Pathogenesis of Mycobacterium tuberculosis Flashcards

Question

Answer 1

target 23S ribosomal RNA, inhinbiting peptidyl transferase

Answer 2

inhibs mycolic acid synthesis

Answer 3

inhibs cell wall synthesis

Answer 4

found in the cell wall helps the organism survive inside macrophages

Answer 5

drugs cannot penetrate cell wall low pH- renders drug inactive efflux pumps- drug removed from cell before it reaches the target anaerobic conditions lead to dormant/ non-replicating state- drugs that block metabolic processes have no effect during state of dormancy

Answer 6

slow replicative rate- more time for mutations to accrew mutations to TSG and proto-oncogenes lead to multiple drug resistance alterations in enzymes means that pro-drugs arent converted to their active forms alteration of drug target composition means that the drug cant be recognised

Answer 7

MDR-TB X-DR

Answer 8

develeoping during treatment process to 2 (isoniazid and rifampcin) this is natural. treat with second line drugs

Answer 9

extended. includes resistance to secind and third line drugs. there is no standardized treatment available

Answer 10

group of organisms that will casue infections in humans Mycobacterium tuberculosis Bovis (BCG) Africanum and many more These can all casue TB iun humans and animals (zoonotic) all members have different host preferences all are obligate pathogens show 990.5% sequence similarity within the group

Answer 11

slightly curved rod shaped bacilli aerobic non motile can show filamentous branching (myco) thick lipid rich cell wall can remain dormant, non-spore forming multiplies slowly **_acid-fast_** resists stain decolouristaion with acid/ alcohol

Answer 12

* peptidoglycan wall aboce lipid bilayer * behaves like gram positive * lipid rich structure- mycolic acids * unique and responsible for much of its virukence * plasma membrane associated proteins * Cord factor-inhibits migration of leukocytes, causes chronic granulomas

Answer 13

characteristic of mycobacterium acid fastness immunostimulatory

Answer 14

* Majority of pathology has been related to the host immune response to infection * Pathogen also plays a role in its own virulence * Some strains are more pathogenic than others * Known virulence factors are used to subvert the host immunity (efflux pumps)

Answer 15

First 4-6 weeks Exposure →innate response (chance for elimination) →adaptive response (Chance for elim) Organism hides from immune system in granulomas →years to decades →granuloma degrades and releases bacteria 

Answer 16

disease course has 3 main stages: 1. **_Invasion-_** pre-cellular immune response 2. **_Persistance-_** post cellular response 3. **_Reactivation-_** secondary acute infection-

Answer 17

* Mtb is a facultative intracellular pathogen requires replication in macrophages * mtb initiates macrophage phagocytosis by making contact with macrophage mannose, complement and TOLL- like 2 receptors * Reside in phagosome * Receptors utilised are those associated with an innate response like C-type lectin receptors (CLRs), nod-like receptors (NLRs), scavenger rectpors, complement receptors and toll-like receptors (TLR) * Some prevent lysis in phagolysosome by preventing fusion * The ability to infect macrophages is a key pathogenic determinant for bacterial spread

Answer 18

* cell wall complexity allows it to interact with multiple receptors * mtb surviving may ne dependant on the receptors incolved during phagocytosis (some receptors normally lead to phagocytosis) * a) e.g., via the CR3 receptor which inhibits macrophage activation

Answer 19

tb can use them to invade cells

Answer 20

* TH1 mediated immunity is crucial * you want more th1 involvement than th2 * production of IFN- gamma by T cells leads to macrophage activation and death of Mtb infected cells cellular immunity is crucial for controllimng TB. HIV targets and kills these cells making reactivation more likely to occur

Answer 21

* interferon gamma overcomes the endosome like arrest that mtb imposes, delivering the vacteria to autolysosomes where growth is stopped. * * mtb fights thhis by resisting oxidatice stress and suverting cell death pathways (necrosis and apoptosis) * if necrotic, pieces will disseminate into other areas

Answer 22

**_Mtb causes:_** * Impaired fusion of phagosome with lysosome * Inhibition of phagosome acidification * Inefficient recruitment of proton ATP-ase pump * Results in lack of acidification of the phagosome * Modified maturation of phagosome * Overexpression of Rab5 on the phagosomes harbouring bacilli causes maturation arrest at early endosomal stage

Answer 23

Organised aggregate of immune cells that surround a foci of infected tissues. classic lesion seen in MTB infection infected macrophages produce a strong pro inflam response TNF-a is key. these signal recuit more cells to the site

Answer 24

macrophages alone arent enough for intiation of the granuloma forming multinucleated giant cells (MGCs) infected macrophages release tnf-a to attract more cells mtb products participate in granuloma production- something mtb wants as part of pathogenesis foamy macrophages T cells and B cells and neutrophils

Answer 25

ficrocalcific non-necrotic caseous suppurative cavitary

Answer 26

ability to alter phagolysosome maturation mtb can persist within endosomes for years centre of the granuloma is hypoxic, little nutrient availabilty, low pH → causes a shift in response (latency associated genes) → dormancy allows organism to survive

Answer 27

likely due to the host immune response caused by immune suppresion of some sort HIV is a potent factor for reactivation for latency Rescusitation promoting factors are critical components for revival tissue destruction allows for bacterial dissemination and transmission