IMMUNOLOGY-TB

Epidemiology

↓CD4=

Leading killer in HIV patients

Deaths>related to antimicrobial resistance

Top infectious killer

Trend>ARVS>role in declining TB incident cases

TRANSMISSION>>Diseased people>coughing/talking >Inhale Droplets>Mtb > host>lungs>alveoli(immune cells-macrophages

In the alveoli

Alveolar macrophage encounter the Mtb> recognize & alerted>activate>expand membrane>engulf the Mtb>phagocytoses(Receptors:TLR1/2)

Mtb secured in phagosome(vacule containing the Mtb)

Alveolar macrophage(receptors & sesors-specialised in >controls TB infection>provides defence

Lysosome>>migrate>match with phagosome>phagolysosome-pH drops>degrade the Mtb>activation of superoxide** >digestion> Pick up some proteins from Mtb(MHC-1 & MHC-2???)

Inflammatory chemokines released(TNF, IL-1Beta, IL-6 , 12 , 18)

Antimicrobial(Released within the macrophage-have Vitamin D receptor) activated by Vitamin D

Mtb can inhibit acidification ,hydrolase activating, &superoxide burst(succeed to escape-fights back) by blocking the fusion of lysosome & phagolysosome)

Alerting of other immune cells by macrophages(innate)-COSTIMULATION

T cell Receptor recognize the protein>>activated> release cytokines>>IFN gamma >> enhance killing

Macrophages present the proteins of Mtb on the surface>>T cells recognise (CD-4)

This ensures the fusion of lysosome & phagolysiosome to occur

Geneticv Variation

Variation of VDR>>Susceptibility to TB(vIT d CANNOT ACTIVATE THE vITAMIN d TO release

Mutations in inflammatory cytokines IL-12>> Macrophage unable to respond>>cannot activate T-cells

Human mutations>>

Immmune regulation complex>>either up/down-regulate

Antibodies

BCG(Only vaccine preventing TB)>protection

Lung immunity when vaccinated:Th1,IL-10,IgA antibodies

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