Immune Response Class Ppt

7/30/2019 Immune Response Class Ppt

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IMMUNE RESPONSE


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The Immune Response

Immunity: Free from burden. Ability of an organism to

recognize and defend itself against specific pathogens or

antigens.

Immune Response: Third line of defense. Involvesproduction of antibodies and generation of specialized

lymphocytes against specific antigens.

Antigen: Molecules from a pathogen or foreign organism

that provoke a specific immune response.


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Immune Response

Specific immunity induced in a host by an

antigenic stimulus.

2 types:

Humoral (Antibody mediated) immunity

Cellular (cell mediated) immunity

Both develop together, one or other maypredominate.


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The Immune System is the Third Line of

Defense Against Infection


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I. Humoral (Antibody-Mediated) Immunity

Involves production of antibodies against foreignantigens.

Antibodies are produced by a subset of lymphocytes

called B cells.

B cells that are stimulated will actively secrete antibodiesand are calledplasma cells.

Antibodies are found in extracellular fluids (blood plasma,

lymph, mucus, etc.) and the surface of B cells.

Defense against bacteria, bacterial toxins, and virusesthat circulate freely in body fluids,before they enter cells.

Also cause certain reactions against transplanted tissue.


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Humoral Immune Response

Production of antibodies consists of 3 steps:

Entry of antigen, its distribution and fate in the tissues and its

contact with appropriate immunocompetent cells.

Processing of Ag by cells and control of Ab forming process(central functions)

Secretion of Ab its distribution in tissues and body fluids and

mainfestation of its effect.


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Primary responses:

Ab response to an initial Ag

slow, sluggish, shortlived.

Ab IgM

Ab more specific, less avid

called early Ab

Secondary responses:

response to subsequent

stimuli with the same Ag

prompt, powerful andprolonged.

Ab IgG

Late Ab


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Fate of Ag in tissues Fate of Ag depends on factors like physical and chemical nature of

Ag, its dose, route of entry and if stimulus is primary or secondary.

Ags introduced IV are localised in liver, kidney, BM etc and brokenby RE cells and excreted in urine.

Ags introduced subcutaneously are mainly localised in draininglymphocytes.

Particulate Ags may be removed in 2 phases:

1. Nonimmune phase Ag is engulfed by phagocytic cells, brokendown and eliminated with appearance of specific Ab.

2. Phase of immune elimination - Ag-Ab complexes are formed andAgs phagocytosed.

Soluble Ags show 3 phases during elimination: Equilibration- Ag diffuse in to extravascular spaces.

Metabolism level of Ag falls due to catabolic decay

Immune elimination elimination of Ag due to Ag-Ab complexformation.


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Ag presentation to immunocompetent cells occurs in 2 ways

by macrophages and dendritic cells in lymphnode follicles.

Ag processing by macrophages appear to be essential for the

primary IR to many Ags, but not for secondary IR.

Ag capture of the dendritic cells of the lymphnode follicles

occur in the presence of pre-existing Ag.

Both dendritic cells and macrophages present Ag in areas

where there is ample lymphocytes so that the appropriate

lymphocytes can recognise the Ag and initiate IR.


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CELLULAR IMMUNE RESPONSE

CMI refers to specific IR that do not involve

Abs.

The only facet of CMI that was investigated to

any extent was delayed hypersensitivity.

CMI is more important than AMI.

CMI depends on the actions of T-

lymphocytes.


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Tlymphocytes are divided into different sub populations

based on functional capacity.

Regulator T cells : a) T -helper cells (TH)

b)T- suppresor cells (TS)Effector T cells: a) cytotoxic T-lymphocytes (CTL)

b) Delayed type hypersensitivity (DTH)

c) Mixed lymphocyte reactivity (MLR)


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TH cells facilitate B cell response to many Ags.

Ts inhibit Ab production by B-cells, and immune reactions by

effector T-cells.

IR regulated by balanced activity of TH and TS cells.

Over activity of TH or decreased acitvity of TS cause abnormal

IRAutoimmunity.

Diminished TH function or increased TS cell activity -

Immunedeficiency


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Induction of CMI sensitise T-lymphocytes against Ag.

When the T-lymphocyte contacts the Ag determinant - blast

transformation and clonal proliferation selectively in

paracortical areas of the lymphnodes.

Activated lymphocytes release biologically active products

lymphokines responsible for CMI.

Macrophages and other macronuclear cells under the effect

of lymphokine effect the destruction of M.O and other

processes in CMI.


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Antibodies are Produced by B Lymphocytes


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Cell Mediated Immunity is Carried Out by T Lymphocytes

i


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AntigensMost are proteins or large polysaccharides from a

foreign organism.

Microbes: Capsules, cell walls, toxins, viral capsids,

flagella, etc.

Nonmicrobes: Pollen, egg white , red blood cell surface

molecules, serum proteins, and surface molecules fromtransplanted tissue.

Lipids and nucleic acids are only antigenic when

combined with proteins or polysaccharides.

Molecular weight of 10,000 or higher. Hapten: Small foreign molecule that is not antigenic. Must be

coupled to a carrier molecule to be antigenic. Once antibodies areformed they will recognize hapten.


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Epitopes: Antigen Regions that Interact with

Antibodies


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Antibody Structure


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How Do B Cells Produce Antibodies?

B cells develop from stem cells in the bone marrow

of adults (liver of fetuses). After maturation B cells migrate to lymphoid

organs (lymph node or spleen).

Clonal Selection: When a B cell encounters an

antigen it recognizes, it is stimulated and divides

into many clones called plasma cells, which actively

secrete antibodies.

Each B cell produces antibodies that will recognize

only one antigenic determinant.

