HUMAN ANATOMY AND PATHOPHYSILOGY

Reticulo-endothelial System
• The reticulo-endothelial system is made
up of Kuppfer cells of the liver and
reticular cells of redbone marrow
• This system defends the body against
hazardous
Phagocytosis
 is a cellular process for ingesting and
eliminating particles larger than 0.5 μm in
Blood composition
diameter, including microorganisms,
55% Plasma (fluid matrix of water, salts, proteins,
foreign substances, and apoptotic cells.
etc.)
 Apoptosis is the process of programmed
45% Cellular elements:
cell death → used during early
 Red Blood Cells (RBCs): 5-6 million
development to eliminate unwanted cells,
RBCs/ml of blood. Contain hemoglobin
used to rid the body of cells that have
which transport oxygen and CO2.
been damaged beyond repair.
 White Blood Cells (WBCs): 5,000-10,000
Phagocytosis is found in many types of cells and it
WBCs/ml of blood. Play an essential role
is, in consequence an essential process for tissue
in immunity and defense. Include:
homeostasis.
 Lymphocytes: T cells and B cells
Blood
 Macrophages: (phagocytes)
- is a body fluid in humans and other animals
 Granulocytes: Neutrophils,
→ delivers necessary substances such as nutrients
basophils, and eosinophils.
and oxygen to the cells →transports metabolic
 Platelets: Cellular fragments, 250,000-
waste products away from those same cells.
400,000/ml of blood. Important in blood
Albumin clotting.
- is the main protein in plasma
- is a protein made by your liver COMPOSITION OF BLOOD
-helps keep fluid in your bloodstream so it doesn't
leak into other tissues.
*Functions:
- to regulate the colloidal osmotic pressure of
blood.
- carries various substances throughout your
body, including hormones, vitamins, and enzymes
→ Low albumin levels can indicate a problem
with your liver or kidneys.
Granulocytes
- are a type of white blood cell that has small
granules. These granules contain proteins.
The specific types of granulocytes are:
 neutrophils
 eosinophils
 basophils.
Granulocytes, specifically neutrophils help the
body fight bacterial infections
A type of immune cell that has granules (small
particles) with enzymes that are released during
infections, allergic reactions, and asthma.

Agranulocytes (lymphocytes and monocytes)

- are a type of white blood cell that lack visible
granules.
- they have a clear cytoplasm that allows for
better visibility of the nucleus.
- are an important part of the body's immune
system.
 What stem cell give rise to all formed elements
Myeloid stem cells
- give rise to all the other formed elements
including:
*erythrocytes
*megakaryocytes that produce platelets
*myeloblast lineage that gives rise to monocytes
and three forms of granular leukocytes:
neutrophils, eosinophils, and basophils.
Myeloid stem cells
- are derived from Hematopoietic stem cells.
- They differentiate into Erythrocyte progenitor
Mechanism of formation of formed elements cell (forms erythrocytes), -Thrombocyte
→ Through the process of Hemopoiesis progenitor cell (forms platelets)
- the formed elements of blood are continually - Granulocyte-Monocyte progenitor cell (forms
produced, replacing the relatively short lived monocytes, macrophages, neutrophils, basophils,
erythrocytes, leukocytes, and platelets. eosinophils, dendritic cells).
Hemopoiesis begins in the red bone marrow, with
hemopoietic stem cells that differentiate into
myeloid and lymphoid lineages.
Before birth:
Hemopoiesis
- the production of blood cells and platelets.
- occurs primarily in the liver and spleen, but
some cells develop in the thymus, lymph nodes,
and red bone marrow.
Erythropoietin
- also known as EPO
- is a hormone that the kidneys produce to
stimulate production and maintenance of crucial Function of RBC
red blood cells. The main job of red blood cells,
The hormone it stimulates bone marrow cells or erythrocytes
→→to produce red blood cells. - is to carry oxygen from the
lungs to the body tissues and
carbon dioxide as a waste
product, away from the tissues and back to the
lungs.
What are formed elements
Hemoglobin (Hgb)
- are cells and cell fragments suspended in the
- is an important protein in the
plasma.
red blood cells that carries
The three classes of formed elements are: oxygen from the lungs to all parts
- erythrocytes (red blood cells) -leukocytes (white of our body.
blood cells) -thrombocytes (platelets) - is a protein produced by your
bone marrow that's stored in red
blood cells.
What does it mean if low RBC The main function of platelets:
A low red blood count or anemia can cause: *the maintenance of hemostasis-depends on
- feelings of fatigue and weakness. three of their properties: -the endothelial
supporting function of platelets,
When people have a lower red blood count than
-the ability to form hemostatic plugs
normal → their body has to work overtime to get
-release lipoprotein material (platelet factor 3).
enough oxygen to the cells.
Coagulation factors
The cells contain hemoglobin, which is a protein
-are proteins in the blood that help control
that carries oxygen around the body.
bleeding.
You have several different coagulation factors in
Function of WBC
your blood.
White blood cells (WBCs), also called leukocytes
When you get a cut or other injury that causes
or leucocytes
bleeding, your coagulation factors work together
- are the cells of the immune system that are
to form a blood clot. →This process is called the
involved in protecting the body against both
coagulation cascade.
infectious disease and foreign invaders.
All white blood cells are produced and derived Platelets
from multipotent cells in the bone marrow known -are tiny blood cells that help your body form
as hematopoietic stem cells. clots to stop bleeding.
If one of your blood vessels gets damaged → it
sends out signals to the platelets → The platelets
then rush to the site of damage → they form a
plug (clot) to fix the damage.
The following are coagulation factors and their
common names:
Factor I - fibrinogen.
Factor II - prothrombin.
Factor III - tissue thromboplastin (tissue factor)
Factor IV - ionized calcium (Ca++)
Factor V-labile factor or proaccelerin.
Factor VI - unassigned.
Function of Platelet Factor VII - stable factor or proconvertin.
Platelets, also called thrombocytes The common pathway factors X, V, II, I, and XIII
- are a component of blood whose function (along -Stuart-Prower factor(X)
with the coagulation factors) is to react to -proaccelerin (V)
bleeding from blood vessel injury by clumping, -prothrombin (II) -fibrinogen (1)
thereby initiating a blood clot. -fibrin-stabilizing factor (XIII)
-eponym Stuart-Prower factor (Factor X)
is an enzyme of the coagulation cascade.
It is a serine endopeptidase.
-synthesized in the liver and requires vitamin K for
its synthesis.
The intrinsic pathway consists of factors: Blood group is determined by the genes you
I-fibrinogen inherit from your parents,
Il-prothrombin
IX-Christmas factor
X-Stuart-Prower factor XI-plasma thromboplastin
XII-Hageman factor.

Fibrinolysis
-is a process that prevents blood clots from
growing and becoming problematic. The ABO system
This process has two types: -is the most familiar way of grouping human
-primary fibrinolysis blood types.
-secondary fibrinolysis. Blood consists of cells and a yellow watery liquid
known as plasma.
In fibrinolysis, a fibrin clot, the product of The blood group depends on what each part of
coagulation is broken down. the blood contains.
The two main blood group systems are ABO
Primary fibrinolysis antigens and Rhesus antigens (including RhD
-refers to the normal breakdown of clots. antigen).
Secondary fibrinolysis.
-is the breakdown of blood clots due to a medical
disorder, medicine, or other cause.
-This may cause severe bleeding.

The most commonly used clot-busting drugs --

also known as thrombolytic agents
Eminase (anistreplase)
Retavase (reteplase)
Streptase (streptokinase, kabikinase)
t-PA (class of drugs that includes Activase)
TNKase (tenecteplase)
Abbokinase, Kinlytic (rokinase) CARDIOVASCULAR SYSTEM

Human blood group and blood type

Human blood is grouped into four types: A, B, AB,
and O.
Each letter refers to a kind of antigen, or protein,
on the surface of red blood cells.
For example, the surface of red blood cells in Type
A blood has antigens known as A-antigens.
 Heart Anatomy The heart has four chambers: two atria and two
ventricles.
The right atrium → receives oxygen-poor blood
from the body and pumps it to the right ventricle.
The right ventricle →pumps the oxygen-poor
blood to the lungs.

Human cardiovascular system

=organ system that conveys blood through vessels
to and from all parts of the body carrying
nutrients and oxygen to tissues and removing The left atrium →receives oxygen-rich blood from
carbon dioxide and other wastes. the lungs and pumps it to the left ventricle.
It is a closed tubular system in which the blood is The left ventricle pumps the oxygen-rich blood to
propelled by a muscular heart. the body
-composed of a heart which pumps blood Atria → receive blood
through a closed system of blood vessels.
Ventricles → pump blood
The heart is composed mostly of cardiac muscle,
or Myocardium. The right atrium receives blood from the superior
and inferior vena cavas and the coronary sinus
Its primary function:
blood then moves to the right ventricle where it is
transport nutrients, water, gases, wastes, and
pumped to the lungs.
chemical signals throughout the body.
Blood enters the heart through two large veins,
Structure of the Heart the inferior and superior vena cav→ emptying
oxygen-poor blood from the body into the right
atrium.
As the atrium contracts → blood flows from your
right atrium into your right ventricle through the
open tricuspid valve.
Structure of the Heart

Septum
Pulmonary circulation Cardiac Output
-moves blood between the heart and the lungs. -simply the amount of blood pumped by the
heart per minute.
It transports deoxygenated blood to the lungs to
-is the product of the heart rate, which is the
absorb oxygen and release carbon dioxide.
number of beats per minute, and the stroke
The oxygenated blood then flows back to the volume, which is amount blood heart pumped
heart. per beat. CO = HR X SV
The cardiac output is usually expressed in
Systemic circulation
liters/minute.
-moves blood between the heart and the rest of
the body.

