Immune Response to Infectious Diseases

INTRODUCTION

Immune system is a defense system that enables us to resist infections. The immune system is composed of two types of immunity: the innate or non-specific immunity and the adaptive or specific immunity. The innate immunity is the first line of defense against invading organisms while the adaptive immunity acts as a second line of defense and also gives protection against re-exposure to the same pathogen. Each type of immunity has both cellular and humoral components by which they carry out their protective function.

Pathogens and disease: Pathogens are defined as microbes such as viruses, bacteria or fungi capable of causing host damage or disease. When host damage reaches a certain threshold, it can manifest itself as a disease. The occurrence of an infectious disease in an individual involves complex interactions between the pathogen and the host.

Important Features of Immunity to Pathogens: Defense against pathogens is mediated by both innate and specific immunity. The innate immune response to pathogens plays an important role in determining the nature of the specific immune response. The immune response is capable of responding in distinct and specialized ways to different pathogens in order to combat these infectious agents most effectively. The survival and pathogenicity of pathogens in a host are critically influenced by their ability to evade or resist protective immunity. Tissue injury and disease in consequent to infections may be caused by the host response to the pathogen and its products.

Viruses

Viruses are obligatory intercellular pathogens that replicate within cells. They use the nucleic acid and protein synthetic machineries of the host cell and infect a variety of cell populations by utilizing normal cell surface molecules as receptors to enter the cell. The immune system produces two types of responses against the virus infection:

  1. Innate response
  2. Specific response
  3. Innate Immune Response to Viruses: Viral infection directly stimulates the production of interferons (INF). Interferons are antiviral proteins, or glycoproteins’s produced by several types of cells in response to viral infections. For example, INFα by leucocytes, INFβ by fibroblast, INFg by natural killers (NK) cells, Natural killer (NK) cells lyse a wide variety of virally infected cells.
  4. Specific Immune Response to Viruses: It is mediated by a combination of humoral and cell mediated immune mechanisms.

Immune Response to Infectious Diseases

(a) Humoral mediated immune response: Antibodies specific for viral surface antigens are often crucial in containing the spread of a virus during acute infection and in protecting against re-infection. Specific antibodies are important in defense against viruses early in the course of infection and in defense against cytopathic viruses that are liberated from lysed infected cells. Opsonization: Opsonizing antibodies may enhance phagocytic clearance of viral particles.

Immune Response to Infectious Diseases

(b) Cell-mediated immune responses: Most important is host defense, once a viral infection is established. CD8+ T, cells (Cytotoxic T lymphocytes; CTLs) and CD4+ TH1 cells (helper T lymphocytes) are the main components of cell-mediated antiviral defense.

Immune Response to Infectious Diseases

Tissue Injury: In some cases, infections with non-cytopathic viruses, CTLs may be responsible for tissue damage to the host.

Evasion of Immune Mechanisms by Viruses: Viruses have evolved numerous mechanisms for evading host immunity. A number of viruses have strategies to evade complement-mediated destruction. Viruses can also escape immune attack by changing their antigens. A large number of viruses evade the immune response by causing generalized immunosuppression.

Bacteria

Immunity to bacterial infections is achieved by means of antibody unless the bacteria are capable of intracellular growth. There are two types of bacterial infection: Extra-cellular and Intracellular.

Extra-cellular bacteria: They replicate outside the host cells and they cause disease by two principle mechanisms

(a) By inducing inflammation

(b) By producing toxins: Endotoxins or/and Exotoxins.

The immune responses against extracellular bacteria are aimed at eliminating the bacteria and neutralizing the effects of their toxins.

Innate Immunity to extra-cellular bacteria: Extra-cellular bacteria can be eliminated through phagocytosis by neutrophils, monocytes, and the tissue macrophages and activation of the compliment system, in the absence of antibody.

Specific Immunity to extra-cellular bacteria: Humoral immunity is the principle specific immune response against extracellular bacteria which includes: Strong IgM responses are caused by polysaccharides and antibodies IgM and IgG against bacteria surface antigens and toxins stimulate three types of effector mechanisms:

  1. IgG antibodies opsonize bacteria and enhance phagocytosis.
  2. Antibodies neutralize bacterial toxins.
  3. IgM and IgG antibodies activate the complement system.

Tissue Injury: The principal injuries of host responses to extracellular bacteria are inflammation and septic shock

Evasion of Immune Mechanisms by Extra-cellular Bacteria:

  1. Genetic variation of the surface antigen is one of the mechanisms used by bacteria to evade specific immunity.
  2. The capsule of many gram-negative and gram-positive bacteria contain one or more sialic acid residues that inhibit complement activation by the alternative pathway
  3. Other mechanisms are shown in Figure 5.

