GENERAL IMMUNOLOGY PHT 324 Dr. Rasheeda Hamid Abdalla Assistant Professor om

OBJECTIVES Anatomy of the Lymphoid System Lymphoid System -Primary and secondary lymphoid organs and it functions Cells of the Immune System and its functions 2

Lymphoid System Lymphoid system: collection of tissues and organs designed to bring B and T cells in contact with antigens. –In order for body to mount appropriate response, immune cells must encounter antigen Lymphoid system includes –Lymphatic vessels –Secondary lymphoid organs –Primary lymphoid organs

Anatomy of the Lymphoid System

The Organs of the Immune System  Bone Marrow All cells of the immune system are initially derived from the bone marrow. They form through a process called hematopoiesis. During hematopoiesis, bone marrow-derived stem cells differentiate into: - mature cells of the immune system -precursors of cells The bone marrow produces B cells, natural killer cells, granulocytes and immature thymocytes, in addition to red blood cells and platelets

The Organs of the Immune System  Thymus Located in the front of the upper chest The function of the thymus is to produce mature T cells. Immature thymocytes, also known as prothymocytes, leave the bone marrow and migrate into the thymus.. T cells that are beneficial to the immune system are spared, while those T cells that might evoke a detrimental autoimmune response are eliminated. The mature T cells are then released into the bloodstream.

Thymus

Spleen The spleen is an immunologic filter of the blood. It is made up of B cells, T cells, macrophages, dendritic cells, natural killer cells and red blood cells. In addition to capturing foreign materials (antigens) from the blood that passes through the spleen, migratory macrophages and dendritic cells bring antigens to the spleen via the bloodstream. In the spleen, B cells become activated and produce large amounts of antibody. Also, old red blood cells are destroyed in the spleen.

Lymph Nodes The lymph nodes function as immunologic filter for the body fluid known as lymph. Lymph nodes are found throughout the body. Inhabited primarily by T cells, B cells, dendritic cells and macrophages, The nodes drain fluid from most of our tissues.

Lymph Nodes(cont’d) Antigens are filtered out of the lymph in the lymph node before returning the lymph to the circulation. In a similar fashion as the spleen, the macrophages and dendritic cells that capture antigens present these foreign materials to T and B cells, consequently initiating an immune response

Cells of the Immune System The immune system is composed of many interdependent cell types that collectively protect the body from bacterial, parasitic, fungal, viral infections and from the growth of tumor cells. Many of these cell types have specialized functions. The cells of the immune system can engulf bacteria, kill parasites or tumor cells, or kill viral-infected cells.

Cells of the Immune System The cells of the immune system arise from a pluripotent stem cell in the bone marrow. Differentiation of these cells will occur along one of two pathways, giving rise to either -a common lymphoid progenitor cell - or a common myeloid progenitor cell.

 The common lymphoid progenitor cell gives rise to B lymphocytes, T lymphocytes, and natural killer (NK) cells.  The myeloid progenitor gives rise to erythrocytes, platelets, basophils, mast cells, eosinophils, neutrophils, monocytes, macrophages, and dendritic cells.

Lymphocytes Lymphocytes normally represent 25-40% of the WBCs (1,500- 4,500/mm 3 of blood). Lymphocytes mediate the adaptive immune responses. Only a small proportion of the body's lymphocytes are found in the blood. The majority are found in lymphoid tissue.

Lymphocytes circulate back and forth between the blood and the lymphoid system of the body. They have a life span of days to years. Once matured, lymphocytes can recognize millions of different antigens. There are 2 major populations of lymphocytes

B lymphocytes, so called because they complete their development in the bone marrow, and T lymphocytes, so called because they pass from their origin in the bone marrow into the thymus, where they complete their development. Both have surface membrane- receptors designed to bind specific antigens

B-lymphocytes (B-cells)  Arise from stem cells in bone marrow.  Upon reaching functionally mature stage, they emigrate to peripheral lymphoid organs.  Mediate humoral immunity (antibody production) and have B-cell receptors on their surface for antigen recognition.  Generally 10-20% of the lymphocyte are B-lymphocytes.

T-lymphocytes (T-cells) Arise from stem cells in the bone marrow. Migrate to the thymus where they differentiate into mature T-cells. - Surface proteins expressed (TCR, CD4 or CD8). Leave thymus: - Circulate in bloodstream. -Go to peripheral lymphoid tissues.

