Cells And Organs Of Is Lec 2

CELLS AND ORGANS OF THE IMMUNE SYSTEM M.KANNAN M.Sc., M.Phil., Ph.D., DEPARTMENT OF MICROBIOLOGY V.H.N.S.N.COLLEGE, VIRUDHUNAGAR

FUNCTIONS OF THE IMMUNE SYSTEM  Defense against infections  Recognition and protective response to newly introduced substances such as proteins and to tissue grafts  Defense against tumors  Preservation of genetic integrity of the individual

TWO TYPES OF IMMUNITY Nonspecific (innate) •Physical and chemical agents •Lysozyme •Acute phase proteins •Complement system •Cytokines (chemokines) •Phagocytes (granulocytes, macrophages) •Natural killer (NK) cells •Dendritic cells •Pattern recognition receptors (PRR)

Specific (adaptive) •Antibodies (B lymphocytes) •T lymphocytes

Major differences between innate and acquired immunity (acc. to U. Koedel & W Pfister 2005) Innate immune system

Acquired immune system

• Immediate maximal response • No immunological memory • Not antigen specific • Receptors: germ line encoded, • In almost all multicellular organisms, • Recognition of conserved molecular patterns, • Perfect self/non-self discrimination • Only hundreds of different

• Lag time (3-4 days) between exposure and max. response • Immunological memory • Antigen specific • Receptors: generated somatically, • Only in vertebrates, • Recognition of details of molecular structure, • Imperfect self/non-self discrimination, • Over 100 000 000 000

THE IMMUNE SYSTEM

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Hematopoiesis

Cells of the immune system Hematopoiesi s

• All blood cells arise from a type of cell called the hematopoiesis stem cell(HSC). • Stem cells are cells that can differentiate into other cell types, they are selfrenewing- they maintain their population level by cell division. • In humans, hematopoiesis, the formation abnd development of red blood cells, begins in the embryonic yolk sac during 7 the first weeks of development.

Hematopoie sis

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Regulation of Hematopoiesis • Hematopoiesis is a continuous process that generally maintains a steady state in which the production of mature blood cells equals their loss (principally from aging). • The average erythrocyte has a life span of 120 days before it is phagocytosed abd digested by macrophages in the spleen. 9

Programmed cell death • Cells undergoing programmed cell death often exhibit distinctive morphologic changes, collectively referred to as apoptosis. • These changes include a pronounced decrease in cell volume, modification of the cytoskelton to result in membrane blebbing, a condensation of the chromatin and degradation of the DNA into smaller fragments. 10

Apoptosi s

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Lymphoid cells • Lymphocytes constitute 20% - 40% of the body’s white blood cells and 99% of the cells in the lymph. • There are approxiamately 1011 (range depending on body size and age: ~1010 – 1012) lymphocytes in the human body. • The lymphocytes can be broadly subdivided into three populations-Bcells, T-cells and null cells-on the basis of function and cell membrane 12

Lymphocytes • Produce antibodies • B-cells mature in bone marrow then concentrate in lymph nodes and spleen • T-cells mature in thymus • B and T cells mature then circulate in the blood and lymph • Circulation ensures they come into contact with pathogens and each other

B -Lymphocytes • There are c.10 million different Blymphocytes, each of which make a different antibody. • The huge variety is caused by genes coding for abs changing slightly during development. • There are a small group of clones of each type of B-lymphocyte

B -Lymphocytes • At the clone stage antibodies do not leave the B-cells. • The abs are embedded in the plasma membrane of the cell and are called antibody receptors. • When the receptors in the membrane recognise and antigen on the surface of the pathogen the B-cell divides rapidly. • The antigens are presented to the B-cells by macrophages

B -Lymphocytes

B -Lymphocytes • Some activated B cells  PLASMA CELLS these produce lots of antibodies, < 1000/sec • The antibodies travel to the blood, lymph, lining of gut and lungs. • The number of plasma cells goes down after a few weeks • Antibodies stay in the blood longer but eventually their numbers go down too.

B -Lymphocytes • Some activated B cells  MEMORY CELLS. • Memory cells divide rapidly as soon as the antigen is reintroduced. • There are many more memory cells than there were clone cells. • When the pathogen/infection infects again it is destroyed before any symptoms show.