Immune Response to Infectious Diseases

Innate Immunity to Intracellular Bacteria: During the innate immune response, the intracellular bacteria phagocytes ingest and attempt to destroy. Intracellular bacteria are resistant to degradation within phagocytes. Intracellular bacteria also activate NK cells, either directly or indirectly by stimulating macrophages production of IL-12 (a powerful NK cell-activating cytokine).

Specific Immunity to Intracellular Bacteria: Cell-mediated immune response is the major-specific immune response against intracellular bacteria. There are two types of cell-mediated reactions:

  1. The killing of phagocytosed intracellular bacteria as a result of macrophage activation by T cel— derived cytokines, particularly IFN-y.
  2. Lysis of infected cells by CTLs.

Tissue Injury: Tissue damage can be caused by macrophage activation that occurs in response to intracellular bacteria and the macrophages accumulate and result in the formation of a granuloma.

Evasion of Immune Mechanisms by Intracellular Bacteria: Ability of intracellular bacteria to resist elimination by phagocytes is an important mechanism for survival in evasion of the immune response. Some intracellular bacteria do this by: (a) inhibiting phagolysosome fusion (b) producing hemolysin that blocks bacterial killing in macrophages.

Fungi

Fungal infections cause serious infections primarily in individuals with impaired immunity. Fungal infections are classified by:

(a) Site of infection—Superficial, cutaneous, subcutaneous, or deep or systemic

(b) Route of acquisition— Exogenous, endogenous

(c) Virulence—primary or opportunistic

Innate Immunity to Fungi: Neutrophils act as the principal mediators of innate immunity against fungi. Neutrophils release fungicidal substances, such as reactive oxygen species and lysosome enzymes and they also phagocytose fungi for intracellular killing.

Specific Immunity to Fungi: Cell-mediated specific immunity is the major defense against fungal infections. Fungi that are present intercellularly in macrophages are eliminated by two types of cell-mediated reactions:

  1. Killing of phagocytosed intracellular fungi as a result of macrophage activation by T cell-derived cytokines, particularly IFN-y.
  2. Lysis of infected cells by CTLs.

Evasion of Immune Mechanisms by Fungi: Since individuals with healthy immune systems are not susceptible to opportunistic fungal infections, very little is known about the ability of fungi to evade host immunity.

PARASITES

Parasitic infections may be defined as the infection caused by the animal parasites, such as protozoa, helminthes, and ecto-parasites. Humans are only part of the complex life cycle of parasites.

Innate Immunity to Parasites

Protozoa and helminthic parasites that enter the blood stream or tissue are often able to survive and replicate because they are resistant to host innate immune responses.

  1. Parasites in human host are usually resistant to complement.
  2. Macrophages can phagocytose protozoa, but the tegument of helminthic parasites makes them resistant to the cytocidal effects of both neutrophils and macrophages.

Specific Immunity to Parasites

Different parasites show quite distinct specific immune responses.

  1. Cell-mediated immunity is the principal defense against protozoa that survive within macrophages.
  2. Protozoa that replicate inside cells and lyse host cells stimulate specific CTL responses, similar to cytopathic viruses.
  3. IgE antibodies and eosinophils mediate defense against many helminthic infections

Tissue injury: Tissue injury can be caused when parasites deposited in the liver stimulate CD4+ T cell and cause macrophages to activate and induce DTH reactions. Sometimes the formation of granulomas may occur.

Evasion of Immune Mechanisms by Parasites: Evolutionary adaptations give parasites their ability to evade and resist immune responses. These include:

  1. Some parasites survive and replicate inside cells.
  2. Others develop cysts that are resistant to immune responses.
  3. Antigen masking is an effective form of immune response evasion by some parasites.
  4. Parasites can develop a tegument that is resistant to damage by antibodies and complement or CTLs.

Some parasites have mechanisms for surface antigen variation which are of two forms

(a) Stage-specific

(b) Continuous variation of major surface antigens.


QUESTIONS

  1. What are pathogens? Give examples.
  2. What are viruses? Discuss the innate and specific response of the immune system against viruses.
  3. Explain the antiviral activity by IFNα and IFNβ.
  4. What are the mechanism evolved by bacterial and viruses to evade host immunity?
  5. Discuss the antibody-mediated mechanism for combating infection by extracellular bacteria.
  6. Explain the classification system of fungal infections.
  7. What is the tissue injury caused in case of fungi and parasites?
  8. What is opsonization?