Immune Response to Parasitic Infections

Immune Response to Infectious Diseases - Parasites

• The immune system has intricate mechanisms for recognizing and responding to parasitic pathogens.
• Parasite pathogens have evolved strategies for evading detection and elimination by the immune system.

Eukaryotic Parasites

• Eukaryotic parasites include helminth worms and protozoa.
• Helminth worms, such as nematodes, trematodes, and cestodes, are large multicellular organisms causing intestinal or systemic infections, often leading to chronic infections lasting years.
• Parasites manipulate the immune response, making long-lasting protection difficult to attain.

Helminths - Immune Response

• The immune response to helminths is mediated by antibodies, Th2 cells, mast cells, eosinophils, complement, and phagocytes.
• IgE binds to parasites and mast cells.
• Mast cells release inflammatory mediators, recruiting eosinophils.
• Eosinophils bind to IgE and release protein damaging the parasite's cell wall, leading to death.
• IgG, complement, and phagocytes also play a role.

Functions of Th2 Cells

• Th2 cells are involved in helminth infections, or protein antigens.
• Th2 cells stimulate B cell proliferation and differentiation.
• Th2 cells produce cytokines IL-4, IL-5, and IL-13, promoting antibody production (IgE, IgG4 [human], IgG1 [mouse]) and mast cell degranulation.
• Cytokine production also leads to intestinal mucus secretion and peristalsis.
• Cytokine production also leads to eosinophil activation.

Protozoa

• Protozoa are unicellular eukaryotic organisms, e.g., Trypanosoma brucei (African Sleeping Sickness), and Plasmodium (malaria).
• Protozoan infections often reside in the blood stream.
• The type of immune response depends on the location of the parasite within the host; some stages are free in the bloodstream, making humoral antibody response more effective.
• Some protozoa can survive within host cells (intracellular growth), requiring cell-mediated immunity for effective host defense.

T. brucei Life Cycle

• T. brucei, the causative agent for African sleeping sickness, has a complex life cycle involving stages in the tsetse fly vector and the human host.
• This cycle involves complex transformations in different body fluids impacting immune response.

Response to T. brucei

• T. brucei is difficult to eradicate.
• It evades the immune system by altering expression of surface proteins.
• It is coated with antigenic glycoproteins masking underlying antigens.
• It has many genes encoding glycoprotein, but only one form is expressed at a time, evading immune targeting.

Plasmodium Life Cycle

• Plasmodium, the causative agent of malaria, has a complex life cycle involving both the mosquito vector and the human host.
• This cycle includes sporozoites entering liver cells and merozoites infecting red blood cells, and gametocytes infecting the mosquito vector.

Malarial Ligands and Innate Responses

• Various proteins, such as GPI (glycosylphosphatidylinositol) on the parasite, interact with receptors on host cells initiating innate immune responses.
• These interactions can be used to induce immune system response to malaria.

Presumed Mechanisms of Adaptive Immunity to Malaria

• Antibodies block the invasion of sporozoites into liver cells.
• Antibodies block invasion of merozoites into erythrocytes.
• Interferon-γ (IFN-γ) and CD8+ T cells inhibit parasite development.
• Antibodies are crucial for neutralizing parasite glycosylphosphatidylinositol.
• IFN-γ and CD4+ T cells activate macrophages.

Linking Innate and Adaptive Immunity to Blood-stage Malaria

• Innate immune systems interact with and impact adaptive immune systems to combat blood-stage malaria.

Immune Evasion

• Parasites periodically alter glycoprotein expression and shed coat.
• These changes prevent antibodies from binding to receptors.
• This prevents immune response suppression.
• Similar evasion strategies are used by other protozoa like Plasmodium.

Immune Evasion of Parasites

• Parasites have evolved various mechanisms to avoid immune system.
• Mechanisms include antigenic variation, evasion from macrophages, preventing lysosome-phagosome fusion, preventing lysosomal toxic action, escaping into the cytoplasm, resisting complement lysis, immune suppression, and producing antioxidant enzymes.

Summary

• The immune system employs complex mechanisms to recognize and respond to parasitic pathogens.
• Parasites have evolved sophisticated strategies to evade detection and elimination by the host's immune system.

Explore the immune mechanisms that combat eukaryotic parasites, including helminths and protozoa. Learn how these pathogens evade immune detection and the complexities of immune responses, such as the roles of antibodies and various immune cells. Test your knowledge on this critical topic in infectious disease.