A portal circulation
-are connecting veins, which are an additional
network of vessels between arterial and venous
circulation.
The veins between the connected capillaries are
called Portal veins.
This circulation of nutrient-rich blood between Blood pressure
the gut and liver is called the portal circulation. -is important because the higher your blood
It enables the liver to remove any harmful pressure is, the higher your risk of health
substances that may have been digested before problems in the future.
the blood enters the main blood circulation
If your blood pressure is high → putting extra
around the body-the systemic circulation.
strain on your arteries and on your heart →may
also cause a heart attack or stroke.

Portal circulation →is the pressure of blood pushing against the

walls of your arteries. Arteries carry blood from
your heart to other parts of your body. Your blood
pressure normally rises and falls throughout the
day.
Kidneys
-provide a hormonal mechanism for the
regulation of blood pressure by managing blood
volume.
The renin-angiotensin-aldosterone system of the
kidneys regulates blood volume.
In response to rising blood pressure, the
juxtaglomerular cells in the kidneys secrete renin
into the blood.

Pathophysiology of Hypertension
is an area which attempts to explain
mechanistically the causes of hypertension, which
is a chronic disease characterized by elevation of
The renin-angiotensin system (RAS), or renin- blood pressure.
angiotensin-aldosterone system (RAAS)
Hypertension can be classified by cause as either:
-is a hormone system that regulates blood
-essential (also known as primary or idiopathic)
pressure and fluid and electrolyte balance, as well
-secondary
as systemic vascular resistance.
Factors that play an important role in the
Peripheral vascular resistance (systemic vascular
pathogenesis of hypertension include:
resistance, SVR)
-genetics
-is the resistance in the circulatory system that is
-activation of neurohormonal systems such as the
used to create blood pressure, the flow of blood
sympathetic nervous system and renin-
and is also a component of cardiac function.
angiotensin
When blood vessels constrict (vasoconstriction) -aldosterone system, obesity, and increased
this→ leads to an increase in SVR. dietary salt intake.
Arterial hypertension
-is the condition of persistent elevation of
systemic blood pressure (BP).
BP is the product of cardiac output and total
peripheral vascular resistance
Hypertension (HTN or HT)
-also known as high blood pressure (HBP)
-is a long-term medical condition in which the
blood pressure in the arteries is persistently
elevated.
When you are stressed → your body sends stress The new approach recommended by the British
hormones - adrenaline and cortisol - into the Hypertension Society is that first-line therapy in
bloodstream. patients over 55 should be a:
These hormones create a temporary spike in -calcium channel blocker or a thiazide-type
blood pressure causing your heart to beat faster diuretic.
and blood vessels to narrow.
For patients who are younger than 55
When the stressful situation is over, blood
-ACE inhibitors are the first-line drug of choice.
pressure goes back to its normal level.
Calcium channel blockers, calcium channel
antagonists or calcium antagonists
-are a group of medications that disrupt the
movement of calcium through calcium channels.
-are used as antihypertensive drugs, i.e., as
Factors that can raise the risk of having essential medications to decrease blood pressure in
hypertension include: patients with hypertension.
-obesity -decrease the excitability of heart muscle and are
-Diabetes therefore used for treating certain types of
-Stress abnormally rapid heart rhythms.
-insufficient intake of potassium, calcium, and
magnesium Examples of calcium channel blockers include:
-lack of physical activity Norvasc (amlodipine)
-chronic alcohol consumption Plendil (felodipine) DynaCirc (isradipine)
Cardene (nicardipine)
STAGE 1 or Prehypertension is 120/80 to 139/89. Procardia XL, Adalat (nifedipine)
STAGE 2 or Mild Hypertension is 140/90 to Cardizem, Dilacor, Tiazac, Diltia XL (diltiazem)
159/99. Sular (Nisoldipine)
STAGE 3 or Moderate Hypertension is 160/100 to Isoptin, Calan, Verelan, Covera-HS (verapamil)
179/109. Calcium channel blocker
STAGE 4 or Severe Hypertension is 180/110 or -drugs reduce the amount of calcium that enters
higher. the smooth muscle in blood vessel walls and
heart muscle. Muscle cells require calcium to
Symptoms of High Blood Pressure contract.
Severe headache.
Fatigue or confusion. Beta blockers
Vision problems. -lower blood pressure in part by decreasing the
Chest pain. rate and force at which the heart pumps blood.
Difficulty breathing.
Thiazide diuretics promote natriuresis and
Irregular heartbeat.
diuresis. Three thiazide diuretics are commonly
Blood in the urine. used:
Pounding in your chest, neck, or ears. -hydrochlorothiazide (HCTZ)
Over time, a lack of sleep could hurt your body's -chlorthalidone
ability to regulate stress hormones -indapamide.
→ leading to high blood pressure.
HCTZ and chlorthalidone are FDA-approved for
Obstructive sleep apnea may be the cause → can clinical use in the management of primary
increase your risk of high blood pressure, as well hypertension.
as heart problems and other health issues. Thiazide diuretics are a type of diuretic (a drug
that increases urine flow)
There are three types of diuretics: Altace (ramipril)
-thiazide diuretics Apresoline (hydralazine)
-loop diuretics Aspirin
-potassium-sparing diuretics Benicar HCT (hydrochlorothiazide and
Each type affects a different part of your kidneys olmesartan) Brilinta (ticagrelor)
and may have different uses, side effects and
Various drugs can be used to treat coronary
precautions.
artery disease including:
Examples of loop diuretics include: Cholesterol-modifying medications....
Bumetanide (Bumex) Aspirin. ...
Ethacrynic acid (Edecrin) Furosemide (Lasix) Beta blockers....
Torsemide (Demadex) Calcium channel blockers.....
Ranolazine.....
Potassium-sparing diuretics
Nitroglycerin....
-are diuretic drugs that do not promote the
Angiotensin-converting enzyme (ACE) inhibitors
secretion of potassium into the urine. -are used
Angiotensin II receptor blockers (ARBS).
as adjunctive therapy, together with other drugs,
in the treatment of hypertension and In general, treatment for heart disease usually
management of congestive heart failure. includes:
Lifestyle changes.
Examples of potassium-sparing diuretics include:
-These include eating a low-fat and low-sodium
Amiloride
diet,
Eplerenone (Inspra)
-getting at least 30 minutes of moderate exercise
Spironolactone (Aldactone, Carospir)
on most days of the week,
Triamterene (Dyrenium)
-quitting smoking, and
Angiotensin-converting-enzyme inhibitors -limiting alcohol intake.
-are a class of medication used primarily for the
The Big 6 Heart Medications
treatment of high blood pressure and heart
Statins to lower LDL cholesterol....
failure.
Aspirin- to prevent blood clots....
-work by causing relaxation of blood vessels as
Clopidogrel to prevent blood clots....
well as a decrease in blood volume which leads to
Warfarin- to prevent blood clots....
lower blood pressure and decreased oxygen
Beta-blockers - to treat heart attack and heart
demand from the heart.
failure and sometimes used to lower blood
Examples of ACE inhibitors include: pressure.....
Benazepril (Lotensin) ACE inhibitors - to treat heart failure and lower
Captopril. blood pressure.
Enalapril (Vasotec)
Fosinopril.
Lisinopril (Prinivil, Zestril)
Moexipril.
Perindopril.
Quinapril (Accupril)
The following are some of the heart disease
medications available
Accupril (quinapril)
Aceon (perindopril)
Adalat (nifedipine)
BODY'S LINE OF DEFENSE Process of Phagocytosis steps
Skin, tears and mucus There are a number of distinct steps in
-are part of the first line of defense in fighting phagocytosis:
infection. Step 1: Activation of the Phagocyte....
-help to protect us against invading pathogens. Step 2: Chemotaxis of Phagocytes (for wandering
macrophages, neutrophils, and eosinophils) ...
You have beneficial bacteria growing on your
Step 3: Attachment of the Phagocyte to the
skin, in your bowel and other places in the body
Microbe or Cell....
(such as the mouth and the gut)
Step 4: Ingestion of the Microbe or Cell by the
→stop other harmful bacteria from taking over.
Phagocyte.
These are three lines of defense
Process of Inflammation steps
First being outer barriers like skin
occurs in four distinct phases:
Second being non-specific immune cells like
(1) initial tissue damage and local activation of
macrophages and dendritic cells
inflammatory factors,
Third line of defense being the specific immune
(2) inflammation-driven breakdown of the blood-
system made of lymphocytes like B- and T- cells,
brain barrier,
which are activated mostly by dendritic cells
(3) recruitment of circulating inflammatory cells
and subsequent secondary immunopathology,
Dendritic cells (DCs)
and
-are antigen-presenting cells (also known as
(4) engagement of tissue repair
accessory cells) of the mammalian immune
system.
The four cardinal signs of inflammation are:
Their main function:
Redness (Latin rubor)
-to process antigen material and present it on the
Heat (calor)
cell surface to the T cells of the immune system.
Swelling (tumor)
-act as messengers between the innate and the
Pain (dolor)
adaptive immune systems.
Subacute inflammation
-is the period between acute and chronic
inflammation and may last 2 to 6 weeks.

