Mycobacteria Flashcards
What diseases are caused by Mycobacterium and identify the causative strains.
- Mycobacterium tuberculosis/ Mycobacterium bovis: Tuberculosis (TB)
- Mycobacterium Leprae- Leprosy
What does Mycobacterium cause in the tissues and what is mycobacterium dependent on in order to ensure its survival within the host?
- Granulomatous lesions (tubercules) in tissues.
- Mycobacterium must be able to survive and multiply within the macrophages of the host.
What kind of bacteria is Mycobacterium?
- Aerobic
- Acid fast bacteria- they bind phenol dyes like carbol fuchsin and resist acid alohol decolorization therefore use a Ziehl-Neelson stain (ZN stain)
- Non spore forming
- Non motile GRAM POSITIVE rods- DO NOT STAIN WELL WITH GRAM STAIN.
- Catalase positive (breaks down H2O2 to survive)
- Can have rapid growth (< 7 days) or slow growth (weeks to months). Most pathogens are slow growth.
- Very unique cell walls. (see next slide)
What is unique about the cell walls of Mycobacterium?
- There cell walls are lipid rich.
- There acid-fastness is related to presence of peptidoglycan but particualary glycolipids.
- Their lipids in the cell wall are related to its pathogencitiy particularly its survival in the phagolysosome of macrophages, resists drying, extreme pH, and other stresses.
Virulence factors of Mycobacterium?
Cell wall components
- Mycolic acids- resist phagocytic digestion.
- Sulfatides- prevent phagocyte activation and phagosome-lysosome fusion.
- Trehalose di-mycolate (cord factor)- inhibits phagocyte chemotaxis, activation, phagolysosome fusion, digestion.
- Lipoarabinomannan (LAM)- prevent phagocyte activation and digestion within the phagocyte.
- Mycosides- prevent intracellular killing and digestion.
Become ingested my host macrophages and due to its virulent lipid rich (glycolipid) capsule containing multiple mycotic virulence factors… it is able to resist lysosome digest, prevent phagolysosome fusion, and replicate within these host macrophages. Once the host macrophage dies, the bacteria will be released and engulfed by surround vialbel phagocytes. Migration of macrophages and their imminent death allows dissemination of the bacteria in the body.
Mycobacterium infection and development of disease.
Less than 10% of those infected develop disease.
- Can infect and be killed by the immune response **causing no disease. (IMMEDIATE RESOLUTION) **
- Can infect and lie dormant for many years (infection contained) This is the most common form.
- Infects, lies dormant for many years, then reactivates causing acute disease. (Reactivation in elderly people)
Infects, lies dormant, reactivates causing rapid acute disease, may disseminate.
Mycobacterium Tuberculosis: TB in man.
Infection is most common in the apices of the lung because that is where most oxygenation occurs.
Coughing disseminates the organism, breathed in by new person, new infection.
Immune Responses to Mycobacterial Infections:
- Immune control of mycobacterium requires a CELL MEDIATED IMMUNE RESPONSE since mycobacterium are intracellular pathogens of macrophages therefore an antibody response is irrelevant for protection.
- An active response results in lymphocyte infiltration, central necrosis in the lesion, tubrcule, may be limited by a fibrous capsule.
- A cell mediated response is initiated by activation of CD4+ T Helper lymphocytes following phagocytosis of bacteria by dendritic cells. CD4+ T-helper cells activate cytokine “IFN-gamma” which activates macrophages to kill intracellular bacteria.
- IL-2 secreted from the dendritic cells activates CD8+ Cytotoxic T cells (lymphocytes) that kill mycobacterial infected cells. The response may kill the disease but will likely only be able to restrict it.
- Reactivation occurs during times of stress/ immunocomprization.
Bovine Tuberculosis:
- **Spread is promoted by high stocking densities and immune suppression. **
- This is normally a primary respiratory infection (inhaled) that leads to tubercule formation in the lungs and lymph nodes (bronchial and retropharyngeal). Transmission can occur via direct contact, sputum, urine, feces, pus (grazing and ingest contaminated excreta). **Tubercules formed can either be open or closed (significant) **
- Infection can spread to intestines via sputum, or further to liver, spleen, brain, kidney via hematogneous route once absorbed through the GIT.
- Animals infected are usually culled. Vertical transmission is also possible if infection spreads to mammary glands and uterus.
- Zoonotic disease however since milk is normally pasteruized very few humans contract. Badgers, deer, pigs can extract.
- If respiratory lesion is open, animal can cough up and acitvely infect others.
Bovine TB:
Immune response and Latent infection.
- Cattle exposed to Mycobacterium Bovis.
- The Innate response of the animal ensues and can either:
**1.clear the Bacilli where no infection occurs (NEGATIVE skin TB Test) **
OR
**2. Bacilli remain viable. **
- If the bacilli remain viable, the cattle adapated immune response ensues and from there the Bacilli can either:
1. Be controlled
**2. Be uncontrolled. **
- If the Bacilli are controlled a latent infection occurs (NEGATIVE Skin TB test). Although in a latent infection (which is the most common for humans) if the animal becomes immunocompromised the bacilli can reactivate and cause actue disease leading to a POSITIVE Skin TB test
- If the bacilli are uncontrolled acute disease will occur and a **POSITIVE Skin TB test will confirm. **
Epidemiology of Bovine TB
- Cattle can spread to other cattle via infected respiratory droplets. Open lesion and coughing. - Respiratory route. They can also spread infection via direct contact (grazing) of infected sputum, urine, feces, pus.
- Badgers transmit M. bovis between themselves by the respiratory route and by biting.
- Cattle can get M. bovis from badgers via grazing on pasture contamnited with badger urine, feces, and bornchial pus or badgers urinate and defecate in cattle feeders.
Milk from TB mastitis
Before pasteurization M. bovis zoonotic infection in man was common. Now it is very rare in humans.
Elderly folk (pre 1930’s) who drank unpasteurized milk, are now becoming older and immunocompromised and their latent infections are reactivating and causing disease.
Describe how the Comparative intradermal test works for testing bovine TB.
Two sites are prepped on the neck 13 cm apart. Each site is clipped with a 2 cm radius. The skin fold is measured.
The top site is injected with M. avium the bottom with M. bovis.
Re measure the fold after 72 hours, if the M. bovis site is 5 mm greater than the M. avium then this is a defined reactor and a positive TB diagnosis.
The 5mm increase is attributed to lymphocyte infiltration into the site because if they were previously exposed, increased TB specific lymphocytes in lesion.
Interferon Gamma Assay
More sensitive than TB test. Usually both tests done together.
Measuring IFN- gamma released from CD4+ T lymphocytes.
Note: Can get a negative TB skin test if you have a massive infection because all the TB specific T lymphocytes which would accumulate at the injection site are being used to fight off the actual infection.
As the bacteria load increases, can get a decline in the interferon gamma assay response however the antibodies will be increasing!
Mycobacterium avium ss. paratuberculosis:
What disease does this cause?
How does infection occur and what are the clinical signs?
Johne’s disease in cattle.
Causes a transmissible chronic and progressive enteritis in cattle sheep and goats.
Infection usually occurs within the first month but may take 6 months to 5 years to become apparent.
Clinical course (1-4 months) starts with general signs of illness ( wt. loss, intermittent diarrhea) followed by severe diarrhea, emaciation, death.
The infected calves get impaired intestinal function due to chronic inflammation. Accumulation of lymphocytes and epitheloid cells in the lamina propria and submucosa.
