Immunology Chapter on Inflammation and Hypersensitivity

Cellular Immune Response in Kidney Disease

• The presentation discusses the cellular immune response in kidney disease.
• Pathogens are categorized into five groups: viruses, bacteria, fungi, protozoa, and helminths (worms).
• Pathogens can be found in various body compartments, requiring different host defense mechanisms.

Immune Response

• Pathogen containment by anatomical barriers is a primary defense mechanism.
• Early induced innate responses occur within 4-96 hours, targeting and removing infectious agents.
• Adaptive immune responses occur after 96 hours.

Anatomic Barriers and Initial Chemical Defenses

• Pathogens cause disease and damage tissues.
• Intracellular pathogens (e.g., viruses) are not accessible to initial defenses but are targeted by natural killer (NK) cells and cytotoxic T cells.
• Macrophage activation by NK or T cells kills invading pathogens.

Extracellular vs. Intracellular

• Pathogens can be either extracellular (in interstitial spaces, blood, lymph, or on epithelial surfaces) or intracellular (cytoplasmic, vesicular).
• Different protective immunities (complement, phagocytosis, antibodies) target extracellular and intracellular pathogens.

Pathogens Can Damage Tissues

• Various mechanisms of pathogen-induced tissue damage are presented.
• Direct mechanisms, such as exotoxin production, endotoxin release, or direct cytopathic effects.
• Indirect mechanisms, such as immune complexes, anti-host antibodies, or cell-mediated immunity.

Complement Activation

• The complement system is a key component of innate immunity.
• Complement activation occurs in stages, starting with pattern recognition that triggers protease cascade amplification. These stages can lead to phagocytosis, inflammation, and membrane attack.

Pathways of Complement Activation

• Complement activation pathways are the alternative pathway, the classical pathway, and the lectin pathway.
• Each pathway triggers complement cascade amplification leading to different effector functions including opsonization and inflammation.

The Classical Pathway

• The classical pathway is crucial in adaptive immunity's humoral arm.
• The classical pathway is initiated by soluble proteins (pentraxins).
• A complement component (MBL) is a member of the collectin family with a hexameric structure.

Immune Complex Disease in Kidney

• Pathological immune complex deposition in kidneys can cause disease.
• Immune complexes, formed from antigen-antibody complexes, are deposited in small blood vessels.
• Immune complexes activate complement, leading to inflammation and, in some instances, necrosis. (Severe and long-lasting tissue injury can result.)

Immune Complex Diseases in Kidneys—Pathogenesis

-   Nephritogenic strains are limited to a few M types and seem to have declined.
-   M protein of some nephritogenic strains share antigenic determinants with glomeruli.
-   The renal injury of acute glomerulonephritis is caused by immune complex deposition.

Clinical Manifestations

• The clinical course of post-streptococcal glomerulonephritis (PSGN) is often benign. There is spontaneous healing over weeks or months but occasionally, a course progresses to renal failure or death.

Diagnosis

• Detecting group A antigen directly from throat swabs is a widely available diagnostic tool.
• Several serological tests were developed to support the diagnosis of PSGN.

Treatment

-   Penicillin G is the antimicrobial of choice for Group A streptococcal infection.
-   Alternative antibacterials may be used for patients with penicillin allergies.

Prevention

• Multivalent vaccines utilizing M protein epitopes are being explored in clinical trials as a prevention measure.

Inflammatory Response

• Leukocytes and plasma proteins are crucial components of the inflammatory response.
• Inflammatory sites have increased blood flow into tissue, leukocyte adhesion to endothelial lining of venules, and changes in vascular permeability.

Function of Macrophages

• Macrophages are crucial parts of the inflammatory response. (They can be activated by cytokines.)
• Macrophage activation leads to enhanced inflammation and killing of microbes. Cytokines like TNF, IL-1, IL-6, IL-12, initiate and regulate macrophage activity, leading to the removal of pathogens.

Local and Systemic Actions of Cytokines

• Cytokines such as TNF, IL-1, IL-6, and chemokines drive the inflammatory response locally as well as systemically.
• Systemically, cytokines (e.g., TNF, IL-1, IL-6) cause changes like fever and increased acute-phase protein production.

Hypersensitivity

• Pathogenic immune reactions lead to hypersensitivity of various types. Immediate hypersensitivity reactions (Type I) are IgE-mediated reactions leading to mast cell activation.

Pathogenesis of immune complex Diseases in Kidneys

- Complexes containing cationic antigens.
- Complex deposits in sites where plasma is ultra-filtered