This tutorial covers how the spleen is involved in the immune response.
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Page 7Up to this point you have been filling in the blanks to the immune response pathway. Test your knowledge of the immune response by filling in the blank in this review pathway.
Page 8Immune response pathway continued. You should be able to fill in the blanks of the adaptive immune response. For a review of the adaptive immune response click here
Wikimedia Commons (n.d.). Red Pulp and White Pulp of the Spleen. Retrieved May 17, 2019, from http://www.medicalgraphics.de/en/free-pictures/organs/comparison-blood-vessels-arteries-veins-dark-429.html
APC also induce the inflammatory response by releasing cytokines which signal for additional leukocytes to come to the site of infection. These leukocytes enter from blood vessels and once in the spleen they fight the infection via phagocytosis/other mechanisms. Each time they kill a pathogen or cells are damaged more proinflammatory cytokines are released.
Proinflammatory cytokines also causes vasodilation which increases / decreases / doesn't affect blood flow and increases / decreases / doesn't affect permeability; allowing the cells to move to the spleen faster.
Mary Jane went to the doctor and was told she had an enlarged spleen.
Image of an enlarged spleen.
Wikimedia Commons. (n.d.). Splenomegalie bei CLL (labeled). Retrieved May 17, 2019, from https://commons.wikimedia.org/wiki/File:Splenomegalie_bei_CLL_(labeled).jpg
Why did Hepatitis B cause her spleen to be enlarged?
Page 11The doctor prescribed Mary Jane medication that helped fight the infection. Her liver was able to recover, and spleen is back to normal size. Mary Jane lives to see another day!
Full Completed Flow ChartSummary of immune response involving the spleen: The invader penetrates the physical and chemical barrier. The pathogen is recognized by PRR on the Monocyte. The APC are then activated in the spleen. APC phagocytize the pathogen. APC then displays the antigen on its surface. The APC carries the antigen to the white pulp where the adaptive immune system is initiated. Helper T-cells receive the antigen and differentiate into Cytotoxic T-cells, more Helper T-cells, Suppressor T-cells, and Memory T-cells. Some Helper T-cells then recognize the antigen and activate B-cells that can recognize the antigen. Some of these B-cells then differentiate into plasma cells and Memory B-cells. The plasma cells then produce antibodies.
Lymphatic System by U.S. National Cancer Institute's SEER Program, Public Domain.
Hepatitis B is a dangerous blood borne pathogen that is contracted through blood, semen, and other bodily fluids. It is caused by a virus that mainly affects the liver but is known to cause splenomegaly (an enlarged spleen). In this case study you will take a closer look at the role of the spleen in the immune response.
As a reminder, when pathogens enter the body (unless they are in the blood) the pathogen will be processed through the lymphatic system. As shown in green, the lymphatic system consists of various parts of the body,(thymus, bone marrow, lymph nodes, etc) that work together to detect pathogens. This case study begins examining the patient, Mary Jane, and the Hepatitis B pathogen currently in her circulatory system.
Throughout the tutorial there will be fill-in the blanks. Please select the answer that best completes the sentence. We will begin with the ignition of the immune system.
The first main protection our bodies provides from invaders are our skin and mucous membranes which are known as physical barriers. At these surfaces our bodies uses chemical barriers such as sweat, saliva enzymes, and antimicrobial proteins to prevent pathogens from entering the body.
This picture is showing how inside the blood, the pathogen recognition receptors (PRR), on monocytes detect the pathogen associated molecular patterns (PAMPs) on microbes. Specifcally, you can see the PRR binding to the PAMP ligand.
The roles of the spleen are to repair/destroy damaged RBC and scan the blood for pathogens. The RBCs are processed in the red pulp of the spleen, while the white pulp processes the pathogen to initiate the adaptive immune response. In both these areas, WBC use special cell surface receptors called Pathogen Recognition Receptors (PRRs) to identify generic Pathogen Associated Molecular Patterns (PAMPs).
Specifically, PAMPs are located on the surface of microbes and are recognized by immune cells via their unique patterns - referring to their shapes and chemistry. PRR are located extracellularly and intracellularly on all nucleated cells. These bind to ligands, (PAMPs) on microbes. One of the main types of WBCs in blood are Monocytes. They use their PRR to look for surface markers on microbes inside the capillary. Once found, the Monocyte will bind to the microbe and carry it away.
Anatomical location of the spleen.
National Cancer Institute SEER training modules (n.d.) Spleen. Public domain image.
The monocyte with the attached microbe is now circulating to the spleen, the spleen is divided into three sections: the red pulp, the marginal zone, and the white pulp. The spleen is only connected to the circulatory system not the lymphatic system. Thus, the only way in is through the splenic artery where the monocytes will be dumped with the blood into the marginal zone. Located here are macrophages (APC) and B-cells.
All RBCs will be sent to the red pulp that has a sinusoid network with macrophages and lymphocytes (T-cells, B-cells, and NK cells). There the RBCs will either be repaired or destroyed. For a review of Red Blood Cell Life Cycle, click here The blood will then exit through the splenic vein back into the circulatory system.
Anatomical locations of the white pulp, red pulp, marginal zone, and types of cell in these regions
Modified from: Figure 2f from: Irimia R, Gottschling M (2016) Taxonomic revision of Rochefortia Sw. (Ehretiaceae, Boraginales). Biodiversity Data Journal 4: e7720. https://doi.org/10.3897/BDJ.4.e7720
Anything that is not a RBC it will be taken to the white pulp which will be discussed in slide six. To see what APCs do with the antigen continue with slide four and five.
The process of phagocytosis inside an Antigen Presenting Cell
In the marginal zone, the monocyte passes the microbe off by sending cytokines to the Professional Antigen Presenting Cells, (APCs) who begin phagocytizing the pathogen. Cytokines are signals released by cells to communicate to other cells. These signals are actually molecules received via cytokine receptors.
The process of phagocytosis begins with the APC's membrane extending around the microbe. The ingestion of the microbe by the phagocyte results in the formation of a phagosome. The phagosome is then fused with lysosome to form a phagolysosome. Inside the phagolysome the microbe is degraded by ROS which stands for Reactive Oxygen Species. This waste material is then expelled out of the APC.
Phagocytosis Review: In the chart below, select the answer that best completes the sentence.
The APCs / neutrophils / WBCs are activated.
This picture is showing the placement of T-cells, B-cells, and Antigen Presenting Cells (APCs), inside the marginal zone and white pulp of the spleen. white pulp/red pulp/lymph nodeNow that the pathogen has been phagocytosed, the APC migrates to the white pulp and presents the hepatitis antigen to the T-cell which resides there. The T-cell then activates a B-cell, which is also located in the white pulp. The T and B cells then begin to replicate and differentiate to initiate the adaptive immune response, ultimately causing the pathogen to be destroyed. For a review of the adaptive immune response click here
Oláh, I., & Glick, B. (1982). Splenic white pulp and associated vascular channels in chicken spleen. American Journal of Anatomy, 165(4), 445-480. doi:10.1002/aja.1001650408
In the spleen, A is pointing to?
In the spleen, B is pointing to?
Which type of cell is located in all portions of the spleen? (Hint: On slide 3 there was a picture with all the types listed out)
Copyright Donna Zehner, 2019: firstname.lastname@example.org