Introduction

This tutorial covers how the spleen is involved in the immune response.

You can navigate through this tutorial using the buttons at the top of the screen.

The tutorial will ask you questions. Click on your chosen answer to see feedback; click the answer again to make the feedback disappear. When you're finished with one page, click the navigation button for the next page to move ahead. If a word is bolded; click on the word to see additional information; click the word again to make this information disappear.

Have fun! Click on button '1' to see the first page of the tutorial.

Page 7

Up 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.

1 should be physical/immune

2 should be membrane/chemical

3 should be PAMPS/PRR/APCs

4 should be activated/phagocytosed/presented

5 should be engulf/digest/phagocytize

6 should be epitope/antibody/antigen

Page 8

Immune 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

7 should be white pulp/red pulp/lymph node

8 should be destroyed/located/ initiated

9 should be Helper T-cells/Memory T-cells/Cytotoxic T-cells

10 should be Cytotoxic T-cells/B-cells/APCs

11 should be Cytotoxic T-cells/APCs/Suppressor T-cells

12 should be Monocytes/Memory T-cells/APCs

13 should be B-cells/plasma cells/APCs

14 should be Helper B-cells/plasma cells/more B-cells

15 should be Memory B-cells/APCs/antibodies

16 should be cytokines/antigens /antibodies

Page 9

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.

Page 10

Mary Jane went to the doctor and was told she had an enlarged spleen.

Why did Hepatitis B cause her spleen to be enlarged?

A. Her spleen had proliferating immune cells and cells being called in to fight the infection

B. The virus attacks the spleen

C. She was misdiagnosed

Page 11

The 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!

Summary 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.

Page 1

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.

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.

Page 2

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.

Page 3

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.

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.

Page 4

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.

Page 5

Phagocytosis Review: In the chart below, select the answer that best completes the sentence.

Page 6

Now 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