The Immune Response

Immune Response
• Protection of the individual from infectious
pathogens
• Mechanisms fall into two categories
– Innate immunity (natural or native) – mechanisms
present even before infection and have evolved to
specifically recognize microbes
– Adaptive immunity(acquired or specific)-
mechanisms stimulated by (adapt to) microbes and
are capable of recognizing non microbial substances
called antigens
 Innate Immunity
• An ancient form of immune
defense
• Components include
– Epithelial barriers
– Phagocytic cells (macrophages,
neutrophils)
– Natural killer cells (NK cells)
– Several plasma proteins
including the complement
 Adaptive Immunity
• Generation of antigen receptors on T and B
lymphocytes by gene rearrangements
• Two types
– Cell mediated immunity – T lymphocytes (thymus derived)
– Humoral immunity – B lymphocytes (bone marrow
derived)
 T Lymphocytes
• Generated from immature precursors in the
thymus
• Mature T lymphocytes are found in the blood
(60-70% of lym),lymph nodes and spleen
• Mainly act against intracellular antigens
• Each T-cell has a specific Ag receptor called TCR
• Antigen should be presented to them bound to
MHC molecules on APC (Ag presenting cell)
 T Lymphocytes
• There are two types of T lymphocytes
– T-helper cells ( CD4 cells)- master regulators
• Secrete cytokines that influence other immune cells
– Cytotoxic T cells (CD8 cells)- mainly killers or
effector cells
 B Lymphocytes
• Develop from immature precursors in the bone
marrow
• Mature B-cells are found in the blood (10-20%
lymphocytes), lymph nodes, spleen, tonsils, GI
• After stimulation with Ags, B cells develop into
plasma cells which secrete immunoglobulin
(antibodies)
• Usually effective against extracellular pathogens
and their toxins
 Immunoglobulins
• Products of differentiated B- cells (plasma
cells) which bind to and inactivate the
offending agent
• There are five isotopes (IgG, IgA, IgM, IgE, IgD)
 Macrophages
• Part of the mononuclear phagocyte system
• Macrophage functions
– Process microbes and proteins and present
peptide fragments to T cells (APC)
– Important effecter cells in both cell mediated and
humoral immune response
• Opsonization, delayed type hypersensitivity
 Natural Killer Cells
• They comprise 10-15% of peripheral
lymphocytes
• Larger than mature lymphocytes and have
abundant cytoplasmic granules
• Part of the innate immune system
 Granulocytes
• Present in nearly all forms of inflammation
and act as effectors of the innate immune
response
• Three types of granulocytes
– Neutrophil
– Eosinophil
– Basophil
Inflammation
 Inflammation-Introduction
• Inflammation – it is a protective response to
injury in a vascularized tissue
• Inflammation neutralizes and dilutes the
inflammatory agent, removes necrotic material
and establishes an environment suitable for
healing and repair.
• There are two types of inflammation
– Acute inflammation
– Chronic inflammation
 Acute Inflammation
• It is a rapid response to injurious agent to deliver
mediators of host defense towards the site of injury
• Stimuli for acute inflammation
– Infection
– Trauma
– Physical and chemical agents
– Necrosis from any cause
– Foreign body
– Immune reactions (hypersensitivity)
 Acute Inflammation - Continued
• Whatever the cause
inflammatory responses have
common features
• Two major components
– Vascular changes
• Alteration in vascular caliber and
increased blood flow
• Increased permeability of
microvasculature
– Cellular changes
• Emigration of WBC (Leukocytes)
 1. Vascular Changes
• Changes in vessel caliber and blood flow
– Transient vasoconstriction
– Vasodilation of arterioles and opening of new
capillary beds
– The above results in an increase in blood flow
– Induced by the effect of mediators like histamine
and nitric oxide on vascular smooth muscle cells
 Vascular Changes - Continued
• Vasodilatation is immediately followed by
increased permeability
• Results in edema formation
• Stasis due to increased viscosity
• WBC s marginate to the endothelium and
eventually migrate through the vessel wall
Increased Vascular Permeability
 Mechanisms of Increased Permeability