Chronic inflammation
-is also referred to as slow, long-term
inflammation lasting for prolonged periods of
Process of Phagocytosis steps several months to years
There are a number of distinct steps involved
Erythrocyte sediment
-C-reactive protein (CRP) and
-Plasma viscosity (PV) blood tests
=are commonly used to detect increase in protein
in the blood. -used as markers of inflammation.
Symptoms of Chronic Inflammation
Body pain, arthralgia, myalgia.
Chronic fatigue and insomnia.
Depression, anxiety and mood disorders
Gastrointestinal complications like constipation,
diarrhea, and acid reflux.
Weight gain or weight loss. Antigen-antibody binding
Frequent infections. The antigens and antibodies combine by a
Skin rashes, such as eczema or psoriasis. process called agglutination.
Nose-Excessive mucus production (ie, always
-a reaction in which particles (as red blood cells or
needing to clear your throat or blow your
bacteria) suspended in a liquid collect into clumps
nose)
and which occurs especially as a serological
response to a specific antibody.
PRODUCTION OF LYMPH
-It forms when tissue fluids/blood plasma (mostly It is the fundamental reaction in the body by
water, with proteins and other dissolved which the body is protected from complex foreign
substances) drain into the lymphatic system. molecules, such as pathogens and their chemical
It contains a high number of lymphocytes (white toxins,
cells that fight infection).
The specificity of the binding is due to specific
It contains both red tissue, and white lymphatic
chemical constitution of each antibody.
tissue

Lymph (from Latin, lympha meaning "water")

-is the fluid that flows through the lymphatic
system, a system composed of:
lymph vessels (channels)
intervening lymph nodes

Function: like the venous system) Antigen

-to return fluid from the tissues to the central -any substance (such as an immunogen or a
circulation. hapten) foreign to the body that evokes an
immune response either alone or after forming a
How does lymphatic system drain excess fluid? complex with a larger molecule (such as a
Drain excess fluid: as the blood circulates through protein) and that is capable of binding with a
the body's tissues, it leaves behind waste product (such as an antibody or T cell) of the
products such as proteins and fluids. immune response

Excess fluid is drained through capillaries and into

the lymphatic system where it is filtered and
returned to the blood.

Antibody
-a blood protein produced in response to and
counteracting a specific antigen.
Antibodies combine chemically with substances
which the body recognizes as alien, such as
bacteria, viruses, and foreign substances in the
blood.
Role of antibody that tend to damage the tissues and
Antibodies, also known as immunoglobulins, are organs. The capability is called immunity.
Y-shaped proteins that are produced by Natural and acquired immunity
the immune system to help stop intruders from
Natural Immunity
harming the body.
1. Is a nonspecific immunity present at birth
When an intruder enters the body, the immune
2. responses to a foreign invader are very similar
system springs into action.
from one encounter to the next.
These invaders, which are called antigens, can be
viruses, bacteria, or other chemicals. Acquired Immunity
1. Specific immunity develops after birth
2. Increases in intensity with repeated exposure
to the invading agent.

Natural (Innate immunity)

 The basis of natural defense mechanisms
is the ability to distinguish between friend
Process of phagocytosis and foe or self and non-self.
There are a number of distinct steps involved in  Such natural mechanisms include
phagocytosis: 1. Physical and chemical barriers
Step 1: Activation of the Phagocyte.... - Skin and mucous membrane
Step 2: Chemotaxis of Phagocytes (for wandering Antimicrobial substance in body secretions
macrophages, neutrophils, and eosinophils)... 2. The action of WBCS
Step 3: Attachment of the Phagocyte to the 3. Inflammatory response.
Microbe or Cell....
Step 4: Ingestion of the Microbe or Cell by the Physical and chemical barriers
Phagocyte. Skin and mucous membrane
 When skin and mucous membrane are
Process of Immunity intact and healthy they provide a physical
barrier to invading microbes.
Objectives
1. Define Immunity  Sebum and sweat secreted on to the skin
2. Classify immunity surface contains antibacterial and
3. Explain mechanisms of natural and acquired antifungal substances.
immunity  Hairs in the nose acts as a coarse filter.
4. Discuss the response  One way flow of urine from the bladder
microorganisms. during micturation
to invasion by
5. Describe abnormal immune response Antimicrobial substance in body secretions
6. Discuss nursing process related, to immune 1. Hydrochloric acid in gastric juice
system 2. Lysosomes
3. Saliva
Immunity 4. Immunoglobulin in nasal secretions and saliva
 The term immunity refers to the body's 5. Interferons
specific protective response to an invading
foreign agent or organism.
 The human body has the ability to resist
almost all types of organisms or toxins
White blood cell action Response to invasion
 WBCs participate in both the natural and When the body is invaded or attacked by bacteria,
the acquired immune responses. viruses, or other pathogens, it has three means of
 Granulocytes include neutrophils, defending itself:
eosinophils and basophils. 1. The phagocytic immune response
 Nongranular leucocytes include 2. The humoral or antibody immune response
monocytes or macrophages and 3. The cellular immune response
lymphocytes.
 Lymphocytes consisting of B cells and T Humoral and cellular immune response
cells, play major role in humoral and cell  A second response, the humoral immune
mediated immune responses. (sometimes called the antibody response),
begins with the B lymphocytes, which can
Inflammatory response transform themselves into plasma cells
 Major function of the natural (non specific that manufacture antibodies.
or innate) immune system.  The third mechanism of defense, the
 Chemical mediators assist this response by cellular immune response, also involves
minimizing blood loss, walling off the the T lymphocytes, which can turn into
invading organism, activating phagocytes special cytotoxic (or Killer) T cells that can
and promoting formation of fibrous scar attack the pathogens themselves.
tissue and regeneration of injured tissue
Humoral immune response cont...
Dysfunction of the natural immune system 5. Some of the lymphoblasts further differentiate
 Immunodeficiency to form plasmablasts, which are precursor of
 Persistent inflammatory response plasma cells.
 Autoimmune bodies
6. The mature plasma cells then produces gamma
Acquired immunity globulin antibodies.
 Usually develops as a result of prior 7. Other B lymphocytes differentiate into B-
exposure to immunization an antigen memory for the lymphocyte clones with a
through antigen.
contracting a disease.
 Weeks or months after exposure to the Antibodies
disease or vaccine, the body produces an The antibodies can inactivate the invading agent
immune response that is sufficient to in one of the several ways, as follows:
defend against the disease upon re- 1. Agglutination: in which the multiple large
exposure to it. particles with antigens on their surface.
2. Precipitation: in which the molecular complex
Active and passive immunity of soluble antigen and antibody becomes so large
1. Active immunity: Active immunity means that that it is rendered insoluble and precipitates.
the individual has responded to an antigen and 3. Neutralization: in which the antibodies cover
produced his own antibodies, lymphocytes are the toxic sites of the antigenic agent.
activated and the memory cells formed provide 4. Lysis: in which some potent antibodies are
long lasting resistance. occasionally capable of directly attacking
2. Passive immunity: In passive immunity the membranes of cellular agents and thereby cause
individual is given antibodies produced by rupture of the agent.
someone else
 IgE
IgE (0.004% of immunoglobulins)
 Appears in serums
 Takes part in allergic and hypersensitivity
of
 reactions
 Combats parasitic infections.

Complement system
IgG Complement mediated immune response are
IgG (75% of total immunoglobulin) summarized as:
 Appears in serum and tissues (interstitial 1. Cytolysis: Lysis and destruction of cell
fluid) membranes of body cells or pathogens.
 Assumes a major role in bloodborne and 2. Isosonization: Targeting of the antigen so that
tissue infections. it can be easily engulfed and digested by the
 Activates the complement system. macrophages and other phagocytic cells.
 Enhances phagocytosis 3. Chemotaxis: chemical attraction of neutrophils
 Crosses the placenta and phagocytic cells to the antigen.
IgA 4. Anaphylaxis: activation of mast cells and
IgA (15% of total immunoglobulins) basophils with release of inflammatory mediators
 Appears in body fluids (blood, saliva, that produce smooth muscle contraction and
tears, breast milk, and pulmonary, increased vascular permeability.
gastrointestinal, prostatic and vaginal
secretions). Abnormal immune reactions
 Protection against respiratory, 1. Antibody mediated
gastrointestinal and genitourinary 2. Cell-mediated
infections. 3. Mixed antibody
 Prevents absorption of antigens from
food. Antibody mediated reactions
 Passes to neonate in breast milk for  These occur within minutes of exposure to
protection. an allergen (antigen).
 The most common manifestations of this
IgM type of allergic reaction include: food
IgM (10% of total immunoglobulins) allergies, childhood eczema, hay fever,
 Appears mostly in intravascular serum extrinsic asthma.
 Appears as the first immunoglobulin  In these conditions the released chemicals
produced in response to bacterial and viral act locally, causing different effects that
infections. depend on the site.
 Activates the complement system.
Acute systemic anaphylaxis (anaphylactic shock)
IgD  It is caused by the entry of an allergen into
IgD (0.2% of immunoglobulins) the blood e.g. snake venom, injectable
penicillin.
 Appears in small amounts in serum
 There are profound effects throughout the
 Possibly influences B-lymphocytes
body, including generalized vasodilatation,
differentiation, but role is unclear.
 leading to severe hypotension and Innate immunity
contraction of smooth muscle in the -refers to nonspecific defense mechanisms that
respiratory tract, causing acute breathing come into play immediately or within hours of an
difficulties. antigen's appearance in the body.
These mechanisms include physical barriers such
Cell mediated reactions
as skin, chemicals in the blood, and immune
The antigen include:
system cells that attack foreign cells in the body.
1. Intracellular microbes, e.g. tuberculosis,
measles, mumps. those causing
Lupus
2. Some vaccines, e.g. against smallpox.
-is a disease that occurs when your body's
3. Some metals and compounds that combine
immune system attacks your own tissues and
with protein in the skin and cause allergic contact
organs (autoimmune disease).
dermatitis.
Inflammation caused by lupus can affect many
Mixed reactions different body systems - including your joints,
Autoimmune diseases: skin, kidneys, blood cells, brain, heart and lungs.
 Tissue damage and signs of disease as the
Lupus can be difficult to diagnose because its
body fails to recognize its own tissues.
signs and symptoms often mimic those of other
Destruction of the body's own cells may
ailments.
be either humoral or cell-mediated.
 Thyroid- Hashimoto's thyroiditis The most distinctive sign of lupus - a facial rash
 Stomach- Addisonian pernicious anemia that resembles the wings of a butterfly unfolding
 Cortex of the adrenal gland- addison's across both cheeks-occurs in many but not all
disease. cases of lupus.
 Pancreas-type I diabetes mellitus
Some people are born with a tendency toward
Organ transplantation and rejection developing lupus, which may be triggered by:
Infections
SLE (Systemic lupus erythematosus) certain drugs
-is characterized by a global loss of self-tolerance even sunlight.
with activation of autoreactive T and B cells
While there's no cure for lupus, treatments can
→leading to production of pathogenic
help control symptoms.
autoantibodies and tissue injury.
Innate immune mechanisms are necessary for the
Symptoms
aberrant adaptive immune responses in SLE
No two cases of lupus are exactly alike.

