Lecture 10 - Immune Responses to Parasite (Malaria) Infection Flashcards

1
Q

Genus Plasmodium

A

Single celled, protozoan. Eg P. falciparum, P vivax

Causative agent of malaria.

Parasitic organism with mosquito and mammalian hosts.

500m illnesses/year with 1m deaths.
Causes 20% of childhood deaths in Africa - one every 30 seconds

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2
Q

Genus Anopheles

A

Mosquito vector for Plasmodium.

Male and female drink nectar. Female also drinks blood.

Females are classical disease vectors, transporting pathogens from one host to another. Vectors for yellow fever and malaria - killing millions of humans

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3
Q

Red Blood Cell Malaria Infection

A

Var genes cause infected RBC to adhere to endothelium.

Infected RBC express parasite (var) antigens on their surface (makes it hard for T and B cell recognition).

RBCs lack nuclei and do not express MHC I

and therefore infected cells are not targets for CD8 T cells

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4
Q

How Malaria Infection begins

A
  1. Mosquito injects saliva with proboscis containing sporozoites with blood
  2. Sporozoites rapidly (30 min.) infect liver.
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5
Q

Proboscis

A

Mosquito organ for retrieving blood meal. Serrated edges minimize pain. One tube sucks blood. Second tube injects saliva. Saliva contains anti-hemostatic and anti-inflammatory agents stops clotting and blocks pain response. Feed undetected up to 1.5 min

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6
Q

Sporozoite

A

The bacteria in mosquitos that cause malaria by infecting the liver, which replicate in hepatocytes, mature into merozoites, burst out and infect RBCs in blood

It sheds its coat readily and diverts antibody responses by reducing antibody-mediated complement fixation or opsonization

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7
Q

Pre-liver defenses

A

IgM attacks Sporozoites

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8
Q

Post-liver defenses

A

Parasite antigens are presented to naïve CD8 T cells in the spleen. CD8 T cells are activated, expand clonally and mature.

Active CD8 T cells migrate to the liver.

Infected hepatocytes present antigens and are destroyed by CD8 T cells

Takes time!

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9
Q

Duffy antigen

A

Receptor whose mutations prevent P. vivax entry into RBC

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10
Q

Hemoglobin mutations: HbS, sickle cell trait

A

Cause the RBC to lyse faster after infection, disrupting parasite growth

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11
Q

Variant (var) Surface Proteins

A

Found on RBCs, after sporozoite infection

Encoded by the Plasmodium gene

Var genes cause infected RBC to adhere to endothelium.

Every day or so, var gene expression switches and an entirely new surface antigen is formed.

These ‘new’ plasmodium replicate in RBC and making it more difficult to induce both T and B cell-dependent immunity.

Eventually by adulthood there are memory cells to all variants of var and relatively good immunity is in place.

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12
Q

Splenic Filtraion

A
  1. Merozoite antigen filtered in spleen, captured by APC and displayed on MHC class II
  2. Naïve CD4+ T cell interacts with peptide/MHC II on APC (1st signal).
  3. APC delivers second signal required for T cell activation.
  4. CD4+ T cells expands clonally and matures into helper T cell
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13
Q

Opsonization/Phagocytosis

A
  1. Anti-var antibody opsonizes (coats) microbes.
  2. Macrophage Fc-receptors bind opsonized microbes.
  3. Signals from Fcγ receptors activate phagocytosis.
  4. Phagocytes internalizes antibody-coated microbe.
  5. Phagocyte destroys internalized microbe. Peptides may be displayed on MHC II for CD4 activation.
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14
Q

Natural Killer Cells (NK Cells)

A

Innate Immune lymphocytes that detect and destroy infected cells.

Express receptors that recognize cell surface molecules of stressed (i.e. infected cells) or normal cells.

NK cells degranulate on target cells, triggering apoptosis in the target

Engagement of NK cell activating receptors can result in NK cell activation and destruction of the infected cell.

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15
Q

NK Cell Antibody-dependent Cell-mediated Cytotoxicity (ADCC)

A
  1. Antibodies bind antigens on the surface of target cells
  2. NK cell CD16 Fc receptors recognise cell-bound antibodies
  3. Cross-linking of CD16 triggers degranulation into a lytic synapse
  4. Tumor cells or pathogen infected cell die by apoptosis
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16
Q

Degranulation

A

Mast Cells and Eosinophils can recognize antibodies (IgE) opsonized on the parasite

Activation of FceR on the surface of the cell by the antibody induces receptor activation

Cell induces degranulation to destroy parasite directly