1. Lecture 2- Cells and organs of the immune system
Dr. Syeda Saleha Hassan
Molecular Immunology
BIOT 307

2. Lecture Objectives
After this lecture and the appropriate reading you should know
The process of cell production-haematopoiesis
Some key features of cells involved in the immune response
How cells circulate in the body
Primary and secondary lymphoid organs

3. Haematopoeisis

4. Normal Adult blood cell counts

5. Cellular Elements of Blood

6. Uses of adult stem cells to treat disease
Illustration by Cell Imaging Core of the Center for Reproductive Sciences

7. How does haemotopoiesis work?
Bone marrow stromal cells support the growth and differentiation of stem cells
Stromal cells include: Fat cells, endothelial cells, fibroblasts and macrophages
Provide a supporting matrix for cell growth (cell to cell contact)
Provide soluble growth factors for cell differentiation e.g. erythropoietin
How is haemotopoiesis controlled?
Expression of certain genes control development of certain cell types
Removal of some cells by induction of programmed cell death-apoptosis

8. Functions and characteristics of cells of the immune system
Mainly found in tissues
Release of granules containing histamine and other compounds
Important in inflammation and allergy
Smallest WBC in circulation
Function unknown
Maybe similar to mast cells
Attack and killing of large antibody coated parasites such as worms
All these cells are degranulating cells

9. Functions and characteristics of cells of the immune system
Only enter tissues when instructed
Phagocytosis
Bactericidal killing mechanisms e.g. respiratoy burst
Resident in tissues
Phagocytosis
Bactericidal killing mechanisms e.g. nitric oxide production
Antigen processing and presentation
Antigen recognition/uptake
Antigen presentation-produce cytokines to direct T cell response e.g. IL-12

10. Functions and characteristics of cells of the immune system
Important in innate immune response recognises foreign/infected cells
Destroys them by release of toxic granules
Releases cytokines e.g. Interferon gamma (IFN-γ)
CD4 T cells:
Important in specific immune response produce cytokines to activate macrophages and B cells and to regulate the immune response
CD8 T cells:
Important in specific immune response recognise and kill infected cells in a specific manner.
Produce cytokines

11. Functions and characteristics of cells of the immune system
Important in adaptive immune response
Synthesise and secrete antibodies (Immunoglobulin Ig)

12. Identification of cell types- CD molecules

13. Organs of the immune system
Primary:
Thymus
Bone Marrow
Secondary:
Spleen
Lymph nodes
Mucosal Associated Lymphoid Tissue
Blood
Lymphatics

14. Bone Marrow-site of lymphocyte production and B cell maturation
T cells produced in bone marrow migrate to thymus to develop in humans and mice B cells originate and develop in bone marrow
Interactions with cell adhesion molecules on stromal cells promote B cell growth production of IL-7 promotes maturation
x40 magnification of bone marrow

15. Thymus-site of T cell maturation
Cortex-densely packed with immature T cells (thymocytes)
Medulla-fewer thymocytes
Stromal cell network interaction with developing thymocytes
Production of thymic hormones
Expression of MHC molecules important in positive and negative selection of T cells

16. Thymus declines with age
Absence of thymus results in no T cell development-severe immunodeficiency
Mouse- Nude Mouse
Humans-DiGeorge’s syndrome

17. Thymus details
Derived from the third and fourth pharyngeal pouches during the embryonic life and attracts (by chemoattractive molecules) circulating T- cell precursors derived from HSC in the bone marrow.
Site of T-cell development and maturation.
Flat, bilobed organ situated behind the sternum, above and in front of the heart.
Each lobe surrounded by a capsule and divided into lobules, which are separated from each other by strands of connective tissue called trabeculae.
Each lobule is organized into two compartments.
Cortex: The outer compartment, is densely packed with immature T cells, called thymocytes.
Medulla: The inner compartment, is sparsely populated with thymocytes.