• Formation of endothelial gaps

• Direct endothelial injury
• Transcytosis across the endothelial cytoplasm
• Leakage from new capillaries
 2. Cellular Events
• Leukocyte extravasation and phagocytosis
• WBC –
– Ingest offending agent
– Kill bacteria
– Get rid of necrotic tissue and foreign substances
– Tissue damage along the way
 Cellular Events - continued

• Steps in extravasations
1. Margination, rolling and adhesion to endothelium
2. Transmigration (diapedesis)
3. Migration in the interstitium towards the
chemotactic stimulus
Steps in Leukocyte Extravasation
 Chemotaxis
• Locomotion oriented along a chemical
gradient
– Bacterial product
– Components of complement system – C5a
– Products of the lipoxygenase pathway – LTB4
– Cytokines – IL-6
 Phagocytosis
• Responsible for elimination of the injurious
agents ; it involves
– Recognition
– attachement
– Engulfment
– Killing or degradation of the ingested material
• Oxygen dependent killing
• Oxygen independent killing
Phagocytosis
 Morphologic Features
• Exudation – escape of fluid, proteins, and
cellular elements (Sg of exudate- >1.020)
• Transudation – escape of fluid with relatively
lower protein content (Sg < 1.012)
• Edema – excess interstitial fluid either a
transudate or an exudate
• Pus or purulent exudate – rich in WBC s, debris
of dead cells and most of the time microbes
 Morphologic Patterns of Inflammation

• Serous inflammation – outpouring of thin fluid

– Plural effusion
– Skin blisters after burn injury
Pleural Effusion/ Blister
 Morphologic Patterns of Inflammation

• Catarrhal inflammation – usually occurs in

tissues rich in mucus producing cells
– Example – runny nose with common cold
 Morphologic Patterns of Inflammation
• Fibrinous inflammation – fibrin rich exudate
– Example – fibrinous pericarditis
Fibrinous Pericarditis
 Morphologic Patterns of Inflammation
• Suppurative or purulent inflammation
– Large amount of pus or purulent exudate
composed of neutrophils, necrotic cells and
edema fluid +/- bacteria
– Example - Appendicitis
Brain Abscess
Acute Purulent Meningitis
Tonsillitis (purulent)
• Pseudo membranous inf.
– Extensive confluent necrosis of the surface
epithelium of an inflamed mucosa & severe acute
inflammation of the underlying tissue.
– Eg. Diphetric infection of larynx & pharynx
Clostridium infection of large intestine
 Effects of acute inflammation
• 1. Beneficial Effects
 Dilution of toxins
 Protective abs
 Fibrin formation – Decrease bacterial spread
 Plasma mediator system provisions
 cell nutrition
 Promotion of immunity
 2. Harmful effects

 Tissue destruction
 Swelling
 Inappropriate response (hypersensitivity
reaction)
 Inflammation Outcome
Chronic
Inflammation

Acute
Healing
Injur Inflammation
y

Abscess

Fistula Ulcer Sinus

Clinical Manifestations of Acute Inflammation

• Local manifestations ( 5 cardinal signs)

– Redness (rubor) – hyperemia
– Heat (color) – Increased blood flow & metabolism
– Pain (dolor) – change in pH, histamine,
Prostaglandin
– Swelling (tumor)- fluid shift to interstitial space
(edema)
– Loss of function (function laesa)– swelling ,pain
Clinical Manifestations - Continued
• Systemic manifestations
– Leukocytosis with left shift
• 15,000 – 20,000 cells/mm3
• bacterial – nutrophilia
• Viral – lymphocytosis
• Asthma - eosinophilia
– Fever
• Pyrogenes (endogenous, exogenous)
– Malaise
– Tachycardia
– Anorexia / weight loss
 Outcomes of Acute Inflammation
1. complete resolution
– Neutralization or decay of the mediators
– Return of normal vascular permeability
– Cessation of WBC infiltration
– Death of neutrophils ( apoptosis)
– Removal of edema fluid
Outcome of Acute Inflammation - continued

