Cells and Organs

of the Immune System

Copyright © 2007 by W. H. Freeman and Company

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• All blood cells arise from a type of cell called the hematopoietic stem cell (HSC).
• Stem cells are cells that can differentiate into other cell types; they are self-renewing — they maintain their population level by cell division.
• The process by which HSCs differentiate into mature�blood cells is called hematopoiesis.
• In humans, hematopoiesis, begins in the embryonic yolk sac during the first weeks of development.

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

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Surface proteins expressed by immune cells are often referred to by the cluster of differentiation (CD or cluster of designation)

Lymphocytes

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

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

Lymphocytes

• T Lymphocytes (T cells)
• Site of maturation
• 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 (T_H)
• T cytotoxic (T_C)
• And now T regulatory (T_reg)

Three signals are required for activation of a naïve T cell. �

Lymphocytes

• T helper cells
• CD4 glycoprotein
• “help” activation of B cells, T_C cells, macrophages in immune response

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

Lymphocytes

• T regulatory cells
• CD4 and CD25 glycoproteins
• Help suppress the immune system

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

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

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• Activated macrophages are more effective than resting ones

• Macrophages enlarges five- to ten-fold;
• its intracellular organelles increase in both number and complexity; and
• it acquires increased phagocytic ability,
• produces higher levels of hydrolytic enzymes, and begins to secrete a variety of soluble factors.
• Residence fixed macrophages in particular tissues, whereas others remain motile and are called free, or wandering, macrophages

Other Leukocytes

• Mononuclear phagocytes

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• 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

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• Phagocytosis is enhanced when antibody is attached to the antigen
• Antibody acts as opsonin: molecule that binds to both antigen and phagocyte

Differences in the properties of antigen-presenting cells �

Differences in the properties of antigen-presenting cells �

PHAGOCYTOSIS

Macrophages are attracted by and move

toward Ag – Chemotaxis.

Adherence of the antigen to the macrophage

cell membrane

Adherence induces membrane protrusions, called

pseudopodia,

pseudopodia encloses the material within a membrane-bounded structure called a phagosome,

phagosome moves toward the cell interior, where it fuses with a lysosome to form a phagolysosome

The digested contents of the phagolysosome are then eliminated in a process called exocytosis

a) Oxygen-dependent killing mechanisms

• Activated phagocytes produce reactive oxygen intermediates (ROIs) and reactive nitrogen intermediates.
• Respiratory burst- activation of a membrane-bound oxidase that catalyzes the reduction of oxygen to superoxide anion
• express high levels of nitric oxide synthetase (NOS), oxidizes L-arginine to yield L-citrulline and nitric oxide (NO)

b) Oxygen-independent killing mechanisms

• Activated macrophages also synthesize lysozyme and various hydrolytic enzymes whose degradative activities do not require oxygen.
• Also produce a group of antimicrobial and cytotoxic peptides, known as defensins.
• cysteine-rich cationic peptides containing 29–35 amino-acid residues.
• Can form ion-permeable channels in bacterial cell membranes
• Can kill Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa,and Haemophilus influenzae.
• also secrete tumor necrosis factor-α (TNF-α)

Other Leukocytes

• Granulocytes – Neutrophils
• Multi-lobed nucleus, light granules
• 1^st to arrive at site of inflammation
• High #’s is 1^st indication of infection
• Phagocytize
• Generate antimicrobial agents
• The larger, denser primary granules are a type of lysosome containing peroxidase, lysozyme, and various hydrolytic enzymes.
• The smaller secondary granules contain collagenase, lactoferrin, and lysozyme.

Other Leukocytes

• Granulocytes – Eosinophils
• Phagocytize
• can migrate from the blood into tissue spaces.
• Play a role in parasitic organisms

BASOPHILS

• nonphagocytic granulocytes
• release pharmacologically active substances.
• These substances play a major role in certain allergic responses.

MAST CELLS

• Found in skin, connective tissues of various organs, and mucosal epithelial tissue of the respiratory, genitourinary, and digestive tracts.
• these cells have large numbers of cytoplasmic granules that contain histamine and other pharmacologically active substances.
• Mast cells, together with blood basophils, play an important role in the development of allergies

Other Leukocytes

• 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

Organs of the Immune System

• The thymus and bone marrow are the primary (or central) lymphoid organs, where maturation of lymphocytes takes place.
• The lymph nodes, spleen, and various mucosal-associated lymphoid tissues (MALT) such as gut-associated lymphoid tissue (GALT) are the secondary (or peripheral) lymphoid organs,
• tertiary lymphoid tissues: cutaneous-associated lymphoid tissues.

