lectures in immunology 01 (dr hend)

8/8/2019 Lectures in Immunology 01 (Dr Hend)

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Definition


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The Immune ResponseImmunity: Free from burden. Ability of an

organism to recognize and defend itself against specificpathogens or antigens.

Immune Response:Th

ird line of defense.Involves production 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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The Immune System is the Third

Line of Defense Against Infection


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Overview

What is an antigen?

What does an antigen do?

The Lymphatic System and

Body Defenses Nonspecific Defenses

Physical barriers

Phagocytes

Immunological surveillance

Interferons

Complement

Inflammation

Fever

Specific Defenses: The ImmuneResponse Overview of immune response

T cells and cell-mediatedimmunity

B cells and antibody-mediatedimmunity


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What is an antigen?

Antigen = antibody generating molecule any chemical substance that, when introduced into

the body, causes the body to produce specificantibodies that can react with the antigen

Properties of antigens: Foreign proteins or polysaccharides

Examples:

Cell membranes, flagella, viruses, toxins, enzymes,pollen, transplanted tissues & organs, markers on redblood cells


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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 surfacemolecules from transplanted tissue.

Lipids and nucleic acids are only antigenic when

combined with proteins or polysaccharides.

Molecular weight of 10,000 orhigher. Hapten: Small foreign molecule that is not antigenic.

Must be coupled to a carriermolecule to be antigenic.Once antibodies are formed they will recognize hapten.


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AntigensEpitope:

Small part of an antigen that interacts withan antibody.

Any given antigen may have several

epitopes.

Each epitope is recognized by a different

antibody.


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Epitopes: Antigen Regions that

Interact with Antibodies


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Pathogens: microorganisms responsible

for human diseases

Bacteria Viruses

Fungi

Parasites

Lymphatic system

Keeps us alive and healthy


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What does an antigen do?

Antigen with its antigenic determinant stimulates

the formation of specific antibodies

The antigenic determinant, a portion of the

antigen, reacts with an antibody to form anantigen-antibody complex

The formation of the antigen-antibody complex

ultimately leads to inactivation and removal ofthe antigen


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Antigenic Determinants on an

Antigen


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Derivation and Distribution of

Lymphocytes


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The Lymphatic System and Body

Defenses Nonspecific Defenses Do not distinguish one

threat from another

Physical barriers

Phagocytic cells

Immunological surveillance

Interferons

Complement

Inflammation Fever

Specific Defenses

Protect against particular

threats

Develop after birth

Dependent on activity of

lymphocytes

B cells

T cells


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The Complement System


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Macrophage


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Specific Defense: The Immune

Response

Respond to specific antigens

T cells

Cell-mediated immunity (cellular immunity)

Provide defense against abnormal cells and

pathogens in living cells

B cells

Antibody-mediated immunity (humoral immunity)

Provide a defense against antigens and pathogens in

body fluids


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Lymphocytes and the

Immune Response


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T Cells and Cell-Mediated

Immunity

T cells recognize antigens when bound to

membranes of other cells

Membrane receptors called major

histocompatibility complex (MHC) proteins

2 classes

Class I MHC proteins

Class II MHC proteins


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Class I MHC Proteins

Found on the surfaces of all of our cells

MHC proteins bind small peptide

molecules normally present on cellmembrane

Normal peptides: T cell ignores

Abnormal, virus, or bacteria (nonself): T cell

activated

Destroys abnormal/infected cell


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Class II MHC Proteins

Found only on membranes of lymphocytes andphagocytic antigen-presenting cells (APCs) Such as monocyte-macrophage group, free and fixed

macrophages

Specialized for activating T cells against foreign cellsand proteins

Phagocytic APCs engulf and break down foreignantigens or pathogens Fragments of foreign antigens displayed on

phagocytic cells membrane Bind to Class II MHC proteins

T cells come in contact and become activated, starting theimmune response


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T Cells

T cell activation for both occur when MHCprotein contains specific antigen T cellprogrammed to detect

Once activated, T cells divide and differentiatein to cells with specific function in immuneresponse