2. Healing by connective tissue replacement

(fibrosis)
– Usually after substantial tissue destruction
– Tissue incapable of regeneration
– Abundant fibrinous exudate
3. Progression of tissue response to Chronic
Inflammation
4.suppuration
 Chronic Inflammation
• Inflammation of prolonged duration (weeks-
months) in which active inflammation, tissue
destruction and attempts at repair are
proceeding simultaneously.
• It can follow an acute inflammatory response
or may start as a chronic inflammation from
the onset
 Causes of Chronic Inflammation
• Persistent infection by certain organisms
– Tb, Treponema pallidum , certain viruses, fungi
and parasites
• Prolonged exposure to potentially toxic agent
either exogenous or endogenous
– Silica
• Autoimmunity – reaction against own tissue
– Rheumatoid arthritis, SLE
 Morphologic Features
• Infiltration with mononuclear cells
– Macrophages, lymphocytes, plasma cells
• Tissue destruction
• Healing by connective tissue replacement,
angiogenesis and fibrosis
 Acute Vs Chronic
• Flush, Flare & Weal • Little signs - Fibrosis,
• Acute inflammatory • Chronic
cells - Neutrophils inflammatory cells –
Lymphocytes
• Vascular damage
• Neo-vascularisation
• More exudation • No/less exudation
• Little or no fibrosis • Prominent fibrosis
 Chronic…….ctd

• Two type based on histologic type

– Specific(Granulomatous) inf
– Non-specific

?
 Systemic effects of inflammation
• Fever
• Endocrine & Metabolic responses
• Autonomic responses
• Behavioral responses
• Leukocytosis
• Leucopenia
• Weight loss
• Sepsis
 Fever
• Most important
• Coordinated by hypothalamus & by
cytokines>IL-1
>IL-6
>TNF-a
 Autonomic response
• PR and BP increases
• Redirection of blood flow from the cutaneous
to the deep vascular bed
• Sweating.
 Leukocytosis
• leukocyte count typically increases to 15,000 or
20,000 cells per μL (normal = 4000 to 11,000 The
cells per μL) but may climb as high as 40,000 to
100,000 cells per μL, a so-called leukemoid reaction.
• Leukocytosis initially results from the release of cells
from the bone marrow (caused by IL-1 and TNF) and
is associated with an increased number of relatively
immature neutrophils in the blood ("left-shift").
 Weight loss
• Due to IL-1 & TNF-a
• Increase catabolism in skeletal muscle,
adipose & liver.
•

