1. Innate and Adaptive Immunity

2. Types of
Adaptive
Immunity

3. Cells and Tissues of the Immune System
Lecture 2
Cells and Tissues of the Immune System

4. OVERVIEW OF THE IMMUNE SYSTEM
Cells: lymphocytes, macrophages & monocytes, dendritic
cells, granulocytes. All arise from pluripotent
hematopoietic stem cells in bone marrow.
Organs: lymph nodes (found in various locations), thymus,
spleen - these constitute the lymphoid organs
Thymus and bursa (bone marrow) are called central
lymphoid organs
Peripheral Lymphoid Organs: Except lymph nodes,
spleen, and tonsils, liver, intestine and skin are also
are also important parts of the immune system.

5. Hematopoiesis
Pluripotent

6. Lymphocytes

8. Lymphocytes
B Cells
T Cells
NK Cells

9. Origin of T Cells
Jacques Miller found that removal of thymus (thymectomy) from neonatal mice resulted in fewer lymphocytes and no antibody to sheep red blood cells (1962). Later on, in thymectomized animals, the ability to reject allografts and to mount delayed hypersensitivity responses was drastically reduced.
By the mid-1960s, immunologists were convinced that there were indeed two separate arms of the immune system: one dealing exclusively with the production of circulating antibodies (humoral immunity), and another that is involved in the delayed hypersensitivity-type reactions and graft rejections (cell-mediated immunity). To have a good immune response, both have to exist.

11. Classes of Lymphocytes

12. Null Cells (NK Cells) Do Not Express Classical Lymphocyte Markers
Predominantly NK Cells (CD56)
Eliminate Tumor Cells and Virally Infected Cells
Express Low Affinity FcRIII (CD16)
Using CD16 They Can Carry Out ADCC
Reduction of MHC I Can Activate Them

13. A T Cell ?

14. A B Cell?

15. Immune Cells Can Be Analyzed by Flow Cytometry

16. Phenotypic Markers to Distinguish
Lymphocyte Subsets
T Cytotoxic
CD8+
B Cell
CD19+
T Helper
CD4+

17. Phases of Lymphocyte Activation
Naive
Activated
Effector
Phases of
Lymphocyte
Activation

19. T vs B Cells T cells B cells
Ag receptor TCR related to Ig BCR is membrane-bound Ig
but not Ig (plus accessory molecules)
Ag recognition in context of MHC can recognize Ag alone
on APC or accessory cells
Functional Th (helper) and subsets of B cells only
subsets Tc (cytolytic) subtly different in function
Secrete Cytokines Ig (as Ab) and cytokines
When Become (proliferating) Become lymphoblasts, then
activated lymphoblasts become plasma cells

20. Accessory Cells Mononuclear Phagocytes Dendritic Cells
Monocytes and Macrophages
Dendritic Cells

21. Monocytes and Macrophages
Functions
Phagocytosis
Antigen processing and presentation (APCs)
Activation of T cells

22. Origin and Development of Macrophages

23. MONOCYTES AND MACROPHAGES
Monocytes are immature macrophages; monos circulate in blood & accum-
ulate at sites of inflammation. Macrophages may differentiate in tissue in
absence of antigen (Kupffer cells in liver, e.g.) or differentiate in response to
inflammation. They are Ag-presenting cells (APC). Also phagocytose
microbes; contain bacteriocidal mechanisms.
mono in blood smear
Wright-Giemsa
macrophage in tissue, H&E stain

24. Monocyte
Activated Mac

25. MONOS AND MACS CONTINUED
*Express CD14, a receptor for a wide variety of bacterial envelope molecules: LPS, components of bacterial cell walls. Ligation of CD14 leads to macrophage activation.
*Are activated by T cell derived cytokines such as interferons: leading to increased
phagocytosis and microbicidal activity (increased activity of degradative enzymes, nitrogen and oxygen free radical production and prostaglandins etc.).
*Express receptors for Ab (FcR) and complement.
*Act as scavengers for apoptotic cells, cell debris and senescent cells (e.g., Kupffer cells in the liver bind "old" erythrocytes).

26. Dendritic Cells Transport Antigens to L. nodes
Initiation of T Cell Responses

27. Dendritic Cell Subsets

28. Follicular DCs Do Not Express MHC II Molecules
Found in Lymph Follicles (Rich in B Cell)
Express FcR For Antibodies and Complement
Ag-Ab Complex Shown To Last Very Long (weeks to months)

29. (Myeloid DC)

30. Granulocytes
Neutrophil
Eosinophil
Basophil

32. Lymphoid Organs Secondary Lymphoid Organs
efficient at trapping and concentrating foreign substances
site of Ag-driven proliferation and differentiation; e.g. Ab production
spleen, lymph nodes, diffuse tissues, payers patch, tonsils
Primary (Generative) Lymphoid Organs
maturation site of lymphoid cells
bone marrow, bursa of Fabricius, thymus,

