Innate and Adaptive Immunity Types of Adaptive Immunity

Innate and Adaptive Immunity

Types of Adaptive Immunity

Lecture 2 Cells and Tissues of the Immune System

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 important parts of the immune system.

Hematopoiesis Pluripotent

Lymphocytes

Lymphocytes • B Cells • T Cells • NK Cells

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-1960 s, 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.

Classes of Lymphocytes

Null Cells (NK Cells) • Do Not Express Classical Lymphocyte Markers • Predominantly NK Cells (CD 56) • Eliminate Tumor Cells and Virally Infected Cells • Express Low Affinity Fc RIII (CD 16) • Using CD 16 They Can Carry Out ADCC • Reduction of MHC I Can Activate Them

A T Cell ?

A B Cell?

Immune Cells Can Be Analyzed by Flow Cytometry

Phenotypic Markers to Distinguish Lymphocyte Subsets B Cell CD 19+ T Helper CD 4+ T Cytotoxic CD 8+

Phases of Lymphocyte Activation Naive Activated Effector

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

Accessory Cells • Mononuclear Phagocytes – Monocytes and Macrophages • Dendritic Cells

Monocytes and Macrophages • Functions – Phagocytosis – Antigen processing and presentation (APCs) – Activation of T cells

Origin and Development of Macrophages

MONOCYTES AND MACROPHAGES Monocytes are immature macrophages; monos circulate in blood & accumulate 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

Monocyte Activated Mac

MONOS AND MACS CONTINUED *Express CD 14, a receptor for a wide variety of bacterial envelope molecules: LPS, components of bacterial cell walls. Ligation of CD 14 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 (Fc. R) and complement. *Act as scavengers for apoptotic cells, cell debris and senescent cells (e. g. , Kupffer cells in the liver bind "old" erythrocytes).

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

Dendritic Cell Subsets

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

(Myeloid DC)

Granulocytes Neutrophil Eosinophil Basophil

Lymphoid Organs • Primary (Generative) Lymphoid Organs – maturation site of lymphoid cells – bone marrow, bursa of Fabricius, thymus, • 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

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

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

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.

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

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

LYMPH NODES, CONTINUED Functions of structural elements of lymph nodes 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. Subcapsular Sinus

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.

INSIDE THE SPLEEN White pulp Red pulp Mouse splenic CD 3 expression inperiarteriolar lymphocyte sheath of white pulp and in scattered cells in red pulp.

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.

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

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.

(T Cell Progenitors) Effect of Thymectomy?

Site of T Cell Maturation

Effect of Thymectomy in Adult

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