STUCTURE AND FUCTIONS OF THE IMMUNE SYSTEM

A Presentation By

G. Prashanth Kumar

Department of Microbiology & Parasitology,

Faculty of Medicine, International Medical & Technological University,

Dar-Es-Salaam, Tanzania.

INTRODUCTION • The lymphoreticular system is a complex organization of

cells of diverse morphology, distributed widely in different organs and tissues of the human body, and are responsible for immunity.

• They consist of lymphoid and reticuloendothelialcomponents and are responsible for immune response of the host.

• The lymphoid cells that include lymphocytes and plasma cells are responsible for conferring specific immunity.

• On the other hand, the reticuloendothelial system that consists of the phagocytic cells and plasma cells is responsible for nonspecific immunity.

• These cells kill microbial pathogens and other foreign agents and remove them from the blood and tissue.

LYMPHOID SYSTEM

• The immune system is organized into several special tissues which are collectively termed as lymphoid or immune tissues.

• Those tissues that have evolved to a high degree of specificity of function are termed as lymphoid organs.

1. Lymphoid cells- lymphocytes and plasma cells.

2. Lymphoid organs

- Primary (Central )

- Secondary (Peripheral).

CENTRAL (PRIMARY) LYMPHOID ORGANS.

•Thymus

•Bone marrow

THYMUS• Present behind the upper part

of the sternum.

• Appearance- two lobes surrounded by a fibrous capsule.

• Septa divides the glands to lobules with an outer cortex and inner medulla.

• Cortex- actively proliferating small lymphocytes.

• Medulla- epithelial cells and mature lymphocytes in the middle of which are Hassall’s corpuscles (whorl like aggregates of epithelial cells).

THYMUS

• Observations by Good (1954) of thymoma and impaired immunity and by Miller (1961) of immunodeficiency in thymectomised mice led to the understanding of the pivotal role of Thymus in Cell Mediated Immunity.

• Primary Function- Production of thymic lymphocytes.

• Lymphocytes Thymus Surface Antigen (Thy-antigen) Thymus dependent / T-cells / T-lymphocytes (not dependent on antigenic stimulation).

THYMUS

Effects of Thymectomy/Absent Thymus

• Decreased CMI- DiGeorgesyndrome (congenital aplasia of thymus), ‘nude mice’ (thymectomised mice).

• Decreased antibody response to many antigens (thymus dependent antigen).

• ‘Thymus dependent’ region like in the perilymphatic system (white pulp of spleen, around the central arterioles, and in the paracortical areas of lymph nodes) were found grossly depleted.

BONE MARROW

• Lymphoid cells developing and maturing here are referred to as B cells (B for Bursa of Fabricius or bone marrow).

• Site for proliferation of stem cells and for the origin of pre-B cells and their maturation to become immunoglobulin-producing lymphocytes.

• Like thymic selection during T-cell maturation, a selection process within the bone marrow eliminates B cells with self reactive antibody receptor.

BONE MARROW

BONE MARROW

PERIPHERAL (SECONDARY) LYMPHOID ORGANS

•Lymph nodes

•Spleen

•Mucosa associated lymphoid tissue

LYMPH NODES

• Placed along the course of lymphatics.• Surrounded by a fibrous capsule from which

trabeculae penetrates into the nodes.• Outer cortex- accumulation of lymphocytes (primary

lymphoid follicles) within which germinal centers (secondary follicles) develop during antigenic stimulation. Follicle also contain dendritic macrophages.

• Inner medulla- lymphocytes, plasma cells and macrophages are arranged as elongated branching bands (medullary cords).

LYMPH NODES

• Lymphnode

LYMPH NODES

• Bursa dependent areas: The cortical follicles and medullary cords that contain B-lymphocytes.

• Thymus dependent area: Between the cortical follicles and medullary cords there is an ill-defined intermediate zone (paracortical area) which contains T-lymphocytes.

• Functions:

• Filter for lymph, each group draining specific part of the body.

• Phagocytose foreign materials including microorganisms.

