Intracellular Pathogens Flashcards
What are some of the pros of an intracellular pathogen?
- gain access to protected env.
- protection from immune response
- protection from bacterial competitors
- nutrient rich env.
What are some of the cons of being an intracellular pathogen?
They have to:
- overcome host barriers
- resist innate immunity
- resist adaptive immune responses
- adapt to life in a hostile env.
Viruses by their nature can be referred to as what?
Obligate intracellular parasites
Briefly describe what happens in immediate innate immune
0-4 hours
- recognition by preformed, non-specific and broadly specific effectors
- removal of infectious agent
Briefly describe what happens during the early induced innate response
4-96 hours
- Recognition of microbial-associated molecular patterns
- inflammation recruitment and activation of effector cells
- removal of infectious agent
Briefly describe what happens during the adaptive immune response
> 96 hours
- Transport of antigen to lymphoid organs
- recognition by naive B and T cells
- clonal expansion and differentiation to effector cells
- removal of infectious agent
Describe the microbiology of mycobacterium tuberculosis
Acid-fast rod
24-30 hours doubling time
What are the routes of infection for mycobacterium tuberculosis?
Aerosolised bacterium
May need repeated exposure
Infectious dose approx. 1-10CFU in animals
Repeated infection
What are some of the risk factors for mycobacterium tuberculosis?
Confined spaces Overall poor health and immune status Poverty/unemployment Homelessness Alcoholism/drug use HIV co-infection Steroid immunosupression
Briefly describe measuring the pathology of pulmonary tuberculosis
Sputum or smear culture
Pathology : KC8 caseating granuloma, necrosis, cavity formation
How does pulmonary tuberculosis cause death?
cachexia (constant weight loss when not trying)
respiratory failure
dissemination
massive haemoptysis
What is the infectivity of tuberculosis?
infects 1 in 3 of 2 billion
latent carriers harbour a 2-23% risk of developing TB
risk increases 10% annually should the immune system become suppressed
How does Mtb infect lung resident phagocytes?
(i) passes through epithelial layers in alveoli
(ii) enters phagocytes through natural mechanism
(iii) forms a phagolysosome
(iv) divides until cell lyses
What are some of the antimicrobial activities of phagolysosomes? And what substances cause them?
(i) nutrient deprivation - lactoferrin
(ii) membrane permeabilisation - defesins
(iii) hydrolases - lysozyme, phospholipases, proteases
(iv) production of reactive oxygen and nitrogen species
(v) acidification
In what 2 ways can mycobacterium tuberculosis evade macrophage engulfing?
(i) SapM hydrolyses phosphatidylinositide-3-phosphate and phosphatidylinositide mannoside which promote fusion of early endosomes with Mtb containing phagosomes
(ii) Rab5 is present on arrested phagosomes but fails to recruit other proteins onto the membrane
How are mycobacterium identified for phagocyte engulfing?
ABCs express toll-like receptor to detect PAMPs
pro-inflammatory cytokines causes Vitamin D pathway activation = upregulates expression of vitamin D hydrolase producing the antibacterial peptide cathelicidin
What antimicrobial functions and cytokines released by the following receptor activation?
(i) MHCI and II
(ii) CD40/B7
(iii) TNF/IFNgamma
(iv) Fas
(i) toxic oxygen radicals - IL-12
(ii) Toxic nitrogen radicals - TNF
(iii) Lysosomal enzymes - IL-1
(iv) numbers of granules - IL-18
How are cytokines involved in the response to mycobacterium?
Produces IFNgamma which superactivates macrophages
In mycobacterium infection, what is the difference between antigen presentation on dendritic cells and macrophages
Dendritic - peptide MHC complex is stabilised and persist for T cell priming in LN
Macrophages - presentation is transient and lost in later stages - when bacterium enters latent phase with decreased CD4+ T cell response
Can T cells respond to a whole organism?
No, only to processed antigen fragments
*also very efficient at destroying cancer cells and foreign organs (transplant issues)
What’s the difference between Th1 and Th2 cells?
Th1 - intracellular pathogens (cytotoxic)
requires IFNgamma and IL12
Th2 - extracellular pathogens (Th17 helper cells)
IL-2 essential for skewing Th1 response
Briefly describe Tuberculoid leprosy
Organisms present at low to undetectable levels
Low infectivity
Granulomas and local inflammation (peripheral nerve damage)
Normal serum Ig levels
Normal T-cell responsiveness, specific response to M. leprae antigens
Briefly describe Lepromatous leprosy
Organisms show florid growth in macrophages
High infectivity
Disseminated infection - bone/cartilage/diffuse nerve damage
Hypergammaglobulinemia
low or absent T-cell responsiveness and no response to M. leprae antigens
How do the 2 forms of leprosy arise in different organisms?
Tuberculoid caused by Th1, the milder form
Th2 is the incorrect immune response to mycobacterium infection
causes dissemination to the rest of the body
How are CD4 T cells involved in response to Mtb infection?
Th1 provide stimulus to further activate macrophages:
(i) CD40 sensitises macrophages to IFNgamma
(ii) Th1 cell produce IFNgamma
(also TNFalpha is produced to enhance macrophage response)
*cytokine delivery is polarised for efficiency
What is the last resort against mycobacterium infections?
Formation of a granuloma
- organised aggregates of immune cells surround foci of infected tissues limiting disssemination
Briefly describe research and potential ideas for HIV and biological therapies
Using small antibodies
Targets immune system aspected towards inflammatory diseases (e.g. MS)
e.g. cytokine tumour necrosis factor alpha (major factor for fighting TB)
Briefly describe the properties of herpesviruses
Enveloped, dsDNA Long and short fragment (4 isomers) 3 subfamilies: alpha, beta and gamma Set up latent/persistent infection Reactivation during immunosuppression
What do alpha herpesviruses cause?
HSV-1/2, VZV
