Relationship between cell mediated and humoral immunity response

relationship between cell mediated and humoral immunity response

Humoral immunity or humoural immunity is the aspect of immunity that is mediated by Its aspects involving antibodies are often called antibody- mediated immunity. innate response that lead to a combination of cellular and humoral immunity, . Edit links. This page was last edited on 2 November , at (UTC). The immune system distinguishes two groups of foreign substances. One group consists of antigens that are freely circulating in the body. These include. strated that the humoral and cell-mediated immune responses are activated through No correlation was observed between the humoral antibody titer and the.

Several cytokines such as IL and IL are involved in regulating activation and differentiation of Th17 cells. In the kidney, Th17 effector cells have been demonstrated in biopsy samples in human glomerulonephritis Abdulahad et al.

relationship between cell mediated and humoral immunity response

In contrast, the adaptive immune response by T cells is regulated by T regulatory cell Treg s Jiang and Chess Treg cells are in charge of suppressing potentially deleterious activities of Th cells. Lyn-deficient mice, which increase titers of autoantibodies with age, develop immune complex-mediated glomerulonephritis, and Tregs are expanding in these mice in an effort to control the autoimmune disease, although they are simply overwhelmed by the disease process eventually Tsantikos et al.

Humoral immune response Many forms of glomerulonephritis are autoimmune in nature and loss of self-tolerance and exposure to etiologic agents lead to immune-complex formation, presumably by mechanisms of molecular mimicry and epitope spreading. Causative antigens include normal intrinsic structures of the glomerulus eg. DNA-nucleosome complex in systemic lupus erythematosus Kalaaji et al.

Immune complexes are either formed in the systemic circulation and localize in the glomerulus through passive trapping eg. In the latter case, an antibody either binds specific antigens intrinsic to the glomerulus, or soluble antigens that become localized due to charge interactions with the glomerular capillary wall or by nonspecific uptake by the mesangium. Identification of responsible antigens in human glomerular diseases, however, is difficult, and multiple antigens and routes leading to immune complex formation appear to co-exist in a single disorder.

In systemic lupus erythematosus SLEcirculating immune complexes composed of antibodies against double-stranded DNA and ribonucleoproteins are readily detectable, which correlate with disease activity Izui et al.

Humoral immunity - Wikipedia

However, immune complexes are formed in situ as well, via charge interactions between antibodies and DNA-histone complexes already deposited in the glomerulus Schmiedeke et al. Furthermore, some lupus autoantibodies appear to bind directly to intrinsic glomerular antigens.

Deposits are observed in subepithelial eg. Heymann nephritis model in rats and human membranous nephropathysubendothelial eg. In general, immune complexes formed in situ are more nephritogenic, because they are more capable of activating local complement response Couser and Salantreleasing vasoactive substances, reactive oxygen species, cytokines and procoagulants Couser In fact, it is rather unusual that immunoglobulins themselves induce significant injury in the kidney, except for antibodies against components of the podocyte slit diaphragm Holthofer The complement system is an important mediator of tissue inflammation and injury.

It is a family of more than 20 serum and cell-surface proteins and they operate as a cascade of reactions. The IgG immune complexes bind to complement factor C1q and activate the C1 complex, leading to the formation of C3 convertase and the enzymatic cleavage of the central complement component C3.

C3 then releases the chemotactic factor C3a and the covalent C3b attaches to the host cells, which is an important step for continued activation of the terminal membrane attack complex, C5b-9, and for the amplification through the alternative pathway.

C5b-9 is thought to be the key component responsible for the complement-mediated glomerular injury. It inserts in sublytic amounts into the glomerular membranes, triggers cell activation and mediates injury.

The complement cascade is tightly regulated by short half-lives of its components and a series of endogenous regulatory proteins. Complement regulatory proteins counteract the complement activity and protect glomerular cells from injury Nangaku In vitro, overexpression of CD59 protected cultured glomerular cells from attack Nangaku et al.