• Help in proliferation and circulation of T-cells and B-cells.

• They enlarge during local antigenic stimulation.

SPLEEN• Largest lymphoid organ. Capsule from which trabeculae

descends, dividing the organ into several interconnected compartments.

• White pulp of spleen- constitute ¾th of the organ. Red pulp of spleen.

• Functions:

• Filtering and clearing of infectious organisms.

• Serves as a ‘graveyard’ for affected blood cells.

• As a reserve tank and settling bed for blood and as a systemic filter for trapping circulating blood borne foreign particles.

• The immunological function of spleen is primarily directed against blood borne antigens.

SPLEEN

EFFECTS OF SPLENECTOMY

• Depends on the age at which the spleen is removed.

• In children, splenectomy often leads to an increased incidence of bacterial sepsis caused primarily by Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae.

• Splenectomy in adults has less adverse effects, although in some, it makes the host more susceptible to blood-borne bacterial infection.

MUCOSA ASSOCIATED LYMPHOID TISSUE (MALT)

• The mucosa lining the alimentary, respiratory, genitourinary and other lumina are endowed with a rich collection of lymphoid cell aggregates like the Peyer’s patches or scattered isolated follicles-collectively called MALT.

- Gut associated lymphoid tissue (GALT): gut, adenoids, tonsils and colon.

- Bronchus associated lymphoid tissue (BALT): respiratory tract.

MUCOSA ASSOCIATED LYMPHOID TISSUE (MALT)

• MALT contains lymphoid as well as phagocytic cells.

• Both B and T cells are present.

• While the predominant immunoglobulin produced in the mucosa is secretory IgA, other immunoglobulin classes, IgG, IgM and IgE are also formed locally.

CELLS OF THE IMMUNE SYSTEM

• Cells of the immune system are associated with the lymphatic system of the body and its specialized cells.

• Lymphocytes of the lymphatic system are derived from stem cells of the bone marrow.

• These undifferentiated precursor cells proliferate throughout life and replenish the mature cells of the immune system.

CELLS OF THE IMMUNE SYSTEM

CELLS OF THE IMMUNE SYSTEM

LYMPHOCYTES

• Small, round cells found in peripheral blood, lymph, lymphoid organs and in many other tissues.

• In peripheral blood it constitutes 20-45 per cent of the leucocyte population, while in lymph and lymphoid organs they form the predominant cell type.

• Human body contains 10¹² lymphocytes, approximately 109 of them being renewed daily.

• Only about 1 per cent of the total body lymphocytes are present in the blood.

LYMPHOCYTES

• CLASSIFICATION:

• Depending upon where they undergo development and proliferation:

• In the thymus (thymus derived lymphocytes, or T-cells, and Natural Killer T, or NKT cells).

• In the bone marrow (B lymphocytes or B cells).

• By the types of receptors they possess on their cell surface:

• TCR (T cells and NKT cells)

• BCR, or Immunoglobulins (B cells) or neither (natural killer, or NK cells).

LYMPHOCYTES

• CLASSIFICATION:

• According to size:

• 1.Small (5-8 µm): most numerous, ‘hand-mirror’ form.

• 2.Medium (8-12 µm)

• 3.Large (12-15 µm)

• According to their life span:

• Short lived lymphocytes: about 2 weeks, they are the effector cells in the immune response.

• Long lived lymphocytes: may last for 3 years or more, or even for life, these cells are the storehouse for immunologic memory

LYMPHOCYTES

• Lymphocyte Recirculation.

• Policeman on beat patrol, ceaseless wandering of lymphocytes through the blood, lymph, lymphatic organs and tissues.

• Mount an immune response following antigenic introduction to any part of the body or whenever necessary.

• One cycle completed in about one or two days.

• Recirculation lymphocytes are mainly T-cells.

• B-cells tend to be more sessile.

LYMPHOCYTES

LYMPHOCYTES

• A lymphocyte that has been ‘educated’ by the central lymphoid organs, it is an ‘Immunologically competent cells’.