Signs and symptoms may come on suddenly or

develop slowly, may be mild or severe, and may
be temporary or permanent.

Most people with lupus have mild disease

characterized by episodes - called flares - when
signs and symptoms get worse for a while, then
improve or even disappear completely for a time.
The signs and symptoms of lupus that you
experience will depend on which body systems
are affected by the disease.
The most common signs and symptoms include:
Fatigue
Fever
Joint pain, stiffness and swelling
Butterfly-shaped rash on the face that covers the
cheeks and bridge of the nose or rashes Raynaud's phenomenon
elsewhere on the body -is a problem that causes decreased blood flow to
Skin lesions that appear or worsen with sun the fingers.
exposure In some cases, it also causes less blood flow to
Fingers and toes that turn white or blue when the ears, toes, nipples, knees, or nose.
exposed to cold or during stressful periods →This happens due to spasms of blood vessels in
Shortness of breath. those areas.
Chest pain →The spasms happen in response to cold, stress,
Dry eyes or emotional upset.
Headaches, confusion and memory loss

Causes
As an autoimmune disease, lupus occurs when
your immune system attacks healthy tissue in
your body.
It's likely that lupus results from a combination of
your genetics and your environment.
It appears that people with an inherited
predisposition for lupus may develop the disease
when they come into contact with something in
the environment that can trigger lupus.
The cause of lupus in most cases, however, is
unknown

Lupus
-is a long-term autoimmune disease in which the Four different types of lupus
body's immune system becomes hyperactive and Systemic lupus erythematosus
attacks normal, healthy tissue. -is the most common form of lupus-it's what most
Symptoms include: people mean when they refer to "lupus."
-inflammation -swelling Cutaneous lupus erythematosus
-damage to the joints -skin -form of lupus is limited to the skin and can cause
-kidneys many types of rashes and lesions.
-blood
-heart Drug-induced lupus erythematosus
-lungs
Neonatal lupus Complications
Inflammation caused by lupus can affect many
areas of your body, including your:
Kidneys.
Lupus can cause serious kidney damage, and
kidney failure is one of the leading causes of
death among people with lupus.
Brain and central nervous system.
If your brain is affected by lupus, you may
experience headaches, dizziness, behavior
Some potential triggers include: changes, vision problems, and even strokes or
seizures.
Sunlight. Many people with lupus experience memory
-Exposure to the sun may bring on lupus skin problems and may have difficulty expressing their
lesions or trigger an internal response in thoughts.
susceptible people.
Infections. Blood and blood vessels.
-Having an infection can initiate lupus or cause a -Lupus may lead to blood problems, including a
relapse in some people. reduced number of healthy red blood cells
(anemia) and an increased risk of bleeding or
Medications. blood clotting.
-Lupus can be triggered by certain types of blood It can also cause inflammation of the blood
pressure medications, anti-seizure medications vessels.
and antibiotics.
Lungs.
People who have drug-induced lupus usually get -Having lupus increases your chances of
better when they stop taking the medication. developing an inflammation of the chest cavity
Rarely, symptoms may persist even after the drug lining, which can make breathing painful.
is stopped. Bleeding into lungs and pneumonia also are
possible.
Risk factors
Factors that may increase your risk of lupus Heart.
include: -Lupus can cause inflammation of your heart
muscle, your arteries or heart membrane. The
Your sex. risk of cardiovascular disease and heart attacks
-Lupus is more common in women. increases greatly as well.
Age.
-Although lupus affects people of all ages, it's Bone tissue death.
most often diagnosed between the ages of 15 -This occurs when the blood supply to a bone
and 45. declines, often leading to tiny breaks in the bone
and eventually to the bone's collapse.
Race.
-Lupus is more common in African Americans, Pregnancy complications.
Hispanics and Asian Americans. Women with lupus have an increased risk of
miscarriage.
Lupus increases the risk of high blood pressure Urinalysis.
during pregnancy and preterm birth. To reduce An examination of a sample of your urine may
the risk of these complications, doctors often show an increased protein level or red blood cells
recommend delaying pregnancy until your in the urine, which may occur if lupus has
disease has been under control for at least six affected your kidneys.
months.
Antinuclear antibody (ANA) test.
A positive test for the presence of these
Diagnosis
antibodies-produced by your immune system -
-lupus is difficult because signs and symptoms
indicates a stimulated immune system.
vary considerably from person to person. Signs
and symptoms of lupus may change over time While most people with lupus have a positive
and overlap with those of many other disorders. ANA test, most people with a positive ANA do
not have lupus.
No one test can diagnose lupus.
If you test positive for ANA, your doctor may
The combination of blood and urine tests, signs
advise more-specific antibody testing.
and symptoms, and physical examination
findings →→ leads to the diagnosis.
Imaging tests
If your doctor suspects that lupus is affecting your
Laboratory tests
lungs or heart, he or she may suggest:
Blood and urine tests may include:
Chest X-ray.
Complete blood count.
-An image of your chest may reveal abnormal
-This test measures the number of red blood cells,
shadows that suggest fluid or inflammation in
white blood cells and platelets as well as
your lungs.
the amount of hemoglobin, a protein in red blood
cells. Echocardiogram.
Results may indicate you have anemia, which -This test uses sound waves to produce real-time
commonly occurs in lupus. images of your beating heart.
A low white blood cell or platelet count may It can check for problems with your valves and
occur in lupus as well. other portions of your heart.

Erythrocyte sedimentation rate. Biopsy

-This blood test determines the rate at which red Lupus can harm your kidneys in many different
blood cells settle to the bottom of a tube in an ways, and treatments can vary, depending on the
hour. type of damage that occurs.
A faster than normal rate may indicate a systemic
In some cases, it's necessary to test a small
disease, such as lupus.
sample of kidney tissue to determine what the
The sedimentation rate isn't specific for any one best treatment might be.
disease. The sample can be obtained with a needle or
It may be elevated if you have lupus, an infection, through a small incision.
another inflammatory condition or
Skin biopsy is sometimes performed to confirm a
cancer.
diagnosis of lupus affecting the skin.
Kidney and liver assessment.
-Blood tests can assess how well your kidneys and Treatment
liver are functioning. Treatment for lupus depends on your signs and
Lupus can affect these organs. symptoms.
Determining whether you should be treated and The risk of side effects increases with higher
what medications to use requires a careful doses and longer term therapy.
discussion of the benefits and risks with your
doctor. Immunosuppressants.
Drugs that suppress the immune system may be
As signs and symptoms flare and subside, doctor
helpful in serious cases of lupus.
may find the need to change medications or
dosages. Examples include azathioprine (Imuran, Azasan),
mycophenolate (Cellcept), methotrexate (Trexall,
The medications most commonly used to control Xatmep, others), cyclosporine (Sandimmune,
lupus include: Neoral, Gengraf) and leflunomide (Arava).
Nonsteroidal anti-inflammatory drugs (NSAIDs).
-Over-the-counter NSAIDs, such as naproxen
Potential side effects may include:
sodium (Aleve) and ibuprofen (Advil, Motrin IB,
-increased risk of infection
others), may be used to treat pain, swelling and
-liver damage
fever associated with lupus.
-decreased fertility
Stronger NSAIDs are available by prescription.
-increased risk of cancer.
Side effects of NSAIDs may include stomach
bleeding, kidney problems and an increased risk Biologics.
of heart problems. A different type of medication, belimumab
(Benlysta) administered intravenously, also
Antimalarial drugs. reduces lupus symptoms in some people.
-Medications commonly used to treat malaria,
Side effects include nausea, diarrhea and
such as hydroxychloroquine (Plaquenil),
infections. Rarely, worsening of depression can
affect the immune system and can help decrease
occur.
the risk of lupus flares.
Rituximab (Rituxan, Truxima) may be beneficial
Side effects can include:
for some people in whom other medications
-stomach upset
haven't helped.
very rarely, damage to the retina of the eye.
Regular eye exams are recommended when Side effects include allergic reaction to the
taking these medications. intravenous infusion and infections.
In clinical trials, voclosporin has been shown to
Corticosteroids. be effective in treating lupus.
Prednisone and other types of corticosteroids can
counter the inflammation of lupus. High doses of
steroids such as methylprednisolone (Medrol) are
often used to control serious disease that involves
the kidneys and brain.
Side effects include:
weight gain
easy bruising
thinning bones
high blood pressure
Diabetes
increased risk of infection.
Pathophysiology of HIV/AIDS These drugs have reduced AIDS deaths in many
-commonly transmitted via unprotected sexual developed nations.
activity, blood transfusions, hypodermic needles,
and from mother to child. The symptoms of HIV and AIDS vary depending
Upon acquisition of the virus, the virus replicates on the phase of infection
inside and kills T helper cells → which are Primary infection (Acute HMV)
required for almost all adaptive immune Some people infected by HIV develop a flu-like
responses. within two to four weeks after the virus enters
the body
Pathophysiology of HIV/AIDS This illness, known as primary (acute) HIV
A retrovirus unknown until early 1980s infection, may last for a few weeks.
1. Cannot replicate outside of living host cells
Possible signs and symptoms include
2. Contains only RNA; no DNA
Fever
a. Destroys the body's ability to fight infections.
Headache
4. Infects CD4 cells - the primary target of HIV
Muscle aches and joint pain
Infection
Rash
Sore throat and painful mouth sores
Swollen lymph glands, mainly on the neck
Diarrhea
Weight loss
Cough

