Test: Inflammation- 2 - NEET PG MCQ

Direct quote from Robbins: “Endothelial cell contraction is traditionally observed in venules measuring between 20 to 60 µm in diameter, while the capillaries and arterioles remain unaffected.” For further information, please refer to the text.

The clinical characteristics and history presented in the question stem align with a diagnosis of leukocyte adhesion deficiency. Associated clinical signs of this syndrome comprise:

• Delayed separation of the umbilical cord
• Poor wound healing
• Recurrent skin infections (without pus formation)
• Gingivitis and periodontitis

In cases of immune deficiencies, a delayed separation of the umbilical cord should prompt consideration of leukocyte adhesion deficiency type I (LAD I). LAD I is an autosomal recessive disorder caused by the absence of the CD18 antigen, which is crucial for the formation of integrins (Choice c). Integrins play a vital role in the migration of leukocytes from blood vessels to tissues to perform their functions. A leukocyte travelling through a blood vessel experiences a well-established multistep process to reach the site of infection:

• The initial step involves rolling mediated by selectins.
• The following step is firm adhesion, which is facilitated by integrins.
• This is then followed by transmigration and chemotaxis.

Effective wound healing, umbilical cord detachment, and the body's response to skin infections rely on the ability of neutrophils to exit the intravascular space and trigger inflammation in the skin.

• (Choice a) A deficiency in late complement components (i.e., C5b-9) leads to an inability to form the complement membrane attack complex, resulting in an increased risk of severe infections from Neisseria organisms.
• (Choice b) Transcobalamin II serves as a carrier protein for vitamin B₁₂ post-absorption in the ileum; its deficiency does not correlate with immunodeficiency.
• (Choice d) α₂-globulins are normal serum proteins (including haptoglobin, ceruloplasmin, and α₂-macroglobulin) produced by the liver and kidneys.

Patients with a deficiency in the complement factors that create the membrane attack complex (MAC, specifically the C5b-9 complex) often suffer from recurrent infections caused by Neisseria species (Choice d). The Neisseria infections in these individuals tend to be mild since the rest of the immune system remains functional.

• MAC is the ultimate product of complement activation and it creates a pore in the bacterial cell membrane, resulting in cell lysis. (Choice A)

Pure T-cell dysfunction is observed as thymic hypoplasia in Di George syndrome. This condition is characterised by the congenital absence of the thymus and parathyroid glands, stemming from the improper development of the 3rd and 4th pharyngeal pouches.

• Consequently, patients exhibit pure T-cell lymphopenia, leading to recurrent viral and fungal infections, as well as hypocalcaemia. (Choice B)

Chronic granulomatous disease (CGD) represents a case of deficient intracellular killing due to a lack of NADPH oxidase. (Choice C) Young adults who are infected with Neisseria meningitidis may have an elevated risk of disseminated infection if they produce excessive serum IgA antibodies. In these cases, IgA binds to the bacteria and hinders the attachment of IgM and IgG antibodies, which are responsible for initiating complement-mediated bacterial lysis.

• Typically, the actions of IgM and IgG are crucial for safeguarding against bacterial dissemination.

Chediak-Higashi syndrome is a genetic disorder inherited in an autosomal recessive manner, distinguished by the unusual fusion of phagosomes with lysosomes. This leads to:

• inefficient bactericidal functions of neutrophils and monocytes.
• the formation of large intracytoplasmic lysosomes in these atypical leukocytes.

Additionally, the abnormal production of melanosomes in affected individuals causes oculocutaneous albinism. A significant number of patients later progress to an “accelerated phase”, characterised by an aggressive lymphoproliferative disease, potentially triggered by an Epstein-Barr viral infection, which can result in pancytopenia and ultimately death.

• Enhances vascular permeability
• Causes contraction of smooth muscles
• Promotes dilation of blood vessels
• Induces pain when administered into the skin

Among these effects, the enhancement of vessel permeability stands out as it is a defining characteristic of acute inflammation.

Pyrogens are agents that induce fever. They can be categorised as either exogenous or endogenous. The endogenous pyrogens, also known as pyrogenic cytokines, encompass:

• IL-1β
• IL-6
• Tumour necrosis factor (TNF)
• Ciliary neurotrophic factor (CNTF)
• IFN-α

Harrison notes that IL-18, a member of the IL-1 family, does not seem to function as a pyrogenic cytokine. Key points regarding the regulation of body temperature include:

• PGE₂ acts as the final mediator that raises the thermoregulatory set point by enhancing the concentration of cAMP.
• Exogenous pyrogens consist of microbial products and toxins; a classical example is endotoxin produced by gram-negative bacteria.
• The hypothalamus is responsible for regulating body temperature.
• Most individuals with hypothalamic damage exhibit subnormal rather than supranormal body temperatures.

• Angioneurotic oedema is a localised, non-pitting oedema involving the deeper layers of the skin and subcutaneous tissue.
• This condition is inherited in an autosomal dominant manner, resulting from a deficiency of C1 inhibitor protein (a complement regulatory protein), and is linked to increased levels of bradykinin.
• It is more prevalent in females.

