cell and organs of the immune system

8/13/2019 Cell and Organs of the Immune System

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Lymphoid Organs


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Hematopoiesis the formation of red and white blood cells

Occurs via pluripotent hematopoietic stem cells (HSCs)

Self renewing

Yolk sac --> Liver --> Spleen -- (adulthood) --> Bone

Marrow (BM) Present at low concentrations in BM (less than 1-in-

5x104)

High proliferative capacity

HSCs differentiate towards a myeloidor lymphoid

lineage

Stem cells differentiate into committed progenitor cells

(which do not self-renew)


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Fig. 2-1

Generation

of Leukocytes,

Platelets and

Erythrocytes

from HSCs


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Growth and Death of HSCs

In the BM, HSCs require stromal cells

(stroma) to growGrowth of HSCs is dependent on

hematopoietic growth factors and cytokines

IL-3 M-CSF, G-CSF, GM-CSF

Erythropoietin (EPO)

Differentiation is regulated by hematopoiesisgenes

Cell number is limited by programmed cell

death (apoptosis)


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Primary Lymphoid Organs - sites

of lymphocyte maturation; include

the BM and thymus

Secondary Lymphoid Organs -

sites where antigen is trapped,

and brought into contact with

lymphocytes (differentiation)

Lymphatic System network of

vessels which collect fluidcomponent of blood after it has

drained to tissues; collects

antigen from tissues and brings it

to secondary lymphoid organs


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Thymus Bi-lobed organ sits

above the heart Site of maturationand selection of Tcells

Thymocytes which

cannot recognizeself MHC proteins,or which bind selfantigen, are deletedby apoptosis

Medulla containsmature T cells

Cortex containsmainly of immaturecells

Atrophies with age(thymic involution)


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Thymus

T Cell Development and Thymic Maturation

Thymocyte

TCR

TCR

CD4

TCR

CD8

Approximately 90 - 95% of all thymocytes

die in the thymus!!!

TCR

CD4

CD4

T Cell(Helper T Cell)

TCR

CD8

CD8

T Cell

(Cytotoxic(killer)

T Cell)


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Bone Marrow

Site of generation,maturation and

selection of B cells B cells interact directly

with stromal cellsduring selection

Mature, immunocom-petent B cells exit BMand migrate tosecondary lymphoidorgans (only ~ 10%)

Site of generation of Tprogenitor cells


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Secondary Lymphoid Organs Consist of lymph nodes (LN), spleen, and

mucosal-associated lymphoid tissue (MALT) whichinclude tonsils, Peyers patches and appendix

Antigen in tissues is transported by lymphaticsystem to secondary lymphoid organs where it istrapped

Newly-developed, immunocompetent lymphocytes(T and B) migrate to secondary lymphoid organswhere they interact with antigen, becomeactivated, differentiate and mutate, divide and

multiply


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Lymph Node

Spleen


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SpleenLargest secondary lymphoid organ

Major organ in the body in which antibodiesare synthesized and from which they arereleased into the circulation

Function: filters blood and traps blood-borne antigens; can respond to systemicinfection

Consists of white and red pulp

50% of cells are B cells, 30 40% are T cellsand the remaining population are plasma

cells and macrophages


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Lymph Nodes located along lymphatic ducts and serve as central

collecting joints for lymph fluid from adjacenttissues

main function is filtration; ideal site forphagocytosis

Medulla consist mainly of plasma cells while thecortex contains T cells and macrophages

where the blast transformation of B cells take place(germinal center)

plasma cells, memory cells are also present in thegerminal center

its primary function is the generation of B cellmemory

contains immobile B lymphocytes

Oth L h id Ti


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Other Lymphoid Tissues Includes GUT-associated lymphoid

tissues and MALT

At MALT macrophages and lymphocytesare localized at some of the main portalsof entry for foreign organisms

Peyers patches specialized type ofMALT, located at the lower ileum ofthe intestinal tract

Oth L h id Ti


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Other Lymphoid Tissues Tonsils small masses of

lymphoid tissue found in themucous membrane lining of theoral and pharyngeal cavities

Appendix also consideredMALT


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Lymphoid Cells

Approximately 1011 lymphocytes in thehuman body

Three main types of lymphocytes:

B Cells

T Cells

Null Cells (Large granular lymphocytes (LGLs)

or Natural Killer (NK) Cells)Transition through cell cycle from small

lymphocytes (nave) --> lymphoblasts -->

effector cells or memory cells


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Fig. 2-7


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Clonal Selection of B Cells is Caused by Antigenic Stimulation


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Humoral Response to T Dependent Antigens


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B Lymphocytes

Distinguishing cell-surface markers include:

B220 (CD45), MHC Class II, CD80 (B7-1) and

CD86 (B7-2), CD40, CD19, CD21, etc.

Bursa of

fabricius

First identified in the Bursa of Fabricius in

birds

In humans, B cells develop in the Bone

Marrow

Can be divided into memoryandplasma B

cells

Primary effectors of humoral immunity, viaantibody production

Recognize antigen by means of surface-expressed antigen receptor


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T Lymphocytes

Distinguishing cell-surface markers include TCR,

CD3, CD2, CD4 or CD8, CD28, and CD45

T cells derive from stem cells in the bone marrow,

mature in the thymus, and then are released into the

periphery

Similarities between T and B cells: Antigen receptor on surface (T cell receptor or TCR)

Recognize single, specific antigen

Expand through clonal selection

Some T cells exist as long-lived memory cells

Primary effectors of cellular immunity

Can be divided (broadly) into helperT cells (Th) and

cytotoxicT cells (Tc), usually found in a 2:1 ratio

70% T cells (5 10% B cells and 10 15% are nulls cells)


