The immune system in disease

Some diseases due to immunological abnormalities are common in clinical practice, for example rheumatoid arthritis, thyroid disease and allergy. Immunodeficiency is relatively rare, but the occurrence of certain infections in the context of specific immune defects can illuminate the physiological role of those parts of immune defence in control of infection.


General principles

Infection is the result of microbial virulence on the one hand and host defence on the other. Pathogenic organisms have mechanisms of evading normal defence mechanisms. Organisms of low virulence can only cause disease if the host defence mechanisms that normally control them are defective.

Opportunist infections

Organisms taking advantage of the opportunity of impaired host defence mechanisms are called opportunists. Different host defence defects cause increased susceptibility to different groups of organisms. Therefore, recognizing a pattern of infections can provide the best clinical clue to the type of underlying defence defect. Patterns of opportunist infection Examples of opportunist organisms in the setting of nonimmunological defence defects include: staphylococci and Pseudomonas in burns patients; Haemophilus influenzae and pneumococci in smokers; Pseudomonas in cystic fibrosis patients; Gram-negative infections where there is urinary obstruction; staphylococcal and candidal infections with indwelling venous catheters and other foreign bodies; Candida and pathogenic Escherichia coli following elimination of gut flora after antibiotic therapy.

Interaction of the immune system with the hypothalamo-pituitary axis regulating adrenocortical secretion. In response to infection, activated T cells release cytokines which induce the hypothalamic release of corticotrophinreleasing hormone (CRH) and vasopressin (VP). This overrides the normal negative feedback relationship between corticotrophin and cortisol. Circulating cortisol also acts on peripheral immunocompetent cells to inhibit their activation and secretion of cytokines and other mediators of inflammation. ACH, acetylcholine; NA, noradrenaline; TNF, tumour necrosis factor. (From Reichlim 5 (1993) New England Journal of Medicine, 329, 1246. With permission.)
Interaction of the immune system with the hypothalamo-pituitary axis regulating adrenocortical secretion. In response to infection, activated T cells release cytokines which induce the hypothalamic release of corticotrophinreleasing hormone (CRH) and vasopressin (VP). This overrides the normal negative feedback relationship between corticotrophin and cortisol. Circulating cortisol also acts on peripheral immunocompetent cells to inhibit their activation and secretion of cytokines and other mediators of inflammation. ACH, acetylcholine; NA, noradrenaline; TNF, tumour necrosis factor. (From Reichlim 5 (1993) New England Journal of Medicine, 329, 1246. With permission.)

the main infecting organisms for the principal classes of immunodeficiency. In broad terms, the following principles apply:
• ‘EUTROPHIL DEFECTS lead to staphylococcal, Gramnegative enteric and systemic fungal infections
PSONIC DEFECTS, due to antibody deficiencies or defects of the main complement pathways, and splenectomy lead to infection with capsulated organisms
JEFECTS OF THE LYTIC PATHWAY OF COMPLEMENT cause susceptibility to disseminated infections with Gram-negative cocci (Neisseria)
ELL-MEDIATED IMMUNE DEFECTS, affecting the cooperation between CD4 T cells and macrophages, lead o susceptibility to infection with facultative intracellupathogens and herpesviruses ongenital immunodeficiencies enital defects of specific metabolic or developmental ders can lead to characteristic deficiencies and are e main categories of immunodeficiency by host =d:anis’ m are as follows:


with or without accompanying defects in the related phagocytes of the monocyte/macrophage lineage


B-CELL DEFECTS, causing various types of antibody deficiency
T-CELL DEFECTS, impairing cell-mediated immunity
COMBINED T AND B CELL DEFECTS, which cause some of the most severe immunodeficiencies . the more important examples.

Acquired immunodeficiencies

Acquired immunodeficiencies are much more common but are often less precisely defined in terms of immunological mechanisms. They can in many cases be best understood against the background of the more specific defects. They include:
IATROGENIC DEFECTS resulting from deliberate immunosuppression or unwanted complications of certain therapies; malnutrition; splenectomy IMMUNOSUPPRESSION resulting from specific diseases that affect immune competence, such as tumours of the immune system and autoimmune disorders; and transient or progressive immunosuppression caused by certain infections.
The most important of the latter is of course the acquired immunodeficiency syndrome (AIDS) resulting from HIV infection, which is to be covered in some detail for the main categories

Immune defects and opportunist organisms
Immune defects and opportunist organisms

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