without
scarring or treatment.
• Release of toxins, including hemolysins, categorizing them
as alpha-hemolytic, beta-hemolytic, or autoinoculation.
Streptococcal Skin Infection
• Streptococci and Staphylococci cause bacterial skin
infections, causing diseases like meningitis, pneumonia,
sore throat, and dental caries, primarily due to their gram-
positive spherical growth.
Streptococcal Growth and Toxins
• Streptococci elongate before division, secreting virulence
factors like hemolysins, causing red blood cell lysis.
Symptoms include rupturing lesions and crusting in the
host's response
Rheumatic Fever
• Caused by Streptococcus pyogenes infections.
• Common in individuals aged 4 to 18, often following a
streptococcal sore throat.
• Symptoms include arthritis, fever, and potential
autoimmune-related heart valve damage
Sydenham 's Chorea
• Unusual complication affecting up to 10% of rheumatic
fever cases.
• Typically emerges months after rheumatic fever, more
common in females.
• Manifests as purposeless, involuntary movements during
waking hours.
• Sedation may be necessary to prevent self-injury.
• Generally resolves within a few months.
Streptococcal Pharyngitis
• Upper respiratory infection caused by Group A
Streptococci (GAS), specifically Streptococcus pyogenes.
• Pharyngitis characterized by local inflammation and fever
• Common symptoms include throat inflammation,
difficulty swallowing, and the presence of white patches
on the tonsils.
• Frequent complication includes otitis media. Mainly
transmitted through respiratory secretions, but past
epidemics resulted from streptococcal pharyngitis spread
by unpasteurized milk.
• Complications, such as rheumatic fever and acute
glomerulonephritis, underscore the importance of early
detection and prompt treatment.
• Globally prevalent, streptococcal pharyngitis primarily inactivated toxin that induces the production of
affects children, underscoring the need for early diagnosis antibodies against the diphtheria toxin.
and intervention. • While C. diphtheriae typically does not invade tissues,
• Rapid antigen detection tests since the 1980s have lysogenized strains can produce a potent exotoxin. This
improved the diagnosis of GAS from throat swabs, but toxin circulates in the bloodstream, interfering with protein
negative results may require culture. GAS infections in synthesis.
children over 3 years require treatment. • Diphtheria was the first disease for which a toxic cause
• Effective treatment involves antibiotics, with penicillin was identified, and a small amount of the toxin can be
remaining a key choice. Completing the prescribed course fatal. Complications can affect the heart, kidneys, or
is essential for preventing recurrence. nerves, leading to rapid fatality or partial paralysis.
• Laboratory diagnosis is challenging, requiring selective
Scarlet Fever and differential media. Antibiotics like erythromycin and
• When certain strains of Streptococcus pyogenes, the penicillin control bacterial growth but do not neutralize the
bacterium responsible for streptococcal pharyngitis (strep toxin.
throat), produce an erythrogenic (reddening) toxin, it can • Treatment involves antibiotics in conjunction with antitoxin
lead to a distinct clinical condition known as scarlet fever. administration, emphasizing the need for early
• Skin Rash: The erythrogenic toxin induces a pinkish-red intervention to prevent complications
skin rash. This rash is likely the result of the skin's
hypersensitivity reaction to the circulating toxin.
• Patients with scarlet fever typically experience a high
fever.
• The tongue initially has a spotted, strawberry-like
appearance. As the upper membrane is lost, the tongue
becomes very red and enlarged.
• Traditionally, scarlet fever has been closely associated
with streptococcal pharyngitis, often occurring as a
complication of a throat infection caused by
Streptococcus pyogenes.
• While classically linked to streptococcal pharyngitis,
scarlet fever may also accompany streptococcal skin
infections
• Scarlet fever is generally considered a mild illness, but
antibiotic treatment is recommended.
• The primary reason for antibiotic therapy is to prevent the
later development of rheumatic fever, a more severe and
potentially serious complication associated with certain
streptococcal infections

Diphtheria
• Diphtheria is a bacterial infection of the upper respiratory
system caused by Corynebacterium diphtheriae, a gram-
positive, non-endosporeforming rod with pleomorphic
and club-shaped morphology. Historically, it was a
significant infectious killer of children in the United States
until the introduction of the DTaP vaccine.
• Diphtheria typically begins with a sore throat, fever,
general malaise, and neck swelling. A distinctive feature is
the formation of a tough grayish membrane in the throat,
containing fibrin, dead tissue, and bacterial cells. This
membrane can obstruct the air passage to the lungs.
• C. diphtheriae is well adapted to droplet transmission and
is resistant to drying. In immunized populations, relatively
nonvirulent strains are found in the throats of
symptomless carriers. The disease has become rare in the
United States due to widespread immunization.
• Part of the routine immunization program is the DTaP
vaccine, which protects against diphtheria, tetanus, and
pertussis. The vaccine includes diphtheria toxoid, an