Lecture 8: Acid fast bacteria -Mycobacterium Flashcards
1) Lipid cell wall features of Mycobacterium 2) Pathogenesis of tuberculosis 3) Clinical manifestations of Mycobacterium tuberculosis 4) Clinical manifestations of Mycobacterium leprae
Mycobacterium
- 2 important pathogenic species
- who’s infected?
- shape
- staining
- classification
- growth speed
- 2 important pathogenic sps.
- Mycobacterium tuberculosis, M.leprae
- humans are only species infected
- thin rods w/lipid laden cell walls makes them acid fast on staining
- obligate aerobe
- grows very slowly, taking up to 6 wks for visible growth
- mycosides
_________-_ are the class of lipid that only acid fast organisms have.
Mycosides
Mycolic acid
a large fatty acid
Mycoside
a mycolic acid bound to a carbohydrate, forming a glycolipid
Cord factor
- a mycoside formed by the union of 2 mycolic acids with a disaccharide (trehalose)
- found only in virulent strains of M.tuberculosis the - inhibits neutrophil migration and damages mitochondria
Sulfatides
- mycosides that resemble cord factor with sulfates attached to the disaccharide
- inhibit the phagosome fusion with lysosome that contains bacteriocidal enzymes
Wax D
a complicated mycoside that acts as an adjuvant and may be the part of M.tuberculosis that activates the protective cellular immune system
Pathogenesis of Tuberculosis
-Facultative Intracellular Growth
- with the first exposure (usually by inhalation) the host has no specific immunity
- the inhaled bacteria cause a local infiltration of neutrophils and macrophages
- due to various virulence factors the phagocytosed bacteria are not destroyed, they multiply and survive in the macrophages
- the bacteria cruise the lymphatics and blood to inhabit distant sites
Pathogenesis of Tuberculosis
-Cell-mediated immunity
- some of the macrophages succeed in phagocytosing and breaking up the invading bacteria
- the macrophages then run toward a lymph node and present bacterial peptides to T-helper cells (CD4+ T cells)
- the CD4+ T cells differentiate into Th1 cells that produce IFN-gamma and TNF-alpha, which together with IFN-gamma and IL-1 produced by macrophages further activating killing mechanisms in macrophages
- the macrophage attack results in local destruction and necrosis of the lung tissue
- the bacteria is kept at bay but remain viable, at some time in the future the bacteria may grow again when the host’s resistance is challenged
PPD Skin Test
- what type of hypersensitivity?
- size and timing of postive test
- what does (+)PPD mean?
- following induction of cell-mediated immunity against M.tuberculosis, any additional exposure causes a localized delayed type hypersensitivity (Type IV)
- intradermal injection of antigenic protein particles from killed M.tuberculosis called PPD (Purified Protein Derivative), results in a localized induration that is bigger in diameter than 10mm after 48hrs
- (+)PPD is considered to have latent tuberculosis
- (+)PPD is present in persons with active infection, latent infection, and those who have been cured of their infection
PPD Skin Test
-False positive test
- some people from other countries have had the BCG (Bacillus Calmette-Guerin) vaccine for tuberculosis
- *this vaccine is debatably effective in precenting tuberculosis but it may result in positive PPD
PPD Skin Test
-False negative test
-some patients do not react to PPD even if they have been infected, these patients are anergic and lack a normal immune response due to steroid use, malnutrition, AIDS, etc.
PPD Skin Test
-Alternate Test
-QuantiFERON TB, that measures IFN-gamma produced in response to addition of specific tuberculosis antigens
Clinical Manifestations
-Primary Tuberculosis
- M.tuberculosis transmitted via aerosolized droplet from respiratory secretions of an infected individual
- droplets land in areas of lung: middle & lower lung zones & cause a small area of pneumonitis
- bacteria enter macrophages, multiply and spread via lymphatics
Clinical Manifestations
-Asymptomatic Primary Infection
- the cell mediated immunity kicks in and contains the bacteria in caseous granulomas
- the organism in these lesions are viable, a calcified tubercle in the middle or lower lung zone is called a Ghon focus
PAMP
Pathogen Associated Molecular Pattern
See slide 11-12 for explanation of Progression of active Tuberculosis Infection
Don’t forget
____% of individuals, M.tuberculosis enters bronchi and is transmitted via coughing -patient infectious
5%
____% of individuals, M.tuberculosis spreads to other organs where it remains latent (in ________) under the control of the _______ immune system until __________
95%; adaptive; change in immunocompetency and reactivation
Symptomatic Primary Tuberculosis
-occurs in who?
occurs more commonly in children, the elderly, and immunocompromised (HIV infected)
Secondary or Reactivation Tuberculosis
-occurs when?
occurence after the bacteria has remained dormant for some time
Pulmonary Tuberculosis
- most common site of __________tuberculosis
- infection occurs where?
