anatomy and biology of immune response

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


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


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


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


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


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


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


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


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


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


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


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


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)


B lymphocytes may mature into plasma cells in which form they remain fixed in the tissues and function as secretors of antibody


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


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


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


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


T lymphocytes Two subsets CD4+ T cells or T helper cells

(66%) CD8+ T cells or T

cytotoxic/suppressor cells (33%)


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


Instead, lymphocytes have the distinctive feature of recirculation between the blood, tissues and lymphoid organs


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


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


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


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


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 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 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


Primary lymphoid organs in humans are the bone marrow and thymus, since they are the sites of development and maturation of the lymphocytes


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


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)


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


The thymus is at its largest, in proportion to body mass, at birth and thereafter shows a relative decline in size


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


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


Secondary follicles arise following stimulation of a local immune response

The germinal centre of the follicle enlarges and B lymphocytes undergo proliferation and differentiation


The germinal centre is surrounded by a mantle of smaller, resting B lymphocytes


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


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


They do so via large cuboidal endothelial cells present on specialized structures called high endothelial venules (HEV)


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


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


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


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


Adaptiveness The ability to respond to previously

unseen molecules that may in fact never have existed before on earth


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


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

anatomy and biology of immune response

Documents

t cells

immune system dendritic

production of immune

immune system lymphocytes

precursor cells

white cells

kupffer cells

microglial cells