Preface

Agam is a group of budding medicos, who are currently doing their under graduation in
various Medical Colleges across Tamil Nadu and Pondicherry. The group was initiated on 18th
November 2017, in the vision of uniting medicos for various social and professional causes.

We feel delighted to present you Agam Pathology notes prepared by Agam Divide and Rule
2020 Team to guide our fellow medicos to prepare for university examinations.

This is a reference work of 2017 batch medical students from various colleges. The team
took effort to refer many books and make them into simple notes. We are not the authors of the
following work. The images used in the documents are not copyrighted by us and is obtained from
various sources.

Dear readers, we request you to use this material as a reference note, or revision note, or
recall notes. Please do not learn the topics for the 1st time from this material, as this contain just the
required points, for revision.
Acknowledgement

On behalf of the team, Agam would like to thank all the doctors who taught us Pathology.
Agam would like to whole heartedly appreciate and thank everyone who contributed towards the
making of this material. A special thanks to Vignesh M, who took the responsibility of leading the
team. The following are the name list of the team who worked together, to bring out the material in
good form.

• Neelavathi S
• Manivasagam R
• Artheshivani S M
• Kavya M
• Vikram R R
• Subhashree B
• Praveen S P
• Vignesh. M
• Varsha L
• Muthamil Selvi E
• Kaushik N R
 INFECTIOUS DISEASES
ESSAY:
1. Define gangrene, types, details about gas gangrene
2. Typhoid ulcer
3. Describe the pathogenesis, morphology and clinical features of TB

SHORT NOTES:
1. Mycetoma
2. Morphology and evolution of tubercle
3. Immunology of leprosy
4. Difference between Tuberculous leprosy and lepromatous leprosy
5. Microscopic appearance of lepromatous leprosy
6. Difference between Dry and Wet gangrene
7. Pathogenesis of gangrene
8. Tertiary Syphilis
9. Viral Hemorrhagic Fever
10.Actinomycosis

SHORT ANSWERS:
1. Cysticercosis
2. Hematocrit in Dengue fever
3. Black Water Fever
4. Gross Appearance of Mycetoma
5. Fungal granuloma
6. Rhinosporidiosis
7. Negri Bodies

UPDATES

PATHOLOGY AGAM
ESSAY
1. GANGRENE:
A form of necrosis of tissues with superadded putrefaction. Here the necrosis
undergoes liquefaction by the action of Putrefactive Bacteria.

TYPES:
 Dry gangrene.
 Wet gangrene
 Gas gangrene( a type of wet gangrene )

GAS GANGRENE:
Deep wound infection, destructive of tissues caused by combination of 2 or more
species.

CAUSATIVE AGENT:
 Clostridium perfringens
 Clostridium novyi
 Clostridium septicum

PATHOGENESIS:

Spores enter devitalized tissues

Germinate

Bacterial multiplication

Release toxins

Local: Muscle Necrosis + Gas formation Systemic: Cardiac Depression & MOF

AGAM PATHOLOGY
MORPHOLOGY:
GROSS:
 Affected area is swollen, oedematous, painful and crepitant due to accumulation of gas
bubbles of CO2
 Subsequently, the affected tissue become Dark Black and foul smelling.

MICROSCOPY:
 Muscle fibres undergo Coagulative necrosis with Liquefaction.
 Large number of Gram +ve bacilli are seen.
 At Periphery, a leucocytic infiltration, Oedema and Congestion are found.
 Capillary and Venous thrombi are common.

SYMPTOMS:
 High fever
 Shock
 Massive tissue destruction
 Blackening of skin
 Blisters with gas bubbles from infected area.

TREATMENT:
 High dose of antibiotic – Penicillin
 Dead tissue is removed / Limbs amputated
 No vaccine.

PATHOLOGY AGAM
2. TYPHOID ULCER:
CAUSATIVE AGENT:
 Salmonella typhimurium
 Salmonella paratyphi

PATHOGENESIS:
 Salmonella possesses virulence genes that encode a type3 secretion system capable of
transferring bacterial proteins into the enterocytes.
 Transferred proteins activate host cell Rho GTPases, bacterial uptake that allow bacterial
growth within phagosomes.
 Flagellin, the core protein of bacterial flagella, activates TLR5 on host cell and increase
local inflammatory response.