Cl l S l i f B C ll i C d b


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Clonal Selection of B Cells is Caused by

Antigenic Stimulation


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Humoral Immunity (Continued)

Apoptosis

Programmed cell death (Falling away).

Human body makes 100 million lymphocytes every

day. If an equivalent number doesnt die, will

develop leukemia. B cells that do not encounter stimulating antigen

will self-destruct and send signals to phagocytes to

dispose of their remains.

Many virus infected cells will undergo apoptosis, tohelp prevent spread of the infection.


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Clonal Selection

Clonal Selection: B cells (and T cells) thatencounter stimulating antigen will proliferate into

a large group of cells.

Why dont we produce antibodies against our ownantigens? We have developed tolerance to them.

Clonal Deletion: B and T cells that react against self

antigens appear to be destroyed during fetal

development. Process is poorly understood.


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Consequences of Antigen-Antibody Binding

Antigen-Antibody Complex: Formed when anantibody binds to an antigen it recognizes.

Affinity: A measure of binding strength.

1. Agglutination: Antibodies cause antigens(microbes) to clump together.

IgM (decavalent) is more effective that IgG (bivalent). Hemagglutination: Agglutination of red blood cells.

Used to determine ABO blood types and to detectinfluenza and measles viruses.

2. Opsonization: Antigen (microbe) is covered withantibodies that enhances its ingestion and lysis byphagocytic cells.


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Consequences of Antibody Binding


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3. Neutralization: IgG inactivates viruses by binding

to their surface and neutralize toxins by blockingtheir active sites.

4. Antibody-dependent cell-mediated cytotoxicity:

Used to destroy large organisms (e.g.: worms).

Target organism is coated with antibodies andbombarded with chemicals from nonspecific

immune cells.

5. Complement Activation: Both IgG and IgM triggerthe complement system which results in cell lysis

and inflammation.


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Consequences of Antibody Binding


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Immunological Memory

secondary Response:

Subsequent exposure to the same antigen displaysa faster and more intense antibody response.

Increased antibody response is due to the

existence of memory cells, which rapidly produce

plasma cells upon antigen stimulation.


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T Cells and Cell Mediated Immunity

Antigens that stimulate this response are mainly

intracellular.Requires constant presence of antigen to remain

effective.

Unlike humoral immunity, cell mediated immunity is

not transferred to the fetus.

Cytokines: Chemical messengers of immune cells.

Over 100 have been identified.

Stimulate and/or regulate immune responses.

Interleukins: Communication between WBCs.

Interferons: Protect against viral infections.

Chemokines: Attract WBCs to infected areas.


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T C ll d C ll M di t d I it


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T Cells and Cell Mediated Immunity

Types of T cells

1. T Helper (TH) Cells: Central role in immuneresponse.

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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Types of T cells2. 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 viruses or bacteria.

Recognize and kill cancer cells.

Recognize and destroy transplanted tissue.

Release protein calledperforin which forms a pore in

target cell, causing lysis of infected cells.

Undergo apoptosis when stimulating antigen is gone.


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Cytotoxic T Cells Lyse Infected Cells


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Types of T cells3. Delayed Hypersensitivity T (TD) Cells: Mostly T

helper and a few cytotoxic T cells that are involvedin some allergic reactions (poison ivy) and rejection

of transplanted tissue.

4. T Suppressor (Ts) Cells: May shut down immune

response.


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Nonspecific Cellular Components1. Activated Macrophages: Stimulated phagocytes.

Stimulated by ingestion of antigen Larger and more effective phagocytes.

Enhanced ability to eliminate intracellular bacteria,

virus-infected and cancerous cells.

2. Natural Killer (NK) Cells: Lymphocytes that destroy virus infected and tumor cells.

Not specific. Dont require antigen stimulation.

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


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Relationship Between Cell-Mediated and HumoralImmunity

1. Antibody ProductionT-Dependent Antigens:

Antibody production requires assistance from T helper cells. A macrophage cells ingest antigen and presents it to TH cell.

TH cell stimulates B cells specific for antigen to become plasma cells.

Antigens are mainly proteins on viruses, bacteria, foreign red blood cells, andhapten-carrier molecules.

T-Independent Antigens:

Antibody production does not require assistance from T cells. Antigens are mainly polysaccharides or lipopolysaccharides with repeating

subunits (bacterial capsules).

Weaker immune response than for T-dependent antigens.


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Humoral Response to T Dependent Antigens


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Destruction of Large Parasites by Antibody Dependent

Cell-mediated CytotoxicityADCC

Overview of the Immune Response


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Overview of the Immune Response


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Major Histocompatibility Complex

MHC cluster of genes in mammals.

Associated with intercellular recognition and with self and

non-self recognition.

A region of multiple loci that plays a imp role in determining if

the transplanted tissue will be accepted as self

(histocompatible)/ rejected (histoincompatible)

MHC collection of genes on chr 6 in humans and chr 17 in

mice.

MHC in humans Human Leukocyte Antigen (HLA), in mice

H-2 complex

Present in almost all tissues on PM


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3 classes of MHC:

Class I MHC found on almost all types of nucleatedbody cells.

Class II MHC found on leukocytes involved in Thelper cell related IR (macrophages, APCs, B cells)

Class III MHC include various secreted proteins withimmune functions. (complement component c2, c4factor B), inflammatory cytokines, tumor necrosis

factors.

These are not membrane protiens, hence no role inantigen presentation.


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Class II MHC:

Transmembrane protein with & chains of

mass 34 and 28 kda

Both folded to give 2 domains.


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The presence of foreign peptides in MHC

groove alerts immune system and activates T-

cells which in turn activate macrophages.

Class I and II molecules present peptides that

arise in different places within cells as a result

of Antigen processing.

Class I molecule binds to peptides thatoriginate in cytoplasm.


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Immune Response Class Ppt