• Mature T and B cells, before they encounter antigens, are called ‘naïve cells’, though not engaged in an immunological response, are nevertheless fully qualified to undertake appropriate actions.

• They sub serve the following functions:

• Recognition of antigens,

• Storage of immunological memory and

• Immune response to specific antigens.

LYMPHOCYTES

• ORIGIN:• The transformation of stem cells into B-lymphocytes and T-

lymphocytes begins about the fifth month after fertilization, and a full set is complete a few months after birth.

• These cells then migrate to the lymphoid organs in the lymph nodes, spleen, tonsils, adenoids, and other organs of the lymphatic system.

• To initiate the immune response, microorganisms are phagocytized and their antigens are processed in phagocytic cells such as macrophages.

• The antigenic determinants are displayed on the surface of the phagocytic cells and presented to the appropriate B-lymphocytes and T-lymphocytes to provoke an immune response.

Stem cells from the yolk sac enter the abdomen of the

foetus through the umbilical cord.

Umbilical cord

Uterus

Foetus

Liver

A

B The stem cells differentiate in

the liver of the foetus.

BONE MARROW

C The hematopoietic stem cells mature in the bone

marrow.

D Stem cells then become Lymphoid

progenitors.

E Other stem cells become myeloid progenitors that

differentiate into red blood cells and most white blood

cells.

B-Lymphocyte differentiation T-Lymphocyte differentiation

F

Some lymphoid progenitors

differentiate to B lymphocytes in the

bone marrow.

G Other lymphoid progenitors differentiate to T

Lymphocytes in the Thymus.

H B Lymphocytes take up residence in

the outer cortex of a Lymph node.

I T Lymphocytes take up residence in

the inner medulla of a Lymph node.

THE ORIGIN OF B AND T

LYMPHOCYTES.

LYMPHOCYTES

• A number of surface antigens or markers have been identified on lymphocytes and other leucocytes by means of monoclonal antibodies.

• These markers reflect the stage of differentiation and functional properties of the cell.

• At the International Workshops for Leucocytes Differentiation Antigens order was given by comparing the specificities of different antisera.

• When a cluster of monoclonal antibodies was found to react with a particular antigen, it was defined as a separate marker and given a CD (Cluster Differentiation) number.

• Over 150 CD markers have been identified so far.

T-CELLS

• These are Thymus derived cells.

• Key players in adaptive immunity. Governs cell mediated immune response.

• 65-80% of the circulating pool of small lymphocytes.

• Found in the inner subcortical regions but not in the germinal centers of the lymph nodes.

• Longer life span (months or years) than B cells.

• On exposure to certain mitogens like phytohemagglutininor Concavalin A, the T cells can be stimulated to divide.

• Most T cells in humans have receptors for sheep RBC on their surface and have the ability to form rosettes with them.

Development in the thymus

• All T cells originate from haematopoietic stem cells in the bone marrow.

• Haematopoietic progenitors derived from haematopoietic stem cells populate the thymus and expand by cell division to generate a large population of immature thymocytes.

• The earliest thymocytes express neither CD4 nor CD8, and are therefore classed as double-negative (CD4‾ CD8‾) cells.

• As they progress through their development they become double-positive thymocytes (CD4+ CD8+), and finally mature to single-positive (CD4+CD8‾ or CD4‾CD8+) thymocytes that are then released from the thymus to peripheral tissues.

Development in the thymus

• About 98% of thymocytes die during the development processes in the thymus by failing either positive selection or negative selection, whereas the other 2% survive and leave the thymus to become mature immunocompetent T cells.

• The thymus contributes more naïve T cells at younger ages.

• As the thymus shrinks by about 3% a year throughout middle age, there is a corresponding fall in the thymic production of naïve T cells, leaving peripheral T cell expansion to play a greater role in protecting older subjects.

Development in the thymus

• Positive selection selects for T cells that are capable of recognizing self antigens through MHC.

• Negative selection selects for T cells that bind too strongly to self antigens.

• These two selection processes allow for Tolerance of self by the immune system. They do not necessarily occur in a chronological order and can occur simultaneously in the thymus.