Cytotoxic T cells

Helper T cells Memory T cells

Suppressor T cells


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T Cells Only Recognize Antigen

Associated with MHC Molecules on

Cell Surfaces


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Cytotoxic T Cells

Responsible for cell-mediated immunity

Activated by exposure to antigens bound

to Class IMH

C proteins Activated cells under cell division that produce

active cytotoxic T cells and memory cells

Track down and attack bacteria, fungi,

protozoa, or foreign transplanted tissue


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A TC Cell Lyses an Infected Cell


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Apoptosis and Macrophages


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Helper T Cells (TH

Cells)

Assist in the regulation and coordination of heimmune response

Steps of regulation

1. Processing Macrophage phagocytizes antigen, presents it on its surface

2. Recognition Appropriate TH cell binds to the macrophage

3. Stimulation Macrophage stimulates THcell to form a clone of TH cells

Cloned cells produce cytokines

Stimulate B cells and TC cells

4. Response TC cells kill infected cells, B cells produce antibodies


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The Role ofHelper T Cells as

Mediators of Immune Responses


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Central Role ofHelperT Cells


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Suppressor T Cells

When activated, depress responses of

other T and B cells

Does not occur immediately Takes much longer for these cells to become

activated

Act after initial immune response


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B Cell Activation

Activated B cells divide several times

Produce daughter cells that differentiate into:

Plasma cells

Synthesize and secrete large numbers of antibodies on

surface of sensitized B cells

Memory cells

Similar to memory T cells

If exposed to same antigen, will differentiate into plasmacells


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2 Methods of Antibody

Production T cell independent production B cells differentiate without the interaction of

TH

cells

T cell dependent production

B cells differentiate with the interaction of TH

cells


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T cell Independent Antigens


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T cell Dependent Antigens &

Antibody Production


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Outcome of Antibody

Production by B cells


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What is an antibody?

Large Proteins

Basic subunit has minimum of two binding sites

at which it combines with antigens

Also known as immunoglobulins


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Antibody Structure

Consist of short and heavy chains ofpolypeptides Each chain has constant and variable segments

Constant heavy chains form base of antibody molecule

B cells produce only 5 types of constant segments Specificity depends on variable segments of light and

heavy chains Free tips contain antigen binding sites (very specific for each

type of antigen)

Antigen-antibody complex Forms when antibody binds to proper antigen Binds to sites and leads to B cell sensitization and an

immune response


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Antibody Configuration


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Classes of Antibodies

(Immunoglobins Igs) IgG

Largest and most diverse

Resist many viruses, bacteria, bacterial toxins

Can cross placenta What type of immunity is that?

IgM Circulate; attack bacteria IgA

Found in exocrine secretions Ex?

Attack pathogens before they enter the body

IgE When bound to antigen, stimulates basophils and mast cells to releasechemicals to stimulate inflammation

IgD Attached to B cell and involved in their activation


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Antibody Function

Neutralization

Agglutination and Precipitation

Activation of a complement Attraction of phagocytes

Enhancement of phagocytosis

Stimulation of inflammation

C f A ib d


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Consequences of Antibody

Binding


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Primary and Secondary Responses

to Antigen Exposure


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Immunological Memory

Antibody Titer: The amount of antibody in the

serum.Pattern of Antibody Levels During Infection

Primary Response:

Afterinitialexposure to antigen, no

antibodies are found in serum for several

days.

A gradual increase in titer, first of IgM and

th

en of IgG is observed. Most B cells become plasma cells, but some

B cells become long living memorycells.

Gradual decline of antibodies follows.


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Immunological Memory (Continued)

Secondary Response:

Subsequent exposure to the same antigendisplays a faster and more intense antibody

response.

Increased antibody response is due to the

existence of memory cells, which rapidlyproduce plasma cells upon antigen

stimulation.


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Antibody Response After Exposure to

Antigen

Relationship Between Cell Mediated and


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Relationship Between Cell-Mediated and

Humoral Immunity

1. Antibody Production

T-Dependent Antigens:

Antibody production requires assistance fromThelper

cells.