MORPHOLOGY:
 Affects ileum and colon.
 Present as longitudinal ulcers over the Peyer's patches.
 Neutrophil accumulate within the superficial layers & macrophages containing bacteria,
RBCs, Nuclear debris mix with lymphocytes & Plasma cells in LP.
 Mucosal shedding create oval longitudinal ulcers.
 The Base of Ulcer is Black due to the Sloughed mucosa.
 The Margins of the Ulcers are slightly raised due to inflammatory oedema and Cellular
Proliferation.
 No Significant Fibrosis.
 Fibrous stenosis seldom occur in healed Typhoid Lesions.
 Regional Lymph nodes are invariably enlarged.
 Blunting of villi.
 Mucosal congestion & edema.

CLINICAL FEATURES:
 Anorexia, Abdominal pain, Bloating, Nausea, Vomiting & Bloody diarrhoea.
 Blood cultures are positive.
 In chronic phase- Rose spots are seen on chest & abdomen.
 Extra intestinal complications.

AGAM PATHOLOGY
3. TUBERCULOSIS
A serious, communicable chronic granulomatous pulmonary & systemic disease caused
by Mycobacterium tuberculosis.

PATHOGENESIS:
The outcome of infection depends on development of anti-mycobacterial T-Cell mediated
immunity.
 Entry into macrophages: By binding to Mannose binding lectin receptor & CR3.
 Replication in macrophages: Blocks Phagolysosome formation by inhibiting Ca2+ signals.
 TH1 response: Activated by IL-12 produced by action of mycobacterial ligand on TLR-2.
 TH1 mediated macrophage activation and killing of bacteria: IFN Gamma expose
Bacteria to acidic environment, Express iNOS, mobilize anti-microbial peptide (Defensin).
 Granulomatous inflammation and Tissue damage: TH1 response orchestrates the
formation of granuloma and caseous necrosis.
 Role of other immune cells: NKT cells recognize mycobacteria lipid antigens bound to
CD1 produce IFN-G.
 Host susceptibility to infections:
 Polymorphism in IL-12,
 IFN – Gamma & its receptor Vulnerable state
 HLA
 Immunological state in active TB: Neutrophils of active TB patients have upregulated
Type 1 & 2 IFN gene.

MORPHOLOGY:
PRIMARY TUBERCULOSIS:
 Caseating and noncaseating tubercles are seen microscopically
 The granulomas are usually enclosed within a fibroblastic rim punctuated by lymphocytes.
 Multinucleated giant cells are present in the granulomas.

PATHOLOGY AGAM
 Inhaled bacilli implant in the distal airspaces of lower part of the upper lobe or upper part
of lower lobe close to pleura

Sensitization develops

1-1.5cm are of grey white inflammation with consolidation emerges – Ghon’s focus

Center undergoes caseous necrosis

This combination of parenchymal lung lesion and lymph nodal development is

Ghon’s complex

In 95% cases, cell mediated immunity controls infection

In remaining cases, Progressive fibrosis of Ghon’s complex

Radiologically detectable calcification – Ranke’s complex

Seed into organs without any lesions

SECONDARY TUBERCULOSIS:
 The initial lesion is usually a small focus of consolidation, less than 2 cm in diameter.
 Foci are sharply circumscribed, firm and gray-white to yellow in color, and have variable
degrees of central caseation and peripheral fibrosis.
 Active lesions show characteristic coalescent tubercles with central caseation.

PROGRESSIVE PULMONARY TUBERCULOSIS:

 In older adults and immunosuppressed people.
 Expand to adjacent lung and erodes Bronchi and vessels.
 Erosion of Blood Vessels result in Haemoptysis.