Symptoms can be so mild that you might not even

notice them.
However, the amount of virus in your
Acquired Immuno Deficiency Syndrome (AIDS) bloodstream (viral load) is quite high at this time.
-is a chronic, potentially life-threatening condition
As a result, the infection spreads more easily
caused by the human immunodeficiency virus
during primary infection than during the next
(HIV).
stage.
By damaging your immune system → HIV
interferes with your body's ability to fight Symptomatic HIV infection
infection and disease. As the virus continues to multiply and destroy
your immune cells- the cells in your body that
HIV help fight off germs - you may develop mild
sexually transmitted infection (STI). infections or chronic signs and symptoms such as:
-can also be spread by contact with infected Fever
blood or from mother to child during pregnancy, Fatigue
childbirth or breast-feeding. Swollen lymph nodes - often one of the first signs
of HIV infection
Without medication, it may take years before HIV
Diarrhea
weakens your immune system to the point that
Weight loss
you have AIDS.
Oral yeast infection (thrush)
There's no cure for HIV/AIDS, but medications can Shingles (herpes zoster)
dramatically slow the progression of the disease. Pneumonia
Progression to AIDS Sexual activity:
With better antiviral treatments→→most people Heterosexual and homosexual activity is the most
with HIV today don't develop AIDS. common mechanism of transmission of HIV.
Untreated → HIV typically turns into AIDS in HIV is present in seminal fluid as well as vaginal
about 8 to 10 years. and cervical secretions.
When AIDS occurs→→your immune system has During or following intercourse → the viral
been severely damaged. particles penetrate tiny ulcerations in the vaginal,
rectal, penile, or urethral mucosa.
=more likely to develop opportunistic infections
or opportunistic cancers- diseases that wouldn't
Women are 20x more likely than men to get HIV
usually cause illness in a person with a healthy
with vaginal intercourse
immune system.
-likely because of the prolonged exposure of the
vagina, cervix, and uterus, to seminal fluid.
The signs and symptoms of some of these
infections may include: Receptive anal intercourse appears to increase
Sweats the risk of transmission
Chills =likely secondary to mucosal trauma of the thin
Recurring fever rectal wall.
Chronic diarrhea
Swollen lymph glands Sexually transmitted diseases also increase the
Persistent white spots or unusual lesions on your risk of transmission.
tongue or in your mouth Organisms such as: Treponema pallidum herpes
Persistent, unexplained fatigue simplex virus Chlamydia trachomatis
Weakness Neisseria gonorrhoeae
Weight loss cause mucosal erosions and may even increase
Skin rashes or bumps the concentration of HIV in semen and vaginal
fluids.
Causes
(Inflammation of the epididymis, urethra, and
HIV is caused by a virus.
vaginal mucosa results in an increase in HIV laden
It can spread through sexual contact or blood, or
macrophages and lymphocytes.)
from mother to child during pregnancy, childbirth
or breast-feeding. Oral sex is much less likely to result in
transmission.
The disease is transmitted in 2 patterns:
1) In the Americas and Europe 90% of cases are 2) Blood product transfusion:
among homosexuals and IV drug users resulting HIV can be transmitted in whole blood,
in more infected men than women. concentrated red blood cells, platelets, white
2) In developing areas, namely sub-Saharan blood cells, concentrated clotting factors, and
Africa, spread is heterosexual with equal male plasma.
and female infection.
Gamma-globulin has not been associated with
The HIV virus is spread by the parenteral route, transmission.
much like hepatitis B virus.
To reduce the risk of transmission via blood
products → blood donors are screened for self
reported risk factors and serologic markers of HIV
infection.
The latter includes screening for antibodies to Cell Infection
HIV-1 and HIV-2 (by ELISA) and for p24 antigen. Once the HIV virion is in the bloodstream, its gp
= reduced the risk of blood product transmission. 160
(composed at gp 120 and gp 41) glycoproteins
3) Intravenous drug use with needle sharing: →bind to the CD4 receptor on target cells. This
This has led to growing numbers of infected CD4 receptor is present in high concentration on
persons. T-helper lymphocytes.
4) Transplacental viral spread from mother to (referred as CD4+ T-helper cells).
fetus: Other cells that possess CD4 receptors in lower
The rate of transmission is about 30%, and concentrations and which can become infected
infection occurs trans placentally, during delivery, are macrophages, monocytes, and central
and perinatally. nervous system dendritic cells.
Following HIV binding to the CD4 receptor, the
5) Note for students and health care providers:
viral envelope fuses with the infected host Cell-
The risk of contracting HIV from a stick with a
allowing capsid entry.
needle, contaminated with HIV infected blood, is
3 out of a thousand (0.3%).
Capsid is the protein shell of a virus, enclosing its
The risk is much lower for accidental body fluid genetic material
contact with broken skin.
There is virtually no risk in touching an HIV
infected patient, unless there is contact with
blood or body fluid.

The risk goes up if the injury is:

deep, the needle was in a patient's artery or vein,
or
Had blood visible on it, or if the patient has a high
viral load
To put the risk of transmission of HIV by needle
Part of the mystery of how HIV binds to the CD4
stick (0.3% transmission risk)
receptor is as follows.
Comparison (hepatitis) There are two cell surface proteins:
The risk of transmission of Hepatitis B virus after -Fusin
a needle stick from a patient who is Hepatitis B e -CKRS
antigen positive is about 30%, and for Hepatitis C = that are produced by T-lymphocytes and
virus is about 3%. macrophages.
They serve as co-factors with the CD4 molecule
6) Epidemiologic evidence indicates that the virus
for binding of HIV to lymphocytes and
is NOT spread by mosquito bites or casual contact
macrophages.
(kissing, sharing food).
There is NO evidence that saliva, urine, tears, or
Patients who fail to produce normal levels of
sweat, can transmit the virus.
CKR5 proteins → appear to be resistant to HIV
infection, and certain lymphocyte derived
proteins (RANTES, MIP1-alpha, and MIP1-Beta)
that bind to CKR5 →appear to inhibit HIV An acute viral illness like mononucleosis (fever,
infection. malaise, lymphadenopathy, pharyngitis, etc.)
develops in 80% about 1 month after initial
This is how new classes of drugs that block fusin
exposure.
and CKRS!
There are high levels of blood-borne HIV (viremia)
The viral RNA is reverse transcribed into DNA in at this stage → viruses spread to infect lymph
the cytoplasm→ nodes and macrophages.
Double stranded DNA is formed and transported
An HIV-specific immune response arises resulting
into the nucleus where integration into the host
in decreased viremia and resolution of the above
DNA occurs integrated DNA may lie latent or may
symptoms.
activate to orchestrate viral replication.
There is some evidence that certain infections, However, HIV replication continues in lymph
such as with tuberculosis, Pneumocystis carinii nodes and peripheral blood
pneumonia (PCP), cytomegalovirus, herpes,
Mycoplasma or Immunizations → will activate T 2) A clinical latency follows for a median of 8
cells and may promote viral replication within years during which there are no symptoms of
the T-cells. AIDS, although some patients develop a dramatic
Stimulation of Tcell → results in production of generalized lymphadenopathy (possibly
proteins that bind to the secondary to an aggressive immune attack against
HIV LTR → promoting viral transcription. HIV harbored in the lymph nodes).
This is not a true viral latency without viral
following viral replication → the new capsids form
replication;
around the new RNA dimer → virion buds
HIV continues to replicate in the lymphoid tissue
through the host cell membrane->stealing
→ there is a steady gradual destruction of CD4 T-
portions of the membrane to use as an
lymphocytes (helper) cells.
envelope → leaving the T-cell dead.
CD4+ T-helper cells are the number one target of
Immunology and Pathogenesis HIV. The virus reproduces in these cells and
Following initial infection->HIV can begin destroys them.
replication Immediately resulting in rapid
progression to AIDS, or there can be a chronic Toward the end of the 8 years, patients are more
latent course. susceptible to bacterial and skin infections, and
can develop constitutional (systemic) symptoms
The former, most common pattern occurs in 3
such as:
stages starting with initial
fever,
Infection →marked by an acute mononucleosis-
weight loss
like viral illness.
night sweats
This progresses for a variable number of years adenopathy
(median 8 but range of less than 1 to greater than
20) of disease-free latency. 3) AIDS develops for a median of 2 years
followed by death.
After AIDS develops most patients die within 2
AIDS is now defined as having a CD4 T
years if they do not receive effective antiretroviral
lymphocyte count of less than 200 (with serologic
therapy
evidence of HIV infection such as a positive ELISA
or Western blot test)
-and/or one of many AIDS-defining opportunistic Viral Load
infections, which are infections that usually only CD4 counts are used to:
patients with AIDS develop. -determine severity of HIV infection, -risk of
opportunistic infection,
These include:
-prognosis
-Candida esophagitis,
-response to anti-viral therapy.
-Pneumocystis carinii pneumonia
-Malignancy Kaposi's sarcoma, and many others. Measure plasma HIV RNA by the polymerase
chain reaction (PCR) or branched chain DNA
The clinical course of HIV infection (acute viral assay.
illness, clinical latency, and AIDS)→CD4+ T-cells There is mounting evidence that higher plasma
decline over time, and the opportunistic HIV RNA levels (viral load) correlate with a greater
infections that develop at specific CD4 T cell risk of →opportunistic infection, progression to
counts. AIDS, and risk of death (Mellors, 1996; Galetto-
Lacour, 1996).
1) Normal CD4+ T-cell counts are 1000 cells/μl
blood. CD4 counts are still the best predictor of a
In HIV-infected persons the count declines by patient's current risk for particular opportunis
about 60 cells/ml blood/year. infections.

