Specific Defenses of the HostSpecific Defenses of the HostMicrobiology 2314

Innate ResistanceInnate Resistance

• An individual’s genetically predetermined resistance to certain diseases

• We are born with this resistance.

• Ex. Resistance to AIDS due to a Delta-32 gene

Humans Have Innate Resistance to a Humans Have Innate Resistance to a Number of Different ThingsNumber of Different Things

• Bacteria• Viruses• Fungi• Protozoa

• Insect Venom• Transplanted Tissue• Cancer Cells• Diseases

Individual Resistance Individual Resistance is Affected Byis Affected By

• Gender

• Age

• Nutritional Status

• General Health

Resistance Leads to ImmunityResistance Leads to Immunity• The ability of the body to specifically counteract

foreign organisms or substances called antigens.

• Results from the production of specialized lymphocytes and antibodies (proteins)

Serology Serology

• Looks at reactions between antibodies and antigens

• A specialized branch of microbiology.

• Uses serum samples

Remember!Remember!

• Antigens provoke an immune response.

• Antibodies are produced to respond to antigens.

Antigens Antigens Antibodies Antibodies Protection Protection

Immunity Obtained After BirthImmunity Obtained After BirthTyp es o f Im m u n ity

A c tiveS im p le E xp osu re

L ife lon g o r S h ort Term

P ass iveTran sp lacen ta l Tran s fe r

C o lu s tru m

N atu ra lly A cq u ired Im m u n ity(In fec tion )

A c tiveV acc in a tion

Im m u n iza tion

P ass iveU se o f A n tise ra

A rtific ia lly A cq u ired Im m u n ity(In jec tion )

A cq u ired Im m u n ity

Naturally Naturally Acquired Acquired

Active ImmunityActive Immunity

• Immunity Resulting from Infection

• May be Long TermTyp es o f Im m u n ity

A c tiveS im p le E xp osu re

L ife lon g o r S h ort Term

P ass iveTran sp lacen ta l Tran s fe r

C o lu s tru m

N atu ra lly A cq u ired Im m u n ity(In fec tion )

A c tiveV acc in a tion

Im m u n iza tion

P ass iveU se o f A n tisera

A rtific ia lly A cq u ired Im m u n ity(In jec tion )

A cq u ired Im m u n ity

Naturally Acquired Naturally Acquired Passive ImmunityPassive Immunity• Mother to Fetus

• Transplacental Transfer

• Colostrum• Few Months Duration

Typ es o f Im m u n ity

A c tiveS im p le E xp os u re

L ife lon g o r S h ort Te rm

P as s iveTran s p lac en ta l T ran s fe r

C o lu s tru m

N atu ra lly A c q u ired Im m u n ity(In fec tion )

A c tiveV ac c in a tion

Im m u n iz a tion

P as s iveU s e o f A n tis e ra

A rtific ia lly A c q u ired Im m u n ity(In jec tion )

A c q u ired Im m u n ity

Artificially Artificially Acquired Acquired

Active ImmunityActive Immunity

• Immunity Resulting from Injection

(Vaccination)• Attenuated Vaccines• Inactivated Vaccines• Killed Vaccines• Toxoid Vaccines

Typ es o f Im m u n ity

A c tiveS im p le E xp osu re

L ife lon g or S h ort Term

P ass iveTran sp lacen ta l Tran s fer

C o lu s tru m

N atu ra lly A cq u ired Im m u n ity(In fec tion )

A c tiveV acc in a tion

Im m u n iza tion

P ass iveU se o f A n tisera

A rtific ia lly A cq u ired Im m u n ity(In jec tion )

A cq u ired Im m u n ity

Artificially Acquired Passive ImmunityArtificially Acquired Passive Immunity

• Humoral Antibodies Acquired By Injection

• Lasts for Few Weeks• Antisera

Typ es o f Im m u n ity

A c tiveS im p le E xp osu re

L ife lon g o r S h ort Term

P ass iveTran sp lacen ta l Tran s fe r

C o lu s tru m

N atu ra lly A cq u ired Im m u n ity(In fec tion )

A c tiveV acc in a tion

Im m u n iza tion

P ass iveU se o f A n tisera

A rtific ia lly A cq u ired Im m u n ity(In jec tion )

A cq u ired Im m u n ity

Gel Electrophoresis is Used to Gel Electrophoresis is Used to Check for AntibodiesCheck for Antibodies

Albumen

Alpha

Beta

Gamma

Globulins

By taking advantage of distinct physical characteristics of different polypeptide species such as size, electrical charge, and shape, a complex mixture of proteins can be resolved electrophoretically by applying the sample to a gel matrix in the presence of an electric current.