T-CELLS ACTIVATION

TYPES OF T-CELLS

• T helper cells / TH cells / CD4+ T cells.

• Cytotoxic T Cells / Tc cells / CLT / CD8+ T cells.

• Memory T cells.

• Regulatory T cells / Treg cells also formerly known as Suppressor T cells.

• Natural Killer T cells / NKT cells.

• gd T cells / gamma delta T cells.

TYPES OF T-CELLS

HELPER ( CD4+ ) T CELLS

• About 65% of peripheral T cells

• Found mainly in the thymic medulla, tonsils and blood.

• Recognize a nonpeptide-binding portion of MHC Class II molecules.

• Hence CD4 T cells are restricted to the recognition of pMHC Class II complexes.

HELPER ( CD4+ ) T CELLS

• These cells are also known as CD4+ T cells because they express the CD4 protein on their surface.

• Helper T cells become activated when they are presented with peptide antigens by MHC class II molecules that are expressed on the surface of Antigen Presenting Cells (APCs).

• Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or assist in the active immune response.

• These cells can differentiate into one of several subtypes, including TH1, TH2, TH3, TH17, or TFH which secrete different cytokines to facilitate a different type of immune response.

• The mechanism by which T cells are directed into a particular subtype is poorly understood, though signaling patterns from the APC are thought to play an important role.

HELPER ( CD4+ ) T CELLS

• Involved in the induction and regulation of immune response. They perform the following helper functions:

i. They help B cells to be transformed to plasma cells.

ii. CD8 T cells to become activated cytotoxic T cells, and

iii. Macrophages to mediate delayed type Hypersensitivity reactions.

• Main functions:

1. Help in the antigen specific activation of B cells and effector T cells.

2. Th-1 cytokines activates cytotoxic inflammatory and delayed hypersensitivity reactions.

3. Th-2 cells help in the production of interleukins which encourage production of antibodies especially IgE.

4. Th-2 cytokines are associated with regulation of strong antibody and allergic response.

CYTOTOXIC (CD8+ ) T CELLS

• Account for approximately one-third of all mature CD3+ cells.

• Found mainly in the bone marrow and gut lymphoid tissue.

• Recognize a nonpeptide-binding portion of MHC Class I molecules (which is present on the surface of nearly every cells of the body).

• Hence, CD8 T cells, also known as cytotoxic T cells are restricted to the recognition of pMHCClass I complexes.

FUNCTIONS OF CD8 T-CELLS

• They kill: Virus-infected cells, Allograft cells, Tumor cells.

• T-cell mediated cytotoxicity is an apoptotic process that appears to be mediated by two separate pathways:

i. Involving the release of proteins known as Perforins, which insert themselves into the target cell membranes forming channels. These channels allow the diffusion of enzymes (granzymes) into the cytoplasm. Granzyme-induced apoptosis is calcium dependant.

ii. Signal delivery by cytotoxic cells to the target cells which require cell-to-cell contact. This pathway is calcium independent.

Difference between helper T cells (CD4) and cytotoxic T (CD8) cells

Helper T cells Cytotoxic T cells

Carries CD4 marker Carries CD8 cells

Helps or induce immune response. Predominantly cytotoxic

Recognizes antigens in

association with class II MHC

Recognize antigens in association

with class I MHC

APCs are activated to kill

intracellular microorganisms by

secreting cytokines.

Destroy virus-infected and tumor

cells directly

MEMORY T CELLSi. Memory cells live for many years or have the capacity to

reproduce them.

ii. A large number of memory cells are produced, and so secondary response is enhanced and is greater than the primary response (‘memory against past infection’).

iii. They are activated by small quantities of antigens and require less co-stimulation than do the naïve and unactivated T cells.

iv. Activated memory cells produce greater amounts of interleukins than do naïve T cells when they are first activated.

• Comprise two subtypes: Central memory T cells (TCM cells) and Effector memory T cells (TEM cells). Memory cells may be either CD4+ or CD8+.

