5 Hemat Physiology

8/13/2019 5 Hemat Physiology

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Blood PhysiologyResistance of the Body to Infection:

Immunity and Allergy


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Formation of Memory Cells-Difference Between Primary Response andSecondary Response : A few of the lymphoblasts formed by activation of a clone of B

lymphocytes do not go on to form plasma cells but instead form

moderate numbers of new B lymphocytes similar to those of the

original clone

They circulate throughout the body to populate all the lymphoid

tissue; they remain immunologically dormant until activated once

again by a new quantity of the same antigen.

These lymphocytes are called memory cells.

Subsequent exposure to the same antigen will cause a much more

rapid and much more potent antibody response

Specific Attributes of the B-Lymphocyte System-Humoral

Immunity and the Antibodies


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The differences between the primaryresponsefor forming antibodies thatoccurs on first exposure to a specificantigen and the secondary responsethat occurs after second exposure tothe same antigen.-Note the 1-week delay in theappearance of the primary response,its weak potency, and its short life.-The secondary response, by contrast,begins rapidly after exposure to theantigen (often within hours), is farmore potent, and forms antibodies formany months rather than for only afew weeks.




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Nature of the Antibodies: The antibodies are glycoprotein of gamma globulins called

immunoglobulin(g)that interact specifically with an Agdeterminant They usually constitute about 20 % of all theplasma proteins An antibody immunoglobulin is a Y shaped molecule ,consistof 2 identical light chains and 2 identical heavy chains bound bydisulfid bonds The constant region is the C-terminal end and contains similaramino acids for each class of antibody. The isolated caboxyl-terminal portion of the heavy chain

molecules is called Fc region. The Ag-binding site of an Ab consist of the variable regions ofone heavy and one light chain, thus each Ab has 2 Ag-bindingsites, both for the same Ag.




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Humoral Immunity and the Antibodies

Structure of the typical IgG antibody, showing it to be composed of two heavypolypeptide chains and two light polypeptide chains. The antigen binds at twodifferent sites on the variable portions of the chains


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Classes of Antibodies:The five major classes of heavy chain are

1. IgG - Gamma heavy chains

a) IgG1 - Gamma 1 heavy chains

b) IgG2 - Gamma 2 heavy chains

c) IgG3 - Gamma 3 heavy chainsd) IgG4 - Gamma 4 heavy chains

2. IgM - Mu heavy chains

3. IgA - Alpha heavy chains

a) IgA1 - Alpha 1 heavy chains

b) IgA2 - Alpha 2 heavy chains

4. IgD - Delta heavy chains

5. IgE - Epsilon heavy chains

Each of these classes differ in their locations in our body and

how they stimulate the innate system to remove antigen



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Mechanisms of Action of Antibodies

Antibodies act mainly in two ways to protect the body against invading

agents:

(1) By direct attack on the invader(2) By activation of the "complement system" that then has multiple

means of its own for destroying the invader



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Direct Action of Antibodies on Invading Agents:The antibodies can inactivate the invading agent in one of several ways, as

follows:

Agglutination, in which multiple large particles with antigens on their

surfaces, such as bacteria or red cells, are bound together into a clump

Precipitation, in which the molecular complex of soluble antigen (such as

tetanus toxin) and antibody becomes so large that it is rendered insoluble andprecipitates

Neutralization, in which the antibodies cover the toxic sites of the antigenic

agent

Lysis, in which some potent antibodies are occasionally capable of directly

attacking membranes of cellular agents and thereby cause rupture of the

agent

These direct actions of antibodies attacking the antigenic invaders often are

not strong enough to play a major role in protecting the body against the

invader. Most of the protection comes through the amplifyingeffects of the

complement system



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Complement System forAntibody Action

"Complement" is a collective

term that describes a system of

about 20 proteins, many of

which are enzyme precursors.

The principal actors in this

system are 11 proteins

designated C1 through C9, B,

and D

All these are present normally

among the plasma proteins in

the blood as well as among the

proteins that leak out of the

capillaries into the tissue

spaces.

The enzyme precursors are

normally inactive, but they can

be activated mainly by the so-

called classic pathway.



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Classic Pathway: It is initiated by an AgAb reaction, when an antibody binds

with an antigen becomes uncovered, or "activated," and thisin turn binds directly with the C1 molecule of thecomplement system, setting into motion a "cascade" ofsequential reactions, beginning with activation of the

proenzyme C1 itself.

