Post on 11-May-2015
Anatomy and Biology of the Immune Response
The bone marrow is the source of the precursor cells that ultimately give rise to the cellular constituents of the immune system, save for one period during fetal life when the liver is also a site of immune cell development
Anatomy and Biology of the Immune Response
The production of immune cells is one component of haemopoiesis Process by which all cells that circulate in
the blood arise and mature There is a single precursor cell that is
capable of giving rise to all blood cell lineages ranging from platelets to lymphocytes pluripotent haemopoietic stem cell
Anatomy and Biology of the Immune Response
Both the microenvironment within the marrow and the influence of soluble mediators that act as colony stimulating factors are important determinants for the mechanism by which a pluripotent stem cell in the bone marrow matures into any one of the immune cells
Cells of the Immune System
Granulocytes The granulocyte/monocyte lineage
gives rise to precursors that mature within the bone marrow and are released into the blood
Constitute ~65% of all white cells and derive their name from the large numbers of granules found in their cytoplasm
Cells of the Immune System
Granules with intense blue staining are found in basophils, which make up 0.5-1% of granulocytes
Red-staining granules are present in eosinophils (3-5%)
Neutrophils (90-95%) have granules that remain relatively unstained
Cells of the Immune System
Polymorphonuclear cell describes the multilobed nuclei of granulocytes; synonymous with neutrophils which constitute by far the majority of granulocytes but eosinophil nuclei may have a similar appearance
Cells of the Immune System
Granulocytes circulate in the blood and migrate into the tissues particularly during inflammatory responses; exception is the mast cell which is fixed in the tissues
Cells of the Immune System
Monocytes and Dendritic Cells Monocytes form between 5 and 10%
of circulating WBC, have a short half-life spending approx. 24 hrs in blood
Enter extravascular pool and become resident in the tissues where they are termed macrophages
Cells of the Immune System
Macrophages may also arise following division of immature forms of monocytes
Monocyte and macrophage are larger than neutrophils and lymphocytes, have a single nucleus and abundant granular cytoplasm
Cells of the Immune System
Several specialized forms of the mature cell exist including alveolar macrophages in the lung, Kupffer cells in the liver, mesangial cells in the kidney, microglial cells in the brain, osteoclasts in bone and other macrophages lining channels in the spleen and lymph nodes
Cells of the Immune System
Dendritic cells are bone marrow derived and have a specialized function in the activation and priming of lymphocytes
Some specialized forms of these cells exist: for example, follicular dendritic cells in the lymph nodes
Cells of the Immune System
Lymphocytes Make up the final 25-35% of white cells
and derive their name from a close association with the lymphatic system
Lymphocytes are divided into two subtypes B and T present in blood in a ratio of
1:5
Cells of the Immune System
Are found in the blood, lymphoid organs or tissues and also at sites of chronic inflammation
B lymphocytes differentiate within the bone marrow before being released into the circulation
Cells of the Immune System
During fetal life, the liver is also an important site of B lymphocyte development
The primary role of these cells is the recognition of macromolecules (termed antigens) through surface receptors (called antibodies)
Cells of the Immune System
B lymphocytes may mature into plasma cells in which form they remain fixed in the tissues and function as secretors of antibody
Cells of the Immune System
The B lymphocyte obtained its name from early studies on antibody production in birds showing that removal of a lymphoid organ known as the bursa of Fabricius from near the hindgut of a chick results in a complete inability to produce antibody
These antibody-producing cells then became known as bursa-derived, or B lymphocytes
Cells of the Immune System
Removal of the thymus from adult mice appeared to have little effect on the animals or their lymphocytes, but thymectomy performed soon after birth had profound consequences reducing the numbers of lymphocytes in circulation and leaving the mice prone to death from infection
Cells of the Immune System
T lymphocyte involvement with the thymus takes place in early life and is critical to their development
During this period, they acquire the ability to recognize and bring about the death of transplanted foreign tissues in a process termed graft rejection which implies an ability to distinguish self and non-self
Cells of the Immune System
In the absence of T lymphocytes, protection against infection is fatally impaired
Though not capable of producing antibody themselves, T lymphocytes make a telling contribution to B lymphocyte function
Cells of the Immune System
T lymphocytes Two subsets CD4+ T cells or T helper cells
(66%) CD8+ T cells or T
cytotoxic/suppressor cells (33%)
Cells of the Immune System
The total number of lymphocytes in a healthy adult is about 1012, of which 0.1% are renewed daily
Collectively they weigh almost half as much as the liver, yet they do not reside in any single organ
Cells of the Immune System
Instead, lymphocytes have the distinctive feature of recirculation between the blood, tissues and lymphoid organs
Cells of the Immune System
Recirculation times vary from cell to cell, depending upon what is encountered during the journey, but on average, a lymphocyte will complete a cycle in 1-2 days
Cells of the Immune System
Rather than being random, recirculation is a highly regulated process of immune surveillance, controlled according to cell type and anatomy
B lymphocytes have a greater tendency to migrate to mucosal lymphoid tissue than do T lymphocytes
Cells of the Immune System
Natural killer (NK) cells Is a functional definition: cells with