End of inflammation
Hypersensitivity
 Mechanisms of Hypersensitivity
• Hypersensitivity – Exaggerated immune
response which becomes damaging to tissue
• May be evoked by:
– Exogenous environmental antigens
– Endogenous tissue antigens
• Classified on the basis of immunologic
mechanisms that mediate the disease
 Hypersensitivity
1. Type I (Immediate) hypersensitivity
2. Type II (antibody mediated) hypersensitivity
3. Type III (immune complex mediated)
hypersensitivity
4. Type IV (cell mediated) hypersensitivity
 1. Type I Hypersensitivity
• Rapidly developing immunologic reaction
occurring within minutes
• Antigens bind to antibodies on the surface of
mast cells
• Occurs in individuals who are previously
sensitized to the antigen
• May occur as a systemic disorder or as a local
reaction
 Pathogenesis
• Mast cells are central
• They are bone marrow
derived cells with
cytoplasmic granules
containing active mediators
like histamine
• Activated by cross linking of
IgE Fc receptors on their
membrane
Mast Cell Activation
 Type I Hypersensitivity
A. Systemic anaphylaxis
• Vascular shock, widespread edema and
difficulty in breathing
• Follows administration of foreign proteins,
hormones, polysaccharides, drugs (penicillin)
• Itching, hives, skin erythema, contraction of
respiratory bronchioles, laryngeal edema,
shock and even death
 Immediate Hypersensitivity
B. Local Immediate Hypersensitivity
• Could be evoked by pollen, animal dander,
house dust, food
• Diseases include
– Urticaria, angioedema, allergic rhinitis, Asthma
• Usually have two phases
– Immediate (initial) response
– Second (late phase) reaction
 Phases in Type I hypersensitivity
1. Immediate-
vasodilation, vascular
leakage,smooth
muscle spasm,
glandular secretion
2. Late phase-
infiltration with
eosinophils,
nutrophils, basophils,
CD4 cells, with tissue
destruction
Urticaria
 2. Antibody Mediated (Type II)
Hypersensitivity
• Mediated by Ab’s directed against antigens
present on cell surfaces or extracellular matrix
• Antigen may be intrinsic to the cell or
exogenous Ag absorbed on the cell
• Mechanisms of injury
– Opsonization and phagocytosis
– Complement or Fc receptor mediated inflammation
– Antibody mediated cellular dysfunction
 Diseases Caused by Type II Hypersensitivity
Disease Target Antigen
Autoimune hemolytic anemia RBC memb proteins
Autoimmune thrombocytopenic purpura Platelate memb proteins
Pemphigus vulgaris Proteins in intracellilar junction of
epidermal cells
Good pasture syndrome Basement memb proteins in glomeruli
and alveoli
Acute rheumatic fever Strept cell wall Ag which cross reacts with
myocardial Ag
Myastenia gravis Acetylcholine receptor
Grave’s disease TSH reseptor
Insulin resistant Diabetes Insulin receptor
Pernicious anemia Intrinsic factor of gastric parietal cells
 Acute Rheumatic Fever/RF
• is an acute, immunologically mediated, multisystem
inflammatory disease that occurs a few weeks
following an episode of group A streptococcal
pharyngitis.
• Suspected that acute rheumatic fever is a
hypersensitivity reaction induced by group A
streptococci
• Antibodies directed against the M proteins of certain
strains of streptococci cross-react with glycoprotein
antigens in the heart, joints, and other tissues
 Rheumatic Fever
• Typically occurs 10 days to 6 weeks after an episode of
pharyngitis caused by group A streptococci in about 3% of
patients
• RF is characterized by a constellation of findings that
includes as major manifestations
(1) migratory polyarthritis of the large joints,
(2) carditis,
(3) subcutaneous nodules,
(4) erythema marginatum of the skin, and
(5) Sydenham chorea, a neurologic disorder with involuntary
purposeless, rapid movements.
 Graves Disease
• Is an autoimmune disorder in which a variety of
antibodies may be present in the serum, including
antibodies to the TSH receptor
1.  Hyperthyroidism owing to hyperfunctional, diffuse
enlargement of the thyroid
2.  Infiltrative ophthalmopathy with resultant exophthalmos
3.  Localized, infiltrative dermopathy, sometimes called
pretibial myxedema, which is present in a minority of
patients
Graves Disease
 3. Type III Hypersensitivity
• Immune complex mediated
• Ag-Ab complexes produce tissue damage mainly
by initiating inflammation at sites of deposition
• Ag could be endogenous or exogenous
• Immune complexes formed in the circulation
can deposit in tissue or immune complexes can
be formed in the tissue over previously
deposited Ag
 Type III Hypersensitivity
• Generalized – immune complexes formed in the
circulation are deposited in many organs
• Localized – immune complex deposition in
kidney (glomerulonephritis), joint (Arthritis),
small blood vessels in the skin (vasculitis)
• Examples – Systemic lupus erythematosus,
polyarteritis nodosa, post streptococcal
glomerulonephritis, serum sickness, Arthus
reaction
 Acute Serum Sickness
• Seen after administration of immune serum from
horses used for passive immunization/diphteria
1. A week after exposure formation of immune complex
in the circulation takes place
2. Deposition of immune complex in various tissues
3. Around 10 days after exposure inflammatory reaction
at sites of immune complex deposition results in the
clinical manifestations like fever, urticaria, arthralgias,
lymph node enlargement, and proteinuria
 Serum Sickness - Continued
• Favored sites of immune complex deposition
– Renal glomeruli – glomerulonephritis
– Joint – arthritis
– Skin – vasculitis
– Heart –myocarditis
– Small blood vessels – vasculitis
– Serosal surfaces – pericarditis, peritonitis, plurisy
4. Type IV (cell mediated) Hypersensitivity

• Initiated by sensitized T- Lymphocytes

• Examples – Type I DM, multiple sclerosis,
Rheumatoid arthritis, Peripheral neuropathy
(GBS), contact dermatitis, Tuberculosis and
other intracellular pathogens, graft rejection
• Tuberclin skin test- Intradermal injection of PPD
in a previously sensitized individual causes
redness and indurations at the site starting 8-12
hrs later
Type IV Hypersensitivity – Contact Dermatitis
• On repeat exposure to Ag, sensitized CD4 T
cells accumulate in the dermis and epidermis
result in the formation of intraepidermal
vesicles
End of hypersensitivity
Autoimmunity
 Autoimmunity - Introduction
• Immune reaction against self antigens
• Important cause of some diseases
 Autoimmunity
• Type I DM – Auto reactive T cells and Ab’s
which are specific for beta cells of the
pancreas result in insulin deficiency.
• Multiple sclerosis – Auto reactive T cells
against CNS myelin
• SLE – Ab’s against DNA, platelets, RBC and
protein phospolipid complexes
 SLE (systemic lupus erythematosus)