How Does This Work?How Does This Work?

• A charged protein will migrate in an electric field relative to its net charge.

• However, as the molecule migrates through the gel matrix in response to the electric current, its mobility will be retarded as a function of the size and shape of the protein by the sieving effect of the gel matrix.

Antibodies are found in the gamma fraction of the serum and are termed serum globulin or gamma

globulin

AlbumenAlbumen

Alpha Beta GammaAlpha Beta Gamma

Normal Values

Normal Values    Total protein: 6.4 to 8.3 g/dL Albumin: 3.5 to 5.0 g/dL Alpha-1 globulin: 0.1 to 0.3 g/dL Alpha-2 globulin: 0.6 to 1.0 g/dL Beta globulin: 0.7 to 1.2 g/dL Gamma globulin: 0.7 to 1.6 g/dL

Decreased total protein may indicate:• Malnutrition• Nephrotic syndrome• Gastrointestinal protein-losing enteropathy

Increased alpha-1 globulin proteins may indicate: • Chronic inflammatory disease (for example,

rheumatoid arthritis, SLE) • Acute inflammatory disease • Malignancy

Decreased alpha-1 globulin proteins may indicate: • Alpha-1 antitrypsin deficiency

Increased alpha-2 globulin proteins may indicate: • Acute inflammation • Chronic inflammation

Decreased alpha-2 globulin proteins may indicate: • Hemolysis

Increased beta globulin proteins may indicate: • Hyperlipoproteinemia (for example, familial

hypercholesterolemia) • Estrogen therapy

Decreased beta globulin proteins may indicate: • Congenital coagulation disorder• Consumptive coagulopathy• Disseminated intravascular coagulation

Increased gamma globulin proteins may indicate: • Multiple myeloma • Chronic inflammatory disease (e.g., rheumatoid

arthritis, SLE) • Hyperimmunization• Acute infection • Waldenstrom's macroglobulinemia • Chronic liver disease

NormalNormal

Significantly Significantly Increased Increased Gamma Gamma GlobulinGlobulin

AlbumenAlbumen

• Albumin is synthesized by the liver using dietary protein.

• Its presence in the plasma creates an osmotic force that maintains fluid volume within the vascular space.

• A very strong predictor of health; low albumin is a sign of poor health and a predictor of a bad outcome.

Horizontal Ridges in Fingernails is a Sign of Horizontal Ridges in Fingernails is a Sign of Low AlbumenLow Albumen

Low Albumen Can IndicateLow Albumen Can Indicate

• Dehydration • Hypothyroidism • Chronic debilitating diseases• Malnutrition - Protein deficiency • Dilution by excess H2O (drinking too much water, which is

termed “polydipsia,” or excess administration of IV fluids) • Kidney losses (Nephrotic Syndrome) • Protein losing-enteropathy (protein is lost from the

gastrointestinal tract during diarrhea) • Skin losses (burns, exfoliative dermatitis) • Liver dysfunction (the body is not synthesizing enough

albumin and indicates very poor liver function)

Humoral and Cell MediatedHumoral and Cell Mediated

Our Immunity is Expressed Via Our Immunity is Expressed Via Two Different MechanismsTwo Different Mechanisms

Humoral Immunity = AntibodiesHumoral Immunity = Antibodies

• Found in Body Fluids

• Involves Specialized Lymphocytes Called B Cells that Produce Antibodies

• Produced in Response to a Specific Antigen

• Defend the Body Against Bacteria, Viruses, and Toxins in Blood Plasma and Lymph (Extracellular Presence)

An Antibody Molecule is shaped like the Letter Y and has TWO Identical ANTIGEN BINDING SITES that precisely fit the shape of a ParticularAntigen.  Lock and Key.

These sites allow each Antibody to bind to TWO Antigens.

By binding to two By binding to two antigens, antibodies antigens, antibodies make antigens clump make antigens clump together. together. (AGGLUTINATION)(AGGLUTINATION)

• The clumped Antigens are not active. 

• Macrophages ENGULF and DESTROY the Clumped Antigens..