2) CD4+ T-cell count of 400-200 (about 7 years): Mechanism of T-Cell Death

Constitutional symptoms (weight loss, fever, night The CD4 receptor appears to be involved in T-cell
sweats, adenopathy) develop as well as annoying death.
skin infections, such as severe athlete's foot, oral
Monocytes and macrophages which possess
thrush (Candida albicans), and herpes zoster.
lower CD4 receptor concentrations → are not
Bacterial infections→Mycobacterium tuberculosis destroyed as extensively as are T-cells.
become more common as CD4 counts drop below
When a T-helper cell is infected, and the virus
400!!
produces its structural proteins, gp 160
(composed of gp 120 and gp 41 is integrated into
3) CD4+ T-cell count less than 200 (about 8
the T-helper cell cytoplasmic membrane.
years):
As the immune system fails, the serious The virion will bud at the site of gp 160
opportunistic killers set in, such as: insertion→ stealing this portion of the membrane
form its envelope.
Pneumocystis carinii pneumonia
Cryptococcus neoformans
Viral envelope
Toxoplasma gondii
=is the outermost layer of many types of viruses.
=It protects the genetic material in their life-cycle
4) CD4+ T-cell count less than 50:
when traveling between host cells.
At this level the immune system is almost
Not all viruses have envelopes
completely down.

Mycobacterium avium-intracellulare → normally

only causing infection in birds causes
disseminated disease in the AIDS patients.
Cytomegalovirus infections also rise as the count
moves from 50 to zero.
Three mechanisms of T-cell death have been This is clinically significant in 2 ways:
observed: 1) Monocytes and macrophages serve as
1) When the virion is budding, the gp 160 (in the reservoirs for HIV as it replicates, protected within
Tcell membrane) may bind to adjacent CD4 these cells from the immune system
receptors on the same T-helper cell
2) These cells migrate across the blood-brain
membrane→tearing the T-cell membrane and
barrier, carrying HIV to the central nervous
destroying the cell.
system → causes brain disease, and the
predominant cell type harboring HIV in the
2) A second phenomenon occurs between
central nervous system is the monocyte-
infected cells and noninfected CD4 cells. The gp
macrophage line.
160 in the infected cells binds to other CD4 T-
helper cell→resulting in cell-to-cell fusion.
BIG PICTURE:
One infected cell can fuse with as many as 500 HIV infection diminishes CD4 T-lymphocyte
uninfected CD4+ T-helper cells → forming (helper) cell numbers and function.
multinucleated giant cells.
The CD4 T-helper cells are involved in all immune
Multinucleated giant cells (MNGCs) are a special responses. So all immune cells have some kind of
class of giant cell formed by the fusion of altered function.
monocytes/macrophages abundantly found in
As T-cell numbers decline the host becomes
human tissues
susceptible to unusual infections and
malignancies that normally are easily controlled
3) Gp 160 in the T-cell membrane may mark the
by an intact immune system.
cell as non- self → resulting in autoimmune T-cell
destruction by cytotoxic CD8 T lymphocytes
ACQUIRED IMMUNODEFICIENCY SYNDROME
HIV probably also kills T-cells directly → by
(AIDS)
inhibiting host cell protein synthesis
-is an extremely complex disease. To better
understand this complexity, consider 2 processes
Multinucleated giant cells:
that occur.
This T-cell to T-cell fusion
The HIV virus causes:
→ allows the virus to pass from an infected cell to
1) direct viral disease
an uninfected cell without contacting the blood.
2) disease secondary to the immunodeficiency
This may protect the virus from circulating
state.
antibodies.
The most 1) Direct viral disease
important dysfunction that occurs is Constitutional (widespread body) symptoms
diminished ability to produce antibodies in Neurologic damage
response to new antigens or immunization. 2) Disease secondary to the immunodeficiency
This is very serious in infants with AIDS because state. Failure of the immune surveillance system
they cannot develop humoral immunity to the that prevents malignancies Secondary infections
vast number of new antigens they are exposed to. by pathogens and normal flora (opportunistic
infections)
Monocytes and macrophages:
HIV infects these cells and actively divides within
them. However, these cells are not destroyed by
HIV.
Constitutional Illness HHV-8 DNA sequences have been found in
AIDS patients suffer from: Kaposi's sarcoma, and antibodies to HHV-8 are
-night sweats -Fevers found in high concentrations in most patients
-enlarged (80%) with Kaposi's sarcoma and in 35% of
-lymph nodes homosexual HIV positive men (Moore, 1995;
-severe weight loss Kedes, 1996; Gao, 1996).

The weight loss is often referred to as the wasting

Kaposi's sarcoma
syndrome.
The lesions are red to purple, plaques or nodules,
and arise on the skin all over the body.
Neurologic Disease
The course can range from nonaggressive disease,
The HIV virus is carried to the central nervous
with limited spread and only skin involvement, to
system by the monocyte- macrophage cells.
an aggressive process involving skin, lymph
It is unclear at this time whether the neuronal nodes, lungs, and GI tract.
damage is caused by the inhibition of neuronal
growth by the HIV envelope proteins or an Opportunistic Infections
autoimmune damage caused by the infected The most common manifestation of AIDS is the
monocyte-macrophages themselves. secondary infection by opportunists.
These are bugs that are normally pushovers to
Many patients with HIV infection suffer from
the intact immune system but wreak havoc in the
some form of neurological dysfunction. The brain
absence of T-helper defenses
can suffer diffuse damage (encephalopathy)→
resulting in a progressive decline in cognitive
Bacterial Infections
function → referred to as the AIDS dementia
AIDS patients often have many permanent
complex.
indwelling intravenous lines or are in the hospital
Meningeal infection results in → aseptic
with central venous lines.
meningitis.
These serve as entry points for bacteremia caused
spinal cord can become infected → resulting in
by Staphylococcus aureus or Staphylococcus
myelopathy
epidermidis.
peripheral nerve involvement→ results in a
The poorly functioning B-cells and their impaired
neuropathy
humoral
immunity → result in more infections with
Malignancies
encapsulated organisms such as:
AIDS patients suffer from a high incidence of B-
Haemophilus influenzae and
cell lymphoma, often presenting as a brain
Streptococcus pneumoniae.
mass.
Half of B-cell lymphomas in AIDS patients are
Mycobacterium tuberculosis:
found to contain Epstein-Barr virus DNA. Another
AIDS patients have a higher chance of
common AIDS associated malignancy is Kaposi's
tuberculosis reactivation (about 10% chance per
sarcoma.
year).
Most cases of Kaposi's sarcoma (96%) occur in
homosexual men, which suggests that there may
be a co-factor, which appears to be a new herpes
virus called HHV-8.
Mycobacterium avium-intracellulare (MAI): Histoplasma capsulatum and Coccidioides
This atypical mycobacterium, also called immitis:
Mycobacterium avium-complex (MAC), can be These fungi produce disseminated disease inAIDS
isolated from many sites (GI tract, liver, bone patients, infecting meninges, lungs, skin, and
marrow, lymph nodes, lungs, blood) in infected other areas.
patients.
Epstein-Barr virus, another herpes family virus, is
It causes a smoldering, wasting disease
thought to cause oral hairy leukoplakia (OHL).
characterized by fever, night sweats, weight loss,
and often diarrhea (GI tract infection) and OHL usually develops when CD4 counts are <400
elevated liver function tests. and is characterized by white hairlike projections
arising from the side of the tongue.
Fungal Infections
This is differentiated from Candidal thrush by the
Candida albicans: This yeast is very common in
fact that OHL will not rub off with a tongue blade.
HIV-infected patients.
It causes oral thrush and esophagitis.
Protozoal Infections
Thrush looks like white plaques on the oral Pneumocystis carinii pneumonia (PCP):
mucosa and when scraped off with a tongue This is the most common opportunistic infection.
blade leaves a red bleeding base. Without prophylactic treatment there is a 15%
chance each year of infection when the CD4+ T-
Cryptococcus neoformans: This fungus causes a cell count is below 200.
meningitis in about 10% of AIDS patients. Fever,
AIDS patients who develop PCP have cough and
nausea, and vomiting may hint at cryptococcal
hypoxia.
meningitis.
The chest X-ray can be normal or show an
interstitial infiltrates.
Important: AIDS patients are similar to the elderly
and children: Pneumothorax complicates 2% of PCP cases.
Without a full immune system they often do not About 80% of AIDS patients will get this at least
exhibit meningeal inflammation. once in their lifetime unless prophylactic
Only 25% of AIDS patients with cryptococcal antibiotics are taken.
meningitis will present with headache, mental
status changes, or meningeal signs. Toxoplasma gondii:
This parasite causes mass lesions
For example:
in the brain in 15% of AIDS patients.
A normal host with meningitis would have
meningeal inflammation with Patients present with fever, headache, and focal
meningismus (positive Kernig's and Brudzinski's neurologic deficits (seizure, weakness, aphasia).
sign, stiff neck, headache). An AIDS patie can A CT scan will show contrast-enhancing masses in
have a raging meningitis with only fever. the brain.
-high level of suspicion and always consider doing
a lumbar puncture, for cerebrospinal fluid Cryptosporidium
testing, on AIDS patients with fever. Microsporidia
Isospora belli.
=These parasites cause chronic diarrhea in
patients with AIDS
Other complications: Use post exposure prophylaxis (PEP) if you've
Wasting syndrome. been exposed to HIV
-Untreated HIV/AIDS can cause significant weight If you think you've been exposed through sex,
loss, often accompanied by diarrhea, chronic needles or in the workplace, contact your doctor
weakness and fever. or go to the emergency department.

