Chapter 2

Cells and Organs of the Immune System

Dr. Capers

Kuby IMMUNOLOGYSixth Edition

Chapter 2:Cells and Organs

of the Immune System

Copyright © 2007 by W. H. Freeman and Company

Kindt • Goldsby • Osborne

Hematopoiesis

All blood cells arise from Hematopoietic Stem Cells (HSC)Study of these cells is difficult

○ Scarce○ Difficult to grow in vitro

Hematopoiesis

Early in hematopoiesis, stem cell differentiates to either

○ Lymphoid progenitor cell○ Myeloid progenitor cell

- Progenitor cells have lost ability for self renewal and are committed to particular cell lineage

Organized hierarchyMost of proliferation

takes place in differentiated precursors (that are NOT self-renewing) rather than hematopoietic stem cell

Lowers chance of cancer

Hematopoiesis

Regulated at gene level○ Transcription factors play important roles in

hematopoiesis○ Studies using “knockout” mice

- Gene inactivated, if RBC or a particular WBC fails to develop, it is concluded that protein was involved in development of that cell

Hematopoietic Homeostasis Erythrocyte

○ Average life span: 120 days○ Phagocytosed by macrophages in spleen

WBC - LEUKOCYTES○ Life spans from 1 day to 20-30 years

Apoptosis – programmed cell death

Normal WBC WBC going through apoptosis

Cells of the Immune System Lymphocytes

○ 20-40% of WBC○ 3 populations

- B cells- T cells- Natural Killer Cells

Lymphocytes

B cells and T cellsAdaptive immunitySmall lymphocytesThose that have not interacted with antigen

are called naïveInteraction with antigen – proliferation into

effector cells (i.e. plasma cells) and memory cells

Lymphocytes

B and T cells

Lymphocytes B Lymphocytes (B cells)

Site of maturation○ Bursa of fabriscus in birds○ Bone marrow in mammals

Display membrane-bound immunoglobulin (antibody)

Once antigen is encountered:Differentiation

- Plasma cells – antibody can be secreted, die within 1-2 weeks

- Memory B cells – same membrane-bound antibody as parent B cell, longer life span

Lymphocytes T Lymphocytes (T cells)

Site of maturation○ Thymus

T cell receptor○ Only recognize antigen that is bound to cell membrane

proteins called major histocompatibility complex (MHC)○ Once antigen in encountered with MHC:

Differentiation- Effector T cells- Memory T cells

2 subpopulations T helper (TH) T cytotoxic (TC) And now T regulatory (Treg)

Lymphocytes

T helper cells○ CD4 glycoprotein

○ “help” activation of B cells, TC cells, macrophages in immune response

Lymphocytes

T cytotoxic cellsCD8 glycoproteinRecognition of MHC-antigen complex

initiates differentiation into effector cell called cytotoxic T lymphocyte

Eliminates infected cells or cancerous cells

Lymphocytes

T regulatory cellsCD4 and CD25 glycoproteinsHelp suppress the immune system

Lymphocytes

Natural Killer CellsInnate immune responseLarge, granularRecognize tumor or virus-infected cellsCD16 – which can recognize a region of

antibody that has attached to cell infected by virus

Other Leukocytes Mononuclear phagocytes

Monocytes circulate in blood and then migrate into tissue and differentiate into specific macrophage

Macrophages Intestinal macrophages in gut Alveolar macrophages in lung Histiocytes in connective tissue Kupffer cells in the liver Mesangial cells in the kidney Microglial cells in the brain Osteoclasts in bone

Activated macrophages are more effective than resting ones

Other Leukocytes Mononuclear phagocytes

○ Complex antigens are phagocytized, the resulting phagosome fuses with a lysosome

○ The digested antigen is then eliminated through exocytosis

- Some of it is presented on membrane on MHC

○ Phagocytosis is enhanced when antibody is attached to the antigen

- Antibody acts as opsonin: molecule that binds to both antigen and phagocyte

Macrophage and bacteria

Other Leukocytes

Granulocytes○ Neutrophils○ Eosinophils○ Basophils

Other Leukocytes

Granulocytes – NeutrophilsMulti-lobed nucleus, light granules1st to arrive at site of inflammationHigh #’s is 1st indication of infectionPhagocytizeGenerate antimicrobial agents

Other Leukocytes

Granulocytes – EosinophilsPhagocytizePlay a role in parasitic organisms

Other Leukocytes

Granulocytes – BasophilsNonphagocyticPlay a role in allergic reactions

Other Leukocytes

Mast cellsPlay important role in development of

allergies

Other Leukocytes Dendritic cells

Long membranous extensions, look like dendrites on nerve cells

Antigen presentation4 major groups:

Langerhans DCInterstitial DCMonocyte-derived DCPlasmacytoid-derived DC

Follicular dendritic cellsInvolved with B cell maturation

Organs of the Immune System Primary

○ Thymus and bone marrow○ Place of maturation of lymphocytes

Secondary○ Lymph nodes, spleen, mucosa-associated

lymphoid tissues such as gut-associated lymphoid tissues

○ Mature lymphocytes interact with antigen

Primary Lymphoid Organs Bone marrow

Lymphocytes arise there, T cells go to thymus to mature

B cells mature here90% of plasma IgG and IgA comes from B

cells in the bone marrow

Primary Lymphoid Organs Thymus

○ T cell development and maturation○ Bilobed organ above heart

- Surrounded by capsule and divided into lobules- Outer part of lobule is cortex, inner is medulla- Network of epithelial cells, dendritic cells, and

macrophages

○ Thymus will induce death of those T cells that can’t:

- Recognize self-MHC molecules- Those that interact with MHC molecules too strongly

(could produce autoimmune disorder)

○ Function decreases with age

Lymphatic System Interstitial fluid (the portion that doesn’t

enter venous system) is returned to circulatory system by lymphatic vessels

Largest lymphatic vessel – thoracic duct○ Enters left subclavian vein○ Lymph from right arm and right side of head enters

through right lymphatic duct, drains into right subclavian

Antigen is carried by lymph to lymph nodes

Secondary Lymphoid Organs Primary follicle

Unactivated lymphoid follicle

Secondary follicleFollicle that is

activated by antigenRing of B cells that

surround germinal center

Proliferating B cells and T helper cells

Secondary Lymphoid Organs Lymph Nodes

Encapsulated3 regions:

○ CortexB cells, macrophages, dendritic cellsPrimary follicles

○ ParacortexT cells, dendritic cells

○ MedullaPlasma cells secreting antibody

Secondary Lymphoid Organs Spleen

Filters blood, traps blood-bourne antigens○ Important in systemic infections

Blood enters through splenic arteryEncapsulatedStructure:

○ Projections from capsule form trabeculae○ Compartments:

Red pulp- Macrophages, red blood cells

White pulp- Surrounds branches of splenic artery- Forms PALS (periarteriolar lymphoid sheath)- Primary follicles rich in B cells

Secondary Lymphoid Organs Mucosa-Associated Lymphoid Tissue

MALTOrganized areas along digestive,

respiratory, and urogenital tractsVery well organized areas in intestine are referred to

as Peyer’s patchesIncludes tonsils and appendix