Chronic Inflammation and Granulomatous Diseases | Chronic Inflammation

[00:00] Now, that we have gone through a detailed comparison between the acute and chronic inflammation. And we have already a video on acute inflammation on scottea.com. So, let's now focus on the topic of the day, chronic inflammation. Well, you can define it as...

[00:20] A prolonged inflammation characterized by mononuclear infiltration, which leads to simultaneous tissue destruction and repair, including angiogenesis and fibrosis, may be preceded by an acute inflammation. Now, the tissues affected by

[00:40] chronic inflammation commonly show evidence of some pathologic processes. These processes include immune response and the manifestations of the immune response in injured tissue include the presence of lymphocytes, plasma cells, and macrophages. Also, plasma immunoglobulin

[01:00] levels may be elevated. Next is phabesthetosis, which can be either immune phabestosis or non-immune phabestosis. Immune phagocytosis is mediated by macrophages that have been activated by T cell.

[01:20] and it involves antigens that have obcinin attached to their surfaces, while the non-immune phagocytosis is directed against foreign non-antigenic particles. Next, some degree of necrosis is also common that may affect only scattered individual

[01:40] cells, or may be extensive. And lastly, the repair of tissues damaged by persistent injury is characterized by new blood vessel formation called angiogenesis, fibroblastic proliferation, and collagen deposition called fibrosis. In most cases,

[02:00] The persistent injurious agent is antigenic and leads to an immune response, involving T-cells, B-cells, and macrophages. Foreign body granuloma formation, on the other hand, appears to be a direct phagocytic response to inert and the non-antigenic material and the

[02:20] immune response is not involved. While, the most agents associated with chronic inflammation cause insidious, but progressive and often extensive tissue necrosis, accompanied by ongoing repair by fibrosis. So now we will be discussing

[02:40] chronic inflammation in two different types of responses. Firstly, in response to antigenic injurious agents. And next, we will have a look at chronic inflammation in response to the non-antigenic injurious agents. So, starting with the first one. Chronic inflammation usually

[03:00] occurs in response to an injurious agent that is antigenic, like a microorganism, but it may also develop in response to self-antigens released from damaged tissues. The immune response is triggered by the first contact with the antigen, but it takes some days to become apparent in the tissue.

[03:20] Now, the local persistence of the antigen then leads to accumulation of activated T-lymphocytes, plasma cells, and macrophages at the site of injury, because these cells are the prominent cell types in chronic inflammation. Effector cells of the immune response are also called

[03:40] called chronic inflammatory cells. Simple uncomplicated acute inflammation usually resolves upon removal of antigen before any apparent sign of immune response. Well, the macrophages are recruited to the lesion from the blood by such chemotactic factors.

[04:00] the C5A and transforming growth factor beta, or TGF beta. Now the local activation occurs under the influence of multiple cytokines, particularly gamma interferon and interleukin-4. Now macrophages in turn release over

[04:20] variety of factors that promote the developing immune response, including cytokines like interleukin I, interleukin VI, and tumor necrosis factor alpha or TNF alpha. Complement components, prostaglandins, and various growth factors.

[04:40] such as fibroblast growth factor or FGF, platelet-derived growth factor or PGF, and transforming growth factor beta or TGF beta. Multiple proteases and hydrolysis also contribute to the phagocytic and microbacidal effect.

[05:00] Now, moving forward, on the basis of morphology, we can classify the chronic inflammation as granulomatous chronic inflammation and non-granulomatous chronic inflammation. So, starting off with the granulomatous chronic inflammation.

[05:20] The granulomatous chronic inflammation is a special type of chronic inflammation characterized by the formation of granuloma. Now, what is granuloma? Well, granuloma is a focal collection of inflammatory cells at sites of tissue infection.

[05:40] inflammation, and includes activated macrophages, epithelial cells, langan's giant cells, and lymphocytes. Granulomas wall off a resistant stimulus without completely eradicating or degrading it. This leads to persistent inflammation, fibrosis, or scurrying.

