Type III Hypersensitivity | Immune Complex Diseases

[00:00] So, the last part of the video. The immune complex diseases. Though, we just saw how immune complexes help us to get rid of foreign materials, like bacteria, viruses, and cell debris in a few minutes. But, what if these immune complex

[00:20] complexes are not cleared rapidly. Obviously, they will cause damage by activating components of the innate immune system. We know that the immune complexes activate complement. Although this process helps to clear complexes. Low molecular weight anaphylotoxins are produced.

[00:40] Antifilatoxins, also known as complement peptides, are fragments C3A, C4A, and C5A of the complement system. These antifilatoxins increase permeability of blood vessels. In addition, they are also

[01:00] a tactic for leukocytes. Now, complexes bind to and activate cells, such as neutrophils, mast cells, and platelets. Among them, neutrophils and mast cells release proteolytic enzymes, which damage blood.

[01:20] blood vessels, and initiate inflammation. While, the activated platelets bind to the endothelium and form thrombi. Now, that you got to know the underlying mechanism of immune complex diseases, let's discuss some conditions classified under type 3 hyper-disease.

[01:40] sensitivity or immune complex diseases. So, we used a mnemonic SPAR to memorize these examples.

[02:00] post-directococcal glomerulonephritis, A for arthas reaction, and R for rheumatoid arthritis. So, let's dive into their details. Well, the immune complex diseases can either be localized or they can be systemic.

[02:20] As I mentioned previously, if antigen is present predominantly at one site, immune complexes cause localized damage, examples being the arthas reaction and farmer's lung. So, starting off with arthas reaction, which is an

[02:40] acute localized inflammatory response that usually occurs after vaccination. In individuals who have already made IgG antibody against an antigen, the same antigen injected into the skin forms immune complexes with IgG antibody that has to

[03:00] diffused out of the capillaries.

[03:20] and the complement component C5A contributes to sensitizing the mast cell to respond to immune complexes. As a result of mast cell activation, inflammatory cells invade the site, and blood vessel permeability, as well as the blood flow, are increased.

[03:40] Platelets also accumulate inside the vessel at the site, ultimately leading to vessel occlusion. And if the reaction is severe, all these changes can lead to tissue necrosis. Now, the farmer's lung is also a localized immune complex disease, also known

[04:00] known as Extrinsic Allergic Alveolitis, Hypersensitivity Alveolitis, or more generally, Hypersensitivity Pneumonatous. It is an immunologically mediated inflammatory disease of the lung, involving the terminal airways, the alveoli.

[04:20] Well, this condition is associated with intense or repeated exposure to inhaled biologic dusts, usually from inhalation exposure to thermophilic actinomisis species, and occasionally from exposure to various aspergillus species. Next up is the systemic reaction.

[04:40] infection, known as serum sickness, a probitopic and mutant complex disease. It can result from the injection of large quantities of a poorly catabolized foreign antigen. It takes approximately 6 to 10 days for antibodies to develop and form antigen-antibody complexes.

[05:00] Do you remember from the previous part of this video that which type of complexes are produced when we have antigen in excess? Yes. Small complexes produced where there is an excess of antigen. So, when large quantities of a poorly catabolized

[05:20] an antigen, enters the circulation, it forms small circulating immune complexes. If the macrophage activating system is not functioning properly, these complexes will become saturated in the circulation. Leading to immune complex deposition, most commonly in perinkemultin,

[05:40] tissues, and synovial joint fluid, causing pain and swelling. The deposition of immune complexes may also activate the classical complement pathway, leading to lower levels of circulating C3 and C4. Also, the activation of the complement system will trigger

[06:00] histamine release and increase vascular permeability, which leads to an inflammatory response in the tissues and joints. Also, the activation of the complement system will trigger histamine release and increase vascular permeability, which leads to an inflammatory response in the tissue.

[06:20] tissues, and joints.

[06:40] A person with serum sickness usually presents with fever, urticaria, arthralgia, proteinuria, and lymphadenopathy, typically one to two weeks after antigen exposure. Now after Artha's reaction, Farmer's lung,

[07:00] serum sickness. I would like to discuss the immune complex disease in the kidney, one of the most important type III hypersensitivity. Well, the involvement of the kidney in type III hypersensitivity is a common cause of renal failure. Now, what can be the possible reason for

[07:20] kidney to be affected the most.

[07:40] increases immune complex deposition in vessel walls. Also, the glomerular cells express the complement receptor CR1, which may predispose to immune complex deposition at the site. Well, the immune complex disease in the kidney can result in two clinically-

[08:00] defined syndromes, the nephrotic syndrome, in which protein leaks into the urine and there is gradual onset renal failure, and the nephrotis, in which there is rapid onset renal failure, protein and blood in the urine, and hypertension.

[08:20] Now, both types of disease are produced by inflammation in the glomerulae called glomerulonephritis. In the nephrotic syndrome, immune complexes are deposited in the glomerular basement membrane, where they activate complement. This usually causes subtle damage to the basement membrane.

