Immuno2 Cells of the Immune System

8/7/2019 Immuno2 Cells of the Immune System

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Clonal Selection Theory

1. T and B cells exist with almost unlimited specificitiesbefore any contact with foreign Ags

2. Ag-specific receptors that recognize foreign Ags:

1. Abs are the B cell receptors on the surface of B cell &

2. T-cell receptor (TCR) on T cell

3. Each lymphocyte has a single specificity

4. The antigenic determinant (epitope) on the Ag binds

with lymphocyte (B or T) and triggers theirdifferentiation and proliferation

5. Negative selectionby self Ags shut off cells thatrecognize them during maturation


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Clonal Selection

Epitopes

2, 103, 821

No specialized

receptor

Epitopes

2, 103, 821


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Harmful Effects of the Immune System Hypersensitivity or allergic reactions:

Type I, immediate hypersensitivity Type II, cytotoxic Ab-mediated reactions

Type III,immune complex Ab-mediated

Type IV, delayed-type cell-mediated

Autoimmune diseases The immune system attacks bodys own Ags causing diseases

like rheumatoid arthritis, diabetes mellitus and systemic lupuserythematosus

Immunodeficiencies

Occur when one or more components of the immune system failto function properly

This can be result of genetic defect (SCID) or acquired (AIDS)

Graft rejection

Occurs because of immune response against transplants Ags


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Genetic Recombination & Immune

Response Diversity 106-107 of antigenic specificities might exist

If 1 gene = 1 response, are 107 genes needed?

No

Genetic recombination within a gene thatencodes the Ig proteins is the answer

So, the basic Ab is composed of 2 types of

polypeptides: H-chain, L-chain and each chainhas a variable domain

This mechanism generates Ab & T cell receptor(TCR) specificity


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Regulation of the immune system

Why regulation? Immune response proliferation and increased

synthesis of specific molecules that will not be

useful after their job is finished (infection

response cure)

Homeostasis or equilibrium must be establishedby shutting down the system

Deregulation of the immune system has severeconsequences

Immune response to self Ags Autoimmunity


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LECOM-Pharmacy School

Immunology 02

Cells, Tissues & Organs of the Immune

SystemDr. Saber Hussein


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Objectives1. B and T lymphocytes and NK cells

2. T cells Subpopulations:Helper, cytotoxic and suppressor3. Antigen presenting cells

4. Phagocytes: Monocytes (macrophages) & granulocytes(eosinophil, neutrophil, basophil & mast cells)

5. granulocyte and platelet role in inflammatory response

6. Primary tissues of the Immune System:

1. Bone marrow &

2. Thymus

7. Secondary tissues:

1. Lymph nodes,

2. spleen,

3. Payers patches


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Cells of the Immune System

Lymphoid Lineage

T helper cells (TH) Cytotoxic T cells (Tc or CTL)

B cells

Natural Killer [NK cells. A type of white blood cell that containsgranules with enzymes that can kill tumor cells or microbial cells.Also called large granular lymphocytes (LGL)]

Myeloid Lineage

Polymorphonuclear granulocytes

Neutrophil

Basophil & Mast cells Eosinophil

Mononuclear phagocytes

Dendritic cells & Macrophages

Megakaryocytic Lineage

Platelets


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Hematopoiesis

Hematopoiesis is the process of blood cell maturationfrom the stem cell to the active, functional blood cell(red or white)

Red blood cells and white blood cells are formed in thebone marrow

Stem cells are totipotent orpluripotent

Totipotency - The ability of a cell, such as an egg, to giverise to unlike cells [differentiate] and thus to develop into orgenerate a new organism or part.

