cells and organs of is lec 2

8/14/2019 Cells and Organs of is Lec 2

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CELLS AND ORGANS OF

THE IMMUNE SYSTEM

M.KANNAN M.Sc., M.Phil., Ph.D.,

DEPARTMENT OF MICROBIOLOGYV.H.N.S.N.COLLEGE, VIRUDHUNAGAR


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FUNCTIONS OF THE IMMUNE SYSTEM

Defense against infections

Recognition and protective response to

newly introduced substances such asproteins and to tissue grafts

Defense against tumors

Preservation of genetic integrity of theindividual


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TWO TYPES OF IMMUNITY

Nonspecific (innate)Physical and chemicalagents

Lysozyme

Acute phase proteinsComplement system

Cytokines (chemokines)

Phagocytes (granulocytes,macrophages)

Natural killer (NK) cellsDendritic cells

Pattern recognition receptors

(PRR)

Specific (adaptive)Antibodies

(B lymphocytes)

T lymphocytes


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Major differences between innateand acquired immunity (acc. to U.

Koedel & W Pfister 2005)

Innate immunesystem

Immediate maximalresponse

No immunological memory

Not antigen specific

Receptors: germ lineencoded,

In almost all multicellularorganisms,

Recognition of conservedmolecular patterns,

Perfect self/non-self

discrimination Only hundreds of different

Acquired immunesystem

Lag time (3-4 days) betweenexposure and max.

response Immunological memory

Antigen specific

Receptors: generatedsomatically,

Only in vertebrates,

Recognition of details ofmolecular structure,

Imperfect self/non-self

discrimination, Over 100 000 000 000


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THE IMMUNE SYSTEM

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Hematopoiesis


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Cells of the immune system

All blood cells arise from a type of cellcalled the hematopoiesis stem cell(HSC).

Stem cells are cells that can differentiateinto other cell types, they are self-renewing- 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

the first weeks of development.

Hematopoiesis


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Hematopoie

sis


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Regulation ofHematopoiesis

Hematopoiesis is a continuousprocess that generally maintains asteady state in which the production

of mature blood cells equals theirloss (principally from aging).

The average erythrocyte has a life

span of 120 days before it isphagocytosed abd digested bymacrophages in the spleen.


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Programmed cell death

Cells undergoing programmed cell deathoften exhibit distinctive morphologicchanges, collectively referred to as

apoptosis.

These changes include a pronounceddecrease in cell volume, modification ofthe cytoskelton to result in membraneblebbing, a condensation of the chromatinand degradation of the DNA into smaller

fragments.


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Apoptosi

s


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Lymphoid cells

Lymphocytes constitute 20% - 40%of the bodys white blood cells and99% of the cells in the lymph.

There are approxiamately 1011

(range depending on body size andage: ~1010 1012) lymphocytes in thehuman body.

The lymphocytes can be broadlysubdivided into three populations-B-cells, T-cells and null cells-on thebasis of function and cell membrane


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Lymphocytes

Produce antibodies

B-cells mature in bone marrow thenconcentrate in lymph nodes andspleen

T-cells mature in thymus

B and T cells mature then circulate inthe blood and lymph

Circulation ensures they come intocontact with pathogens and eachother


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B -Lymphocytes

There are c.10 million different B-lymphocytes, each of which make adifferent antibody.

The huge variety is caused by genescoding for abs changing slightlyduring development.

There are a small group of clones ofeach type of B-lymphocyte


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B -Lymphocytes

At the clone stage antibodies do not leavethe B-cells.

The abs are embedded in the plasma

membrane of the cell and arecalled antibody receptors.

When the receptors in the membranerecognise and antigen on the surface of

the pathogen the B-cell divides rapidly. The antigens are presented to the B-cells

by macrophages
http://www.sanidadanimal.info/inmun/images/fig2.gifhttp://www.sanidadanimal.info/inmun/images/fig2.gif


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B -Lymphocytes


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B -Lymphocytes

Some activated B cells PLASMACELLS these produce lots ofantibodies, < 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 godown too.


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B -Lymphocytes

Some activated B cells MEMORYCELLS.