REGULATORY T-CELLS

• Formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus.

• Two major classes of CD4+ regulatory T cells have been described, including the naturally occurring Treg cells and the adaptive Treg

cells.

• Naturally occurring Treg cells arise in the thymus, whereas the adaptive Treg cells may originate during a normal immune response.

• Naturally occurring Treg cells can be distinguished from other T cells by the presence of an intracellular molecule called FoxP3. Mutations of the FOXP3 gene can prevent regulatory T cell development, causing the fatal autoimmune disease IPEX

NATURAL KILLER T-CELLS

• NKT cells are a special kind of lymphocyte that bridges the adaptive immune system with the innate immune system.

• Unlike conventional T cells that recognize peptide antigen presented by major histocompatibility complex (MHC) molecules, NKT cells recognize glycolipid antigen presented by a molecule called CD1d.

• Once activated, these cells can perform functions ascribed to both TH and TC cells (i.e., cytokine production and release of cytolytic/cell killing molecules).

• They are also able to recognize and eliminate some tumor cells and cells infected with herpes viruses.

gd T-CELLS• Gamma delta T cells represent a small subset of T cells that

possess a distinct T cell receptor (TCR) on their surface. • A majority of T cells have a TCR composed of two glycoprotein

chains called α- and β- TCR chains. • However, in gd T cells, the TCR is made up of one g-chain and

one d-chain. • This group of T cells is much less common (2% of total T cells)

than the αβ T cells, but are found at their highest abundance in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes (IELs).

• The antigenic molecules that activate gd T cells are still widely unknown.

• However, gd T cells are not MHC restricted and seem to be able to recognize whole proteins rather than requiring peptides to be presented by MHC molecules on antigen presenting cells.

T-CELL RECEPTOR / TCR• Consists of two polypeptides: alpha and beta, and they are

associated with CD3 proteins.

• Each T cell has a unique TCR on its surface, thereby implying that hundreds and millions of different T cell occur in each person.

• T cell alpha and beta polypeptides show many similarities to immunoglobulin heavy chain in following ways:

i. There are V (variable), D (diversity), J (joining), and C (constant) segments that rearrange to provide diversity, thereby resulting in more than 107 different receptor proteins.

ii. RAG-1 and RAG-2 are the two genes that encode the recombinase enzymes that catalyze these gene rearrangements and are similar in T and B cells.

T-CELL RECEPTOR / TCR

• However differ to immunoglobulins by

i. Having two chains rather than having four in immunoglobulins and

ii. Recognizing antigens only in conjunction with MHC proteins, whereas immunoglobulins can recognize free antigens.

EFFECTOR FUNCTIONS OF T CELLS

• Cytotoxicity.

• Cytotoxicity of virus-infected cells:

a. By inserting perforins and granzymes.

b. By the Fas-Fas ligand (FasL) interaction

c. By Antibody Dependant Cellular Cytotoxicity (ADCC).

• Role in graft (allograft) rejection.

• Delayed Hypersensitivity.

REGULATORY FUNCTIONS OF T CELLS

• Regulation of antibody production.

• Stimulation of Helper and Cytotoxic T cells to participate in the Cell Mediated Immunity.

• Suppression of certain immune response by Suppressor T cells.

B-CELLS

• Pro B cells produced from foetal liver during embryonic life.

• Afterwards bone marrow throughout life.

• Nearly 30% of circulating small lymphocytes.

• Short life span of days or weeks.

• Nearly 109 B cell produced daily.

• These are found in the germinal centers of lymph nodes, in the white pulp of spleen, and in the MALT.

B-CELLS

• Play a large role in the humoral immune response.

• THE PRINCIPAL FUNCTIONS OF B CELLS:

• Differentiate into plasma cells and produce antibodies against antigens.

• Perform the role of antigen-presenting cells to Helper T cells, and

• Eventually develop into memory B cells after activation by antigen interaction.

• B cells are an essential component of the adaptive immune system.

• The abbreviation "B", in B cell, comes from the bursa of Fabricius in birds. In mammals, immature B cells are formed in the bone marrow, which is used as a acronym for the cells' name.