Pluripotency - The potential of a cell to develop into morethan one type of mature cell, depending on environment

Myeloid cells and lymphoid cells are pluripotent cellswith a common ancestor, a totipotent cell


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Hematopoiesis

Myeloid cell Erythrocyte;

Neutrophil,

Monocyte Macrophage;

Eosinophil;

Basophil & Mast cell;

Megakaryocyte Platelet

Lymphoid cell Lymphocytes:

T cell

B cell Plasma cell

NK cell


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Cells involved in the immune responseCells involved in the immune response


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Polymorphonuclear

neutrophil

Subject to chemotacticstimulation by:

Complement fragments (C5a)

Products of platelets & leukocytes Bacterial products

Other protein products offibrinolysis

Lysosomes containi. Primary granules(Azurophilic) contain

Hydrolases

Peroxidases

Lysozyme

ii. Secondary, specific,granules contain:

Lactoferrin

Lysozyme

Primary

granules

Secondary

granules


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Neutrophils Have multilobed nuclei

Their primary function is Phagocytosis

enhanced by opsonization with complement and Abs

Important secondary function

promote inflammation Neutrophils produce

reactive oxygen metabolites

hydrolytic enzymes

nitric oxide and antibiotic proteins such as

defensins

seprocidins

cathelicidins

bacterial permeability inducing protein


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Polymorphonuclear Granulocytes PMNs include

Mainly neutrophils

Eosinophils

Basophil & mast cells

From bone marrow at 7 million/minute

Short lived (2-3 days)

About 60-70% of WBCs

Diapedesis:

PMNs leave the circulation by adhering to the endothelium& squeezing out

It is promoted by chemokines

IL-1

IL-8 (RANTES [Regulated on activation, normal T expressed andsecreted])


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Functions of PMNs Important part in acute inflammation

No specificity for Ags

Cooperate with Abs & complement

Phagocytosis

Polymorph extravasation deficient

individuals and those with low numbersof PMNs increased susiptibility toinfections


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Basophils &

Mast cells

Basophils are in circulation

Have S-shaped nucleus

Are round Mast cells are stationary:

1. Mucosal mast cells (MMC)

2. Connective tissue mast cells

(CTMC)

Granules contents are

called mediators such as:

Heparin,

Histamine

SRS-A (slow-reacting

substance of anaphylaxis)

ECF-A (eosinophil

chemotactic factor A)


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Basophils and

mast cells

Basophils and mast cells arethe least prevalent of theleukocytes

They possess high affinity Fcreceptors for IgE

They release the chemicalmediators of immediatehypersensitivity, including:

Histamine Prostaglandins

Thromboxanes

Leukotrienes

Heparin

They also produce eosinophilchemotactic factor (ECF)

which causes eosinophils toenter the area of worminfestation or allergenlocalization

MC


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Eosinophils

Bilobed nucleus Granules stain with acid

dyes- eosin

Capable of

phagocytosing & killingmicroorganisms

Degranulation: releaseof contents in

surrounding area Can kill parasites with

basicproteins andcationic proteins

Schistosoma mansoni


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Monocytes/Macrophages

Monocytes enter circulation from

bone marrow then migrate intovarious organs and tissues

There they mature into:

macrophages

Kupffer cells (liver)

histiocytes (M* found in connective

tissue)

dendritic cells (lymph nodes, spleen)

glial cells (brain)

Langerhans' cells (skin) Collectively, these cells form a

network known as the

reticuloendothelial system (RES)

or the mononuclear phagocyte

system

M* in the process

of surrounding

tumor cell


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Differential White Blood Cell Count

CELL TYPE % OF WBC'S CELLS/cmm

Neutrophil

Eosinophil

Basophil

Lymphocyte

T cell

B cell

NK cell

Monocyte

50 60

1 4

0.5 220 40

80 - 85*

5 - 15*

5 - 15*

2 - 9

3000 - 7000

50 400

25 1001000 4000

100 - 600

*% of lymphocytes in peripheral blood


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Reticuloendothelial

System

(mononuclear phagocyteSystem)


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Platelets Anucleate Derived from

megakaryocytes

Contain granules at theultrastructural level

Their major functions are

blood clotting

inflammation

Following injury toendothelial cells, plateletsadhere to the surface of the

damaged tissue, where theyrelease substances that increase vascular

permeability,

activate complement and

attract leukocytes

Platelets aggregating

at the site of a wound

in a blood vessel


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NK

Functions of Lymphocytes


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B and T lymphocytes

T cells develop in the thymus

B cells differentiate

in fetal liver &

in postnatal bone marrow

Ag recognition via specific receptors

NK (natural killer) cells do not express Ag receptor

Lymphocytes have high N:C (nucleus : cytoplasm) ratio

LGL (NK; Large granular lymphocytes) have

lower N:C ratio


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T Cells

Majority of T cellsexpress EF-TCR

T-helper cells (TH)