• Characterized by anti nuclear antibodies (ANA)

• It is a chronic remitting & relapsing often
febrile illness characterized by injury to the
skin, joints kidney and serosal membranes
• It is predominantly a disease of women in the
reproductive age.
 Etiology and Pathogenesis
• Auto antibodies have been identified to
various nuclear and cytoplasmic components
of the cell
• Environmental factors like drugs, UV light
• Sex hormones – SLE 10X more common in
women during reproductive age
• Most of the injury is mediated by immune
complex (type III) hypersensitivity
 SLE- Clinical Manifestations
• Multisystem disease with highly variable clinical
manifestations
– Butterfly rush over the face
– Fever
– Pain with no deformity over the joints
– Pluritic chest pain
– Photosensitivity
– Hematuria, RBC casts, proteinuria
– Anemia , thrombocytopenia
– Psychosis and convulsion
– Infections due to immune dysfunction
Malar Rash
 Rheumatoid Arthritis
• Chronic inflammatory disorder that affects
primarily the joints but rarely skin, blood
vessel, heart, lung and muscles
• It is thought to be an autoimmune disease
triggered by exposure of a genetically
susceptible host to an unknown antigen
 RA- Clinical Manifestations
• Clinical course is variable
– Small joints are usually affected before large ones
– Joint swelling, pain and stiffness
– Course is fluctuating over a period of years
– Destruction of tendons, ligaments and joint
capsule leading to deformities
– Death usually due to complications
• Vasculitis, GI bleeding (NSAID), infections (steroid)
Immune Deficiency
 Immunodeficiency syndromes
A. Primary immune deficiencies – genetically
determined
B. Secondary immunodeficiency – infection,
malnutrition, aging and iatrogenic
(chemotherapy, radiotherapy)
 A. Primary Immunodeficiency
1. X-linked Agammaglobulinemia of Bruton
• Characterized by failure of B-cell maturation
• Seen almost entirly in males
• Disease doesn’t become apparent until 6 months because of
the maternal Abs
• Recurrent respiratory infections (pharyngitis, otitis media,
bronchitis, pnumonia)
• Organisms Heamophilus influenza, streptococcus pnumonea,
Staphylococcus aureus – normally cleared after opsonozation
• Paralytic poliomyelitis after polio vaccination
• T cell mediated immunity is normal
 Primary Immunodeficiency
2. Common variable immunodeficiency
– Hypogammaglobulinemia generally affects all Ig
classes but sometimes only IgG
– Problem of B cell differentiation into plasma cells
– Recurrent sinopulmonary pyogenic infections
3. Isolated IgA deficiency
– Low level of serum and secretory IgA
– Mucosal defenses are weakened leading to
respiratory, GI, urogenital infections
 Primary Immunodeficiency
4. Di George syndrome (Thymic hypoplasia)
– T-cell deficiency that results from failure in the
normal development of the thymus
– Also failure of development of parathyroid - tetany
– Poor defense against viral and fungal infections
– Results from deletion of gene that maps to
chromosome 22q11
 Primary Immunodeficiency
5. Severe combined Immunodeficiency disease
(SCID)
– Defects in both humoral and cell mediated immune
responses
– Presentation-oral trush, extensive diaper rash, and
failure to thrive
– Wide range of infections Candida albicans, Pnumocystis
carini, psudomonas, Cytomegalovirus, varicella etc
– Without bone marrow transplantation death occurs in
the first year of life
 B. Secondary Immunodeficiency
• Could be caused by infection, malnutrition,
aging, chemotherapy and radiotherapy for
cancer, immunosuppressive therapy after
transplant
• The most devastating example of secondary
immunodeficiency is AIDS
 AIDS
• Disease caused by a retrovirus(HIV), and
characterized by profound immunosuppresion that
leads to opportunistic infections, secondary
neoplasms and neurologic manifestations
• First recognized in USA in1981 – report of 5
pnumocistis jiroveci pneumonia and 26 kaposi
sarcoma all in homosexual males, shortly followed by
IDU and hemophilic patients
• In 1983 HIV was isolated and in 1985 ELISA test
developed
 Etiology
• HIV- Lentivirus family
• Two genetically different but related forms of HIV
1. HIV-1 – Central Africa, US, Europe
2. HIV-2 – West Africa, India
• HIV-1 isolates have considerable variation in their
genome
M (Major) – several subtypes (clades) A to K
O (outlier)
N( neither M nor O)
• Ethiopia HIV-1 M Clade C
Geographic Distribution of the Subtypes
(HIV1)
 Structure of HIV
• HIV viron particle is spherical and contains a central core
surrounded by a lipid envelope derived from host cell
membrane
• Core is composed of
– Major capsid protein P24
– Nucleocapsid protein P7/P9
– Two copies of genomic RNA
– Three viral enzymes (reverse transcriptase, protease, integrase)
• Viral core is surrounded by matrix protein called P17
• Studding the viral envelope are viral glycoproteins (gp120
and gp41)
HIV Viron
 Transmission
• Sexual contact (both hetro and homosexual)
• Blood and blood products
• Mother to child (intrapartum, perinatally and
breast milk)
Pathogenesis of HIV infection and AIDS
• The two major targets of HIV infection are the
immune system and CNS
• Profound immunosupression predominantly
affects Cell mediated immunity
• This results from infection and loss of CD4 cells
as well as impairment of the surviving T helper
cells
• Macrophages and dendritic cells are additional
targets
 Pathogenesis Continued
• HIV enters through mucosal surfaces or the
blood and first infects T cells as well as
dendritic cells and macrophages
• Infection becomes established in lymphoid
tissues where virus may remain latent for long
period
 Life cycle of HIV
• CD4 molecules are the high affinity receeptors for HIV
1. gp120 binds to CD4 molecules
2. gp120 binds to co-receptors (CCR5, CXCR4)
3. Conformational change in gp41 resulting in fussion
4. Core containing viral genome enters host cytoplasm
5. RNA of the virus undergoes reverse transcription –RNA to
cDNA (proviral DNA)
6. Integration into the host genome
7. Proviral DNA transcribed with formation of viral particles that
buds from the cell surface
8. Cell lysis or death
HIV Life Cycle
 Mechanisms of T- Cell Immunodeficiency