Taking PEP as soon as possible within the first 72

Neurological complications.
hours can greatly reduce your risk of becoming
HIV can cause neurological symptoms such as
infected with HIV. You will need to take
confusion, forgetfulness, depression, anxiety and
medication for 28 days.
difficulty walking.
HIV-associated neurocognitive disorders (HAND) Use a new condom every time you have sex.
can range from mild symptoms of behavioral Use a new condom every time you have anal or
changes and reduced mental functioning to vaginal sex.
severe dementia causing weakness and inability Women can use a female condom.
to function. If using a lubricant, make sure it's water-based.
Oil-based lubricants can weaken condoms and
Kidney disease. cause them to break.
HIV-associated nephropathy (HIVAN) is an During oral sex use a nonlubricated, cut-open
inflammation of the tiny filters in your kidneys condom or a dental dam- a piece of medical-
that remove excess fluid and wastes from your grade latex.
blood and pass them to your urine.
It most often affects Black or Hispanic people. Consider preexposure prophylaxis (PrEP).
The combination drugs emtricitabine plus
Liver disease.
tenofovir (Truvada) and emtricitabine plus
-also a major complication, especially in people
tenofovir alafenamide (Descovy) can reduce the
who also have hepatitis B or hepatitis C.
risk of sexually transmitted HIV infection in
people at very high risk.
Prevention
There's no vaccine to prevent HIV infection and PrEP can reduce your risk of getting HIV from sex
no cure for AIDS. But you can protect yourself and by more than 90% and from injection drug use by
others from infection. more than 70%, according to the Centers for
Disease Control and Prevention. Descovy hasn't
To help prevent the spread of HIV:
been studied in people who have receptive
Use treatment as prevention (TasP). vaginal sex.
If you're living with HIV, taking HIV medication
can keep your partner from becoming infected Your doctor will prescribe these drugs for HIV
with the virus. prevention only if you don't already have HIV
If you make sure your viral load stays infection.
undetectable - a blood test doesn't show any
You will need an HIV test before you start taking
virus - you won't transmit the virus to anyone
PrEP and then every three months as long as
else.
you're taking it.
Using TasP means taking your medication exactly
as prescribed and getting regular checkups. Doctor will also test your kidney function before
prescribing Truvada and continue to test it every
six months.
Need to take the drugs every day. DIAGNOSIS of HIV and AIDS
They don't prevent other STIs, so you'll still need Following infection with HIV, viral RNA or antigens
to practice safe sex. (such as p24) can be detected in the blood within
weeks. Three to 6 weeks later antibodies against
If you have hepatitis B, you should be evaluated
HIV antigens appear. The enzyme-linked
by an infectious disease or liver specialist before
immunosorbent assay (ELISA) test detects
beginning therapy.
antibodies. This test is very sensitive at detecting
Tell your sexual partners if you have HIV. HIV infection (sensitivity of 99.5%) but it often
It's important to tell all your current and past gives false positive results. To decrease this rate
sexual partners that you're HIV-positive. They'll of false positives, a second ELISA is recommended
need to be tested. on the original sample and if this is positive again,
do a western blot test.
Use a clean needle.
If you use a needle to inject drugs, make sure it's
Western blot test. In this
sterile and don't share it. Take advantage of
test, HIV antigens (gag, pol, and enu proteins) are
needle-exchange programs in your community.
separated in bands on paper by molecular weight.
Consider seeking help for your drug use.
The person's serum is then added to this paper. If
If you're pregnant, get medical care right away. If the serum contains antibodies against HIV
you're HIV-positive, you may pass the infection to antigens they will stick to the antigens on the
your baby. paper.
But if you receive treatment during pregnancy,
Lastly, antihuman antibodies (labeled with
you can significantly cut your baby's risk.
enzymes) are added; these stick to the antibodies
Consider male circumcision. There's evidence that on the antigens, lighting up "bands" on the paper.
male circumcision can help reduce the risk of A western blot is considered positive if it has
getting HIV infection. bands to 2 HIV gene products (p24, gp41, gp120