T-cytotoxic cells (Tc) TCR is an

immunoglobulin

Carry Gall body (Gb) in

the cytoplasm Gb: A cluster of lysosomes

+ Lipid droplet

MHC-I

CD4CD8

THCell

TC Cell


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Subpopulations of T cells

KH T

TH

CD4

EFT

TH2

Tc

CD

TH

1

T0


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NK Cell

H

ave LGL morphology Contain larger number of

azurophilic granules than

granular T cells

Have no specific receptorfor Ag recognition

Derived from lymphoid

cell progenitors in the

bone marrow How can you distinguish NK from T &B?

1. No specific receptor

2. NK can lyse certain tumor cell lines

in vitro without prior sensitization


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APCs are heterogenous leucocytes

They present Ags to TH or Tc cells

Ability to digest protein Ags is important

Present primarily in:

Skin

Spleen

Lymph nodes

Antigen presenting cells


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What cells can serve as APC?

1. Langerhans cells (LC)

2. Dendritic cells

1. Interdigitating dendritic cells (IDC)

2. Follicular dendritic cells (FDC)

3. Germinal center dendritic cells (GCDC)

3. B cells

4. Macrophages


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Lymphoid organs

The lymphoid organs are those organs in which maturation,

differentiation and proliferation of lymphocytes take place

The primary, orcentral, lymphoid organs are those in which T and

B lymphocytes begin expressing their antigen receptors

The secondary lymphoid organs are those in which lymphocytes are

induced to proliferate and differentiateby contact with antigen


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Primary lymphoid organs Bone marrow in which B cells develop

Thymus, where T cells develop. Progenitor cells from the bone

marrow migrate to the thymus gland to develop into T cells The thymus is a bilobed structure, whose size reaches its maximum at birth,

then atrophies with age.

The cortex contains mostly immature thymocytes, some of which

mature & migrate to the medulla, where they learn to discriminatebetween self and nonself during fetal development and for a short timeafter birth.

T cells leave the medulla to enter the peripheral blood circulation, throughwhich they are transported

to the secondary

lymphoid organs

DiGeorge syndrome:congenital absence of thymus

results in an immediate and

drastic reduction in T cells

that produces a potentially

lethal wasting disease


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Secondary lymphoid organs

The secondary lymphoid organs have two majorfunctions:

they trap and concentrate foreign substances, and

they are the main sites of production of antibodies andantigen-specific T cells

The major secondary lymphoid organs include the Spleen, which is responsive to blood-borne antigens

Lymph nodes, which protect the body from antigens thatcome from skin or internal surfaces via the lymphatic

system Mucosa-associated lymphoid tissue (MALT) scattered

along mucosal linings, which protects the body fromantigens entering the body directly through mucosalsurfaces


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Spleen

Schematic representation of the spleen and a cross-section

of the periarteriolar lymphoid sheath (PALS)


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Lymph nodes

Clusters of lymph nodes (ovoid structures usually less than 1 cm indiameter) are strategically placed in the neck, axillae, groin,

mediastinum and abdominal cavity, where they act to filterantigens from the interstitial tissue fluid and the lymph during itspassage from the periphery to the thoracic duct

Somatic nodes: Lymph nodes that protect the skin

Visceral nodes: Deep lymph nodes protecting the respiratory,digestive and genitourinary tracts


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Mucosa-associated lymphoid tissue (MALT) The bulk of the body's lymphoid tissue (>50%) is found associated

with the mucosal system.

MALT is composed of gut-associated lymphoid tissues (GALT) lining the intestinal tract,

bronchus-associated lymphoid tissue (BALT) lining the respiratory tract,

lymphoid tissue lining the genitourinary tract.

The major effector mechanism at these sites is secretory IgA (sIgA)secreted directly onto the mucosal epithelial surfaces. Examples ofMALT include the Peyer's patches lining the small intestine,

the tonsils and

the appendix. "M" cells (because they have numerous microfolds on their luminal surface)

absorb,

transport,

process and

present antigens to subepithelial lymphoid cells

Immuno2 Cells of the Immune System

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