Specific Defenses of the Host

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Specific Defenses of the Host

• Microbiology 2314

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Innate Resistance

• An individuals genetically predetermined
  resistance to certain diseases
• We are born with this resistance.
• Ex. Resistance to AIDS due to a Delta-32 gene

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Humans Have Innate Resistance to a Number of
Different Things

• Bacteria
• Viruses
• Fungi
• Protozoa

• Insect Venom
• Transplanted Tissue
• Cancer Cells
• Diseases

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Individual Resistance is Affected By

• Gender
• Age
• Nutritional Status
• General Health

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Resistance 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)

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Serology

• Looks at reactions between antibodies and
  antigens
• A specialized branch of microbiology.
• Uses serum samples

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Remember!

• Antigens provoke an immune response.
• Antibodies are produced to respond to antigens.

Antigens ? Antibodies ? Protection
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Immunity Obtained After Birth
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Naturally Acquired Active Immunity

• Immunity Resulting from Infection
• May be Long Term

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Naturally Acquired Passive Immunity

• Mother to Fetus
• Transplacental Transfer
• Colostrum
• Few Months Duration

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Artificially Acquired Active Immunity

• Immunity Resulting from Injection
• (Vaccination)
• Attenuated Vaccines
• Inactivated Vaccines
• Killed Vaccines
• Toxoid Vaccines

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Artificially Acquired Passive Immunity

• Humoral Antibodies Acquired By Injection
• Lasts for Few Weeks
• Antisera

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Gel Electrophoresis is Used to Check for
Antibodies
Albumen
Alpha
Beta
Globulins
Gamma
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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.
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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.

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Antibodies are found in the gamma fraction of the
serum and are termed serum globulin or gamma
globulin
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Albumen
Alpha Beta Gamma
Normal Values
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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
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• 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

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• 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

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• 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

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Normal
Significantly Increased Gamma Globulin
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Albumen

• 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.

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

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Humoral and Cell Mediated
Our Immunity is Expressed Via Two Different
Mechanisms
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Humoral 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)

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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.
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By binding to two antigens, antibodies make
antigens clump together. (AGGLUTINATION)
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• The clumped Antigens are not active. 
• Macrophages ENGULF and DESTROY the Clumped
  Antigens..

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• 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 produce
• antibodies.

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Cell-Mediated Immunity

• 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

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T-Cells Attacking a Cancer Cell
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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

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Non-Microbial Antigens

• Pollen
• Egg White
• Transplanted Tissue
• Peanut Butter

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Most Antigens are Components of Invading Microbes
Large Polysaccharides - Cell Walls -
Capsules - Flagella - Toxins

• Proteins
• - Nucleoproteins
• - Lipoproteins
• - Glycoproteins

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The Nature of Antibodies
An 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.
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Antibody Structure

• Monomer Single Bivalent Antibody
• Four Polypeptide Chains
• Two Heavy Chains
• Two Light Chains
• Variable Region
• Constant Region
• Y or T shaped

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The Variable Region forms the tips of the
monomer. The constant regions form the Base and
the Stem Region The Stem Region can Attach a Host
Cell or Complement (The Stem is called Fc as it
is a fragment that crystallizes when cold)
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Immunoglobulin Classes

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

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IgG
Y

• 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)

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IgM
Y
Y
Y
Y
Y

• Five Monomers, Largest
• Found in Blood and Lymph
• Involved in Agglutination in Blood Typing
• Participate in Complement Fixation
• Compose 5-10
• Cant Move Freely / Stay in Blood Vessels
• First Responder to Infection
• Short Lived

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IgA
Y
Y

• 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.

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IgD

• 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

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IgE

• 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.

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

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Immunological Memory

• Titers for IgM usually rise abruptly at the time
  of infectionacute phase and fall slowly during
  the 'convalescent' phase,
• IgG then increases and stays elevated for life.

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Apoptosis

• Programmed Cell Death that Unneeded Lymphocytes
  Undergo
• 100 Million Daily Produced and Destroyed
• Shrink / Ingested
• Violent Death (Bursting) Triggers Inflammation