AGAM PATHOLOGY
MILIARY TUBERCULOSIS: (Can be asked in Short Notes)
Disseminated form of Tuberculosis

When disseminated to

To lungs: To other organs:

Miliary Pulmonary Disease Systemic Miliary TB

By Lymphatic spread By Arterial spread

A. MILIARY PULMONARY DISEASE:

MODE OF DEVELOPMENT:

Tubercle Infiltrate Venous Right side Pulmonary

Bacillus Lymphatics circulation of heart artery

MORPHOLOGY:
Multiple, small, yellow, nodular lesion in lung parenchyma as millets so called Miliary.

B. SYSTEMIC MILIARY TUBERCULOSIS:

MORPHOLOGY:
Mostly involved organs:
 Liver
 Spleen
 Bone marrow
 Adrenals
 Kidney
 Meninges
 Fallopian tubes
 Vertebra
 Epididymis

PATHOLOGY AGAM
ENDOBRONCHIAL, ENDOTRACHEAL AND LARYNGEAL TUBERCULOSIS:
 May develop by spread through lymphatic channels or from expectorated infectious
material.
 The mucosal lining may be studded with minute granulomatous lesions that may only be
apparent microscopically.

ISOLATED TUBERCULOSIS:
 May appear in any of the organs or tissues seeded hematogenously and may be the
presenting manifestation.
 Organs that are commonly involved include the:
 Meninges (tuberculous meningitis),
 Kidneys (renal tuberculosis),
 Adrenals (formerly an important cause of Addison disease),
 Bones (osteomyelitis), and
 Fallopian tubes (salpingitis).
 When the vertebrae are affected, the disease is referred to as Pott disease
 Para spinal “cold” abscesses in these patients may track along tissue planes and present
as an abdominal or pelvic mass.

LYMPHADENITIS:
 Most frequent presentation of extra-pulmonary tuberculosis, usually occurring in the
cervical region (“scrofula”).
 In HIV-negative individuals, lymphadenitis tends to be unifocal and localized.
 In HIV-positive people, on the other hand, almost always have multifocal disease,
systemic symptoms, and either pulmonary or other organ involvement by active
tuberculosis.

CLINICAL FEATURES:
 Primary TB: Occurs in previously unexposed unsensitized individuals. Acute bacterial
Pneumonia, Hilar adenopathy and Pleural effusion.
 Secondary TB: Arise in previously sensitized host. Due to Reactivation of latent infection or
Reinfection.
 Secondary Pulmonary TB: Cavity formation in lungs which erodes into airways, Malaise,
Anorexia, Weight loss & Fever, Night sweats and Pleuritic pain.
 TB and HIV: Low CD4+ count leads to TB. There is Focal lesion to multifocal infiltrates to
Localized apical disease with cavitation.
AGAM PATHOLOGY
DIAGNOSIS:
 Acid-fast smears and cultures of the sputum.
 Comprehensive antibiotic susceptibility testing
 PCR
 IFN-γ release assays (IGRAs) - Production of IFN-γ by the T cells is measured to assess the
level of T-cell immunity to the organism.
 The Tuberculin test (purified protein derivative [PPD] - The tuberculin skin test is
performed by intracutaneous injection of purified protein derivative of M. tuberculosis.
 Mantoux skin test:
 False-negative reactions - certain viral infections, sarcoidosis, malnutrition, Hodgkin
lymphoma, immunosuppression, and (notably) active tuberculous disease.
 False-positive tuberculin - Infection by atypical mycobacteria or prior vaccination
with BCG

TREATMENT:
 Antiretroviral therapy (ART)
 Immunosuppressive therapy
 Antibiotics

PATHOLOGY AGAM
SHORT NOTES
1. MYCETOMA:
 CHRONIC SUPPURATIVE INFECTION
 LIMBS ARE USUALLY INVOLVED

CHARACTERISTICS:
Sinus  material discharge is form of grain with colonies of fungi and bacteria
2 MAIN TYPES:
 Mycetoma caused by actinomyces Actinomycetoma (60% cases)
 Eumycetoma caused by true fungi  Madurella mycetomatis / M.grisea

