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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