Granulomatous Diseases

Question 1

What is granulomatous disease?

Answer 1

Type of chronic inflammation
Secondary response to endogenous or exogenous antigen

Question 2

What cells are predominant in granulomatous disease?

Answer 2

○ Macrophages
○ Epithelioid macrophages (activated)
○ Multi-nucleated giant cells

If neutrophils = pyogranuloma

Question 3

What causes granulomatous disease?

Answer 3

Microbial agents
Autoimmune diseases
Foreign bodies
Idiopathic conditions

Question 4

Bacteria that cause granulomatous disease

Answer 4

○ Rhodococcus equi
○ Mycobacterium spp. - Johne’s and bTB
○ Actinobacillus spp. - Wooden tongue
○ Burkholderia mallei - Glanders
○ Brucella spp.

Question 5

Superficial mycoses which cause granulomatous disease

Answer 5

Candida albicans
Aspergillus fumigatus

Question 6

Systemic mycoses which cause granulomatous disease

Answer 6

Histoplasma capsulatum
Blastomyces dermatitidis
Coccidioides immitis
Cryptococcus neoformans

Question 7

Rhodococcus equi

Answer 7

Intracellular gram +ve bacterium
1. Produces molecules which suppress acidification of phagosome-lysosome
2. Proliferates within macrophage leading to lysis
3. Strong cell mediated inflammation response
4. cytokines activate macrophages and neutrophils leading to pyogranuloma

Virulent forms produce a plasmid encoding for vapA

Question 8

vapA

Answer 8

virulence associate protein A
* Allows bacteria to survive within macrophages

Question 9

How does Rhodococcus equi affect foals

Answer 9

Infects via inhalation
* Leads to pyogranulomatous bronchopneumonia
* Can also cause ulcerative enterocolitis inside Peyer’s patches

Question 10

Johne’s Disease

Answer 10

Mycobacterium avium paratuberculosis (MAP)
* Acid fast gram +ve nonmotile intracellular bacillus
* Causes chronic enteritis in cattle (ileum and LI)
○ Leads to diarrhoea
○ Progressive emaciation
○ Death
* Needs high concentration of iron
○ Highest in ileocecal region

Question 11

How do cows get infected with MAP?

Answer 11

Ingested with contaminated faeces, milk, colosseum, water

Question 12

How do cows get infected with MAP?

Answer 12

Ingested with contaminated faeces, milk, colosseum, water

Question 13

Mechanism of Johne’s Disease

Answer 13

Once bacteria reaches epithelium over Peyer’s patches
○ Reach macrophages within Peyer’s patches
○ Mycobacterium inhibits phagosome-lysosome
○ Prolonged incubation
○ Persistent proliferation of macrophages
○ Thickening of intestinal lamina propria - filled with macrophages
○ Granulomatous enteritis

Question 14

bTB

Answer 14

Bovine Tuberculosis
Mycobacterium bovis
* Intracellular aerobic gram +ve non-motile coccobacilli
* Acid fast (mycolic acids and high lipid content in cell wall)

Question 15

Mechanism of bTB

Answer 15

○ Mycobacteria survive in macrophages
○ T-cell immune mediate response produces INFgamma
Recruits more macrophages

Question 16

Virulence factors of bTB

Answer 16

○ Cord factor
Inhibits chemotaxis
○ Lipoarabinomannan (LAM)
Induces activation of macrophages to secrete more TNFalpha
○ ESAT-6
Lysis of phagosomes
Helps expansion of granuloma

Question 17

Wooden tongue

Answer 17

Actinobacillus lignieresii
* Aerobic. non-motile gram -ve coccobacilli
Commonly affects soft tissue of head and neck
Oral cavity commensal

Question 18

Mechanism of Wooden Tongue

Answer 18

○ Mucosal trauma leads to local invasion
○ Causes local infection
○ Spread via lymphatics
○ Leads to pyogranulomatous lymphadenitis

Question 19

Glanders

Answer 19

Burkholderia mallei
* Non-motile gram-ve bacillus
Highly contagious
Zoonotic disease
Notifiable disease

Infection caused by ingestion/inhalation of infected excretion
Pathogenesis not fully understood
* Bacteria can cross intestinal mucosa and cause septicaemia

Question 20

Virulence factors of glanders

Answer 20

○ Glycocalyx biofilm
○ Adhesins
○ BpaB protein - involved in adhesion to target cells

Question 21

Brucellosis

Answer 21

Brucella suis - pigs
Brucella canis - dogs
Brucella ovis - sheep
Brucella melitensis - sheep and goats

All are zoonotic except B. ovis

Transmission by contact with infected tissues, secretions or excretions
○ Milk
○ Urine
○ Fetal tissues
○ Placenta

Question 22

Brucella canis - dogs

Answer 22

Epididymitis
Placentitis
Discospondylitis

Question 23

Brucella ovis - sheep

Answer 23

Epididymitis
Placental lesions

Question 24

Brucella melitensis - sheep and goats

Answer 24

Inflammation in mammary glands and pregnant uterus

Question 25

Mechanism of brucellosis

Answer 25

○ Penetration of mucosa
○ Spreads to regional lymph node (lymphadenitis)
○ Replication within macrophages
* Can cause severe bacteraemia
Disseminate in many organs

Question 26

What is dimorphic fungi?

Answer 26

Two forms in life cycle
* Yeasts - unicellular
* Moulds - Branched filamentous pseudohyphal or hyphal forms

Question 27

Superficial mycoses examples

Answer 27

Candida albicans
Aspergillus fumigatus

Question 28

Systemic mycoses examples

Answer 28

○ Histoplasma capsulatum
○ Blastomyces dermatitidis
○ Coccidioides immitis
○ Cryptococcus neoformans

Question 29

Pathogenesis of dimorphic fungi causing granulomatous disease

Answer 29

1. Present as vegetative hyphae (mycelia) during mould phase
2. Release spores which are ingested or inhaled
3. Germinate into yeasts in the yeast phase
4. Multiple and return to environment in mould phase

Question 30

How do fungi cause granulomatous inflammation?

Answer 30

Contain complex molecules which protect them from phagocytosis
* Can’t be completely degraded and removed by acute inflammation
* Virulence factors allow activation of macrophages
* Results in secretion of chemokines and cytokines
* Recruits more macrophages

Question 31

Histoplasmosis

Answer 31

• Primary pulmonary disease
• Microconidia from soil are inhaled
• Yeast proliferates in macrophages
• Yeasts are eliminated by cell mediated response
  If response is incomplete - granuloma formation