this activity are capable of lysing virus-infected cells and tumor cells
Like lymphocytes, NK cells are also identifiable by the presence of specialized surface glycoproteins
Cells of the Immune System
A population of cells defined morphologically as large granular lymphocytes (LGL) also have natural killer function
This term is limited, however, since T lymphocytes actively involved in an immune response may appear large and granular
Cells of the Immune System
Unlike T lymphocytes, NK cells do not require the thymus for their maturation, though a small population of thymus-derived cells with NK function has been identified
Cells of the Immune System
Cells of the Innate Immune System:Cells of the Innate Immune System:
PHAGOCYTESPHAGOCYTES-------------------------------------------Monocyte-macrophagesystem: (monocytes,macrophages, dendriticcells, alveolar macrophages,mesangial cells, microglial cells
Neutrophils (PMNs) &Eosinophils
CYTOTOXIC CELLSCYTOTOXIC CELLS-------------------------------------------Natural killer cells (NK cells)
Cells of the Immune System
Cells of the Adaptive Immune SystemCells of the Adaptive Immune System--------------------------------------------------------------------------------------------
Lymphocyte classification: CellCell--surface receptorsurface receptor
T lymphocytes T-cell receptor Cell Mediated Immunity (CD4 and CD8)
B lymphocytes B-cell receptorHumoral Immunity (antibody production)
Organs of the Immune System
Organs of the lymphoid system are divided into:- primary and secondary organs
Organs of the Immune System
Primary lymphoid organs in humans are the bone marrow and thymus, since they are the sites of development and maturation of the lymphocytes
Organs of the Immune System
Secondary lymphoid organs (lymph nodes and spleen) are not essential for the generation of lymphocytes but have a key role in the maturation of these cells and the development of immunity
Organs of the Immune System
Lymph nodes in particular anatomical sites are highly specialized, those surrounding the upper and lower respiratory tracts being known as the mucosa-associated lymphoid tissue (MALT) and those in the gut, the gut-associated lymphoid tissue (GALT)
Organs of the Immune System
The thymus develops from the third and fourth pharyngeal pouches in the 6th week of fetal life
Immature cells enter the cortex and receive the close attention of a mixture of thymic epithelial and macrophage-derived cells, resulting in their development into immature T lymphocytes
Organs of the Immune System
The thymus is at its largest, in proportion to body mass, at birth and thereafter shows a relative decline in size
Organs of the Immune System
Lymph nodes Lymphocytes enter the lymph
nodes either through the lymphatics or from the blood
The cortex of the lymph node contains follicles which are organized aggregates of lymphoid cells
Organs of the Immune System
Primary follicles are characteristic of a resting state and suggest no recent immune activity
Are composed of B lymphocytes, macrophages and specialized macrophages with long cytoplasmic processes known as follicular dendritic cells
Organs of the Immune System
Secondary follicles arise following stimulation of a local immune response
The germinal centre of the follicle enlarges and B lymphocytes undergo proliferation and differentiation
Organs of the Immune System
The germinal centre is surrounded by a mantle of smaller, resting B lymphocytes
Organs of the Immune System
The paracortical area of the node is predominantly composed of T lymphocytes as well as the specialized interdigitating dendritic cells which are important accessory cells in T lymphocyte responses
Organs of the Immune System
The medulla has characteristic medullary cords of lymphoid cells which tend to become populated with plasma cells during immune reactions
Lymphocytes may also enter lymph nodes via the blood
Organs of the Immune System
They do so via large cuboidal endothelial cells present on specialized structures called high endothelial venules (HEV)
Organs of the Immune System
Payer's patches are lymphoid aggregates with follicles, germinal centers and a surrounding T cell area but they differ from peripheral lymph nodes in lacking a capsule and afferent lymphatics
Organs of the Immune System
Spleen Has a white pulp comprising
lymphoid tissue and a red pulp comprising reticular tissue and sinuses bathed in blood
Is a combination of lymphoid organ, filter bed and reclamation site
Organs of the Immune System
The red pulp is an important site for the removal of defective red and white blood cells which are cannibalized by resident macrophages
Cross section of white pulp Marginal zone – macrophage-rich area Follicle – B cell area Periarterial lymphatic sheath – T cell
area
Organs of the Immune System
The importance of the spleen in protection against encapsulated organisms (S pneumoniae) probably results from a combination of its ability to slow and filter circulating blood and its capacity to act as a rapid response unit in generating specific antimicrobial antibodies
Characteristics of the Immune Response
Specificity The ability to discriminate among
different molecular entities presented to it and to respond only to those uniquely required, rather than making a random, undifferentiated response
Characteristics of the Immune Response
Adaptiveness The ability to respond to previously
unseen molecules that may in fact never have existed before on earth
Characteristics of the Immune Response
Discrimination between self and nonself
The ability to recognize and respond to molecules that are foreign or nonself and avoid making a response to those molecules that are self
The distinction and the recognition of foreign antigen is conferred by specialized cells namely lymphocytes which bear on their surface receptors specific for foreign antigen
Characteristics of the Immune Response
Memory The ability to recall previous
contact with a foreign molecule and respond to it in a learned manner i.e. a more rapid and larger response