Mediate cellular immunity (the production of cytotoxic T- lymphocytes and cytokines) regulate the adaptive immune responses. Generally 60-80% of the lymphocytes are T-lymphocytes. Based on biochemical markers on their surface, there are two major classes of T-lymphocytes:

T Lymphocytes Cytotoxic T cells (CD8 killer T cells) –Proliferate and differentiate to destroy infected or cancerous “self” cells –Have CD8 marker –Recognize MHC class I Helper T cells (CD4 T helper cells ) –Multiply and develop into cells that activate B cells and macrophages –Stimulate other T cells; orchestrate immune response –Have CD4 marker –Recognize antigen display by MHC class II

NATURAL KILLER (NK) CELLS Considered part of innate immunity while B and T cells participate in adaptive immunity Are lymphocytes that lack B-cell receptors and T-cell receptors. They kill cells bound by antibody or lacking MHC-I molecules on their surface. Like cytotoxic Tcells, NK cells kill infected or damaged cells but have receptors that are much less specific.

Natural killer cells, often referred to as NK cells, are similar to the killer T cell subset (CD8+ T cells). They function as effector cells that directly kill certain tumors such as melanomas, lymphomas and viral-infected cells, most notably herpes and cytomegalovirus-infected cells.

Granulocytes or Polymorphonuclear (PMN) Leukocytes Group of white blood cells is collectively referred to as granulocytes or polymorphonuclear leukocytes (PMNs). Granulocytes are composed of three cell types identified as : -neutrophils, eosinophils and basophils, based on their staining characteristics with certain dyes. These cells are predominantly important in the removal of bacteria and parasites from the body. They engulf these foreign bodies and degrade them using their powerful enzymes

Macrophages When monocytes leave the blood and enter the tissue, they become activated and differentiate into macrophages.  Wandering macrophages: those that have recently left the blood during inflammation and move to the site of infection through positive chemotaxis.  Fixed macrophages a relatively immotile macrophage found in connective tissue, lymph nodes, spleen, and bone marrow

They, along with B and T-lymphocytes, are found supported by reticular fibers in lymph nodules, lymph nodes, and the spleen where they filter out and phagocytose foreign matter such as microbes Macrophages are important in the regulation of immune responses They are often referred to as scavengers or antigen-presenting cells (APC) because they pick up and ingest foreign materials and present these antigens to other cells of the immune system such as T cells and B cells.

Macrophage Function s Macrophages actually have a number of very important functions in body defense including: 1. Killing of microbes, infected cells, and tumor cells by phagocytosis. 2. Processing antigens so they can be recognized by T-lymphocytes during the adaptive immune responses. 3. Secreting proteins called cytokines (sometimes called monokines when produced by monocytes or macrophages) that play a variety of roles in nonspecific body defense.

Dendritic Cells Originate in the bone marrow and function as antigen presenting cells (APC). Dendritic cells are more efficient APCs than macrophages. They are found in the structural compartment of the lymphoid organs such as the thymus, lymph nodes and spleen. They are also found in the bloodstream and other tissues of the body.

DENDRITIC and LANGERHANS' CELLS - Highly branched dendritic cytoplasmic processes. - Dendritic cells found in lymphoid tissues. - Called langerhans cells when found in epidermis. - Poorly phagocytic. - Highly efficient antigen presenting cells (APC).

Immature dendritic cells are found under the skin and mucous membranes where -they engulf microorganisms and molecules through -phagocytosis and - pinocytosis The immature dendritic cells migrate to the follicles of secondary lymphoid organs such as lymph nodules, lymph nodes and the spleen and in the process, mature into professional antigen- presenting cells (APCs).

Like macrophages, dendritic cells engulf the microorganisms and other materials and degrade them with their lysosomes. Dendritic cells produce the same cytokines as the macrophages, namely tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8).

Mast cells Mast cells, found in the connective tissue of the skin and mucous membranes, Carry out the same functions as basophils. Release histamine, Leukotrienes and prostaglandins -chemicals that promotes inflammation by causing vasodilation Increasing capillary permeability, and increasing mucous production. Mast cells are the cells that usually first initiate the inflammatory response.

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