Blood Lec 18 by Dr Sadia

7/30/2019 Blood Lec 18 by Dr Sadia

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At first, it was a mystery how few genes

code for the millions of difft specificities ofantibody or T cells produced by thelymphoid tissue

espe a single gene is usually necessary forthe formation of each difft type of protein.

Whole gene for forming each type of T cellor B cell is never present in the original stemcells.


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There are only gene segmentsactually,hundreds of such segmentsbut not wholegenes.

During preprocessing, these gene segmentsbecome mixed with one another .

B/c there are several hundred types of genesegments,& millions of difft combinations inwhich the segments can be arranged in singlecells, the millions of difft cell gene types thatcan occur.


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Role of Macrophages in the ActivationProcess.

In lymphoid tissue, millions ofmacrophages are present line thesinusoids of the lymph nodes,

spleen,& other lymphoid tissue. Invading organisms are first

phagocytized & partially digested by

the macrophages

antigenicproducts are liberated into themacrophage cytosol.


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Macrophages pass these antigens

by cell-to-cell contact directly to thelymphocytes activation of thespecified lymphocytic clones.

Secrete Interleukin-1 promotesgrowth and reproduction of specific

lymphocytes.


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Role of the T Cells in Activation of the BLymphocytes

Most antigens activate both T & Blymphocytes at the same time.

T cells, called helper T cells, secretespecific substancescalled

lymphokinesactivate thespecific Blymphocytes.


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Mechanism for Activating a Clone of BLymphocytes

B lymphocytes, each of these has on thesurface about 100,000 antibodymoleculesreact highly specifically with

only one specific type of antigen.On entry of a foreign antigen,macrophages phagocytize the antigen

present it to adjacentB lymphocytes.Antigen is also presented toTcells

activated helper T cells formed.


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B lymphocytes specific for the antigen immediatelyenlarge and take on the appearance of lymphoblasts. lymphoblasts further differentiateto form

plasmablasts,

In plasmablasts, the cytoplasmexpands and the roughendoplasmic reticulum vastly proliferates.Plasmablasts then begin to divide at a rapid rate ,givingin 4 days a total population of about 500cells for eachoriginal plasmablast.

Mature plasma cell then produces gamma globulin

antibodiesabout 2000 molecules per second for eachplasma cell


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Formation of Memory CellsFew lymphoblasts do not form plasma cells but form

new B lymphocytes similar to those of the originalclone.

Bcell population of the specifically activated clonebecomes greatly enhanced, and the new B lymphocytesare added to the original lymphocytes of theSame clone.

Immunologically, remain dormant until activated onceagain by a new quantity of the same antigen.These lymphocytes are called memory cells.


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Differences b/w theprimary response for forming antibodies that occurs onfirst exposure to a specific antigen and the secondaryresponse that occurs after second exposure to the sameantigen.Primary response 1-week delay in the appearance of the primary response, weak potency shortlife

Secondary response,begins rapidly after exposure to the antigen (often withinhours) more potent forms antibodies for many months rather than for only a

few weeks.


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1. Immunocompetent B cells

exposed to antigen. Antigen

Binds to B cells with

complementary receptors.

2. B cell displays processed

antigen fragments. Helper

T cell binds to B cell and

Secretes lymphokines.

3. Lymphokines stimulateB cell to divide repeatedly

and form a clone.

4. Some cells of the clone

become memory B cells.

Most differentiate intoplasma cells.

5. Plasma cells synthesize

and secrete antibody

Helper T cellB cell


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B cell Plasma cell


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Nature of the Antibodies Antibodies are gamma globulins calledimmunoglobulins

They usually constitute about 20% of allthe plasma proteins.

All the immunoglobulins are composed of

combinations of lightand heavypolypeptide chains.


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Structure of immunoglobulins Combination of two light and two heavy

chains,

Some have combinations of as many as 10heavy and 10 light chains.

Each heavy chain is paralleled by a lightchain at one of its ends, thus forming aheavy-light pair.

There are at least 2 and as many as 10such pairs in each immunoglobulin molecule.


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Each light and heavy chain, contains

variable portion

Constant portion.

The variable portion is different for eachspecificity of antibody.

It is this portion that attaches specificallyto a particular type of antigen..


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CONSTANT PORTION OFIMMUNOGLOBULIN

Constant portion of the antibody determines otherproperties of the antibody:

Diffusivity of the antibody in the tissues,

Adherence of the antibody to specific structures within thetissues,

Attachment to the complement complex,

The ease with which the antibodies pass through

membranes,


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Specificity of Antibodies

Each antibody is specific for a particularantigen; This is caused by its unique structural

organization of amino acids in the variable

portions of both the light and heavychains. The amino acid organization has a

different steric shape for each antigen

specificity,


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When an antigen comes in contact withitmultiple prosthetic groups of the

antigen fit as a mirror image with theantibody.

Allowing rapid and tight bonding betweenthe antibody and the antigen.

Wh n th ntib d is hi hl sp ifi


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When the antibody is highly specificmany bonding sites between the antibody-antigen.

