Situational task № 1. Leukocytes’ substances increase the emigration of leukocytes and vascular permeability. In inflammation, the administration of hydrocortisone suppresses the emigration of leukocytes, somewhat weakens the permeability of the vascular wall, but the latter remains high. Explain the mechanisms of maintaining high vascular wall permeability in this case.

In inflammation, the high vascular wall permeability is maintained by several mechanisms:

1. Inflammatory mediators: Inflammation triggers the release of various inflammatory mediators such as histamine, bradykinin, and prostaglandins. These mediators act on the endothelial cells of the blood vessels, causing them to retract and become more permeable. Even though hydrocortisone may weaken this effect to some extent, the presence of other inflammatory mediators can still contribute to maintaining high vascular permeability.

2. Endothelial cell activation: Inflammation leads to the activation of endothelial cells, which results in the expression of adhesion molecules and the reorganization of the cytoskeleton. These changes in endothelial cell behavior contribute to increased vascular permeability by allowing for the passage of leukocytes and other immune cells through the vessel walls.

3. Leukocyte activation: Leukocytes themselves can release factors that further increase vascular permeability. For example, neutrophils release enzymes such as elastase and collagenase, which can degrade the extracellular matrix and basement membrane of blood vessels, leading to increased permeability.

4. Feedback loops: Inflammation involves complex feedback loops between various cells and mediators in the immune response. These feedback loops can sustain the inflammatory process and maintain high vascular permeability even in the presence of anti-inflammatory agents like hydrocortisone.

Overall, the maintenance of high vascular wall permeability in inflammation is a complex process involving multiple factors and mechanisms that work together to facilitate the immune response and tissue repair.

The changes in the physicochemical properties of tissues in the focus of inflammation specifically promote the migration of leukocytes while not affecting red blood cells due to several reasons:

1. Chemotactic substances: The presence of chemotactic substances in the inflamed tissue, such as cytokines, chemokines, and bacterial products, specifically attract leukocytes towards the site of inflammation. These substances bind to specific receptors on leukocytes, triggering a signaling cascade that leads to their migration towards the inflamed tissue. Red blood cells do not possess the same receptors for chemotactic substances and therefore are not affected by them.

2. Adhesion molecules: The altered physicochemical properties of the inflamed tissue result in the upregulation of adhesion molecules on the endothelial cells lining the blood vessels. These adhesion molecules facilitate the adhesion of leukocytes to the endothelium and their subsequent migration across the vessel wall. Red blood cells do not express the same adhesion molecules and therefore do not participate in this process.

3. Size and structure: Leukocytes are larger and more flexible than red blood cells, allowing them to squeeze through the gaps in the endothelial cells and migrate towards the site of inflammation. Red blood cells, being smaller and more rigid, are unable to undergo the same process of diapedesis and are thus not involved in the migration towards the inflamed tissue.

4. Specific receptors: Leukocytes express specific receptors that recognize and respond to the signals present in the inflamed tissue, allowing them to selectively migrate towards the site of inflammation. Red blood cells lack these receptors and therefore do not respond to the signals that promote leukocyte migration.

Overall, the changes in the focus of inflammation selectively promote the migration of leukocytes due to the presence of specific chemotactic substances, adhesion molecules, size differences, and receptor specificity that are not applicable to red blood cells.

The passage of leukocytes through the basement membrane of blood vessels, despite their larger size compared to the pores in the membrane, is facilitated by several mechanisms:

1. Diapedesis: Diapedesis is the process by which leukocytes migrate from the bloodstream into the surrounding tissue. It involves a series of steps including rolling, adhesion, crawling, and transmigration. During the transmigration step, leukocytes actively deform and squeeze through the small gaps in the endothelial cells and basement membrane to reach the site of inflammation.

2. Enzymatic degradation: Leukocytes release enzymes such as collagenases and elastases that can degrade components of the extracellular matrix, including the basement membrane. By breaking down the structural proteins of the basement membrane, leukocytes create pathways for themselves to pass through, despite their larger size.

3. Chemotaxis: Chemotactic substances released at the site of inflammation attract leukocytes towards the source of the inflammatory stimulus. As leukocytes follow these chemical signals, they undergo cytoskeletal rearrangements that allow them to deform and pass through the basement membrane and endothelial cell junctions.

4. Endothelial cell retraction: In response to inflammatory signals, endothelial cells lining the blood vessels undergo cytoskeletal changes that lead to their retraction and the opening of gaps between them. This retraction creates space for leukocytes to pass through the basement membrane and enter the tissue.

5. Leukocyte activation: Upon encountering inflammatory stimuli, leukocytes become activated and change their shape and structure. This activation allows them to deform and squeeze through tight junctions and pores in the basement membrane that would normally be too small for their size.

Overall, the passage of leukocytes through the basement membrane of blood vessels in inflammation is facilitated by a combination of active processes such as diapedesis, enzymatic degradation, chemotaxis, endothelial cell retraction, and leukocyte activation, which collectively allow these immune cells to reach the site of inflammation despite their larger size.

1. Interpretation of the immunogram data:

• CD3: 45% (within normal range): CD3 is a marker of mature T-cells. The percentage falls within the normal range.
• CD4: 29% (slightly below normal range): CD4 T-cells are helper T-cells that play a crucial role in coordinating the immune response. A lower percentage of CD4 cells may indicate a weakened immune system.
• CD8: 15% (within normal range): CD8 T-cells are cytotoxic T-cells that destroy infected or abnormal cells. The percentage falls within the normal range.
• CD20: 7% (below normal range): CD20 is a marker for B-cells. A lower percentage of CD20 cells may suggest a decreased ability to produce antibodies.
• sIg A: 0.9 (within normal range): Secretory IgA is an antibody found in mucosal surfaces. The level is within the normal range.
• IgA: 2.25 g/l (within normal range): IgA is an antibody that plays a role in mucosal immunity. The level is within the normal range.
• IgG: 5.6 g/l (below normal range): IgG is the most abundant antibody in the blood and is important for long-term immunity. A lower level of IgG may indicate a decreased ability to fight infections.
• IgM: 0.98 g/l (below normal range): IgM is the first antibody produced in response to an infection. A lower level of IgM may suggest a decreased ability to mount an initial immune response.

2. Functions of CD4 and CD8 cells:

• CD4 T-cells (helper T-cells) play a central role in coordinating the immune response by activating and directing other immune cells. They help B-cells produce antibodies, activate macrophages, and stimulate cytotoxic T-cells.
• CD8 T-cells (cytotoxic T-cells) are responsible for directly killing infected or abnormal cells. They recognize and destroy cells that are infected with viruses or have become cancerous.

3. Methods used to determine T-lymphocytes:
   T-lymphocytes, including CD3, CD4, and CD8 cells, can be measured using flow cytometry, a technique that allows for the simultaneous identification and quantification of different cell types based on their surface markers. Flow cytometry uses fluorescently labeled antibodies that specifically bind to T-cell surface markers, allowing for their detection and quantification.