Antiparasitic immunity

Immune response to Plasmodium invasion

Defense against the malaria agent involves the coordinated action of several links of the immune system, but has significant limitations in its effectiveness.

The humoral arm of anti-plasmodial immunity is formed and deployed mainly in the lymphoid follicles of the spleen. In parallel, a powerful T-cell immune response develops, which proceeds in two main forms:

1. Inflammatory form. Carried out with the direct participation of CD4+ T-lymphocytes (helpers) and macrophages. The process is localized in the marginal zone and red pulp of the spleen and is accompanied by the massive release of various cytokines. This particular form makes the most significant contribution to limiting the spread of infection when the pathogen is at the merozoite stage.
2. Cytotoxic form. Mediated by CD8+ T-killers and unfolds directly in the liver. It is important to note that this process is inextricably linked with significant damage to the host's own hepatocytes.

Despite the mobilization of both humoral and cellular immunity, complete destruction (eradication) of Plasmodium does not occur. The parasite successfully reaches the gametocyte stage, enters the systemic circulation, and is unhinderedly transmitted to the intermediate host — the mosquito.

Main reasons for the inefficiency of immune defense:

• Pronounced antigenic variation of Plasmodium.
• Regular changes in the developmental stages of the pathogen. Each new stage has its own specific localization in the host organism and expresses a completely different set of surface antigens, rendering the previous immune response useless.

Features of defense against helminths

Anti-helminthic immunity remains the least studied area among all forms of immune defense to date. The effectiveness of the response largely depends on where exactly the worm parasitizes.

When localized in the intestine (where helminths enter along with food), the mucous membrane of the digestive tract itself acts as a kind of barrier isolating the parasite from active contact with the immune system. If helminths penetrate hematogenously into other organs (such as the liver, lungs, brain tissue, or blood vessel walls), they use a different strategy. In these tissues, a protective glycolipid or glycoprotein capsule forms around the parasite. The paradox is that this capsule is created by the host cells themselves, yet reliably shields the helminth from the destructive factors of immunity.

Recognition of parasites by innate immunity Recognition cells are the first to encounter helminths: macrophages, dendritic cells, and intestinal mucosal enterocytes. They identify foreign components (PAMPs) using specific receptors:

• Lysophosphatidylserine is recognized by the TLR-2 receptor.
• Lipoproteins enriched with phosphorylcholine bind to TLR-4.
• Glycans are captured by lectin receptors (e.g., DC-SIGN).
• The immune system also responds to chitin and proteases secreted by the helminths themselves.

Formation of adaptive Th2 response

Encounter with parasite antigens triggers a chain of adaptive immunity reactions. Activated dendritic cells transform into immature DC2-type cells. Their appearance is critically important, as they stimulate the differentiation of T-helper cells along the Th2 pathway. As a result, a Th2 response is formed — the predominant and most effective (protective) form of defense in helminth infections.

Th2 cells begin to actively secrete specific cytokines, each performing its own task:

• IL-4: is of paramount importance, as it triggers the isotype switching of synthesized antibodies to produce IgE.
• IL-5: purposefully attracts eosinophils to the lesion focus.
• IL-13: not only attracts basophils and eosinophils but is also responsible for morphogenetic rearrangements (remodeling) of affected tissues.

A key effector mechanism is the action of IgE class antibodies. These immunoglobulins bind to pre-sensitized mast cells. This interaction leads to mast cell degranulation and a powerful release of biologically active factors with anti-helminthic activity.

Cellular reactions and helminth elimination

Under the action of cytokines, eosinophils and basophils accumulate around the helminth, forming a dense protective wall. These cells release potent effector molecules capable of causing parasite death. Eosinophil toxic proteins play a decisive role:

• MBP (major basic protein).
• ECP (eosinophil cationic protein).

After the parasite dies, the body must get rid of it. Dead specimens are evacuated from the intestine naturally through the digestive tract. If death occurred in internal organs, the helminth remains undergo phagocytosis by cells of the mononuclear phagocytic system.

A major problem of anti-helminthic immunity is that immunological memory after a past infestation remains relatively weak and short-lived. It offers no guarantee of protection against reinfections. For this same reason, effective vaccines against helminthiasis still do not exist.

Basics of protective immunity

In a broader sense, protective immunity in any infectious disease (including parasitic ones) is not just a set of immunological reactions, but the resulting state of organism resistance that prevents disease development. Two varieties are distinguished:

1. Natural immunity. Based on innate species characteristics. It includes biochemical incompatibility between host and pathogen, the absence of host receptors for pathogen invasion, and high tissue resistance to pathogenicity factors. Note: known innate immunity factors are only part of natural immunity.
2. Acquired immunity. Develops only after contact with an antigen. Its essence lies in the accumulation of effector factors (antibodies, specialized cells) that prevent reinfection. Due to immunological memory, these factors are formed much faster upon a new encounter with the pathogen.

Humoral protective immunity provided by antibodies has a limited duration. Its effectiveness strictly depends on two parameters: specificity (antibodies must strike precisely at virulence-related epitopes) and biological activity (the ability to neutralize the agent, activate complement, and bind to phagocyte Fc receptors).

Class and exam questions

What else to study on this topic

• Mechanisms of formation of the glycolipid protective capsule around helminths in internal organs
• Detailed structure and functions of TLR-2, TLR-4, and DC-SIGN receptors in parasite recognition
• The process of tissue remodeling under the influence of interleukin-13
• The role of major basic protein (MBP) and eosinophil cationic protein (ECP) at the molecular level
• Species biochemical features providing natural protective immunity

Other topics in the section "Immunity in defense and damage of the organism. Pathology of immunity"

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