Memory cells divide rapidly as soonas the antigen is reintroduced.

There are many more memory cellsthan there were clone cells.

When the pathogen/infection infectsagain it is destroyed before anysymptoms show.


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Do Not Express Classical Lymphocyte

Markers

Predominantly NK Cells (CD56)

Eliminate Tumor Cells and Virally Infected

Cells

Using CD16 They Can Carry Out ADCC

Null Cells


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Mononuclear Cells

Monocytes in Blood, M in Tissues Monocytes 5-10 times smaller than M

M Increases Phagocytic Ability

Secretes cytokines and ProducesHydrolytic Enzymes

Named Based on Tissue They Reside Alveolar (lungs), Kupffer (liver), Microglial

(brain), Osteoclasts (bone) Activated By Phagocytosis or Cytokines

(IFN)

Antigen Presenting Capacity Thru MHC II

Mononuclear Cells


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Macrophages

Larger than neutrophils.

Found in the organs, not the blood.

Made in bone marrow as monocytes,called macrophages once they reachorgans.

Long lived

Initiate immune responses as theydisplay antigens from the pathogensto the lymphocytes.


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Macrophages


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Monocyte vs M


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M Effective APC


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M Capturing Bacteria


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Scarce Cell Type

Discovered in 1972

Early 90s Using GM-CSF/IL4 and Laterflt-3 limitation Was Overcome

Intense Area of Research

Seemed Promising for TumorTreatment

Maybe Better for Tolerance

Dendritic Cells


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Dendritic Cells

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D l t l P th f


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Developmental Pathway ofDCs


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Phagocytosis


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Phagocytosis

If cells are under attack they releasehistamine.

Histamine plus chemicals from pathogens

mean neutrophils are attracted to the siteof attack.

Pathogens are attached to antibodies andneutrophils have antibody receptors.

Enodcytosis of neutrophil membrane phagocytic vacuole.

Lysosomes attach to phagocytic vacuole

pathogen digested by proteases

Organs of the imm ne


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Organs of the immunesystem

A number of morphologically andfunctionally diverse organs and tissueshave various functions in the development

of immune responses. These can be distinguished by function as

the primary and secondary lymphoidorgans.

The thymus and bone marrow are theprimary(or central) lymphoid organs,where maturation of lymphocytestakesplace.


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The lymph nodes, spleen, and various

mucosal-associated lymphoid tissues(MALT) such as gut-associatedlymphoid tissue (GALT) are the

secondary (or peripheral) lymphoidorgans, which trap antigen andprovide sites for mature lymphocytesto interact with that antigen.


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Organs of theimmunesystem


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Thymus

Structure

Gross

Bi-lobed

Lies above heart

Microscopic

Capsular Lobules with outer cortex and inner

medulla


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Thymus

Function

Takes in immature T cells and puts outmature (immunocompetent) T cells

Increased diversity of T cells

T cell selection


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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


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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


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Lymph Nodes

Structure

Gross

Bean-shaped structures

Drains major segments of lymphaticsystem


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Lymph Nodes

Structure

Microscopic

Major cell types Lymphocytes

Macrophages

Dendritic cells

Cortex/paracortex/medulla Follicles

Primary

Secondary


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Lymph Nodes

Function 1st line of response to antigens

Secondary follicle (Germinal center) is site of Bcell proliferation, mutation, differentiation

Specificity is high

>90% of B cells die through apoptosis

After Ag stimualtion lymphocyte numbers up by50X in efferent lymphatic vessel

Lympadenopathy


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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


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Spleen

Function

Filters out older RBCs

Responds to Ag in circulatory system

Produces activated B cells

Splenectomy


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Tonsils

Follicular structure

Contains lymphocytes, macrophages,mast cells

Germinal centers appear in responseto Ag

Protective role in URI


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Appendix

Associated with intestines

Responds to Ag

Role in GI immune response


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MALT

Lymphoid tissues below epithelium

Presence of B cells

Ag presented through unique cell (Mcell)

Preferentially responds with IgAantibody


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cells and organs of is lec 2

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