• The diagnosis of hereditary angioedema is indicated by the absence of pruritus and urticarial lesions, alongside recurrent gastrointestinal colic attacks and episodes of laryngeal swelling.
• While the levels of complement protein C1 are normal, those of C2 and C4 are reduced.

• Danazol is a medication that can be utilised for hereditary angioedema.

The complement proteins can be triggered through three distinct pathways: classical, lectin, and alternative pathways. The terminal pathway is shared among these three routes and occurs at the stage following the activation of C₃. This pathway ultimately results in the formation of the membrane attack complex, which causes cell lysis. As indicated in the text, C₃ is the initial common complement protein activated in both the classical and alternative pathways.

Myeloperoxidase (MPO) is an enzyme found in the primary (or azurophilic) granules of neutrophils. When a halide like Cl⁻ is present, MPO transforms H₂O₂ into HOCl• (hypochlorous radical) during the respiratory burst process.

Nephrocalcinosis refers to the calcification occurring in the renal interstitium and tubules. It is linked to hypercalcemia. In cases of chronic granulomatous inflammation, the key cells involved are macrophages and lymphocytes.

• According to Heptinstall, "Sarcoidosis and other granulomatous diseases can be a cause of hypercalcemia and hypercalciuria due to excess vitamin D from extrarenal conversion of 1,25(OH)₂D₃."
• Nephrocalcinosis was observed in 22% of patients with chronic sarcoidosis.

In various other granulomatous disorders, such as sarcoidosis, metastatic calcification arises from the activation of vitamin D precursors by macrophages.

• Robbins states in the 5th edition of Interstitial Lung Disease that "hypercalciuria is present in nearly one-third of patients with sarcoidosis."
• Serum calcium levels in sarcoidosis increase alongside serum vitamin D levels.
• This dysregulation of calcium metabolism seems to be influenced by the abnormal synthesis of vitamin D by activated pulmonary macrophages and granulomatous tissue, leading to excessive hydroxylation of 25-monohydroxylated vitamin D precursors.
• This may represent an adaptive response to the antigen in sarcoidosis.

Delayed type hypersensitivity, as observed in tuberculosis, is caused by the build-up of mononuclear cells surrounding small veins and venules, leading to a perivascular cuffing effect. Monocytes differentiate into macrophages, which then experience morphological changes to form epithelioid cells.

Microscopic polyangiitis is a type of small vessel vasculitis characterised by:

• the occurrence of necrotising inflammation in the affected vessels
• absence of granuloma formation

Granulomatous inflammation is a unique form of chronic inflammatory response marked by localised clusters of activated macrophages, which frequently acquire an epithelial-like (epithelioid) appearance.
Tuberculosis serves as the classic example of granulomatous diseases; however, other conditions such as:

• sarcoidosis
• Crohn’s disease
• cat-scratch disease
• lymphogranuloma inguinale
• leprosy
• brucellosis
• syphilis
• certain mycotic infections
• berylliosis
• reactions to irritant lipids

are also encompassed within this category.

Friends, it is important to note that fungal and mycobacterial granulomas are typically linked with central necrosis. However, all large caseating granulomas originate from small non-caseating granulomas. Granulomas can be observed in both Byssinosis and Hodgkin’s lymphomas. Additionally, they are present in Hodgkin’s disease.

Histamine is a vasoactive amine found in various body tissues, with particularly high concentrations in the lungs, skin, and gastrointestinal tract. It is stored within mast cells and basophils.

Cytokines are proteins that play a crucial role in the body's immune response. In conditions like sepsis and Systemic Inflammatory Response Syndrome (SIRS), they are primarily secreted by:

• Neutrophils - These are a type of white blood cell that help fight infections.
• Platelets - Besides aiding in blood clotting, they also release cytokines during inflammation.

Other options, such as the adrenal glands and parts of the kidney (collecting duct and renal cortex), do not significantly contribute to cytokine release in these conditions.

The terminal pathway, which is shared by all routes of the complement system, culminates in the formation of the membrane attack complex. This pathway is comprised of the factors C5, C6, C7, C8, and C9, collectively referred to as C_5b6789.

The febrile response in the central nervous system (CNS) is primarily mediated by:

• Bacterial toxins, which can trigger fever.
• IL-1, a cytokine that plays a key role in inflammation and fever.
• IL-6, another cytokine that helps regulate immune responses and can induce fever.
• Interferon, which is involved in the immune response but is less directly related to fever.
• Tumour necrosis factor (TNF), which also contributes to the inflammatory process and fever.

Among these, IL-1 and IL-6 are particularly important for mediating the febrile response in the CNS.

Lipoxins represent a new inclusion in the array of bioactive substances derived from arachidonic acid. They exhibit anti-inflammatory properties, which are detailed in the text.

Kallikreins such as bradykinin, prostaglandins (PGs), and components of the complement system act as mediators in the process of acute inflammation.