• Viral replication in infected cells results in lysis

of CD4 cells
– 100 billion new viral particles are produced/day
– 1-2 billion CD4 T cells die each day
• Early in the disease course the immune system
can replace the dying cells but late in the
course replacement cant keep up with the loss
• There is also qualitative defect in the T cells
• CD4 T cells, macrophages and follicular
dendritic cells contained in the lymphoid
tissues are the major site of HIV infection and
persistence
• CNS – macrophages and microglia cells are
predominant cell types in the brain that are
infected by HIV
 Natural History of HIV Infection
1. Acute retroviral syndrome
2. Middle (chronic) phase
3. Full blown AIDS
Natural History of HIV Infection
Natural History of HIV - Continued
1. Acute retroviral syndrome
– High level of viremia and widespread seeding of
the lymphoid tissues
– 40-90% of the individuals develop the syndrome 3-
6 weeks after infection which resolves in 2-4 weeks
– Self limiting non specific symptoms including sore
throat, myalgia, fever, rash, weight loss, fatigue,
flue like symptoms
– Sometimes LAP, rash, diarrhea, vomiting
 Natural History
2. Middle (chronic) phase
– Clinical latency, immunity largely intact but there
is continuous HIV replication predominantly in
lymphoid tissues which may last for several years
– Usually asymptomatic but sometimes PGL
(persistent generalized lymphadenopathy)
 Natural History
3. AIDS
– Breakdown of host defense
– Increased viral load and clinical disease
– Long lasting fever (1 month)
– Fatigue, wt loss, diarrhea
– Serious opportunistic infections
– Secondary neoplasms
– Clinical neurologic disease
– Without treatment HIV infection progresses to AIDS in 7-10 years
– Long term non progresser - >10yrs stable CD4 and low viral load
– Rapid progresser – 2-3 yrs
 Herpes Zoster (shingles)
• Seen in 20-30% of HIV infected people
• Etiology – Reactivation of varicella-zoster virus
infection
• Usually indicates a modest decline in
immunity
• Lesions normally follow dermatomal
distribution and in HIV patients can involve
several dermatomes simultaneously
Herpes Zoster
 A. Diseases of GIT
1. Oral thrush
– Etiology – fungus Candida albicans
– Occurs in patients with CD4,350 cells/mm3
– Presentation – white cheesy exudate on an erythematous
mucosa in the posterior oropharynx
– Diagnosis – KOH from scraping show psudohyphal elements
2. Oral hairy leukoplakia
– Etiology- epistan barr virus (EPV)
– Presentation – white frondlike lesion along the lateral
border of the tongue and adjacent buccal mucosa
 GI Disease - Continued
3. Diarrheal disease
– Among the most frequent symptoms of HIV
disease
– A wide range of agents can cause diarrhea
• Bacteria – salmonella, shigella, compilobacter
• Fungi – histoplasma, coccidioidomycosis, penicilliosis
• Protozoa – cryptosporidia, microsporidia and isospora
belli,
• Virus – CMV, HIV
• Parasites – strongloids stercolaris
 B. Respiratory infections