• Express immunoglobulins and class II MHC molecules on their surface.

ORIGIN OF B CELLS

• B cell precursor during embryogenesis develop in the foetalliver, bone marrow (main site for maturation in adults)

• After reaching the IgM+ immature stage in the bone marrow, these immature B cells migrate to the spleen, where they are called transitional B cells, and some of these cells differentiate into mature B lymphocytes.

• They do not require thymus for maturation.

• B cells mature in two phases:

• i. The antigen independent phase that consists of stem cells and pre-B cells and

• ii. The antigen dependant phase that consists of activated B cells and plasma cells.

B-CELLS

• B cell development occurs through several stages, each stage representing a change in the genome content at the antibody loci.

• An antibody is composed of two identical light (L) and two identical heavy (H) chains, and the genes specifying them are found in the 'V' (Variable) region and the 'C' (Constant) region.

• In the heavy-chain 'V' region there are three segments; V, D and J, which recombine randomly, in a process called VDJ recombination, to produce a unique variable domain in the immunoglobulin of each individual B cell.

• Similar rearrangements occur for light-chain 'V' region except there are only two segments involved; V and J.

Stage Heavy chain Light chain IgIL-7

receptor

CD

19

Progenitor (or

pre-pro) B cellsgermline germline - No No

Early Pro (or pre-

pre)-B cells

undergoes D-J

rearrangementgermline - No No

Late Pro (or pre-

pre)-B cells

undergoes V-DJ

rearrangementgermline - No Yes

Large Pre-B cells is VDJ rearranged germlineIgM in

cytoplasmYes Yes

Small Pre-B cells is VDJ rearrangedundergoes V-J

rearrangement

IgM in

cytoplasmYes Yes

Immature B cells is VDJ rearranged VJ rearrangedIgM on

surfaceYes Yes

Mature B cells is VDJ rearranged VJ rearrangedIgM and IgD

on surfaceYes Yes

The list above describes the process of immunoglobulin formation

at the different stages of B cell development.

B-CELLS

• Mature B cells are distinguished from other lymphocytes by the synthesis and display of membrane bound immunoglobulin (antibody) molecules.

• Each of the approximately 1.5 X 105 molecules of antibody on the membrane of a single B cell has an identical binding site for antigen.

• B cell has surface IgM which acts as a receptor of antigens.

• Some B cells also carry surface IgD as receptor for antigens.

• Many other molecules expressed on the surface are B220, Class II MHC molecules, CR1 and CR2, CD40 etc.

Mechanism of Action

• A critical difference between B cells and T cells is how each lymphocyte recognizes its antigen.

• B cells recognize their cognate antigen in its native form.

• They recognize free (soluble) antigen in the blood or lymph using their BCR or membrane bound-immunoglobulin.

• In contrast, T cells recognize their cognate antigen in a processed form, as a peptide fragment presented by an antigen presenting cell's MHC molecule to the T cell receptor. T cell-dependent B cell activation, showing

a TH2-cell (left), B cell (right), and several interaction molecules

ACTIVATION

• Cooperation of cells in the immune response

• Antigen-presenting cells (e.g. dendritic cells) present processed antigen to virgin T cells, thereby priming them.

• B cells also process the antigen and present it to the T cells. They then receive signals from the T cells that cause them to divide and differentiate.

• Some B cells form antibody-forming cells while a few form B memory cells.

EFFECTOR FUNCTIONS OF B CELLS

• Production of plasma cells is the end result of activation of B cells.

• The plasma cells in turn produce large amounts of immunoglobulins specific for the antigen.

• Some activated B cells also produce Memory cells, most memory B cells have surface IgG that acts as the antigen receptor, but some have surface IgM.

• Memory T cells produce interleukins that facilitate antibody production by the memory B cells. The presence of these cells is responsible for the rapid appearance of antibody in the secondary immune response.

PLASMA CELLS

• Originate from terminally differentiated B cells.

