Cells and Organs of Immune System

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CELLS OF THE IMMUNE SYSTEM

INTRODUCTION
• The typical vertebrate immune system consists of many types of proteins, cells, organs, and tissues that interact in an elaborate and dynamic network.

• Lymphocytes are the central cells of the immune system, responsible for adaptive immunity and the immunologic attributes of diversity, specificity, memory, and self/nonself recognition. • The other types of white blood cells play important roles, engulfing and destroying microorganisms, presenting antigens, and secreting cytokines.

Lymphoid Cells
• Lymphocytes constitute 20%–40% of the body’s white blood cells and 99% of the cells in the lymph. • The lymphocytes can be broadly subdivided into three populations B cells, T cells, and natural killer cells - on the basis of function and cell-membrane components.

• Natural killer cells (NK cells) are large, granular lymphocytes that do not express the set of surface markers typical of B or T cells. • Resting B and T lymphocytes are small, motile, nonphagocytic cells,which cannot be distinguished morphologically.

naive ( 6 µm)

• B and T lymphocytes that have not interacted with antigen. • NAIVE are resting cells in the G0 phase of the cell cycle.

naive + antigen + certain cytokine

• Induces these cells to enter the cell cycle by progressing from G0 into G1 and subsequently into S, G2, and M.

Lymphoblast ( 15 µm )

• As they progress through the cell cycle, lymphocytes enlarge
into 15 m-diameter blast cells, called lymphoblasts. • Lymphoblasts proliferate and eventually differentiate into effector cells or into memory cells.

T- Helper cells
T-cell lineage (cytokine secreting) Effector cells B-cell lineage (antibody secreting)

T- Cytotoxic cell

Some of the progeny of B and T lymphoblasts differentiate into memory

cells.

Plasma cells

B LYMPHOCYTES
• B cells spend their entire early life in the bone marrow. Upon maturity, their job is to travel throughout the blood and lymph looking for antigens with which they can interlock.

• Once a B cell has identified an antigen, it starts replicating itself. These cloned cells mature into antibody-manufacturing plasma cells.

T LYMPHOCYTES
• Unlike B cells, these cells leave the marrow at an early age and travel to the thymus, where they mature. Here they are imprinted with critical information for recognizing “self” and “non-self” substances.

• Among the subclasses of T cells are helper T cells and cytotoxic (or killer) T cells.

NATURAL KILLER CELLS
• NK cells are cytotoxic; small granules in their cytoplasm contain special proteins such as perforin and proteases known as granzymes. • Upon release in close proximity to a cell slated for killing, perforin forms pores in the cell membrane of the target cell through which the granzymes and associated molecules can enter, inducing apoptosis. • NK cells play a major role in the host-rejection of both tumours and virally infected cells. •

Mononuclear Phagocytes
• The mononuclear phagocytic system consists of monocytes circulating in the blood and macrophages in the tissues.
During hematopoiesis in the bone marrow, granulocyte-monocyte progenitor cells differentiate into promonocytes. Promonocytes enter the blood, where they further differentiate into mature monocytes. Monocytes enlarges and then migrate into the tissues and differentiate into specific tissue macrophages & then into dendritic cells.

Monocytes
• Large, agranular leukocytes with relatively small, eccentric, oval or kidney-shaped nuclei.

Macrophages
• Literally, “large eaters.” These are large, long-lived phagocytes which capture foreign cells, digest them, and present protein fragments (peptides) from these cells and manifest them on their exterior. In this manner, they present the antigens to the T cells.

• Macrophages are strategically located in lymphoid tissues, connective tissues and body cavities, where they are likely to encounter antigens. They also act as effector cells in cell-mediated immunity.

Mechanism of Macrophages
• • PHAGOCYTOSIS ANTIMICROBIAL AND CYTOTOXIC ACTIVITIES




ANTIGEN PROCESSING AND PRESENTATION
SECRETION OF FACTORS

PHAGOCYTOSIS
• Macrophages are capable of ingesting and digesting exogenous antigens, such as whole microorganisms and insoluble particles, and endogenous matter, such as injured or dead host cells, cellular debris, and activated clotting factors.

ANTIMICROBIAL AND CYTOTOXIC ACTIVITIES
• A number of antimicrobial and cytotoxic substances produced by activated macrophages can destroy phagocytosed Microorganisms.

OXYGEN-DEPENDENT KILLING MECHANISMS • Activated phagocytes produce a number of reactive oxygen intermediates (ROIs) and reactive nitrogen intermediates that have potent antimicrobial activity. OXYGEN-INDEPENDENT KILLING MECHANISMS • Activated macrophages also synthesize lysozyme and various hydrolytic enzymes whose degradative activities do not require oxygen. • In addition, activated macrophages produce a group of antimicrobial and cytotoxic peptides, commonly known as defensins.

ANTIGEN PROCESSING AND PRESENTATION
• Phagocytosed antigen is digested within the endocytic processing pathway into peptides that associate with class II MHC molecules; • These peptide–class II MHC complexes then move to the macrophage membrane. • Activation of macrophages induces increased expression of both class II MHC molecules and the co-stimulatory B7 family of membrane molecules, thereby rendering the macrophages more effective in activating TH cells.

SECRETION OF FACTORS
• A number of important proteins central to development of immune responses are secreted by activated macrophages.

• These include a collection of cytokines, such as interleukin 1 (IL-1), TNF- and interleukin 6 (IL-6), that promote inflammatory responses.

Granulocytic Cells
• Leukocytes (white blood cells) containing granules in the cytoplasm. They seem to act as a first line of defense, as they rush toward an infected area and engulf the offending microbes.



• Granulocytes kill microbes by digesting them with killer enzymes contained in small units called lysosomes.

• The granulocytes are classified as neutrophils, eosinophils,or basophils on the basis of cellular morphology and cytoplasmic staining characteristics

NEUTROPHILS
• The neutrophil has a multilobed nucleus and a granulated cytoplasm that stains with both acid and basic dyes; it is often called a polymorphonuclear leukocyte (PMN). In response to many types of infections,the bone marrow releases more than the usual number of neutrophils and these cells generally are the first to arrive at a site of inflammation.



• The resulting transient increase in the number of circulating neutrophils, called leukocytosis,is used medically as an indication of infection.

EOSINOPHILS
• Eosinophils, like neutrophils, are motile phagocytic cells that can migrate from the blood into the tissue spaces.

• Their phagocytic role is significantly less important than that of neutrophils, and it is thought that they play a role in the defense against parasitic organisms. • The secreted contents of eosinophilic granules may damage the parasite membrane.

BASOPHILS
• Basophils are nonphagocytic granulocytes that function by releasing pharmacologically active substances from their cytoplasmic granules.

• These substances play a major role in certain allergic responses.

MAST CELLS
• Mast cells can be found in a wide variety of tissues, including the skin, connective tissues of various organs, and mucosal epithelial tissue of the respiratory, genitourinary and digestive tracts.

• Cells concentrated within the respiratory and gastrointestinal tracts, and within the deep layers of the skin.
• These cells release histamine upon encountering certain antigens, thereby triggering an allergic reaction.

DENDRITIC CELLS
• The dendritic cell (DC) acquired its name because it is covered with long membrane extensions that resemble the dendrites of nerve cells. Dendritic cells can be difficult to isolate because the conventional procedures for cell isolation tend to damage their long extensions. Mostly found in the skin and mucosal epithelium, where they are referred to as Langerhan's cells.





• Unlike macrophages, dendritic cells can also recognize viral particles as non-self. • In addition, they can present antigens via both MHC I and MHC II, and can thus activate both CD8 and CD4 T cells, directly.



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