BONE MARROW

• site of B-cell origin and development.

THYMUS

• site of T-cell development and maturation.
• It is a flat, bilobed organ situated above the heart.
• Each lobe is surrounded by a capsule and is divided into lobules,

DiGeorge’s syndrome

• congenital birth defect in humans in which the thymus fails to develop.
• there is an absence of circulating T cells and of cell-mediated immunity and
• increase in infectious disease.
• In case of mice known as (nude mice)

• Thymus reaches its maximal size at puberty and then atrophies

Lymphatic System

• Once mature lymphocytes have been generated in the primary lymphoid organs, they circulate in the blood and lymphatic system.
• Plasma
• Interstitial fluid
• Lymph

Lymphatic System

• The largest lymphatic vessel, the thoracic duct, empties into the left subclavian vein near the heart.

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• flow of lymph is achieved as the lymph vessels are squeezed by movements of the body’s muscles.

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• When a foreign antigen gains entrance to the tissues, it is picked up by the lymphatic system

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• is carried to various organized lymphoid tissues such as lymph nodes, which trap the foreign antigen.

Secondary Lymphoid Organs

• Lymph nodes and the spleen are the most highly organized of the secondary lymphoid organs;
• Less-organized lymphoid tissue, collectively called mucosal-associated lymphoid tissue (MALT)
• Peyer’s patches (in the small intestine),
• the tonsils, and
• the appendix, as well as numerous lymphoid follicles within the lamina propria of the intestines
• in the mucous membranes lining the upper airways, bronchi, and genital tract.

LYMPH NODES

• They are encapsulated bean-shaped structures.
• Has three regions :the cortex, the paracortex, and the medulla, each of which supports a distinct microenvironment.
• The outermost layer, the cortex, contains lymphocytes (mostly B cells), macrophages, and follicular dendritic cells arranged in primary follicles.
• Beneath the cortex is the paracortex, which is populated largely by T lymphocytes and also contains interdigitating dendritic cells.
• The innermost layer of a lymph node, the medulla, is less populated with lymphoid-lineage cells; of those present, many are plasma cells actively secreting antibody molecules

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SPLEEN

• plays a major role in mounting immune responses to antigens in the blood stream.
• It is a large, ovoid secondary lymphoid organ situated high in the left abdominal cavity.
• the spleen specializes in filtering blood and trapping blood-borne antigens; thus, it can respond to systemic infections.

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The spleen is surrounded by a capsule that extends a number of projections (trabeculae) into the interior to form a compartmentalized structure. The compartments are of two types, the red pulp and white pulp, which are separated by a diffuse marginal zone

• Red Pulp
• Macrophages and numerous red blood cells (erythrocytes) and few lymphocytes;
• it is the site where old and defective red blood cells are destroyed and removed.
• Many of the macrophages within the red pulp contain engulfed red blood cells or iron pigments from degraded haemoglobin.

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White pulp:

• periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes.
• Primary follicles are rich in B cells and some of them contain germinal centers.
• The marginal zone, is populated by lymphocytes and macrophages.

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MUCOSAL-ASSOCIATED LYMPHOID TISSUE

• The tonsils are found in three locations: lingual at the base of the tongue; palatine at the sides of the back of the mouth; and pharyngeal (adenoids) in the roof of the nasopharynx

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• Consists of reticular cells and fibers interspersed with lymphocytes, macrophages, granulocytes, and mast cells.

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• The tonsils defend against antigens entering through the nasal and oral epithelial routes

Cutaneous-Associated Lymphoid Tissue

• The epidermal (outer) layer of the skin is composed largely of specialized epithelial cells called keratinocytes.
• Langerhans cells, a type of dendritic cell, which internalize antigen by phagocytosis or endocytosis. The Langerhans cells then migrate from the epidermis to regional lymph nodes, where they differentiate into interdigitating dendritic cells.
• The epidermis also contains so-called intraepidermal lymphocytes.