A macrophage cells ingest antigen and presents it to TH cell.

TH cell stimulates B cells specific for antigen to becomeplasma cells.

Antigens are mainly proteins on viruses, bacteria, foreign

red blood cells, and hapten-carrier molecules.

T-Independent Antigens:

Antibody production does not require assistance fromT

cells.

Antigens are mainly polysaccharides or

lipopolysaccharides with repeating subunits (bacterial

capsules).

Weaker immune response than forT-dependent antigens.


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Duality of the Immune System


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T Cells and Immunity

1000s of different types of T cells

When an antigen enters the body, only the particularT cell programmed to react with the antigen becomesactivated

Macrophages phagocytize the antigen Macrophages present it to the T cell

T cells increase in size, divide, differentiate Cytotoxic T cells

Helper T cells

Memory T cells

Delayed hypersensitivity T cells

Suppressor T cells


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B Cells

1000s of different kinds of B cells

Each type responds to a specific antigen

When an antigen enters the blood

B cells are activated Become plasma cells

Circulate in blood and lymph to reach site ofinvasion

B cells become memory B cells Respond more rapidly and forcefully should a

2nd invasion occur


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Humoral Response to T Dependent

Antigens



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Antigens

Overview of the Immune response


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Overview of the Immune response


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Disorders of the Immune


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Disorders of the Immune

System Allergy Person is overly reactive to an antigen

Autoimmune diseases

Body has difficulty in discriminating between its own antigens

and foreign antigens

Severe Combined Immunodeficiency (SCID)

Both T cells and B cells are absent or inactive

Acquired Immune Deficiency Syndrome (AIDS)

Human immunodeficiency virus (HIV) Primarily attacks helper T cells


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AntibodiesProteins that recognize and bind to a particular

antigen with very highspecificity.

Made in response to exposure to the antigen.

One virus or microbe may have several antigenic

determinantsites, to which different antibodies may

bind.Each antibody has at least two identical sites that

bind antigen: Antigen bindingsites.

Valence of an antibody: Number of antigen binding

sites. Most are bivalent.Belong to a group of serum proteins called

immunoglobulins (Igs).


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Antibody StructureMonomer: A flexible Y-shaped molecule with four

protein chains:

2 identical lightchains

2 identical heavychains

Variable Regions: Two sections at the end of Ys

arms. Contain the antigen binding sites (Fab).

Identical on the same antibody, but vary from one

antibody to another.

Constant Regions: Stem of monomer and lower

parts of Y arms.Fc region: Stem of monomer only. Important

because they can bind to complement or cells.


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Antibody Structure


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Immunoglobulin Classes

I. IgGStructure: Monomer

Percentage serum antibodies: 80%

Location: Blood, lymph, intestine

Half-life in serum: 23 days

Complement Fixation: Yes

Placental Transfer: Yes

Known Functions: Enhances phagocytosis,

neutralizes toxins and viruses, protects fetus and

newborn.


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II. IgMStructure: Pentamer

Percentage serum antibodies: 5-10%

Location: Blood, lymph, B cell surface (monomer)


Complement Fixation: Yes

Placental Transfer: No

Known Functions: First antibodies produced during

an infection. Effective against microbes and

agglutinating antigens.


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III. IgAStructure: Dimer

Percentage serum antibodies: 10-15%

Location: Secretions (tears, saliva, intestine, milk),

blood and lymph.


Complement Fixation: No


Known Functions: Localized protection ofmucosal

surfaces. Provides immunity to infant digestive tract.


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IV. IgDStructure: Monomer

Percentage serum antibodies: 0.2%

Location: B-cell surface, blood, and lymph




Known Functions: In serum function is unknown. On

B cell surface, initiate immune response.


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V. IgEStructure: Monomer

Percentage serum antibodies: 0.002%

Location: Bound to mast cells and basophils

throughout body. Blood.




Known Functions: Allergic reactions. Possibly lysis

of worms.


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lectures in immunology 01 (dr hend)

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