Lecture 10. Slow Growing Mycobacteria; Mycobacteria tuberculosis Flashcards
What is tuberculosis?
An infectious, air borne disease, caused by Mycobacterium tuberculosis (Mtb)
The immune response can contain Mtb as latent form of disease whilst the active form it is contagious and causes disease symptoms
It is primarily a pulmonary disease (lungs) but can cause disease in most parts of the body
In many low and middle income countries TB is major cause of morbidity and mortality
How can tuberculosis be cured?
With prolonged multi-drug treatment regimes (increasing problems with drug resistance)
BCG vaccine offers some protection
How can other mycobacterium besides Mtb cause tuberculosis?
From the Mycobacterium tuberculosis complex (MTBC) including M. bovis (impacts cattle)
What is something to remember about Mtb?
There are multiple strains of Mtb that are different from the ancestral one
What is the history of tuberculosis?
Has been found in 9000 year old bones
Refereed to throughout written (E.g India 3300 years ago)
In 1600-1800s in Europe TB caused 25% of deaths
Overcrowded and substandard living or working conditions, poor nutrition
Which countries have a high burden of TB?
Found globally but particularly prevalent in sub-saharan Africa and Asia
What does TB co-infect with to cause more disease?
HIV (particularly sub-saharan Africa and parts of South America)
How is TB transmitted?
Primarily an airborne disease
Not highly infectious (3-10 people infected per infectious individual
Long period of infectiousness (without treatment) average >1yr
What determines TB disease progression?
The immune response
How does TB progress within most healthy people (>90%)?
The innate and adaptive immune systems allow most healthy people to control the growth of Mtb, although they harbour latent infection (it is not known whether host immune responses can eliminate infection)
What group of people develop acute TB either as primary progression or a reactivation?
Those with impaired T cell function
How does Mtb get into the phagosome?
M. tuberculosis is phagocytosed by antigen-presenting cells (APCs), including macrophages, monocytes and dendritic cells, and survives in phagosomes
Once in the phagosome, what does Mtb trigger?
Mtb ligands, including lipoproteins and glycolipids, are recognised in APCs by Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD) protein resulting in the secretion of inflammatory cytokines and chemokines.
Where do infected APCs migrate to and what does this cause?
Infected APCs migrate to regional lymphoid tissues, where adaptive immunity develops through antigen presentation to naive T cells
What happens within infected APC cells?
APCs process Mtb antigens by intravacuolar proteolysis to produce peptides that bind to major histocompatibility complex (MHC) class II molecules, which then translocate to the cell surface to mediate presentation of Mtb peptides to CD4+ T cells.
M. tuberculosis peptides are also presented by MHC class I molecules to CD8+ T cells and effector and memory T cells migrate back to sites of infection to control M. tuberculosis growth.
How do granulomas form in response to Mtb?
Granulomas develop through the secretion of tumour necrosis factor and other effector cytokines