The C1 enzymes that are formed then activate successivelyincreasing quantities of enzymesin the later stages of thesystem, so that from a small beginning, an extremely large"amplified" reaction occurs.

Multiple end products are formed, and several of these causeimportant effects that help to prevent damage to the body'stissues caused by the invading organism or toxin.

Among the more important effects are the following:



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Effects of Activated Complement System

1. Opsonization and phagocytosis: C3b, strongly activates

phagocytosis by both neutrophils and macrophages, causing

these cells to engulf the bacteria to which the antigen-

antibody complexes are attached. This process is called

opsonization.

2. Lysis: One of the most important of all the products of thecomplement cascade is the lytic complex, which is a

combination of multiple complement factors and designated

C5b6789.This has a direct effect of rupturing the cell

membranes of bacteria or other invading organisms.

3. Agglutination: The complement products change the

surfaces of the invading organisms, causing them to adhere

to one another, thus promoting agglutination.

4. Neutralization of viruses: The complement enzymes and

other complement products can attack the structures of

some viruses and thereby render them nonvirulent.



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Effects of Activated Complement System(cont.)

5. Chemotaxis: Fragment C5ainitiates chemotaxis of neutrophils and

macrophages

6. Activation of mast cells and basophils: Fragments C3a, C4a, and C5a

activate mast cells and basophils, causing them to releasehistamine, heparin, and several other substances into the local

fluids. These substances cause increased local blood flow,

increased leakage of fluid and plasma protein into the tissue, and

other local tissue reactions that help inactivate or immobilize the

antigenic agent.



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Special Attributes of the T-Lymphocyte System-

Activated T Cells and Cell-Mediated Immunity

Release of Activated T Cells from Lymphoid Tissue andFormation of Memory Cells. On exposure to the proper antigen, the T lymphocytes clone

proliferate and release large numbers of activated,

specifically reacting T cells

T-lymphocyte memory cells: are formed ,when a clone of Tlymphocytes is activated by an antigen, many of the newly

formed lymphocytes are preserved in the lymphoid tissue to

become additional T lymphocytes of that specific clone;

these memory cells spread throughout the lymphoid tissue

of the entire body.

On subsequent exposure to the same antigen, release of

activated T cells occurs far more rapidly and much more

powerfully than had occurred during first exposure.


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Antigen-Presenting Cells, MHC Proteins, and Antigen Receptorson the T Lymphocytes: T-cell responses are extremely antigen specific

Acquired immune responses usually require assistance from

T cells to begin the process, and T cells play a major role in

actually helping to eliminate invading pathogens.

T- lymphocytes respond to antigens only when they are

bound to MHC proteinson the surface of antigen-presenting

cells(APCs) in the lymphoid tissues

The three major types of (APCs) are:

1- Macrophages2- B- lymphocytes

3- Dendritic cells , most potent of the antigen-presenting cells,

are located throughout the body




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The MHC proteins

They are encoded by a large group of genes called the majorhistocompatibility complex (MHC)

The MHC proteins bind peptide fragments of antigen proteinsthat are degraded inside APCs and then transport them to

the cell surface. There are two types of MHC proteins:

(1) MHC I proteins, which present antigens to cytotoxic T cells

(2) MHC II proteins, which present antigens to T helper cells.

The antigens on the surface of APCs bind with receptor

molecules on the surfaces of T cells. These receptormolecules are composed of a variable unit &there are asmany as 100,000 receptor sites on a single T cell.




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Antigen-Presenting Cells, MHC Proteins, and Antigen Receptors on theT Lymphocytes:



Activation of T cells requires

interaction of T-cell receptors

with an antigen that is

transported to the surface ofthe antigen-presenting cell by a

major histocompatibility

complex (MHC) protein.

Cell-to-cell adhesion proteins

enable the T cell to bind to the

antigen-presenting cell longenough to become activated.


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Types of T Cells and Their Different Functions:

T Cells classified into three major groups:

(1) Helper T cells

(2) Suppressor T cells

(3) Cytotoxic T cells (Killer cells)




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1- Helper T Cells: Their Role in Overall Regulation of Immunity

The helper T cells are by far the most numerous of the T cells, usuallyconstituting more than three quarters of all of them.

They helpin the functions of the immune system, and they do so in manyways: They serve as the major regulator of virtually all immune functions.

They do this by forming a series of protein mediators (lymphokines), thatact on other cells of the immune system as well as on bone marrow cells.

