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Pathogenesis

Learning objectives

By the end of this sessions trainees are expected to:

  • Distinguish between infection and disease
  • Understand the immunological responses to leishmania infections
  • Identify the risk factors that play role in disease progression

Recommended facilitation strategy

  • After reading the notes, make the trainees classify and list the cytokines playing role in the pathogenesis

All infections do not progress to disease. Majority remain asymptomatically infected. Asymptomatic infection can be recognized early by positive serology test (antibody detection) and subsequently by the development of cell mediated immunity that can be revealed by leishmanin skin test.

The determinants of progression to diseases are not all clearly understood. However, several factors play role in the pathogenesis of disease.

Broadly classifying the immune response into TH1 – cell mediated and TH2 – humoral, strong TH1 response is needed for control of intracellular infection such as leishmania.

The leishmania parasite produces a gel that contains a filamentous proteophosphoglycan which is injected into the human host during the insect bite. This gel pushes the immune system to the less protective form of immunity (TH2 response - humoral) for an intracellular organism. Sandfly saliva proteins also seem to influence the immune response shifting it to TH2 response. People living in the endemic areas develop antisandfly saliva antibodies and this may be the reason for deceased susceptibility to leishmania with aging.

From the host side, immune suppressive conditions like HIV, malnutrition, concomitant intestinal helminth infestations, aging and host genetic factors may modulate the disease progression.

During HIV/VL co-infection there is decreased production of macrophage activating cytokines (pro-inflammatory) – IFNγ, IL12, IL15, IL18; and increased immunosuppressive cytokines IL4, IL10, IGFβ (anti-inflammatory). Upon successful treatment reversion of this cytokine response is seen. 

References:

Andargie and Ejara, Pro- and Anti-inflammatory cytokines in visceral leishmaniasis, J cell Sci Ther 2015, 6:3
Adem E et al. Successful treatment of Human Visceral Leishmaniasis restores Antigen-specific IFN but not IL-10 production, Plos NTD, Mar 2016

Reflection

What do you understand by TH1 and TH2 immune response?

Case Study

What does pro-inflammatory and anti-inflammatory mean?
List the cytokines for each group on a sheet of paper.