1. Chapter 2 Cells and Organs of the Immune System Dr. Capers
Immunology

2. Kindt • Goldsby • Osborne
Kuby IMMUNOLOGY
Sixth Edition
Chapter 2:
Cells and Organs
of the Immune System
Copyright © 2007 by W. H. Freeman and Company

3. Hematopoiesis
All blood cells arise from Hematopoietic Stem Cells (HSC)
Study of these cells is difficult
Scarce
Difficult to grow in vitro

4. Hematopoiesis
Early in hematopoiesis, stem cell differentiates to either
Lymphoid progenitor cell
Myeloid progenitor cell
Progenitor cells have lost ability for self renewal and are committed to particular cell lineage

5. Organized hierarchy
Most of proliferation takes place in differentiated precursors (that are NOT self-renewing) rather than hematopoietic stem cell
Lowers chance of cancer

6. Hematopoiesis Regulated at gene level
Transcription factors play important roles in hematopoiesis
Studies using “knockout” mice
Gene inactivated, if RBC or a particular WBC fails to develop, it is concluded that protein was involved in development of that cell

8. Hematopoietic Homeostasis
Erythrocyte
Average life span: 120 days
Phagocytosed by macrophages in spleen
WBC - LEUKOCYTES
Life spans from 1 day to years
Apoptosis – programmed cell death

11. Normal WBC
WBC going through apoptosis

12. Cells of the Immune System
Lymphocytes
20-40% of WBC
3 populations
B cells
T cells
Natural Killer Cells

14. Lymphocytes B cells and T cells Adaptive immunity Small lymphocytes
Those that have not interacted with antigen are called naïve
Interaction with antigen – proliferation into effector cells (i.e. plasma cells) and memory cells

15. Lymphocytes
B and T cells

16. Lymphocytes B Lymphocytes (B cells) Site of maturation
Bursa of fabriscus in birds
Bone marrow in mammals
Display membrane-bound immunoglobulin (antibody)
Once antigen is encountered:
Differentiation
Plasma cells – antibody can be secreted, die within 1-2 weeks
Memory B cells – same membrane-bound antibody as parent B cell, longer life span

17. Lymphocytes T Lymphocytes (T cells) Site of maturation T cell receptor
Thymus
T cell receptor
Only recognize antigen that is bound to cell membrane proteins called major histocompatibility complex (MHC)
Once antigen in encountered with MHC:
Differentiation
Effector T cells
Memory T cells
2 subpopulations
T helper (TH)
T cytotoxic (TC)
And now T regulatory (Treg)

18. Lymphocytes T helper cells CD4 glycoprotein
“help” activation of B cells, TC cells, macrophages in immune response

19. Lymphocytes T cytotoxic cells CD8 glycoprotein
Recognition of MHC-antigen complex initiates differentiation into effector cell called cytotoxic T lymphocyte
Eliminates infected cells or cancerous cells

20. Lymphocytes T regulatory cells CD4 and CD25 glycoproteins
Help suppress the immune system

21. Lymphocytes Natural Killer Cells Innate immune response
Large, granular
Recognize tumor or virus-infected cells
CD16 – which can recognize a region of antibody that has attached to cell infected by virus

23. Other Leukocytes Mononuclear phagocytes
Monocytes circulate in blood and then migrate into tissue and differentiate into specific macrophage
Macrophages
Intestinal macrophages in gut
Alveolar macrophages in lung
Histiocytes in connective tissue
Kupffer cells in the liver
Mesangial cells in the kidney
Microglial cells in the brain
Osteoclasts in bone
Activated macrophages are more effective than resting ones

26. Other Leukocytes Mononuclear phagocytes
Complex antigens are phagocytized, the resulting phagosome fuses with a lysosome
The digested antigen is then eliminated through exocytosis
Some of it is presented on membrane on MHC
Phagocytosis is enhanced when antibody is attached to the antigen
Antibody acts as opsonin: molecule that binds to both antigen and phagocyte

27. Macrophage and bacteria

29. Other Leukocytes
Granulocytes
Neutrophils
Eosinophils
Basophils

30. Other Leukocytes Granulocytes – Neutrophils
Multi-lobed nucleus, light granules
1st to arrive at site of inflammation
High #’s is 1st indication of infection
Phagocytize
Generate antimicrobial agents

32. Other Leukocytes Granulocytes – Eosinophils Phagocytize
Play a role in parasitic organisms

34. Other Leukocytes Granulocytes – Basophils Nonphagocytic
Play a role in allergic reactions

36. Other Leukocytes Mast cells
Play important role in development of allergies

37. Other Leukocytes Dendritic cells Follicular dendritic cells
Long membranous extensions, look like dendrites on nerve cells
Antigen presentation
4 major groups:
Langerhans DC
Interstitial DC
Monocyte-derived DC
Plasmacytoid-derived DC
Follicular dendritic cells
Involved with B cell maturation

38. Organs of the Immune System
Primary
Thymus and bone marrow
Place of maturation of lymphocytes
Secondary
Lymph nodes, spleen, mucosa-associated lymphoid tissues such as gut-associated lymphoid tissues
Mature lymphocytes interact with antigen

40. Primary Lymphoid Organs
Bone marrow
Lymphocytes arise there, T cells go to thymus to mature
B cells mature here
90% of plasma IgG and IgA comes from B cells in the bone marrow

41. Primary Lymphoid Organs
Thymus
T cell development and maturation
Bilobed organ above heart
Surrounded by capsule and divided into lobules
Outer part of lobule is cortex, inner is medulla
Network of epithelial cells, dendritic cells, and macrophages
Thymus will induce death of those T cells that can’t:
Recognize self-MHC molecules
Those that interact with MHC molecules too strongly (could produce autoimmune disorder)
Function decreases with age

43. Lymphatic System
Interstitial fluid (the portion that doesn’t enter venous system) is returned to circulatory system by lymphatic vessels
Largest lymphatic vessel – thoracic duct
Enters left subclavian vein
Lymph from right arm and right side of head enters through right lymphatic duct, drains into right subclavian
Antigen is carried by lymph to lymph nodes

44. Secondary Lymphoid Organs
Primary follicle
Unactivated lymphoid follicle
Secondary follicle
Follicle that is activated by antigen
Ring of B cells that surround germinal center
Proliferating B cells and T helper cells

45. Secondary Lymphoid Organs
Lymph Nodes
Encapsulated
3 regions:
Cortex
B cells, macrophages, dendritic cells
Primary follicles
Paracortex
T cells, dendritic cells
Medulla
Plasma cells secreting antibody

49. Secondary Lymphoid Organs
Spleen
Filters blood, traps blood-bourne antigens
Important in systemic infections
Blood enters through splenic artery
Encapsulated
Structure:
Projections from capsule form trabeculae
Compartments:
Red pulp
Macrophages, red blood cells
White pulp
Surrounds branches of splenic artery
Forms PALS (periarteriolar lymphoid sheath)
Primary follicles rich in B cells

52. Secondary Lymphoid Organs
Mucosa-Associated Lymphoid Tissue
MALT
Organized areas along digestive, respiratory, and urogenital tracts
Very well organized areas in intestine are referred to as Peyer’s patches
Includes tonsils and appendix