MORPHOLOGY:
 Foot: Madura foot [swollen foot]
 Penetrate subcutaneous tissue and fascia till bone and draining sinus discharge purulent
material and black grai

2. MORPHOLOGY AND EVOLUTION OF TUBERCLE:

MORPHOLOGY:
FIBROBLAST
S
LYMPHOCYTES

EPITHELOID CELLS FUSES TO FORM GIANT CELLS

CENTRAL CASEOUS NECROSIS

EVOLUTION:
After 3 weeks of exposure , there is a tubercle development

AGAM PATHOLOGY
 Antigen presenting cells

Processes mycobacterial Ag Goes to regional lymph

node
CD4+ T cell TH1 cell

IL-12

MACROPHAGES

MAINROLE IN
INF --GAMMA
GRANULOMA
FORMATION

 MACROPHAGE ACTIVATION AND

 SOME FUSES TO FORM
LANGERHAN GIANT CELLS
 THIS ARRANGEMENT LEADS TO
FORM GRANULOMA ACTIVATION

PATHOLOGY AGAM
3. IMMUNOLOGY OF LEPROSY:
TYPES OF LEPROSY
 Tuberculoid leprosy TT
 Borderline leprosy
 Borderline tuberculoid BT,
 Borderline borderline BB
 Borderline lepromatous BL
 Lepromatous leprosy LL

IMMUNOLOGY OF LEPROMATOUS LEPROSY:

IL-12 production is low / T-cells do not respond to IL-12

Causes ↓ TH1 response

↓ Macrophage stimulation

↓ Cellular Immunity in LL

IL-12

Defective TH1 response Dominant TH2 response

Produces IL-4, IL-5, IL-10

Suppress activation of macrophages

Suppresses Cellular Immunity in LL

AGAM PATHOLOGY
IMMUNOLOGY OF TUBERCULOID LEPROSY
Antigen presenting cells

Produces IL-12

Stimulates TH1 cells γ and δ T-cell receptor lymphocytes

Produces IL-2 and IFN-γ Produces IFN-γ

Induces effective macrophage response

Induces good immune response in Tuberculoid Leprosy

IMMUNOLOGY OF LEPROSY:

PATHOLOGY AGAM
4. DIFFERENCE BETWEEN TUBERCULOUS AND LEPROMATOUS LEPROSY:
GROSS FEATURES TUBERCULOUS LEPROSY LEPROMATOUS LEPROSY
Skin lesions One or few, asymmetrical Many symmetrical
Margin is sharp Margin is irregular
Lesion appear as: Lesion appear as:
 Hypopigmented, annular  Multiple nodules (lepromata)
macules with elevated  Plaques and xantoma-like
borders papules
 Dry, scaly Leonine facies and eyebrow
Tendency towards central alopecia seen
clearing Mostly skin lesions are
anesthetic or hypo-esthetic
Nerve lesions  Early anaesthetic skin lesion  Nerve lesion appear late
 Enlarged thickened nerves  Hypoesthesia is a late sign
 Nerve abscess seen  Symmetric involvement of
 Asymmetric involvement of nerves without inflammation
large peripheral nerves with  Mostly ulnar and peroneal
granulomatous lesions. nerves are involved.
 Facial nerve involvement  Trophic changes follow nerve
eyelid paralysis, keratitis and lesions in hands and feet.
corneal ulcer.
 Nerve degeneration → skin
anesthesia → trauma →
chronic skin ulcers.
 Contractures, paralysis, auto
amputation of fingers and
toes occur.
Inflammation Granulomatous inflammation  No inflammation, Virchow’s
with few langhans cells lepra cells-foamy
macrophages are more in
cigar shaped bundles called
globi.
 Lymph nodes – have bacteria
filled foamy macrophages in
Paracortical and Reactive
germinal centres.
 Macrophages are also seen in
splenic red pulp.