In the rat Heymann nephritis model, simultaneous blockade of complement regulatory proteins by neutralizing antibodies was required to develop proteinuria following injection of anti-megalin antibody Schiller et al. Heymann nephritis model in the rat The role of immune complexes formed in situ has been most extensively studied in the Heymann nephritis model in the rat, a human counterpart of membranous nephropathy MN. This is a non-proliferative form of GN in which the humoral, Th2 responses play an important role.

Following induction of the disease, antibodies against gp, megalin Cavallo ; Ronco and Debiecare deposited at the subepithelial space of the glomerulus and trigger podocyte injury through activation of the complement system, particularly the membrane attack complex, C5b C5b-9 inserts into the podocyte membrane and is then transported across the cell to be extruded into the urinary space, resulting in elevated levels of C5b-9 in the urine Kerjaschki et al.

C5b-9 is thought to be the major mediator of altered glomerular permeability function, although histologic changes are minimal by light microscopy Nangaku et al. Depletion of complement complements using cobra venom factor greatly reduced the amount of proteinuria Salant et al.

At the cellular level, C5b-9 generates hydrogen peroxide Shah ; Neale et al. It also induces apoptosis in podocytes, dissociation of nephrin from the actin cytoskeleton Yuan et al. However, subepithelial deposits in general induce no inflammation, probably because they are located at a site inaccessible to circulating cells. Several caveats exist in translating these findings in rats into human MN. First, the responsible antigen, megalin, shows a distinct pattern of spatial distribution among species.

Humoral immunity

In rats, megalin is expressed both on the brush border of proximal tubules and the soles of podocyte foot processes at which immune complexes are initially formed. In humans, however, megalin is only expressed in proximal tubules and not in podocytes, excluding megalin from the list of responsible self-antigens in human MN.

Cell Mediated Immunity

Nevertheless, findings obtained from the Heymann nephritis provide solid evidence that some components on the podocyte membrane serve as targets for immune complex formation in situ and trigger cascades of humoral immune responses that lead to massive proteinuria. Second, deposition of immunoglobulin in human MN is predominantly of the IgG4 subclass, which is theoretically incapable of triggering complement activation.

This is in contrast to the fact that complements undoubtedly play an important role in the rat Heymann nephritis. It may be a relevant finding that C6-deficient PVG rats incapable of forming C5b-9 also develop massive proteinuria following injection of antisera, suggesting that complement-independent mechanisms may also exist in this model Spicer et al.

To date, much effort has been made to identify podocyte antigens responsible for human MN, which are only beginning to be uncovered. Recent breakthrough studies revealed pathogenic antigens of human MN in podocytes; i.

relationship between cell mediated and humoral immunity response

The proposed mechanisms on the pathogenesis of anti-NEP antibody-mediated neonatal NM was as follows. As a result, antibody against NEP localized on the surface of podocytes, formed immune complex in situ and subepithelial immune deposits and eventually developed neonatal membranous nephropathy in the second baby Debiec et al. Subsequently, families with truncating mutation in the MME gene coding for NEP were reported, in which cases second infants born from MME-mutated mothers developed neonatal MN, indicating that the MME gene product is a cause of alloimmunization during pregnancy Debiec et al.

Clearly, however, NEP is only responsible for a fraction of rare cases of neonatal MN and not likely a universal antigen. PLA2R was expressed in podocytes of normal human glomeruli and colocalized with IgG4 in subepithelial immune deposits Beck et al. These findings were recently supported by independent genomewide association studies of single-nucleotide polymorphisms SNPs in patients with idiopathic MN from three populations of white ancestry Stanescu et al.

relationship between cell mediated and humoral immunity response

The joint analysis of data from the patients studied identified the gene encoding PLA2R as a risk allele of idiopathic MN. Passive transfer of anti-GBM antibodies alone was not sufficient to induce disease in the absence of T cells Kalluri et al.

