BMS655 Vertebrate Immunity to Protozoans

Adaptive immune responses to protozoans

Protozoan infection stimulates humoral and cellular immunity

Balanced response will clear the infection, providing immune protection and increased resistance to reinfection

Inappropriate response will lead to increased morbidity, pathology and/or higher parasitemia

Disease outcomes for leismaniasis based on

Parasite species

Host immune responses

Cutaneous leismaniasis

Most common

Infected macrophages do not move from the site of infection and the lesion eventually heals

Disseminated cutaneous leishmaniasis

Rare

Infected macrophages disseminate into the circulation, sending parasite all over body to form disfiguring lesions everywhere

Patients with TH1 response to leishmaniasis

TH1 cells release IFNg, enhancing ability of phagocytes to kill intracellular amastigotes

Increase cytotoxic T cells, not dependent on antibodies

Localized cutaneous disease

Patients with humoral response to Leishmaniasis

Lots of antibodies produced but they are not effective at killing intracellular amastigotes

Infected macrophages cannot kill internal parasites and travel through body in circulation

Antibodies and intracellular parasites

Apicomplexans are intracellular parasites

Require both humoral and cell mediated immune responses

• antibodies critical for memory

• adaptive humoral immune response is critical for protection against Giardia

Protective immunity and malaria

Most of morbidity and mortality seen in children under 5

Everyone is repeatedly bitten and infected with plasmodium parasites

Once immunological memory has developed, sever disease no longer develops

Malaria and premunition

Immunity to malaria is not sterilizing

Immunity is lost once an immune individual leaves an endemic area for a few months

When they return, vulnerable to serious disease again

Premunition

Repeated and regular exposure to infection is required to prevent serious or debilitating disease

Immune response to Plasmodium

Different antigens at each stage

• sporozoite

• intracellular liver stages

• intracellular blood stages

Most immunological memory is directed at merozoites when they leave RBCs for 1-2 minutes

Innate immunity to malaria

Initiated with binding of parasite PAMP to TLR

Causes release of IL-12, which activates NK cells

Activated NK cells produce IFNg which activates macrophages and increases their ability to kill ingested parasites and release cytotoxic effectors

NK cells also initiate TH1 response

Adaptive immunity to malaria

TH1 cells drive response against liver stage when activated by dendritic cells releasing IL-12

TH1 cells produce IFNg to enhance phagocytosis and killing by macrophages

Activation and proliferation of CD8 T cells, although few antigens for MHC presentation (RBCs)

Adaptive is dependent on humoral

Activated CD4 cells activate B cells, produce IgG and immunological memory

Immune activation regulated by

IL-10 and TGF-B released by Tregs

Antibodies and malaria immunity

Critical for controlling blood stage infection

Neutralizes newly released merozoites before they infect RBC

Recognize antigens on surface of RBCs causing agglutination

Block cytoadherence of infected RBCs