18. Thymus
Both the cortex and the medulla are criss-crossed by a three dimensional stromal cell network composed of epithelial cells, dentritic cells, and macrophages, which make up the framework of the organ and contribute to the growth and maturation of the thymocytes.
The accessory cells are important in the differentiation of the immigrating T cell precursors and their education (positive and negative selection), prior to their migration into the secondary lymphoid tissues.
Thymic epithelial cells produces the hormones thymosin and thymopoietin and in concert with cytokines such as IL-7 are probably important for the development and maturation of thymocytes into mature cells.
The thymic cortex is the major site of activity and thymocyte proliferation, with a complete turnover of cells approximately every 72 hours.

19. Thymus
These thymocytes then move into the medulla, where they undergo further differentiation and selection and finally migrate via circulation to the secondary lymphoid organs/ tissues where they are able to respond to microbial antigens.
Most (95%) of the thymocytes generated each day in the thymus die by apoptosis with less than 5% surrviving.
Molecules important to T cell function such as CD4, CD8 and T cell receptor develop at different stages during the differentiation process.
The main functions of the thymus as a primary lymphoid organ are:
To produce sufficient numbers (millions) of different T cells each expressing unique T cell receptors such that, within this group, there are at least some cells potentially specific for huge number of microbial antigens in our environment (generation of diversity).
To select for survival those T cells which bind weakly to self MHC molecules (positive selection), but then to eliminate those which bind too strongly to these same self MHC molecules (negative selection) so that the chance for an autoimmune response is minimized.

20. Lymph nodes-site where the immune response is mounted
Very important structures first organised structures to see antigen delivered from the tissues via the lymphatic system

21. Lymphatic system
The three layers of a lymph node support distinct microenvironments.

22. Lymphatic system
The left side depicts the arrangement of reticulum and lymphocytes within the various regions of a lymph node. Macrophages and dendritic cells, which trap antigen, are present in the cortex and paracortex. THcells are concentrated in the paracortex; B cells are primarily in the cortex, within follicles and germinal centers. The medulla is populated largely by antibody-producing plasma cells. Lymphocytes circulating in the lymph are carried into the node by afferent lymphatic vessels, they either enter the reticular matrix of the node or pass through it and leave by the efferent lymphatic vessel.
The right side depicts the lymphatic artery and vein and the postcapillary venules. Lymphocytes in the circulation can pass into the node from the postcapillary venules by a process called extravasation (inset)

23. Spleen-site where an immune response is mounted
The spleen, which is about 5 inches long in the adult, is the largest lymphoid organ. It is specialized for trapping blood-borne antigens.
Diagrammatic cross section of the spleen. The splenic artery pierces the capsule and divides into progressively smaller arterioles, ending in vascular sinusoides that drain back into the splenic vein. The erythrocyte-filled red pulp surrounds the sinusoids. The white pulp forms a sleeve, the periarteriolar lymphoid sheath (PALS), around the arterioles; this sheath contains numerous T cells. Closely associated with PALS is the marginal zone, an area rich in B cells that contains lymphoid follicles that can develop into secondary follicles containing germinal centers.
B cells
Macrophages and T cells
T cells

24. Spleen ultrastructure

25. Spleen Human spleen (stained for B cells) RP=red pulp MZ=marginal zone
GC=germinal centre
PALS=periarteriolar lymphoid sheath

26. Mucosal Associated Lymphoid Tissue
Cross-sectional diagram of the mucous membrane ling the intestine, showing a Peyer’s patch lymphoid nodule in the submucosa. The intestinal lamina contains loose clusters of lymphoid cells and diffuse follicles.
Gut associated lymphoid tissue (GALT)
e.g. tonsils, appendix
Peyers Patch under the epithelial layer of the intestine
Loose clusters of B cells, plasma cells, T cells and macrophages

27. Mucosal Associated Lymphoid Tissue
Antigen transported across the epithelial layer by M cells at an inductive site activates B cells in the underlying lymphoid follicles. The activated B cells differentiate into IgA-producing plasma cells, which migrate along the submucosa. The outer mucosal epithelial layer contains intraepithelial lymphocytes, of which are T cells.