[06:00] and may damage the organ. A typical granuloma is shown here. Now, granulomas are typically classified into two types. Epithyloid cell granuloma, which represents an immune response in which the macrophages are activated by lymphokines of specifically stimulated

[06:20] T cells, examples being tuberculosis and leprosy, and foreign body granuloma, which represents non-immune phagocytosis of foreign non-antigenic material by macrophages, for example, psilocosis. As we are talking here about the chronic

[06:40] inflammation in response to antigenic injurious agents. So, we will be focusing mainly on epithelial cell granuloma here. Now, let's dive deeper to have a closer look at characteristic features of granuloma. So, do you know the epithelial cells?

[07:00] Well, the epithelial cells are activated macrophages that appear on microscopic examination as large cells with abundant pale foamy cytoplasm. Wait, I just found the word epithelial, quite resembling the word epithelium. Yes, epithelium.

[07:20] It is, and there's a reason behind this. They are called epithelial cells because of a superficial resemblance to epithelial cells. Well, the epithelial cells appear to have enhanced abilities to secrete lysozyme and a variety of enzymes, but decreased phagocytic potential.

[07:40] So, an epithelial cell granuloma is an aggregate of these activated macrophages, and this aggregation is induced by lymphokines produced by activated T-cells. Granulomas are usually surrounded by lymphocytes, plasma cells, fibroblasts, and collagen.

[08:00] And, a typical feature of epithelial cell granolomas is the formation of Langhen's type giant cells. These are derived from fusion of macrophages and characterized by about 10 to 50 nuclei around the periphery of the cell. On the basis of histology, granolomas have two types.

[08:20] case-eating, and non-case-eating. Case-eating is associated with central necrosis, typically seen with infectious etiologies, like tuberculosis and fungal infections. While the non-case-eating shows no central necrosis, it is typically seen with central necrosis.

[08:40] typically seen with autoimmune diseases, like sarcoidosis and Crohn's disease.

[09:00] Well, epithelial cell granolomas form when two conditions are satisfied. Firstly, when macrophages have successfully fevositosed the injurious agent, but it survives inside them. Secondly, when an active T lymphocyte-mediated cellular immune responds.

[09:20] occurs. Lymphokines produced by activated T lymphocytes inhibit migration of macrophages and cause them to aggregate in the area of injury and form granulomas. Epithyloid granulomas occur in several different types of disease states, including tuberculosis.

[09:40] sclerosis, leprosy, histoplasmosis, coccidioatomycosis, syphilis, Crohn's disease, sarcoidosis, and some other condition as well. Now that you are a way more familiar with what chronic granulomatous inflammation is,

[10:00] What causes granuloma to form? How it is classified into different types? I think this is the right time to move on and learn about the underlying mechanism of chronic granulomatous inflammation. So, let's jump in. Well, when an antigen enters the body,

[10:20] an immune response is generated. As a result, antigen is taken up by the antigen-presenting cell like macrophages. Now these antigen-presenting cells present antigens to CD4 plus helper T cells and secrete interleukin-12 or IL-12.

[10:40] CD4 plus helper T cells then differentiate into helper T cells subtype I. Now these Th1 cells secrete interferon gamma. That results in macrophage activation. Now what macrophages do is that they increase cytokine secreting.

[11:00] secretion, like that of T and F alpha, thus attracting more cells and stimulating macrophages. This leads to the formation of epithelial macrophages and giant cells, and, obviously, resulting in what we call granuloma. So that was it for today.

[11:20] That was about granulomatous chronic inflammation. Now, moving further to the second type, that is non-granulomatous chronic inflammation. Well, non-granulomatous chronic inflammation is characterized by the accumulation of sensitized lymphocytes, specifically

[11:40] activated by antigen, plasma cells, and macrophages in the injured area. These cells are scattered diffusely throughout the tissue. However, they do not form granulomas, the reason for being known as non-granulomatous. Also, the scattered tissue necrosis or cell

[12:00] death, and fibrosis or scaring are common here. Non-granulomatous chronic inflammation represents a composite of several different types of immune response due to different antigenic agents. Well, non-granulomatous chronic inflammation includes chronic viral

[12:20] infections like chronic viral hepatitis and chronic viral infections of the central nervous system. Autoimmune diseases like rheumatoid arthritis and chronic ulcerative colitis. Chronic toxic diseases like chronic

[12:40] alcoholic pancreatitis, and chronic alcoholic liver disease. Also infections like lepromatous leprosy, leishmaniasis, infections with metazoan parasites, and recurrent type I hypersensitivity reactions, including bronchial asthma.