- process
- most common site of reactivation tuberculosis
- infection occurs in the apical areas of the lung around the clavicles and reactivates in the upper lobe as oxygen tension is highest
- slowly they grow, caseate, liquefy, and cavitate
- slow erosive infection occurs as host macrophages and T cell battle to wall off the bacteria
Clinical Manifestations
-Pleural and Pericardial Infection
infection in these spaces results in infected fluid collections around the lung or heart
Clinical Manifestations
-Lymph Node Infection
cervical lymph nodes become swollen, mat together, and drain
Clinical Manifestations
-Kidney
RBCs and WBCs in the urine, but no bacteria. Known as sterile pyuria
Clinical Manifestations
- Skeletal
- > ______’s disease
-involves the thoracic and lumbar spine, destroying intervertebral discs and adjacent vertebral bodies (Pott’s disease)
Clinical Manifestations
-Joints
chronic arthritis of at least one joint
Clinical Manifestations
-Central Nervous System
subacute meningitis and forms granulomas in brain
Clinical Manifestations
-Miliary Tuberculosis
timy millet sized tubercles are spread
Diagnosis of TB
PPD skin test
Chest X-ray
Sputum acid fast stain and culture
Treatment for TB
- Isoniazide, rifampin, ethambutol, streptomycin and pyrazinamide are the first line of drugs used
- Drug reisitance -MDR-TB & XDR-TB strains require multiple-second line agents for an extended period of time (usu. 18-24 mo)
Course of Treatment for TB
-short course treatment
combination of Isoniazide, Rifampin, Ethambutol, and Pyrazinamide for 2 months followed by Isoniazide and Rifampin for further 4 months
Mycobacterium Leprae
- causes what
- clinical manifestations depend on
- # of subdivisions of leprosy
- causes leprosy or Hansen’s disease
- clinical manifestions are dependent on:
a) bacteria grow better in cooler body temps
b) severity of disease depends on host’s cell-mediated immune response - 5 clinical subdivisions of leprosy
Lepromatous Leprosy (LL)
- _________form of leprosy
- can/cannot mount a cell-mediated immune response?
- primarily where?
- symptoms
- eventually leads to _____ if untreated
- severest form of leprosy, patients cannot mount a cell mediated immune response
- LL primarily involves the skin, nerves, eyes, and testes, but the bacilli are found everywhere
- skin lesions cover the body with all sorts of lumps and thickenings
- nasal cartilage can be destroyed creating a saddlenose deformity
- the anterior segment of the eyes become involved, leading to blindness
- most peripheral nerves are thickened and there is loss of sensation in the extremities
- will eventually lead to death if untreated
Tuberculoid Leprosy (TL)
- can/cannot mount a cell-mediated immune response?
- what type of hypersensitivity?
- what test?
- symptoms
- patients are infectious/noninfectious?
- patients with TL can mount a cell-mediated response against bacteria, thus containing the skin damage so that it is not excessive
- delayed hypersensitivity rxn is intact
- lepromin skin test is usually positive
- patients demonstrate localized, superficial, unilateral skin and nerve involvement
- only 1 or 2 skin lesions, well defined, hypopigmented, elevated blotches
- the area within the rash is often hairless with diminished or absent sensation and enlarged nerves near the skin lesions can be palpated
- patients are non-infectious and often spontaneously recover
3 other categories of leprosy
represent a continuum between LL and TL and are called [1] borderline lepromatous (BL), [2] borderline (BB) and [3] borderline tuberculoid (BT)
Treatment for Leprosy
- several drugs are effective including sulfones such as: dapsone, rifampin, and clofazamine
- prolonged treatment with combination of drugs