AGAM PATHOLOGY
GROSS FEATURES TUBERCULOUS LEPROSY LEPROMATOUS LEPROSY
Bacillary Load Paucibacillary Multibacillary
Bacteriological Index 0-1+ 4-6+
Cell-mediated CMI normal CMI low
Immunity (CMI)
Lepromin test Positive Negative
Lymphocyte Positive Negative
transformation test
CD4/CD8 T-cell ratio 2:1 (normal) 1:2
Humoral immunity Normal Exaggerated
Autoantibodies Not seen Elevated
VDRL test VDRL test negative Biological false positive
Antibodies to Elevated in 60% cases Elevated in 95% cases
phenolic glycolipid
(PGL-1)
Macrophages Epithelioid type Foamy type (lipid-laden)
Langerhans giant cells Found Not seen
Grenz /clear zone Absent Present
between inflammatory
cells and epidermis
Systemic involvement Mostly not involved Mostly involved especially eyes,
testes, bones and joints

5. Microscopic appearance of lepromatous leprosy:

 Abundant bacteria due to weak cell mediated immunity and inability to control bacteria
→ readily visualized in tissue sections (“multibacillary”)
 In smears made from skin lesions, bacteria appear in groups, called cigar-like bundles
(globi) of weakly acid fast bacilli present inside lipid laden macrophages called Virchow’s
lepra cells.
 The macrophages are able to phagocytose the lepra bacilli but instead of being killed, the
bacilli proliferate inside the cells.
 Flattened epidermis: Epidermis is thinned and flattened (loss of rete ridges) over the
nodules.
 Grenz (clear) zone: It is a characteristic narrow, uninvolved dermis (normal collagen)
which separates the epidermis from nodular accumulations of macrophages.

PATHOLOGY AGAM
6. DIFFERENCE BETWEEN DRY AND WET GANGRENE
DRY GANGRENE WET GANGRENE
A type of gangrene , which develops in the The type of gangrene caused by a bacterial
presence of arterial obstruction , producing infection in the affected tissue
sharply localized dryness of dead tissue
Mechanism : arterial occlusion Mechanism : venous obstruction
Site : Commonly limbs Site : More Common in Bowel
Characteristics : dryness , shrinkage , and the Characteristics :
black color of the dead tissue , sharply  Softening
demarcated from adjacent tissue by a line of  Swelling
inflammation  Blistering
 Rotten
 Wet and dark appearance
Putrefaction is limited due to very little blood Putrefaction is marked due to the
supply congestion of organs with blood
A line of demarcation is present at the junction There is no clear cut line between the
between healthy and gangrenous parts healthy and gangrenous parts
Bacteria fail to survive Numerous bacteria are present
Can be treated with surgery Requires immediate treatment as it can
cause death in a few days
Prognosis is better due to little septicemia Prognosis is poor due to profound toxemia

7. PATHOGENESIS OF GANGRENE
 Clostridium enters the injured tissue
 Spore produced
 Available in circulation
 Available in anaerobic tissue
 Grow and ferment muscle carbohydrate
 Toxins and enzymes produced
 Enzymes :
 Lecithinase
 Collagenase
 Permease ,
 Hyaluronidase
 Enzymes digest and kill host cell and extend anaerobic environment
 Produce gases and destroy tissues (crepitant tissue)

AGAM PATHOLOGY
8. TERTIARY SYPHILIS
 About 2-3 years following first exposure , tertiary lesions of syphilis occur
 Less infective

TYPES OF 3O SYPHILIS:
 Syphilic gumma:
 Solitary , localized , rubbery lesion with central necrosis
 Seen in liver , testis , bone , brain
 Liver – scarring of hepatic parenchyma (hepar lobatum)
 Diffuse lesions of tertiary syphilis:
 Lesions appear following widespread dissemination of spirochetes in the body

A. CARDIOVASCULAR SYPHILIS
 Also Known as Syphilitic aortitis.
 involves thoracic aorta
 wall of aorta weakened – aortic aneurysm
 incompetence of aortic valve

B. NEUROSYPHILIS:
May be Asymptomatic or Symptomatic
Asymptomatic:
Detected by CSF Examination
 Elevated Protein Levels
 Pleocytosis (Increased number of inflammatory cells)

Symptomatic:
 Meningovascular syphilis – affects meninges
 Tabes dorsalis affecting the spinal cord
 General paresis affecting the brain

PATHOLOGY AGAM
9. VIRAL HEMORRHAGIC FEVER:
Life-threatening multisystem syndrome + vascular dysregulation and damage → shock.