Null Cells • Do Not Express Classical Lymphocyte Markers • Predominantly NK Cells (CD56) • Eliminate Tumor Cells and Virally Infected Cells • Using CD16 They Can Carry Out ADCC

Mononuclear Cells Cells Mononuclear • Monocytes in Blood, MØ in Tissues – Monocytes 5-10 times smaller than MØ

• MØ Increases Phagocytic Ability • Secretes cytokines and Produces Hydrolytic Enzymes • Named Based on Tissue They Reside – Alveolar (lungs), Kupffer (liver), Microglial (brain), Osteoclasts (bone)

• Activated By Phagocytosis or Cytokines (IFNα) • Antigen Presenting Capacity Thru MHC II

Macrophages • Larger than neutrophils. • Found in the organs, not the blood. • Made in bone marrow as monocytes, called macrophages once they reach organs. • Long lived • Initiate immune responses as they display antigens from the pathogens to the lymphocytes.

Macrophages

Monocyte vs MØ

MØ Effective APC

MØ Capturing Bacteria

Dendritic Cells • Professional APCs • Several Types – Langerhans (LC) found in skin – Circuilating DCs • Myeloid (MDC1 and MDC2) • Plasmacytoid

• Interstitial DCs, populate organs such as heart, lungs, liver, intestines • Interdigitating DCs, T-cell areas of lymph nodes and Thymic medulla

Dendritic Cells • Scarce Cell Type • Discovered in 1972 • Early 90s Using GM-CSF/IL4 and Later flt-3 limitation Was Overcome • Intense Area of Research • Seemed Promising for Tumor Treatment • Maybe Better for Tolerance

Dendritic Cells

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Developmental Pathway of DCs

Follicular DCs • Do Not Express MHC II Molecules • Found in Lymph Follicles (Rich in B Cell) • Express FcR For Antibodies and Complement • Ag-Ab Complex Shown To Last Very Long (weeks to months)

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Phagocytosis

Phagocytosis • If cells are under attack they release histamine. • Histamine plus chemicals from pathogens mean neutrophils are attracted to the site of attack. • Pathogens are attached to antibodies and neutrophils have antibody receptors. • Enodcytosis of neutrophil membrane  phagocytic vacuole. • Lysosomes attach to phagocytic vacuole  pathogen digested by proteases

Organs of the immune system • A number of morphologically and functionally diverse organs and tissues have various functions in the development of immune responses. • These can be distinguished by function as the primary and secondary lymphoid organs. • The thymus and bone marrow are the primary(or central) lymphoid organs, where maturation of lymphocytestakes place. 52

• 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, which trap antigen and provide sites for mature lymphocytes to interact with that antigen.

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Organs of the immune system

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Thymus • Structure – Gross • Bi-lobed • Lies above heart

– Microscopic • Capsular • Lobules with outer cortex and inner medulla

Thymus • Function – Takes in immature T cells and puts out mature (immunocompetent) T cells – Increased diversity of T cells – T cell selection

Thymus • T cell selection – Based on MHC/Ag complex recognition • Recognize MHC/Non self AG complexes • Recognize MHC/Self Ag complexes • Do not recognize MHC/Ag complexes

• Athymic condition – Natural – Other

Bone marrow • Structure – Microscopic

• Less well defined than thymus • Role of stromal cells

• Function – – – –

Hematopoiesis B cell maturation B cell selection Puts out mature, naive B cells

Lymph Nodes • Structure – Gross • Bean-shaped structures • Drains major segments of lymphatic system

Lymph Nodes • Structure – Microscopic • Major cell types – Lymphocytes – Macrophages – Dendritic cells

• Cortex/paracortex/medulla • Follicles – Primary – Secondary

Lymph Nodes • Function – 1st line of response to antigens – Secondary follicle (Germinal center) is site of B cell proliferation, mutation, differentiation – Specificity is high – >90% of B cells die through apoptosis – After Ag stimualtion lymphocyte numbers up by 50X in efferent lymphatic vessel – Lympadenopathy

Spleen • Structure – Gross • Ovoid organ in upper left quadrant of abdomen

– Microscopic • Compartmentalized – Red pulp – White pulp

• Periarticualr lymphoid sheath – Site of Ag presentation

• Major cell types – – – –

Lymphocytes Macrophages Dendritic cells RBCs

Spleen • Function – Filters out older RBCs – Responds to Ag in circulatory system – Produces activated B cells

• Splenectomy

Tonsils • Follicular structure • Contains lymphocytes, macrophages, mast cells • Germinal centers appear in response to Ag • Protective role in URI

Appendix

• Associated with intestines • Responds to Ag • Role in GI immune response

MALT • Lymphoid tissues below epithelium • Presence of B cells • Ag presented through unique cell (M cell) • Preferentially responds with IgA antibody