These findings suggested the role of systemic suppression of T cell function in ameliorating disease. In this regard, the possible participation of Tregs is anticipated, but this remains to be proven. Immune complexes then cause injury and subsequent effector responses, leading to pulmonary hemorrhage in affected patients. Poststreptococcal glomerulonephritis The major pathogenic mechanism of poststreptococcal glomerulonephritis PSGN is an in situ immune complex formation due to deposition of streptococcal nephritogenic antigens, such as nephritis-associated plasmin receptor NAPlr and Streptococcal pyrogenic exotoxin B SPE B.

Both are capable of activating the alternate pathway of the complement cascade and enhance the expression of adhesion molecules. SPE B also stimulates the production of chemotactic cytokines. NAPlr was isolated from group A streptococcus and was shown to bind plasmin ogen.

Mechanistically, it is speculated that NAPlr in the mesangium interacts with plasmin ogen and causes glomerular injury by degrading GBM through activation of metalloproteinase precursors. Then, circulating immune complexes move across damaged GBM and accumulate in the subepithelial space Yamakami et al.

Humoral and Cell-Mediated Immune Responses

SPE B is a cationic cysteine proteinase and was found in 12 of 17 biopsies from patients in Latin America and Switzerland. SPE B deposits localized within the subepithelial electron dense deposits humps and colocalized with complement Batsford et al.

Antibodies to SPE B were detected in the convalescent sera in all patients tested. To date, it is speculated that separate antigens may be responsible for PSGN in different parts of the world and among patients with distinct genetic backgrounds Rodriguez-Iturbe and Batsford ; Rodriguez-Iturbe and Musser Immune complex in the subendothelial space and the mesangium Immune complexes can be formed and deposited in other compartments of the glomerulus as well.

relationship between cell mediated and humoral immunity response

They recruit circulating inflammatory cells, such as neutrophils, lymphocytes, macrophages and platelets Adler and Bradyactivate effector responses and cause injury. Local chemotactic factors such as C5a and IL-8 recruit neutrophils to sites of inflammation.

Antibody-antigen reaction[ edit ] Now these antibodies will encounter antigens and bind with them.

Humoral and Cell-Mediated Immune Responses

This will either interfere with the chemical interaction between host and foreign cells, or they may form bridges between their antigenic sites hindering their proper functioning, or their presence will attract macrophages or killer cells to attack and phagocytose them. Complement system The complement system is a biochemical cascade of the innate immune system that helps clear pathogens from an organism.

It is derived from many small blood plasma proteins that work together to disrupt the target cell's plasma membrane leading to cytolysis of the cell. The complement system consists of more than 35 soluble and cell-bound proteins, 12 of which are directly involved in the complement pathways. Activation of this system leads to cytolysischemotaxisopsonizationimmune clearance, and inflammationas well as the marking of pathogens for phagocytosis.

Most of these proteins circulate as zymogenswhich are inactive until proteolytic cleavage. Three biochemical pathways activate the complement system: The classical complement pathway typically requires antibodies for activation and is a specific immune response, while the alternate pathway can be activated without the presence of antibodies and is considered a non-specific immune response. B cell activation is a large part of the humoral immune response.

Antibody Immunoglobulins are glycoproteins in the immunoglobulin superfamily that function as antibodies. The terms antibody and immunoglobulin are often used interchangeably.

They are found in the blood and tissue fluids, as well as many secretions. In structure, they are large Y-shaped globular proteins. In mammals there are five types of antibody: Each immunoglobulin class differs in its biological properties and has evolved to deal with different antigens. An antibody is used by the acquired immune system to identify and neutralize foreign objects like bacteria and viruses.

Each antibody recognizes a specific antigen unique to its target. By binding their specific antigens, antibodies can cause agglutination and precipitation of antibody-antigen products, prime for phagocytosis by macrophages and other cells, block viral receptors, and stimulate other immune responses, such as the complement pathway.