CAUSES:
Enveloped RNA virus

Arena viridae Bunya viridae Filo viridae Flavi viridae

SYMPTOMS:
 Mild Acute Disease  Severe life-threatening disease
 Fever  Sudden hemodynamic deterioration
 Headache  shock
 Myalgia
 Rash
 Thrombocytopenia
 Neutropenia

TRANSMISSION:
 Pass through animal/ insect host
 Humans → incidental host, infected when come in contact with infected animal [rodents]
or insect [rodents, ticks]
 Ebola, Marburg, Lassa → cause haemorrhagic fever → transmitted from person to person.

PATHOGENESIS:
 Hemorrhagic manifestation due to:
 Hepatic injury → Deficiency of clotting factors
 Cytokine induced DIC
Hemorrhagic manifestations
 Platelet dysfunction
(like petechiae)
 Endothelial injury
 Thrombocytopenia

AGAM PATHOLOGY
  Damage to Blood vessels due to
 Injury and damage t endothelial cells
 Infection of dendritic cells and macrophages → Production of inflammatory cytokines
 Hemorrhages → prominent in Congo-Crimean fever → rarely life threatening.
 Necrosis of tissues → secondary to vascular lesions and hemorrhages → varies from mild,
focal to massive → attendant inflammatory response minimal.

10. ACTINOMYCOSIS
 Chronic suppurative disease
 Caused by actinomycetes (A.israelii)
 Infection is always endogenous in origin (not by person to person contact)

MORPHOLOGIC FEATURES:
 Oral cervicofacial actinomycosis:
 Commonest form (60%) – best prognosis.
 Infection enters from tonsils , carious teeth , periodontal disease
 Thoracic actinomycosis : infection in the lungs is due to aspiration of the organism from
oral cavity or extension of infection from abdominal or hepatic lesions
 Abdominal actinomycosis : presents as an abscess , commonly in appendix , caecum ,
liver
 Pelvic actinomycosis : infection in the pelvis occurs most often as a complication of
intrauterine contraceptive devices and begins as endometriosis

MICROSCOPIC EXAMINATION:
 Inflammatory reaction is granuloma with central suppuration
 Sulphur granule

PATHOLOGY AGAM
SHORT ANSWERS
1. CYSTICERCOSIS
 Caused by Taenia solium.
 Eggs ingested through contaminated food and water, hatch into larvae, spread
hematogenously, and encyst in many organs.
 Encystment in brain- Neurocysticercosis.
 Convulsions, increased intracranial pressure and other neurological disturbances occur.
 Most common locations are brain, muscle, heart and skin.
 They may be intraparenchymal, attached to arachnoid or freely floating in ventricles.
 Focal scarring and calcification seen by radiography when cyst degenerates.

2. HAEMATOCRIT IN DENGUE FEVER:

 Haematocrit Elevated due to Haemoconcentration
 Greater than 20%- sign of haemoconcentration and precedes shock.
 Monitored every 24 hours to facilitate early recognition of dengue haemorrhagic fever
and every 3-4 hours in severe cases- dengue shock syndrome.

3. BLACK WATER FEVER:

 Also called malarial hemoglobinuria.
 Caused by Plasmodium falciparum.
 Haemolysis of red cells.
 Rapid pulse, high fever and chills, haemolytic anaemia.
 Urine is black or dark red in colour due to presence of haemoglobin urine.

4. GROSS APPEARANCE OF MYCETOMA:

 Chronic granulomatous disease affecting subcutaneous tissue of the feet and hands.
 Caused by Madurella, Nocardia, Actinomadura and Streptomyces somaliensis.
 Features are:
 Subcutaneous nodular swelling.
 Multiple sinuses.
 Discharge contains granules.
 Bony deformities.

