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Ok. So, good afternoon, I'm gonna talk about er briefly lymphoid tissues, immune evasion, hypersensitivity and anaphylaxis. Today, the outline of the session will start with a brief introduction to lymphoid tissues, then move to primary and secondary lymphoid organs, then talk about immune evasion mechanisms and hypersensitivity reactions followed by anaphylaxis and a little look at clinical relevance in some and a case study. So it's an introduction to lymphoid tissues. What are they, they are specialized tissues that support the growth development and function of lymphocytes. They are structured and they networks of cells and fibers and supporting matrices. Their primary function here is to facilitate immune cell interactions and responses. So, they are really the facilitators of the im immune system and they are critical for antigen presentation, lymphocyte activation and immune response generation. So this is a histology slide of a lymphoid tissue cellularly. Its components comprise lymphocytes. So those are T cells, B cells and natural killer cells. Antigen presenting cells such as dendritic cells and macrophages and stromal cells, which are sort of that matrix like area which include fibroblastic reticular cells and follicular dendritic cells structurally. Um these are composed of reticular fibers and extracellular matrix. And they are arranged and a specialized and there are specialized vascular structures um which contain these things called high endothelial venules. They also contain lymphatic vessels, checking everyone can hear that. So, the organization of lymphoid tissues, there are primary lymphoid organs and then there are secondary lymphoid organs. So, the primary lymphoid organs are the sites of lymphocyte development and maturation. And these are the bone marrow and the thymus. So you can see over here on our picture, the bone marrow and the thymus. Our primary lymphoid organs, our secondary lymphoid organs are the sites of antigen presentation and lymphocyte activation. And these are lymph nodes, spleen and molts which are mucosa associated lymphoid tissues moving on to the primary and secondary lymphoid organs. One of the primary organs being the bone marrow. Its structure is a, there is red and yellow marrow within the medullary cavities of our bones. And the main function is the site. Uh It's a site of Hema hematopoiesis, which is our blood cell production and we get all our white blood cells and red blood cells from this process, immuno immunologically. This is the origin of all our immune cells as our T cells, B cells and natural killer cells are derived from hematopoietic stem cells which come from the bone marrow. And these are the sites of B cell development and maturation and they serve as the microenvironment for stem cell maintenance. Our next primary lymphoid organ is the thymus. Its structure is bilobed and it's in the anterior media sinum which is in that chest cavity and it's divided into the cortex, which is the outer portion and the medulla, which is the inner portion. We can see this here on this histological slide and thymic epithelial cells create specialized micro microenvironments for um immune cell production. And the the function of them is the T cell development and maturation. So to correct myself that the immune cells are created in the bone marrow, essentially through hematopoiesis and then they're developed and matured here in the thymus. How does this happen through a process of positive selection? So, T cells survive um only if they are able to recognize their self N HC uh major compatibility complex, I think. Um and if they can't recognize them, then they are deemed faulty and they're discard in the thymus. Negative selection is a process of elimination of these auto reactive T cells. So, if they are hyper sensitive to our own cells and they're also eliminated and regulatory T cells. So, thymic involution is a process by which the thymus becomes smaller over time. The thymus usually peaks in our tens to twenties. And the process is by progressive reduction in the thymic mass and function with age. And this generally begins after puberty and accelerates with advancing age. As you can see here on this graph, the consequences of this are there are, there's a decreased output of naive T cells and thus reduced T cell diversity. And this is what contributes to an age related immune decline. So as people get older, their immune systems tend to start to falter. And this is a under an underlying mechanism for that. This is a secondary lymphoid organs. So, we're talking about the primary lymphoid organs like the thymus and the bone marrow talked about thymic involution and now moving on to the secondary organs such as lymph nodes. So these are beam shaped and they follow along the lymphatic vessels. Again, there is a cortex which is the outer medulla, which is the inter and this is surrounded by this fibrous capsule. In terms of its organization in the cortex, we've got B cells and B cell follicles. And then in the paracortex, which is in between that, we've got the T cell zones and then the medullary cords and sinuses are also present over here. And the function is to filter lymph and facilitate immune responses, digging a bit deeper. It's microanatomy. So we look at the cortex over here, the outside portion, you've got the B cell follicles, um primary and secondary B cell follicles and then germinal centers which are where B cells are produced and differentiate in the per pericortex. Um This is, this has lots of T cells and high endothelial venules which allow lymphocyte entry and then the medulla, which is, it's the middle portion, more inner portion. We've got the medullary cords and the sinuses and the cords are the site of plasma cells and macrophages and the sinuses are where the lymph drain into the lymph nodes functions. So, one of the functions is antigen capture and presentation. So during the process of lymph filtration, they capture antigens um through dendritic cells and macrophages. Um The next thing is lymphocyte activation by which T cells are activated by dendritic cells and B cells are activated and germinal centers for which B cells are produced are formed, an antibody production. So, plasma cells differentiate here and secrete antibodies into the lymph and into the blood. Another secondary lymphoid organ is the spleen. See here, it's over here and a little bit of the cross section over there. The structure. So it's the second largest secondary lymphoid organ. So larger than all the lymph nodes. And it's divided predominantly into a red pulp and white pulp and it's also surrounded by a fibrous capsule. The white pulp is the lymphoid tissue around the central arterioles. So over here, we can see it there. The central arterial is coming through and the white pulp and the red pulp is the blood filtration and erythrocyte recycling zone. And the marginal zone is this area between the two, which is quite small. We look deeper. We can see that the white pulp um has these things called periarteriolar lymphoid sheaths ps which are where the T cells are found. And white pulp also contains B cell follicles and germinal centers for plasma cells. And the white pulp is the predominant immunological zone in uh in, in the spleen in the marginal zone, we have specialized macrophages and B cells. So we can see red pop and white pulp staining is like this because of the um his chemical studies. But in the marginal zone between the two, we've got specialized macrophages and B cells. And this is our first line of events against blood borne pathogens in the red pulp, which is our light colored p purple hair. Uh We have our splenic cords and sinuses and this is where erythrocyte filtration and destruction occurs, which is the, in most of our minds is probably the the primary function of the spleen. So, immune, the immunological functions of the spleen include filtration of blood borne antigens, immune response against bloodborne pathogens and uh maintenance of B cell populations. And its non immunological functions are removal and of damaged and aged erythrocytes, storage of platelets and extramedullary hematopoiesis in some conditions. So, moving on to one of the structures, er a mucosa associated lymphoid tissue. So these are um scattered across the body and these are lymphoid tissues which are associated with mucosal surfaces. So, there are a few types like GTs, bolts, NTS and there are others in the eyes and the genitals. Um but their primary function is to defend against mucosal pathogens. We look deeper at a molt. We can see um these are mucosal associated lymph or tissues.