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T lymphocytes have the ability to bind sheep erythrocytes, the

clumps of cells formed are called E-rosettes (E+ cells) progenitor T cells appear in fetus as early as 8 weeks

of gestation

surface characteristics:

ability to bind to certain lectins ability to interact with the measles virus

exhibit receptors for FC portion of IgM and IgG


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Antigen Processing and PresentationUnlike B cells, T cells cannot recognize free antigen; it must be:

Presented on the surface of APCs in the context of MHC (major

histocompatibility complex) proteins

Processed (digested) in to smaller fragments within special

antigen presenting cells (APCs)

APCMHC

+

Ag

TCR

APC

T Cell

APC


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Table 2-4CD - Cluster of Differentiation


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T cell subsetsActivator T cells (Ta)

amplify killer to cell differentiation Helper T cell (Th)

helps the B cell to produce antibody in response toantigen

activation of B cell and their differentiation intoantibody-secreting plasma cells

Suppressor T cells (Ts) inhibits initiation or expression of the response of T and

B cells to antigen

Cytotoxic T cells (Tc) or killer cells causes death of the cell and destroy the inciting antigen

against which they specifically sensitized

Delayed type of hypersensitivity (Td or Tdth) res onsible for dela ed t e of h ersensitivit reaction


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Helper T CellsHelper T cells (CD4 T cells) produce proteins(cytokines) which act on B cells, stimulating them to

produce antibodies


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T Helper (TH) Cells: Central role in

immune response. Most are CD4+

Recognize antigen on the surface of

antigen presenting cells (e.g.:macrophage).

Activate macrophages

Induce formation of cytotoxic T cells Stimulate B cells to produce

antibodies.


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Central Role of Helper T Cells


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Cytotoxic (Killer) T Cells

Cytotoxic T cells (CD8 T cells) attack theirtarget cells (e.g. virally-infected cells) and kill

them directly..


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Cytotoxic (Killer) T Cells


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Cytotoxic T (Tc) Cells: Destroy target cells.

Most are CD4 negative (CD4 -).

Recognize antigens on the surface of all cells:

Kill host cells that are infected with virusesor bacteria.

Recognize and kill cancer cells. Recognize and destroy transplanted tissue.

Release protein calledperforinwhich formsa pore in target cell, causing lysis of infected

cells. Undergo apoptosiswhen stimulating antigen

is gone.


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Cytotoxic T Cells Lyse Infected Cells


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Null Cells

Referred to as Null cells because they are

lymphocytes, but lack typical B cell or T cell markers ontheir surface

Also known as large granular lymphocytes (LGLs) ornatural killer(NK) cells

Demonstrate cytotoxicity against tumor cells and somevirus-infected cells

most effect as killer cells in antibody-independentCytotoxic reactions

Not specific. Dont require antigen stimulation.

Not phagocytic, but must contact cell in order to lyse it.

NK1-T cell - Recently identified subset displaying someT cell markers (e.g. TCR), functions


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Other Cells

Plasma cells (Plasmocyte) known as mature antibody-producing cells contain large includsion bodies called Russelbodies

derived from B lymphocytes

Monocytes (peripheral blood)/Macrophage(tissues)

formed in bone marrow, spleen and tissues ofRES function in amoeboid movement and

phagocytosis (immune response)


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GranulocytesNeutrophils important in the bodys defense(phagocytosis & destruction of microorganisms)

process facilitated by complement and antibody

Basophils and Mast cells contain heparin important in immediate hypersensitivity

reactions

found in large numbers in some cell.-mediateddelayed reactions: skin graft or tumor reject,hypersensitivity


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GranulocytesEosinophils has a specialized role in immunity to helminth

infections found in tissues at sites of immune response or

reaction that have been triggered by IgEantibodies

activated when antigen triggers IgE coated mastcells to release an eosinophil chemotactic factorof anaphylaxis

attracted to antigen-antibody complex and can

phagocytize them contain a number of enzymes that can degrade

mediators of immediate hypersensitivity Histamine slow reacting substance of anaphylaxis

PAF (Platelet Aggregating Factor) control ordiminish such hypersensitivity


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Mast Cells

Found in a wide variety of tissues,including:

skin

connective tissues mucosal epithelial tissues of the respiratory,

genitourinary and digestive tracts

Heavily granulated

Granules contain histamine; degranulation

of mast cells results in histamine release,

allergic/inflammatory response

Generation


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Fig. 2-1

Generation

of Leukocytes,

Platelets and

Erythrocytes

from HSCs


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Mononuclear Cells Consist of monocytes (in blood) and

macrophages (in tissues)

Macrophages (ms) are larger,more complex, and produce morehydrolytic enzymes

There are multiple types ofmacrophages, defined by location:

Alveolar macrophages (lungs) Histiocytes (connective tissues)

Kupffer cells (liver)

Mesangial cells (kidney)

Microglial cells (brain)

Osteoclasts (bone)

Splenic macrophages (spleen) Peritoneal macrophages (peritoneal

fluid)

Dendritic cells (lymph nodes)

Langerhans cells (dendritic cells in theskin)


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Functions of Macrophages

Phagocytosis Chemotaxis

Formation ofpseudopodia

Opsonization (by antibody)

Antimicrobial and cytotoxic

activities Antigen processing and

presentation

Protein secretion

Interleukin 1 (IL-1)

IL-6

Complement proteins

TNF-a


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Dendritic Cells

Lineage/origin is not

entirely understood Express high levels of

MHC class II and B7

molecules, making them

extremely potent APCs

Multiple different types,

based on location (similar

to m) Langerhans cells found in

skin and mucous

membranes

cell and organs of the immune system

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