AGAM PATHOLOGY
5. FUNGAL GRANULOMA (Fungus ball)
 A fungus, which is the antigen here, is surrounded by lymphocytes with mast cell .This
arrangement is called fungal granuloma.
 The granuloma
 Has a sharp demarcated borders, discrete spherical appearance.
 Cavitation is present.

6. RHINOSPORIDOSIS
 A chronic granulomatous disease , where friable polyps developed.
 Caused by: Rhinosporidium seeberi(aquatic protozoa)
 Common presentation: U/L or B/L nasal polyps.
 Pathogenesis: present as polypoidal growth in the nasal cavity, lesions can also be seen
in eye, skin, buccal cavity or genitalia.
 Mostly it is mucous membrane. Haematogenous dissemination is rare
 Diagnosis: Polyp biopsy done, we get a spherule with many endospores.
 Treatment: surgical polypectomy (removal of polyp)

7. NEGRI BODIES
 These are inclusion bodies which are located intracytoplasmic
 Virus particles get replicated in the cytoplasm /nucleus, so during that they form
aggregation.
 These negri bodies are characteristic feature of RABIES VIRUS.
 This negri bodies are normally found in hippocampus.

SELLER’S TECHNIQUE
 Negri bodies is detected by Sellers technique.
 Specimen: Impression smears of brain stained by sellers technique
 Stain: Basic fuschin and methylene blue in methanol.
 Fixation and staining are done simultaneously which is an advantage here

PATHOLOGY AGAM
UPDATES:
1. PATHOGENESIS OF GI DISEASE (ADDITIONAL)
 Toxin production.
 Some organisms contaminating food can produce gastrointestinal disease without
necessarily establishing an infection in the host.
 An example is Staphylococcus aureus, which elaborates a powerful exotoxin during its
growth in contaminated food that is responsible for acute food poisoning.
 Bacterial colonoization and toxin production.
 Other bacteria establish an infection and produce damaging toxins.
 Examples include V. cholerae and enterotoxigenic Escherichia coli, which bind to the
intestinal epithelium and multiply in the overlying mucous layer.
 These organisms elaborate potent exotoxins that are responsible for symptomatic
disease.

2. ROLE OF CELL-SURFACE RECEPTORS IN MEASLES:

 Signaling lymphocytic activation molecule family member 1 (SLAMF1) is expressed on
activated lymphocytes, dendritic cells, and monocytes, and it serves as the initial receptor
for viral infection.
 Nectin-4 is found on the basal surface of epithelial cells and is thought to be important for
replication of the virus within the respiratory tract, before spread of the virus in respiratory
secretions.
 CD46 was the first cell-surface receptor identified for measles virus, but it has been found
to be used only by culture-adapted virus (including the vaccine strain), and not wild-type
virus

3. EVASION FROM HOST DEFENCE – LEISHMANIASIS:

To escape killing by neutrophils, Leishmania spp. use the following mechanisms:
 Interfere with the formation of phagolysosomes and fusion with granules
 Localize to nonlytic compartments
 Resist toxicity by reactive oxygen species
 Resist neutrophil extracellular trap (NET) formation by producing endonucleases that digest
the NETs and expressing protease-resistant molecules.

AGAM PATHOLOGY
4. FORMS OF LEISHMANIASIS:
 Old World
 L. major, L. tropica, L. donovani, and L. infantum
 Refers to the Eastern Hemisphere (parts of Asia, the Middle East, Africa (particularly the
tropical region and North Africa), and southern Europe.
 New World
 L. mexicana, L. braziliensis, and L. chagasi
 Refers to the Western Hemisphere (parts of Mexico, Central America, and South
America).

5. REQUIREMENT OF IRON - LEISHMANIASIS

 Leishmania spp. require iron for survival.
 They have an iron transporter from the ZRT-, IRT-like (ZIP) family of membrane proteins
that is expressed on amastigotes and
 The iron transporter stimulates iron entry into the normally low iron environment of
macrophage phagolysosomes.
 The host combats this iron acquisition by using pro-inflammatory cytokines to repress iron
absorption by
 Increasing production of hepcidin - the principal iron exporter
 Activating synthesis of ferritin - binds free iron
 In addition, macrophages downregulate the transferrin receptor and remove iron from the
phagosome.

