Test: Inflammation- 1 - NEET PG MCQ

Typically, the process of phagocytosis for microbes and dead cells begins when receptors on the surface of leukocytes recognise the particles. Two key receptors responsible for binding and ingesting microbes are mannose receptors and scavenger receptors. The effectiveness of phagocytosis significantly increases when microbes are opsonised by specific proteins, known as opsonins, which bind to high-affinity receptors on phagocytes. - When a particle attaches to the receptors of phagocytic leukocytes, it triggers the active phagocytosis of that particle. - During the engulfment phase, extensions of the cytoplasm, referred to as pseudopods, flow around the particle, ultimately resulting in the particle being completely enclosed within a phagosome formed by the cell's plasma membrane. To clarify the distinction, according to Robbins, phagocytosis differs from pinocytosis and receptor-mediated endocytosis. In contrast to phagocytosis, both fluid-phase pinocytosis and receptor-mediated endocytosis of smaller particles involve internalisation into clathrin-coated pits and vesicles, and do not rely on the actin cytoskeleton. - Option ‘a’: Both the Fc fragment of IgG and C3b are necessary for opsonisation, which occurs prior to phagocytosis. - Option ‘c’: The respiratory burst takes place following the formation of the phagolysosome.

Superoxide dismutase (SOD) is an antioxidant enzyme. Some clarification about option ‘d’:

• 'Nitric oxide (NO), a significant chemical mediator produced by endothelial cells, macrophages, neurons, and various other cell types, can function as a free radical.
• It can also be transformed into the highly reactive peroxynitrite anion (ONOO⁻) as well as NO₂ and NO₃⁻.

A defining feature of acute inflammation is the heightened vascular permeability, which results in the leakage of protein-rich exudate into the extravascular tissue, leading to swelling.

Chemotaxis is described as movement that is directed along a chemical gradient.

Within the phagocytes, the subsequent reaction occurs: The enzyme that initiates this process is NADPH oxidase (often referred to as respiratory burst oxidase).

• Examples of antioxidants include glutathione peroxidase, glutathione reductase, and superoxide dismutase.
• These substances help to decrease the formation of free radicals.

The extracellular matrix (ECM) consists of both the interstitial matrix and the basement membrane. The breakdown of collagen and various ECM proteins is facilitated by a group of matrix metalloproteinases (MMPs), which require zinc ions for their function. MMP8 and MMP2 act as collagenases that cut type IV collagen within the basement membranes. Additionally, MMPs contribute to the invasion of tumour cells.

Neutrophils are the most prevalent cells in the initial 6 to 24 hours (a condition known as Neutrophilia). Following this period, they are substituted by monocytes/macrophages within 24 to 48 hours.

In cases of acute inflammation, there is an increase in hydrostatic pressure due to heightened blood flow resulting from vasodilation. Simultaneously, osmotic pressure decreases because of protein leakage caused by heightened permeability.

Granuloma development is a hallmark of chronic granulomatous inflammation and does not occur in acute inflammation. In acute inflammation, the following processes can be observed:

• Vasodilation
• Increased permeability
• Exudation
• Margination
• Rolling

The production of reactive oxygen species arises from the swift activation of an enzyme known as NADPH oxidase, which plays a role in oxygen-dependent elimination.

• Catalase, superoxide dismutase, and glutathione peroxidase function as free radical scavengers.
• They help avert damage caused by oxygen.

Bruton’s agammaglobulinaemia is an X-linked immunodeficiency disorder that is defined by the inability of B-cell precursors (pro-B cells and pre-B cells) to develop into B cells, which occurs due to a mutation in B-cell tyrosine kinase (Btk). This enzyme is essential for the transition from pre-B cells to mature B cells. Consequently, plasma cells that originate from B cells are absent, leading to a reduced production of immunoglobulins.

• The condition predominantly affects males.
• It typically does not manifest until around 6 months of age, when maternal immunoglobulins have been depleted.

Opsonisation refers to the process whereby neutrophils and macrophages preferentially phagocytose opsonised bacteria. This mechanism also necessitates the presence of antibodies. In Bruton’s disease, the opsonisation process is therefore impaired. Further details on alternative options are provided in the review of chapter 2.