Diagnosis Direct viral culture in cell lines, p24 antigen

HIV can be diagnosed through blood or saliva capture, and polymerase chain reaction (PCR) and
testing. Available tests include: BDNA are used to identify HIV whole virus, p24
antigen, and DNA/RNA respectively.
Antigen/antibody tests.
These tests usually involve drawing blood from a HIV infection should be suspected when an at-risk
vein. Antigens are substances on the HIV virus individual (homosexual, IV drug user, sexual
itself and are usually detectable - a positive test- partner of an at-risk individual, etc.) develops
in the blood within a few weeks after exposure to constitutional symptoms such as fevers, night
HIV. sweats, and generalized adenopathy, or suffers
from recurrent bacterial infections, tuberculosis,
Antibodies are produced by your immune system
skin zoster or tinea infections, or oral thrush
when it's exposed to HIV. It can take weeks to
(Candida).
months for antibodies to become detectable. The
combination antigen/antibody tests can take two
AIDS is diagnosed when the CD4 T-lymphocyte
to six weeks after exposure to become positive.
count is less than 200 (with serologic evidence of
HIV infection such as a positive ELISA or western
blot test) and/or the patient has one of many
AIDS-defining opportunistic infections, which are
infections that usually only patients with AIDS
develop.
These include Candida esophagitis, Limiting Viral Growth
Pneumocystis carinii pneumonia, the malignancy Triple drug therapies-Highly Active Antiretroviral
Kaposi's sarcoma, and many others. Therapy (HAART) have been used to bolster the
immune system in HIV-positive and AIDS patients,
CONTROL, TREATMENT, CURE? which has decreased the rate of development of
Efforts directed toward viral control are moving opportunistic infections, including
along 4 lines: Mycobacterium avium, CMV retinitis, &
1) Prevention of HIV viral infection. oropharyngeal candidiasis.
2) Vaccine development.
3) Limiting growth of HIV, once infection has HAART (Highly Active
occurred. AntiRetroviral Therapy) is the foremost theme for
4) Treating the opportunistic infections that those physicians caring for HIV positive patients.
ultimately cause death. HAART refers to the use of several very potent
anti-HIVJAKA
Prevention antiretroviral agents in combination to suppress
Education to avoid high-risk activities (needle vial replication and stop the spread of resistant
sharing, multiple sexual partners, unprotected viruses.
sex). Screening blood products with ELISA and
p24 antigen. There are at least 14 different anti-HIV
medications
Vaccine Development Six nucleoside reverse transcriptase
The goal of vaccination is to stimulate an immune inhibitors zidovudine (AZT, ZDV), didanosine (dd),
response that will counter a subsequent infection. zalcitabine (dc), stavudine (4T), lamivudine (3TC)
and abacavirl;
Most vaccines stimulate an antibody response to
Three non-nucleoside reverse transcriptase
a viral antigen, resulting in the neutralization of
inhibitor (nevirapine, delaviridine and efavirenz)
the virus.
Five protease inhibitors (saquinavir, indinavir,
Persons infected with HIV develop antibodies
ritonavir, nelfinavir and amprenavir).
against HIV determinants
Before representing each of these drugs, let's
Since the above antibody responses develop with
focus on the big picture of how to use them.
HIV infection and with all the ongoing efforts to
1. Antiretroviral therapy should be started for
develop a vaccine, why are we told that
most patients with advanced HIV infection. If
successful vaccination is a distant reality?!?
their CD4 count is high and their viral burden
There are many challenges to the development of
(plasma HIV RNA level) is very low, treatment can
a successful vaccine against HIV-1:
be delayed.
1) Rapid mutation: HIV envelope glycoproteins 2. Three or four drugs should be used because
mutate rapidly, so there are many different the data shows these combinations are more
strains. The rapidly mutating V3 loop of gp 120 effective and prevent emergence of resistance.
and the reverse transcriptase enzyme combined Choice of agents can be tailored to avoid side
with rapid viral reproduction over a long disease effects.
course results in different "quasi-species," even in
the same person. A vaccine would need to target The classic principle behind HAART is the use of
a conserved region like the CD4 binding domain. several different agents with varying mechanisms
of antiviral activity and patterns of resistance.
A three drug combination of two nucleoside 3) Reduces maternal-to-infant transmission of
reverse transcriptase inhibitors and a protease HN when given to the mother orally prior to birth,
inhibitor is the 1st line standard of care intravenously
during delivery, and then to the baby orally for 6
Specific examples weeks. In a recent study, this regimen reduced
of these combinations are shown below. the transmission rate from 25% to 8% (Conner,
Three-drug combinations: 1994)!
zidovudine + lamivudine + protease inhibitor
stavudine + lamivudine + protease inhibitor AIDS knocks out CD4 T-lymphocytes, and
stavudine + didanosine + protease inhibitor AZT (ZDV) knocks out red blood cells (anemia)
and neutrophils (neutropenia).
Protease-sparing combinations
It also causes, other pesky adverse effects
zidovudine + didanosine + nevirapine zidovudine
including headache, insomnia, myalgias, nausea,
+ didanosine + efavirenz
and CNS disturbances (confusion, seizures).
3. Physicians must follow CD4 T-lymphocyte If a patient develops
counts, these problems, the dose can be decreased or
viral load assays, and the patient's clinical status another anti-HIV drug can be used.
to determine if treatments are effective. If CD4
counts drop, viral load increases, or opportunistic Didanosine (ddl), Zalcitabine (ddC), Stavudine
diseases develop, therapy should be changed. If (d4T), and Lamivudine (3TC)
side effects develop, drugs should likewise be
These nucleoside reverse transcriptase inhibitors
changed.
are proving effective in reducing viral RNA load,
increasing CD4 counts, and slowing progression to
NUCLEOSIDE REVERSE
AIDS. When added to zidovudine, they prevent
TRANSCRIPTASE INHIBITORS (NRTIs)
the emergence of zidovudine resistance. The
Zidovudine (ZDV or AZT)
combination of zidovudine and lamivudine (3TC)
This is the first-line anti-HIV medication. Large
has been particularly effective and is considered
studies have shown that zidovudine:
the first line of therapy when combined with a
1) Reduces mortality and opportunistic infections protease inhibitor or non-nucleoside reverse
in symptomatic HIV-infected patients with CD4 T- transcriptase inhibitor
lymphocyte counts less than 200/mm 3 (Fischl,
1987). Lamivudine (3TC)
Lamivudine is generally well tolerated. No dose-
2) Delays progression to AIDS in HIV infected limiting toxic effects have been reported. In
patients with CD4 T-lymphocyte counts less than addition to the treatment of HIV, lamivudine plays
500/mm3 (Volberding, 1990; Fischl, 1990). a very important role in the treatment of hepatitis
The problem with zidovudine is that HIV can B virus (HBV) as monotherapy and in combination
rapidly develop resistance to zidovudine when it with interferon (IFN) alpha. Lamivudine potently
is used alone. This is the rationale for always inhibits hepatitis B viral DNA replication and has a
starting with 2 agents. very favorable side effect profile.
Didanosine (ddl) Non-specific side effects:
This is a synthetic purine nucleoside analogue All of these agents can cause rash, fatigue,
that is unstable in acid conditions, such as the headaches, nausea, vomiting, diarrhea,
gastric environment. Therefore, it is formulated abdominal pain, and insomnia.
with a buffer or antacids, and should be taken on
Physicians may need to juggle these medications
an empty stomach. Didanosine can cause
to find the best agent with the least side effects.
pancreatitis which may be life threatening, in
which case the drug should be discontinued.
The major toxic effect associated with didanosine
Other risk factors for pancreatitis, such as history
(ddl), zalcitabine (ddC) and stavudine (d4T) is
of pancreatitis, alcoholism, and
peripheral neuropathy. Peripheral neuropathy
hypertriglyceridemia, may increase the likelihood
usually manifests with numbness or tingling of
of developing pancreatitis
the feet, seems to be dose related, and is
generally reversible with discontinuation of these
Zalcitabine (ddC)
agents.
Unlike didanosine, zalcitabine is well absorbed
Pre-existing neuropathy or concomitant use of
from the gastrointestinal tract. Pancreatitis occurs
neurotoxic medications increases the likelihood of
less commonly than with didanosine. Severe oral
developing neuropathy. Therefore, you do not
ulcers have been reported in up to 3% of
want to use these agents in combination.
zalcitabine-treated patients
Non-Nucleoside Reverse Transcriptase
Stavudine (d4T)
Inhibitors (NNRTIs)
Mild increases of hepatic transaminases have also
-bind directly and noncompetitively to the
been noted during treatment with stavudine.
enzyme reverse transcriptase.
They block DNA polymerase activity by causing
Abacavir
conformational change and disrupting the
This synthetic carbocyclic NRTI is the newest
catalytic site of the enzyme.
agent in this class.
Hypersensitivity reactions have been the most
Unlike nucleoside analogues, NNRTIs do not need
concerning adverse effect, reported in
phosphorylation to become active, and they are
approximately 5% of patients receiving abacavir.
not incorporated into viral DNA.
A rash is accompanied by systemic signs and
When NNRTIs are administered as a single agent
symptoms such as
or as part of an inadequately suppressive
fever, fatigue, nausea, vomiting, diarrhea or
treatment regimen, resistance emerges rapidly.
abdominal pain.
Mutations conferring resistance to one drug in
These symptoms occur early and usually appear
this class generally confer cross-resistance to
within the first 6 six weeks of treatment.
most other NNRTIs.
Symptoms usually resolve rapidly after
Cross-resistance to nucleoside analogues or
discontinuation of the drug
protease inhibitors has not been observed.
It is important too remember that once abacavir
the Delaviridine
has been discontinued because of a
Delaviridine is metabolized by the cytochrome
hypersensitivity reaction, it should not be
P450 system and also inhibits CYP450 activity,
reintroduced. More severe outcomes, including
including its own metabolism. This inhibition may
death, have been reported to occur when
lead to increase plasma levels of concurrent
abacavir was reinstituted.
medications metabolized through CYP450.
Efavirenz Amprenavir
Efavirenz is the newest NNRTI to be approved by Amprenavir is the latest PI to be approved by the
the FDA. Central Nervous symptoms have been FDA. The most frequently reported side effects
reported in approximately 50% of patients are gastrointestinal (nausea, vomiting, diarrhea
treated with efavirenz. These symptoms include and abdominal pain); most are graded as mild to
abnormal dreams that are often dysphoric in moderate. Other reported side effects include
nature as well as insomnia, dizziness, impaired rash, parasthesias, and depressive or mood
concentration, and somnolence. Symptoms tend disorders.
to diminish with continued therapy but may
increase with concomitant alcohol and Interleukin-2 infusion
psychoactive drug use. Interleukin-2 is a cytokine released by T-
lymphocytes that regulates the proliferation of
Triple therapy with ZDV, ddC, and the protease CD4 (helper-T) T-lymphocytes. In a recent clinical
inhibitor saquinavir, resulted in greater and longer trial HIV infected patients with CD4 counts
lasting elevations of CD4-T cell counts and greater greater that 200 cells/cc were treated with
reductions in viral levels than 2-drug therapy. infusions of interleukin-2. The treatment resulted
in a dramatic rise in CD4 counts from a mean of
Side effects were similar for 3 and 2 drug
400 cells/cc to 900 cells/cc! There was no
regimens
increase or decrease in the viral RNA load
associated with this elevation of CD4 counts to a
Saquinavir
normal level. Whether this will translate into an
Saquinavir was the first PI to be approved by the
improved clinical outcome remains to be
FDA. The biggest problem with saquinavir has
determined (Kovacs, 1996.)
been that a minimal amount of the drug gets
absorbed when taken orally.
Post-Exposure (i.e., Needle Stick)
Fortovase is a soft gel formulation of saquinavir
HIV Prophylaxis
with enhanced bioavailability that has replaced
After a needle-stick or other percutaneous
hard gel saquinavir, Invirase. Fortovase should be
exposure with HIV-infected blood the risk of
taken with a meal to increase oral absorption. The
seroconversion is 0.3%. This risk goes up if the
main side effects are as you might have guessed,
injury is deep, the needle was in the patient's vein
gastrointestinal. These effects include diarrhea,
or artery, the needle had visible blood on it, or
nausea, abdominal discomfort and pain,
the patient died within 60 days of the stick
dyspepsia and vomiting.
(suggesting late-stage AIDS with high levels of
viremia).
Ritonavir
Ritonavir is the most poorly tolerated of the four
Treatment after an exposure with zidovudine
currently available Pls. The most corn only
(ZDV), has been shown in a case-control study to
reported side effects are gastrointestinal,
reduce the of seroconversion by 79%. ZDV +
including nausea, vomiting, diarrhea and
lamivudine (3TC) is more active against ZDV
abdominal pain.
resistant strains of HIV and the protease inhibitors
Nelfinavir further increase HIV killing. So the public health
The most frequently reported side effect service has now recommended that expo health
associated with nelfinavir is diarrhea, noted in up workers at highest risk receive triple therapy with
to 32% of patients. Nelfinavir-associated diarrhea ZDV, 3TC, and indinavir for 4 weeks. Lower risk
is generally mild to moderate. Other reported exposures should receive ZDV and 3TC (MMWR,
side effects include nausea, vomiting, abdominal 1999).
pain, and rash.
Treating the Opportunistic infections Final Word
1) Pneumocystis carinii pneumonia (PCP): AIDS is a disease that has no dignity, a disease
Trimethoprim and sulfamethoxazole are given that cripples the immune system, allowing the
prophylactically when CD4+ T-cell counts drop scourge of all infestations. You are becoming a
below 200-250. Greater than 90% of PCP physician in the dawn of a new epidemic, and you
infections are being prevented with this will certainly play a role in the control of this
prophylactic intervention! epidemic.

2) Toxoplasmosis: Brain lesions are treated with

another tetrahydrofolate reductase inhibitor/sulfa
combination called pyrimethamine/sulfadiazine.
Patients improve rapidly. In fact, if there is no
brain mass shrinkage (as seen by CT scan) by 2-3
weeks, then the diagnosis of toxoplasmosis is
unlikely. Brain biopsy should then be done to
determine whether the mass is a B-cell
lymphoma. The same medicine (trimethoprim
and sulfamethoxazole), used for PCP prophylaxis,
also prevents toxoplasmosis! It prevents two birds
with one stone.

3) Mycobacterium tuberculosis and

Mycobacterium avium-intracellulare:
Azithromycin or clarithromycin can be given
daily for prophylaxis against future MAI
infections.

4) CMV: Treatment with ganciclovir or foscarnet

can prevent progression of visual loss.

5) Herpes, Varicella-zoster: Acyclovir.

6) Candida albicans: Oral clotrimazole, nystatin,

or fluconazole preparations for thrush and
esophagitis. Systemic fungal infections are treated
with intravenous amphotericin B or fluconazole.

7) Bacteria: Appropriate antibiotics.

AIDS patients are now surviving for prolonged
periods with CD4+ T-cell counts approaching zero.
They are often on more than 10 different
medications