1. Bacterial pneumonia
– Can occur in immune competent individuals but risk is
increased 6X among HIV patients
– Most common etiologies Streptococcus pneumonea,
Heamophilus influenzae
– Clinical presentations- sudden onset of cough, sputum
production, chest pain, fever and SOB

• 2. Pnumocystis jiroveci pneumonia

– It is a fungal agent
– Commonly occurs when CD4 <200 ceels/mm3
– Clinical findings- low grade fever, dry cough, dyspnea,
scatered rales in the lung
 Respiratory Infections-cont’d
• 3. Pulmonary tuberculosis
– Mycobacterium tuberculosis is the leading cause of morbidity
and mortality among HIV patients
– Co-infection rate 20-50%
– Tb enhances progression of HIV
– HIV increases risk of infection as well as reactivation of latent
Tb
– Manifestation depends on degree of immunosupression
• Good immunity – typical manifestations like involvement of the lung
apex, cavitation and typical CXR findings
• CD4<200 cells/mm3 – atypical manifestations, lower zone infiltration,
more extra pulmonary Tb
 C. Diseases of Nervous System
1. Toxoplasmosis
– Etiology – protozoan Toxoplasma gondi
– Almost exclusively due to reactivation of late infection
– Greatest risk among patients with CD4 < 50cells/mm3
– Clinical manifestations – headache, confusion, motor weakness and fever, seizure,
stupor and coma
– CT brain – multiple ring enhancing lesions
2. Cryptococcosis
– Etiology – Criptococcus neoformans
– Seen in pts with CD4 < 50 ceels/mm3
– Clinical manifestations – subacute meningitis or meningoencephalits with fever,
malease, headache, neck stiffness and photophobia, altered mentation, personality
change and memory loss
– CSF- increased protein, decreased glucose, lymphocytes, many organisms
(criptococci)
 Neurologic Diseases – cont’d
3.HIV associated neurocognitive impairment (AIDS
dementia complex)
– Primarily due to the pathogenic process of HIV infection
of the brain
– Generally a late complication but can be seen in patients
with CD4 > 350/mm3
– Major manifestations –
• Dementia (decline of cognitive ability from previous level),
decreased concentration, forgetfulness, difficulty reading
• Motor symptoms – poor balance, unsteady gait, tremor
• Behavioral problems – apathy, lack of interest, mania
 D. Opportunistic Malignancies
1. Kaposi Sarcoma
– Caused by HHV-8
– Uniform throughout the course of HIV infection
– Clinical manifestations
• Pigmentes macules, papules, plaques or nodules
• Purple but in black skin dark brown or black
• oral cavity 1/3 of pts
2. Lymphoma
– 120X increased incidence as compared to HIV negative
– CD4<200 calls/mm3
– High grade lymphoma, Burkitt’s lymphoma, primary CNS lymphoma
– Clinical manifestations – focal seizure, mass in oral cavity, persistent unexplained
fever, headache
– CT brain – multiple ring enhancing mass lesions
Kaposi Sarcoma
Lymphoma