The nitroblue-tetrazolium (NBT) test is the initial and most recognised assessment for chronic granulomatous disease.

• It yields a negative result in cases of chronic granulomatous disease.
• In contrast, it is positive in healthy individuals.

It serves to identify the generation of reactive oxygen species within phagocytes. The principles underlying the test have been elaborated upon in the text.

Cachexia, often referred to as wasting linked to cancer, presents with:

• weakness
• weight loss
• anorexia
• anaemia
• infections

The key cytokine associated with these symptoms is tumour necrosis-α (TNF-α). Additionally:

• Fibroblast growth factor plays a role in the process of wound healing.
• Interleukin-2 (IL-2) acts as an immune stimulant produced by activated T cells.
• Vascular endothelial growth factor is crucial for the development of blood vessels within an expanding tumour.

Diapedesis, also known as transmigration, refers to the movement of leukocytes through the endothelium. The key molecule involved in diapedesis is CD31, or PECAM-1 (platelet endothelial cell adhesion molecule). This process primarily takes place in the venules, although in the lungs, it also occurs in capillaries.

Lymphocytosis is linked to viral infections. These cells are typically small, displaying basophilic characteristics with spherical, dark-stained nuclei, and they usually make up nearly 30% of leukocytes.

• There are two primary types of lymphocytes: T cells, which play a role in cell-mediated immunity, and B cells, which are involved in humoral immunity.

Monocytes serve as precursors to osteoclasts and liver Kupffer cells, and they also develop into tissue macrophages and alveolar macrophages. Platelets consist of a peripheral hyalomere and a central granulomere. Neutrophils possess azurophilic granules and have multilobed nuclei, increasing in quantity as a response to bacterial infections.

Endothelium and WBC interact via molecules such as immunoglobulins (a family of molecules including ICAM-1 and VCAM-1), integrins, mucin-like glycoproteins, and selectins. The functions of these molecules and their associated deficiency diseases are as follows:

• Integrin: Firm adhesion; deficiency leads to LAD I.
• Selectin: Rolling and loose adhesion; deficiency results in LAD II.

Defensins are cationic peptides rich in arginine, exhibiting broad antimicrobial activity, and are located in the azurophil granules of neutrophils. Endothelin serves as a potent vasoconstrictor derived from endothelial cells.

Activation of the complement cascade can lead to the local accumulation of C3, detectable through specific histological techniques. If a patient experiences extensive activation of the complement system, serum tests may reveal reduced C3 levels. Specifically, activation of the classical complement pathway results in diminished levels of the early complement components, including C1, C4, and C2. Conversely, activation of the alternative complement pathway lowers C3 levels, while the early factors (C2 and C4) remain at normal levels. A condition linked with the activation of the alternative complement system is IgA nephropathy (Berger’s disease), which is marked by the deposition of IgA in the mesangium of the glomeruli.

Deficiencies in the C1 esterase inhibitor lead to recurrent angioedema, characterised by episodic non-pitting swelling of soft tissues, including the face. Severe abdominal discomfort and cramps, sometimes associated with vomiting, can result from swelling in the gastrointestinal tract (GI).
The C1 inhibitor not only inactivates C1 but also suppresses other pathways, such as the transformation of prekallikrein into kallikrein. This dysfunction results in the overproduction of C2 and bradykinin.

• It is the unregulated activation of bradykinin that causes angioedema.
• A deficiency in decay accelerating factor (DAF), which degrades the C₃ convertase complex, is observed in paroxysmal nocturnal haemoglobinuria (PNH).

The interleukin that is secreted by macrophages and stimulates lymphocytes is known as IL-1. This particular interleukin plays a crucial role in the immune response by promoting the activation and proliferation of lymphocytes, which are essential for fighting infections and diseases.

The enzyme ‘E’ in the figure is NADPH oxidase. It is more important bactericidal agent than defensins and lysozyme. Its deficiency is associated with chronic granulomatous disease.