6. CMV INFECTION
 Adoptive transfer of CMV-specific T cells has been successfully used to prevent CMV
disease after bone marrow transplantation, and the CD8+ T cell response has been thought
to be the most important effector response.
 CD4+ T cells, γδ T cells, and NK cells are known to play a role in immune control of the
infection.
 CMV encodes several Fcγ-binding glycoproteins that effectively operate as adversaries of
host Fcγ receptors, inhibiting IgG-mediated immunity
 CMV has been associated with vasculopathy and neurocognitive impairment with
associated immune markers including the accumulation of multifunctional terminally
differentiated αβ T cells, γδ T cells, and NK cells.

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7. PATHOGENESIS OF CRYPTOCOCCOSIS
 Polysaccharide capsule.
 Cryptococcus spp. can block dendritic cell maturation by reducing MHC class II–
dependent antigen presentation and inhibiting the production of IL-12 and IL-23.
 Cryptococcus spp. can make large cells, called Titan cells that are greater than 12 μm
and have a thickened cell wall.
 Cryptococcus spp. also produce small (micro) cells of 2 to 4 μm that may be adapted for
growth in macrophages.
 Melanin production.
 Enzymes.
 Phospholipases degrade cell wall components and may aid tissue invasion.
 Urease helps neutralize the reactive oxygen species and pH of the phagocytic cell.
 Differential cellular response to phagocytes.
 A mechanism has been hypothesized to explain the outbreak of the C. gattii strain
 In response to reactive oxygen species in the phagocyte, some cells stop growing and
acquire an unusual morphology with tubularization of mitochondria, and other cells
rapidly divide.

8. CLINICAL FEATURES OF HYDATID DISEASE:

 Infection in humans is usually asymptomatic, but large cysts in the liver can cause
abdominal pain or obstruction, and pulmonary cysts can cause pain, cough, and
hemoptysis.
 Caution is warranted if surgical removal of the cyst is considered, as anaphylaxis and/or
dissemination of organisms can result from spillage of the cyst contents.

9. HHV8+ CONDITIONS
 Kaposi Sarcoma
 Primary effusion lymphoma
 Multicentric Castleman disease
 Germinotropic Lympho proliferative disorder
 KSHV Inflammatory Cytokine Syndrome

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10. ONE LINERS:
 Babesia microti and Babesia divergens, are transmitted by ticks, Ixodes scapularis (deer
tick) and Ixodes ricinus (sheep tick),
 Additional cases of babesiosis is due to B. duncani and B. venatorum.
 There are about 21 species of Leishmania that infect humans and about 30 species of
sandflies that serve as vectors.
 Elastases and trypsin-like proteases facilitate invasion of host tissues in lymphatic filariasis.
 Multiplex PCR panels for detection of over 20 pathogens are now in clinical use for
detection of pathogens in stool, respiratory samples, and cerebrospinal fluid, as a well as
positive blood culture broths.
 High-throughput or next-generation sequencing methods, most often following PCR of the
16S rDNA gene for bacteria or the ribosomal internal transcribed spacer (ITS) region for
fungi, allow rapid sequencing of large numbers of DNA molecules.
 Antiretroviral treatment of pregnant women with HIV infection and their newborn infants
can reduce the transmission of HIV to offspring from 25% to less than 1%.
 Brown and Brenn stain are used to identify Bacillus anthracis

11. NEW TOPICS DISCUSSED:

 Pg 352 - Ebola Virus
 Pg 352 - Zika Virus
 Pg 353 - Dengue
 Pg 353 - Novel Coronavirus SARS-CoV-2 (COVID-19)
 Pg 373 - Non-tuberculous mycobacterial infections
 Pg 385 - Candida auris Infections
 Pg 386 - Pneumocystis Infections
 Pg 394 - Toxoplasmosis

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