• Bone Marrow Stem Cells (Plasma Cells) Give Rise to B-Cells

• Liver in Fetus Does Same• B-Cells Migrate to Lymph Nodes• Recognition Process Occurs In Which a Mature

B-Cell will Recognize an Antigen with Antigen Receptors and produceantibodies.

Cell-Mediated Cell-Mediated ImmunityImmunity

• Involves Specialized Lymphocytes Called T-Cells arising from the Thymus Gland

• No Antibody Production is Involved• Protect the Body from

– Intracellular bacteria and viruses– Multi-cellular parasites– Transplanted tissue– Cancer cells

T-Cells Attacking T-Cells Attacking a Cancer Cella Cancer Cell

Review and Remember Review and Remember

• Antigen – (Also Called an Immunogen) A chemical substance that causes the body to produce either specific antibodies or sensitized T-cells.

• Are foreign substances

• Can be microbial or non-microbial

Non-Microbial AntigensNon-Microbial Antigens• Pollen• Egg White• Transplanted Tissue• Peanut Butter

Most Antigens are Components Most Antigens are Components of Invading Microbesof Invading Microbes

• Proteins

- Nucleoproteins

- Lipoproteins

- Glycoproteins

Large Polysaccharides- Cell Walls- Capsules- Flagella- Toxins

The Nature of AntibodiesThe Nature of AntibodiesAn antibody (also called an Immunoglobulin) is a protein produced by B cells in response to the presence of an antigen and is capable of combining specifically with that antigen.

Antibody StructureAntibody Structure

• Monomer Single Bivalent Antibody

• Four Polypeptide Chains

• Two Heavy Chains• Two Light Chains• Variable Region• Constant Region• Y or T shaped

The Variable Region forms the tips of the monomer.The Variable Region forms the tips of the monomer.

The constant regions form the Base and the Stem RegionThe constant regions form the Base and the Stem Region

The Stem Region can Attach a Host Cell or ComplementThe Stem Region can Attach a Host Cell or Complement

(The Stem is called Fc as it is a fragment that crystallizes when cold)(The Stem is called Fc as it is a fragment that crystallizes when cold)

Immunoglobulin ClassesImmunoglobulin Classes

• IgG / Monomer• IgM / Pentamer• IgA / Dimer• IgD / Monomer• IgE / Monomer

IgGIgG

• Prevalent / 75% - 80% in Body Fluids (Serum)

• Provide Naturally Acquired Passive Immunity

• Neutralize Toxins, Fight Bacteria and Viruses

• Participate in Complement Fixation• Enhance Phagocytosis• Cross Blood Vessels• Cross Placenta (Unique to IgG)

YY

IgM IgM • Five Monomers, Largest • Found in Blood and Lymph • Involved in Agglutination in

Blood Typing• Participate in Complement

Fixation• Compose 5-10%• Can’t Move Freely / Stay in

Blood Vessels• First Responder to Infection• Short Lived

YYYY

YYYY YY

IgAIgA• Dimers / Compose 10-15%• Protect Mucosal Surfaces

from Pathogens / Saliva, Tears, Blood

• Repel Respiratory Infections• Present Colostrums • Protect Infants / GI

Infections • A small number of people

do not make IgA antibodies. YY

YY

IgDIgD

• Monomer• IgD antibodies are

found in small amounts primarily in the tissues that line the belly or chest. How they work is not clear.

• Compose 0.2%

IgEIgE

• Binds to Mast Cells and Basophiles• Found in the Lungs, Skin, Mucus Membranes / 0.002%• Protects the host against invading parasites causing the body to

react against foreign substances such as pollen, fungus spores, and animal dander.

• They may occur in allergic reactions to milk, some medicines, and some poisons.

IgE antibody levels are often high in people with allergies IgE antibody levels are often high in people with allergies resulting in release of histomine (redness or hives)resulting in release of histomine (redness or hives)

Antibody TiterAntibody Titer

• The antibody level in the blood is a reflection of the body's past experience or exposure to an antigen, or something that the body does not recognize as self.

Immunological MemoryImmunological Memory• Titers for IgM usually rise abruptly at the time of

infection–acute phase and fall slowly; during the 'convalescent' phase,

• IgG then increases and stays elevated for life.

ApoptosisApoptosis

• Programmed Cell Death that Unneeded Lymphocytes Undergo

• 100 Million Daily Produced and Destroyed

• Shrink / Ingested

• Violent Death (Bursting) Triggers Inflammation