Lymphoid Tissues and Organs: - Leukocytes may be distributed in the body as: 1-Single cells in tissues and circulation. 2-Lymphoid accumulations (Peyer’s patches). 3-Aggregations within Lymphoid organs; Primary and secondary lymphoid organs.

-Primary Lymphoid Organs: Thymus and Bone marrow.-Secondary Lymphoid Organs: Spleen, Lymph nodes, Tonsils, and MALT.

Primary and Secondary Lymphoid Organs:N

N

Primary lymphoid organs: 1- Thymus: -T Lymphocytes develop within this lymphoid organ.-Function: The clonal selection of T lymphocytes. (Lymphocyte educational Center)-It increases in size during fetal and neonatal life.-It is progressively inactivated (curved spirally) following puberty.

-Two important parts: 1-Thymic Cortex. 2-Thymic Medulla.

Primary lymphoid organs: The Thymus and its parts.

The thymus diagram : Parts and location.

N

2-Bone marrow: -B lymphocytes are “home schooled” within this organs. -Function: Primary differentiation of B lymphocytes. B lymphocytes begin to display IgM on their surfaces.-The primary site for cytokines-Immune cell interactions.

-Bone marrow removes the B cells that show self- reactivity by apoptosis.

Secondary Lymphoid Organs: -Secondary lymphoid organs function as filtration devices removing foreign matter, dead cells, and microbial toxins from the circulation.-Blood vessels and lymphatic vessels richly supply these organs.

-Specialized regions of the vasculature (endothelial venules) facilitate movement of immune cells between blood and the tissues of these organs. -The leukocyte-rich nature stimulate cellular interaction.

N

Secondary Lymphoid Organs:1-Lymph nodes: -It acts as filters to purify lymph. -Divided into the cortex and medulla. -The superficial cortex contains lymphocyte-rich nodules (follicles) (mainly B cells). -The deep cortex is the T-cell-rich area.

N

2-The Spleen: -The largest lymphoid organ. -Concentrates blood-borne antigens and microbes. -Contains T cells, B cells, and Large numbers of plasma cells (secreting immunoglobulins into the circulation). -Divided into: 1-Lymphocyte-rich white pulp. 2-Erythrocyte-rich red pulp (also contains macrophages).

N

3-Mucosa-associated lymphoid tissues(MALT): -Other sites for immune-cells interaction. -Tonsils in the nasopharynx. -Peyer’s patches in the sub-mucosal surfaces of small intestine.

The Lymphatic circulatory system: -Leukocytes and their products use two circulatory systems:1-Cardiovascular system.

2-Lymphatic circulatory system. (Textbook : Page 85-86).

Lymphocyte Development:

-Stem cells of bone marrow (prothymocytes; negative for CD4,CD8, and TCR) migrate via the circulation to the thymic cortex.-The newly arrived thymocytes acquire CD4,8, and TCR (Positive cells)-Cortical thymocytes are selected by their interaction to cortical epithelial cells (positive selection).

-Medullary thymocytes are selected (negative selection). -Mature T cells are released into the circulation.

Maturation of T lymphocytes in Thymus:N

Lymphocyte Activation:

Lymphocyte activation occurs according to following consequences: 1-Antigen endocytosis and processing.

2-Antigen presentation.

-Extracellular microbes and toxins are engulfed by endocytosis.(Endocytic pathway).

-Intracellular microbes (viruses) are processed by cytolytic pathway.

N

Endocytosis of extracellular microbes:1-Phagocytosis 2-Receptor-mediated endocytosis.3-Pinocytosis.

Antigen presentation by MHC Class II:

-Endocytic vesicles (phagosomes; derived from phagocytosis) fuse with lysosomes.-Phagolysosome interacts with endoplasmic reticulum vesicles.

-The digested peptides carried by MHC II to cell surface.

Antigen presentation by MHC Class I: -Cytoplasmic protein-ubiquitin reaction.-Proteasome action on the complex.-Fusion of processed peptide with E.R vesicle which carry MHC Class I to the cell surface.

Activation of T Lymphocytes:

-MHC II-epitope-Complex interaction with TCR. -B7(CD80/86) Co-stimulatory interaction with CD28.-IL-2 production from activated T cell.-Overexpression of IL-2R on T cell surface.

N

-In the presence of IL-12, native CD4 lymphocyte is differentiated as a CD4 Th1.

Activation of CD8 (Tc) cell by effector Th1:

N

Activation of B Lymphocytes by effector Th2: -MHC II-epitope-Complex interaction with TCR.-CD40-CD40 Ligand interaction. -Antibody-epitope interaction.

Lymphocyte Effector Functions: Cell-mediated immunity: 1-Role of CD4 T cells in Delayed (- type) hypersensitivity:

N

2-Role of CD8 T cell: T cell Cytotoxicity : A-Target cell recognition. B-Target cell destruction: -Perforins and Granzymes effect.

3-Role of NK cells in cellular immunity:

N

Humoral immunity:

1-Agglutination of invaders.

2-Neutralization (virus, toxins).

3-Opsonization.

4-Complement activation.

5-ADCC: NK cell and Eosinophils.

6-Immediate hypersensitivity.

Humoral immunity and effector lymphocyte function:N

The ADCC Mechanism: N