The important lymphokines secreted by the helper T cells:

- Interleukin-2

- Interleukin-3

- Interleukin-4- Interleukin-5

- Interleukin-6

- Granulocyte-monocyte colony-stimulating factor (GM-CSF)

- Interferon-




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Regulation of the immune system, emphasizing a pivotal role of the helper T cells.




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2- Cytotoxic T Cells (Killer cells)

The cytotoxic T cell is a direct-

attack cell that is capable of killing

micro-organisms and, at times, even

some of the body's own cells. For

this reason, these cells are called

killer cells

The cytotoxic T cell secretes hole-

forming proteins, calledperforins,that literally punch round holes in

the membrane of the attacked cell.

The cytotoxic T cell releases

cytotoxic substances directly into

the attacked cell

Some of the cytotoxic T cells are

especially lethal to tissue cells thathave been invaded by viruses

The cytotoxic cells play an

important role in destroying cancer

cells, heart transplant cells, or other

types of cells that are foreign to the

person's own body




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3- Suppressor T Cells

They are capable of suppressing the functions of both

cytotoxic and helper T cells.

Suppressor functions serve the purpose of preventing the

cytotoxic cells from causing excessive immune reactions

that might be damaging to the body's own tissues (immune

tolerance)




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Immunization by Injection of Antigens

Active immunity : The person's own body develops either antibodies or activated T cells in

response to invasion of the body by a foreign antigen.

Immunizationhas been used for many years to produce acquired immunityagainst specific diseases.

1. A person can be immunized by injecting dead organisms that are no longercapable of causing disease but that still have some of their chemicalantigens. This type of immunization is used to protect against typhoid fever,whooping cough, diphtheria, and many other types of bacterial diseases.

2. Immunity can be achieved against toxins that have been treated withchemicals so that their toxic nature has been destroyed even though theirantigens for causing immunity are still intact. This procedure is used in

immunizing against tetanus, botulism, and other similar toxic diseases.

3. A person can be immunized by being infected with live organisms that havebeen "attenuated." That is, these organisms either have been grown inspecial culture media or have been passed through a series of animals untilthey have mutated enough that they will not cause disease but do still carryspecific antigens required for immunization. This procedure is used toprotect against poliomyelitis, yellow fever, measles, smallpox, and manyother viral diseases.


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Passive Immunity:

Temporary immunity can be achieved in a person without injecting

any antigen. This is done by infusing antibodies, activated T cells, or

both obtained from the blood of someone else or from some other

animal that has been actively immunized against the antigen, such

transfusion of antibodies or T lymphocytes to confer immunity is

calledpassive immunity.

Antibodies last in the body of the recipient for 2 to 3 weeks, and

during that time, the person is protected against the invading

disease.

Activated T cells last for a few weeks if transfused from another

person but only for a few hours to a few days if transfused from an

animal.

Immunization by Injection of Antigens


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ALLERGY AND HYPERSENSITIVITY

An important undesirable side effect of immunity is the

development, under some conditions, ofallergyor other types of

immune hypersensitivity.

There are several types of allergy and other hypersensitivities, some

of which occur only in people who have a specific allergic tendency.

1- Allergy Caused by Activated T Cells (Delayed-Reaction Allergy)

Delayed-reaction allergy is caused by activated T cells and not by antibodies.

In the case of poison ivy, the toxin of poison ivy in itself does not cause much

harm to the tissues. However, on repeated exposure, it does cause the

formation of activated helper and cytotoxic T cells.

After subsequent exposure, within a day or so, the activated T cells diffuse

from the circulating blood in large numbers into the skin to respond to thepoison ivy toxin. And, at the same time, these T cells elicit a cell-mediated

type of immune reaction leading to allergic inflammation localized to the

exposure area.


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2- Allergies in the "Allergic" Person, Who Has Excess IgE

Antibodies

Some people have an "allergic" tendency. Their allergies are called atopic

allergiesbecause they are caused by a nonordinary response of the immune

system.

The allergic tendency is genetically passed from parent to child and ischaracterized by the presence of large quantities of IgE antibodiesin the

blood. These antibodies are called reagins

When an allergenenters the body, an allergen-reagin reaction lakes place, and

a subsequent allergic reaction occurs.

A special characteristic of the IgE antibodies (the reagins) is a strong

propensity to attach to mast cells and basophils, release special agents

immediately or shortly thereafter, including histamine,protease, slow-reacting

substance of anaphylaxis

Among the different types of allergic reactions caused in this manner are theAnaphylaxis, Urticaria, Asthma, and Hay fever.

ALLERGY AND HYPERSENSITIVITY

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5 Hemat Physiology