• Oval or egg-shaped structure characterized by a stellate nucleus, non-staining Golgi and basophilic cytoplasm.

• Found in the bone marrow and perimucosal lymphoid tissue.

• Short life span of 30 days.

• Function: Produce and secrete all the classes of immunoglobulins into the fluids around the cells.

• Secreting thousands of antibodies per second, which are specific to the antigen.

NATURAL KILLER CELLS

• Large granular lymphocytes.• 5-10% of peripheral lymphocytes and are found in spleen and

peripheral blood.• Lack T cell receptor, CD3 proteins, and surface IgM and IgD,

but possess killer activation receptors and killer inhibition receptors.

• Thymus not required for development.• Does not carry antigen receptors of any kind, but can

recognize antibody molecules and destroy target cells using the same mechanism as T cell cytotoxicity (ADCC).

• The IL-12 and gamma interferons are potent activators of NK cells

• Number remains normal in severe combined immunodeficiency, in which mature T cell and B cells are absent.

Functions of NK cells

i. Kill virus infected cells and tumor cells.

ii. Non-specific killing of virus infected cells and tumor cells.

iii.Killing is independent of antigen presentation by MHC proteins.

iv.Mechanism of killing is by perforins and granzymes.

v. Killing is activated by failure of a cell to present antigen with class I MHC proteins on the cell surface.

RETICULOENDOTHELIAL SYSTEM

RETICULOENDOTHELIAL SYSTEM

• The aggregate of the phagocytic cells, including certain cells of the bone marrow, lymphatic system, liver, and spleen, that have reticular and endothelial characteristics and function in the immune system's defense against foreign bodies.

• Collection of cells united by the common property of phagocytosis.• Phagocytosis is part of the natural, or innate, immune process, and

is not an adaptive immune process.• Phagocytosis in man is carried out primarily by three groups of

cells:A. mononuclear phagocytesB. neutrophilsC. eosinophils (to a minor extent)

• The term MONONUCLEAR PHAGOCYTIC SYSTEM has been suggested to replace the Reticuloendothelial System, since it is the mononuclear phagocytes that play the major role in the phagocytosis of foreign material.

PHAGOCYTIC CELLS

Include macrophages and dendritic cells

MACROPHAGES

• The mononuclear phagocytic system consists of monocytes circulating in the blood and macrophages in the tissue.

• Differentiation of a monocyte to a tissue macrophage involves a number of changes as follows

• i. Cell enlarges five to ten fold.

• ii. Intracellular organelles increase in number and complexity.

• iii. It acquires increased phagocytic abilities.

• iv. Produces higher level of hydrolytic enzymes.

• v. Begins to secrete a variety of soluble factors.

• Interferon gamma is a potent activator of macrophages.

MACROPHAGES

• Macrophages are named according to tissue location to

• (a). Alveolar macrophages in the lungs

• (b). Histiocytes in connective tissues

• (c). Kupffer cells in the liver

• (d). Mesangial cells in the kidneys

• (e). Microglial cells in the brains, and

• (f). Osteoclasts in the bones.

IMPORTANT FEATURES OF MACROPHAGES

FEATURES MECHANISMS

Phagocytosis Ingestion and killing of

microbes in

phagolysosomes.

Antimicrobial and cytotoxic

activities

Oxygen dependent killings:

by superoxides, NO, H2O2

Oxygen independent killings:

by TNF, lysozymes,

hydrolytic enzymes.

Antigen processing Phagocytic antigen

DENDRITIC CELLS• Dendritic cells named because of their many long, narrow processes

that resemble neuronal dendrites, which make them very efficient in making contacts with foreign materials.

• Primarily present in the skin (e.g., Langerhans cells) and the mucosa.

• Four types are known:

• 1. Langerhans cells

• 2. Interstitial dendritic cells

• 3. Myeloid cells, and

• 4.Lymphoid dendritic cells.

• Features:

• important for presentation of the antigens to T cells during primary immune response. They are bone marrow derived cells that express class II MHC proteins and present antigens to CD4 T cells.

• little or no phagocytic activity.