They held together by

(1) hydrophobic bonding, (2) hydrogen bonding,

(3) ionic attractions,

(4) van der Waals forces.


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It also obeys the thermodynamic massaction

Ka= Conc. of bound antibody-antigenConc. of antibody x Conc. of antigen

Kais called the affinity constant

measure of how tightly the antibody bindswith the antigen.

Th Fi Cl f A tib di


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The Five Classes of Antibodies Class Structure Location and Function

IgA

Plasma IgA is found in blood plasma;

Secretory IgA is found in mucus, saliva, tears,milk, and intestinal secretions.

IgA prevents pathogens from adhering to epitheliaand penetrating the underlying tissues.

IgD


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IgD

An integral protein of the B cell memb; acts as anantigen receptor.

IgE

Found mainly in tonsils, skin, and mucous

membranes. Stimulates mast cells and basophils release

histamine & other chemical mediators ofinflammation & allergy;

Attracts eosinophils to sites of parasitic infection.


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IgG Constitutes 75% to 85% of circulating antibodies

in plasma.

Crosses placenta and confers temporary immunityon the fetus. Includes the anti-D antibodies ofthe Rh blood group.

The predominant antibody secreted in thesecondary immune response.

IgG and IgM are the only antibodies able to bindcomplement


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IgM Bivalent is an antigen receptor of the B cell

memb;

Pentavalent occurs in blood plasma.

Predominant antibody secreted in the primary

immune response;

very strong agglutinating ability;

includes the anti-A and anti-B agglutinins of theABO blood group.

Mechanisms of Action of Antibodies


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Mechanisms of Action of Antibodies

(1) By direct attack on the Invader

(2)By activation of the complement system

Direct action of antibodies on invading agents: 1. Agglutination,

multiple large particleswith antigens on their

surfaces,

bacteria or red cells, are boundtogether into a clump


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2. Precipitation,

molecular complex ofsoluble antigen (such

as tetanus toxin) & antibody b/c so largethat it is insoluble and precipitates


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3. Neutralization, Antibodies coverthe toxic sites of the antigenicagent

4. Lysis,

Potent antibodies directlycause

rupture of the agent


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C l S f A ib d A i


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Complement System for Antibody Action

Complement is a syst of about 20 proteins, many

of which are enzyme precursors. Most imp are 11proteins designated C1 through

C9, B, and D

Present among plasma proteins in the blood&proteins that leak out of the capillaries into thetissue spaces.

Enzyme precursors are normally inactive

activated mainly by classic pathway.


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Classic Pathway.

Initiated by an antigen-antibody reaction antibody binds with an antigen,specific reactive site on the constantportion of the antibody becomes

activated,

Binds directly with the C1 molecule of thecomplement sys.


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The C1 enzymes that are formedthen -->activate increasing quantitiesof enzymes.

Multiple end products are formedthat prevent damage to the bodystissues caused by the invadingorganism or toxin

Classic Pathway


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ClassicPathway


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Opsonization


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1. Opsonizat ion and phagoc ytos is: activated by

C3b by both neutrophils and macrophages.

2. Lysis :Lytic complex C5b789

3.Agglut inat ion

4. Neutral izat ion o f viru ses.

5. Chemotaxis:C5a causing chemotaxis of neutrophils

and macroophages

6.Ac t ivation of mast cel ls and basophi ls:Fragment

C3a,C4a and C5a


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7. Inflammatory effects.

Several other complement productscontribute to local inflammation. Theseproducts cause

(1) Already increased blood flow toincrease still further

(2) the capillary leakage of proteins to beincreased,

(3) the interstitial fluid proteins tocoagulate in the tissue spaces.


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ALLETERNATET PATHWAY

It is due to protien in circulation

called factor-1. it binds with polysaccharides present

in the cell membrane of the invading

organism. This binding activates C3 &C5 which

attack the antigenic products of

invading organism.


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ActivatedT Cells and Cell-MediatedImmunity

On exposure to an antigen

A: activated T lymphocytes are formed.

B: T- Lymphocyte memory cells are formedand spread to lymphatic tissue of wholebody.

Antigen-Presenting Cells, MHC Proteins,


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Antigen Presenting Cells, MHC Proteins,and Antigen Receptors on the T

Lymphocytes.

T lymphocytes respond to antigens onlywhen they are bound to specific molecules

called MHC proteins onthe surface ofantigen-presenting cells in the lymphoidtissues .


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The three major types of antigen-presenting cells are

macrophages,

B lymphocytes,

dendritic cells. The dendritic cells,arelocated

throughout the body, their only

known function is to present antigento T cells.


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The MHC proteins are encoded by a large

group of genes called the majorhistocompatibility complex (MHC).

The MHC proteins bind peptide fragmentsof antigen proteins degraded insideantigen presenting cells transport them

to the cell surface.


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There are two types of MHC

proteins:

(1)MHC I proteins, which present

antigens to cytotoxic T cells,

(2) MHC II proteins, which present

antigensto T helper cells.

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Blood Lec 18 by Dr Sadia