33. Organs Of Immune System
Primary Lymphoid Organs
Bone Marrow and Thymus
Maturation Site
Secondary Lymphoid Organs
Spleen, lymph nodes,
MALT (mucosal associated lymph tissue)
GALT (gut associated lymph tissue)
Trap antigen, APC, Lymphocyte Proliferation

35. ORGANS OF THE IMMUNE SYSTEM PRIMARY LYMPHOID ORGANS
Primary lymphoid organs are where lymphocytes arise and mature in the
absence of antigenic stimuli. They are the bone marrow and thymus.
Bone marrow: Source of all hematopoietic progenitor (stem) cells, site of B cell maturation post-birth in mammals.
About 1 in every 10,000 to 15,000 bone marrow cells
is thought to be a stem cell.
In the blood stream 1 in 100,000 blood cells.
Chicken Bursa

36. PRIMARY LYMPHOID ORGANS: THYMUS
Thymic epithelial cells are derived from the third pharyngeal pouch.
The thymus is the site where T cells develop.
It gradually enlarges during childhood but after puberty it undergoes a process of involution.
The thymus is arranged into an outer cortex and an inner medulla. Immature lymphoid cells in the cortex. Mature T cells are in the medulla from where mature T lymphocytes enter the circulation.

37. SECONDARY LYMPHOID ORGANS
Peripheral lymphoid organs: lymph nodes, spleen, tonsils, adenoids, and lymphoid tissue associated with other organ systems (gut, skin, mucosa).
LYMPH NODES: filter lymphatic fluid; sites of Ag presentation & cell traffic

38. LYMPH NODES
Lymph nodes have a fibrous capsule from which trabeculae extend towards the center, forming a framework for the lymphatic parenchyma (cortex, paracortex, and medulla).
1 - cortex (B Cells) 2 - paracortical zone (T Cells) 3 – medulla(T, B, Mac) 4 - medullary cords 5 - lymphoid follicle of the cortex 6 - capsule 7 - subcapsular sinus 8 - cortical sinus 9 - medullary sinus

39. Subcapsular Sinus LYMPH NODES, CONTINUED
Functions of structural elements of lymph nodes
Subcapsular
Sinus
Lymph  afferent lymphatics, sinuses lined with macrophages  efferent lymphatic (ultimately all drain into the portal vein).
Lymphocytes enter the node primarily from the blood via HEV  efferent lymphatics.
DCs migrating from tissue enter the node into the T cell areas.
B cells entering nodes from blood must cross the T rich area in transit to the B cell rich areas thus optimizing T-B cooperation.

40. SPLEEN Stained with haematoxylin and eosin
LYMPH NODES, CONTINUED
SPLEEN      Stained with haematoxylin and eosin
1 - lymphoid follicle (white pulp) 2 - red pulp 3 - capsule 4 - trabeculae (connective tissue)
The spleen serves two major functions:
*It is responsible for the destruction of old red blood cells (RBCs) - this occurs in the red pulp;
*It is a major site for mounting the immune response - the white pulp.
The spleen behaves like a lymph node, but instead of filtering lymph, it filters blood.
Has the hematopoiesis function in mice.

41. INSIDE THE SPLEEN White pulp Red pulp
Mouse splenic CD3 expression inperiarteriolar lymphocyte sheath of white pulp and in scattered cells in red pulp.

42. MUCOSA-ASSOCIATED LYMPHOID TISSUE (MALT)
Lymphoid tissue found at the gastrointestinal tract, respiratory tract and urogenital tract.
MALT consists of aggregates of lymphocytes, macrophages, DCs, and other accessory cells.

43. GUT-ASSOCIATED LYMPHOID TISSUE (GALT)
This is comprised of:
* tonsils, adenoids (Waldeyer's ring)
* Peyer's patches
* lymphoid aggregates in the appendix and large intestine
* lymphoid tissue accumulating with age in the stomach
* diffusely distributed lymphoid cells and plasma cells in the lamina propria of the gut

44. SKIN-ASSOCIATED LYMPHOID TISSUE (SALT)
Skin is an active participant in host defense. It has the capability to generate and support local immune and inflammatory responses to foreign Ags that enter the body via the skin.
Cells of SALT include keratinocytes, Langerhans cells (immature DCs found in skin), intraepiethelial T cells, and melanocytes.
Langerhans cells form a continuous epidermal meshwork: they capture Ag, then migrate to draining lymph nodes, where they act as Ag-presenting cells.

45. (T Cell Progenitors)
Effect of Thymectomy?

46. Site of T Cell Maturation

47. Effect of Thymectomy in Adult

49. Circulation of Naïve and Activated/Memory T Lymphocytes
Lymphocyte Circulation in pig?