[13:00] plasma, allergic nasopolyps, and atopic dermatitis. So that was about non-granulomatous chronic inflammation. I hope you are much clearer about these two morphological types of chronic inflammation. We will also discuss about the granulomatous diseases in the next part.

[13:20] By now, we have covered the chronic inflammation in response to antigenic injurious agents. If you remember, there was a second type I mentioned earlier. And that was the chronic inflammation in response to non-antigenic injurious agents. So let's see what it is.

[13:40] foreign material that is large enough that it cannot be fibositose by a single macrophage. Inert means it cannot incite an inflammatory response and non-antigenic means it cannot even initiate an immune response. If such foreign material enters a tissue

[14:00] and persists there, foreign body granulomas are formed. So this non-antigenic material, which includes sutures, tau particles, and inert fibers, is removed by macrophages through non-immune phibocytosis that I mentioned earlier. Now the macrophages and

[14:20] macrophages aggregate around the phogositose particles and form granulomas. These granulomas frequently contain foreign body giant cells, characterized by numerous nuclei dispersed throughout the cell, rather than arranged around the periphery, as occurs in Langan-type giant cells.

[14:40] And, the foreign material is usually identifiable in the center of the granuloma. Foreign body granuloma is of little clinical significance and indicates only that non-digestible foreign material has been introduced into the tissue. Do notice.

[15:00] that tissue necrosis is not an associated feature here. So, finally, we are done with the chronic inflammation in response to both antigenic and non-antigenic injurious agents. Now, I would like to add that the chronic inflammation serves to contain.

[15:20] and over a long period of time remove an injurious agent that is not easily eradicated by the body. To contain and destroy the injurious agent in chronic inflammation is largely dependent on the immunologic reactivity. Well, this can be achieved

[15:40] by direct killing by activated lymphocytes, interaction with antibodies produced by plasma cells, or activation of macrophages by lymphocains produced by the T lymphocytes. Now with the exception of foreign body reactions, chronic inflammation is often

[16:00] associated with tissue necrosis, and this can of course cause serious clinical illness. One example being liver failure in chronic active hepatitis. Well, chronic inflammation is a feature of many chronic diseases that are characterized either by total lack of recovery.

[16:20] or by a long recovery period of months or even years. Now, associated fibrosis, a repair mechanism, is another serious side effect of chronic inflammation if it occurs to an excessive degree. You guys must be familiar that in certain situations, fibrous skin

[16:40] sharing itself causes disease. For example, fibrosis of the pericardial sac in chronic pericarditis may restrict cardiac filling and cause heart failure, and pulmonary fibrosis may cause respiratory failure. Now, what happens is that the injurious agent

[17:00] is ultimately removed or neutralized. The tissue then heals usually by the fibrosis. The chronic inflammatory cells disappear, but you are left within a cellular fibrous scar at the site of injury. So here we come to an end to this part. For a quick recap.

[17:20] We discussed that the inflammation is a part of the body's defense mechanism by which the immune system recognizes and removes harmful and foreign stimuli and begins the healing process. Then we talked about the three types of inflammation as acute, subacute.

[17:40] inflammation. Then we compared the acute and chronic inflammation, four pathological processes that are involved in chronic inflammation, including immune response, ph about ketosis, necrosis, and the repair of tissues. Then the chronic inflammation

[18:00] response to antigenic and non-antigenic injurious agents, granulomatous and non-granulomatous chronic inflammation. Then, we had a detailed discussion on the types of granulomas involving epithelial cell granuloma and foreign body granuloma.

[18:20] case-eating, and non-case-eating granulomas. And lastly, the outcomes of chronic inflammation, necrosis, and fibrosis. Well, video has not ended yet. We are still left with an important part of the video. That is about the granulomatous diseases.

[18:40] So, bear with me.