[08:40] urine, which allows proteins to leak into the urine, while in nephrodists. By comparison, there is a cellular infiltrate in addition to complement activation. Neutrophils are attracted into the glomerulae, and the resulting inflammation causes blood and protein to leak into

[09:00] the urine, impairing the ability of the kidney to excrete toxic metabolites.

[09:20] would short-lived because infection is brought under control by the immune response.

[09:40] cause of glomerulonephritis, but it can be due to any other reason. I hope now you are pretty much clear about the difference between nephrotic syndrome and nephritis and the underlying mechanism of glomerulonephritis. Now, after the immune complex

[10:00] disease of kidney. Next we have systemic lupus erythematosus or SLE or simply lupus. Do you remember the three sources of antigens, infectious antigens, innocuous environmental antigens, and autoantigen.

[10:20] antigens. In systemic lupus erythomatosis, or SLD, the immune complexes contain autoantigens. Well, it is disease of unknown origin, in which autoantibodies develop against nuclear antigens. Means the antibodies are directed to the parts

[10:40] of the nucleus. These, of course, include DNA, RNA, and DNA, RNA-associated proteins, like histones. These antibodies are called anti-nuclear antibodies. So these anti-nuclear antibodies bind to the

[11:00] pieces of nucleus, called nuclear antigens, and form immune complexes. These immune complexes then enter the blood, with the same mechanism as discussed before. Complexes are deposited in the vessel walls and various organs, including kidney, skin, and blood.

[11:20] joints, brain, pleura, and pericardium mostly. These complexes, by the activation of complement system, initiate a local inflammatory response. The immune complexes also stimulate plasmacetoid dendritic cells to produce very high levels of tosylidase.

[11:40] type 1 interferons, which contribute to inflammation. You can memorize the certain features associated with SLE by the mnemonic RASH or PAIN. Where R stands for rash, that includes malar or discoid rash. A stands for arthritis.

[12:00] S for serosidus, which includes pleuritis pericarditis. H for hematologic disorders, like sedopenias. O for oral or nasopharyngeal ulcers. R for renal disease. P stands for fibrin.

[12:20] photosensitivity. A refers to anti-nuclear antibodies. I for immunologic disorders. And lastly, N for neurologic disorders like seizures and psychosis. So that is what systemic lupus erythematosus is.

[12:40] Next up is another immune complex disease called polyarteritis nodosa, or PAN for short. Well, it is a systemic, necrotizing musculatus that typically affects medium-sized muscular arteries, with additional involvement.

[13:00] involvement of small arteries, affecting numerous organs. Mostly, it's idiopathic, means the exact cause is not known. But hepatitis B-related PAN is typically associated with immune complexes, the complexes of hepatitis B antigen with antibody and complex.

[13:20] It usually affects middle-aged males and typically involves the renal and visceral vessels, but not pulmonary arteries. Its common clinical presentations include fever, weight loss, malaise, headache, abdominal pain, melena.

[13:40] hypertension, neurologic dysfunction, cutaneous eruptions, and renal damage. Now the rheumatoid arthritis, another important immune complex disease you are much familiar with. Rheumatoid arthritis features both local,

[14:00] type, damage to joint surfaces, and systemic vasculitis. Though the cause is unknown, but complexes between rheumatoid factors and IgG are a constant finding. What is the rheumatoid factor? Well, immunoglobulin M.

[14:20] or IgM, autoantibodies against the Fc fragment of immunoglobulin G or IgG are called rheumatoid factors or RF for short. These annealed complexes bind to macrophages within joints, inducing the release

[14:40] of tumor necrosis factor alpha. So, rheumatoid arthritis in many patients can be effectively treated by administering antibodies to T and F alpha. Common presentations include tender, warm, and swollen joints, joint stiffness that is usually worse

[15:00] in the mornings and after inactivity, fatigue, fever, and loss of appetite. Now, let me mention here that the skin rashes, joint pains, and renal complications of several infections can also be caused by type III reactions.

[15:20] Now that we took a tour to various immune complex diseases and you are much clear about type 3 hypersensitivity, let me throw some light on how to these diseases can be avoided and treated. Well, the main goal is obviously to deal with the root cause, the antigen. So if it

[15:40] can be avoided, then why not?

[16:00] While, the drug therapy in autoimmune causes of immune complex disease includes corticosteroids, that blocks some of the damage caused by effector cells such as neutrophils. Cyclophosphamide is an alkylating agent that impairs DNA synthesis.

[16:20] and prevents rapid proliferation of cells, such as lymphocytes. Although cyclophosphamide has some effects on T cells, its main benefit is in reducing B cell proliferation, and hence autoantibody levels. It is often used in severe systemic lupus erythimoposis

[16:40] or SLE.

[17:00] reaction, serum sickness, farmer's lung, SLE, polyarteritis nodosa, rheumatoid arthritis, and infectious diseases.

[17:20] you