Specific Defenses of the Host

1. Specific Defenses of the Host Microbiology 2314

3. Innate 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

4. Bacteria Viruses Fungi Protozoa Insect Venom Transplanted Tissue Cancer Cells Diseases Humans Have Innate Resistance to a Number of Different Things

5. Individual Resistance is Affected By • Gender • Age • Nutritional Status • General Health

6. 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)

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

9. Remember! • Antigens provoke an immune response. • Antibodies are produced to respond to antigens. Antigens  Antibodies  Protection

10. Immunity Obtained After Birth

11. Naturally Acquired Active Immunity • Immunity Resulting from Infection • May be Long Term

12. Naturally Acquired Passive Immunity • Mother to Fetus • Transplacental Transfer • Colostrum • Few Months Duration

13. Artificially Acquired Active Immunity • Immunity Resulting from Injection (Vaccination) • Attenuated Vaccines • Inactivated Vaccines • Killed Vaccines • Toxoid Vaccines

14. Artificially Acquired Passive Immunity • Humoral Antibodies Acquired By Injection • Lasts for Few Weeks • Antisera

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

16. 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.

17. 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.

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

20. Albumen Alpha Beta Gamma Normal Values

21. 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

22. 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

23. 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

24. 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

25. Normal Significantly Increased Gamma Globulin

26. 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.

27. Horizontal Ridges in Fingernails is a Sign of Low Albumen

28. 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)

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

30. 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)

31. 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.

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

33. The clumped Antigens are not active.  • Macrophages ENGULF and DESTROY the Clumped Antigens..

34. 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.

35. 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

37. T-Cells Attacking a Cancer Cell

39. 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

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

41. Most Antigens are Components of Invading Microbes Large Polysaccharides - Cell Walls - Capsules - Flagella - Toxins • Proteins - Nucleoproteins - Lipoproteins - Glycoproteins

42. 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.

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

44. 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)

45. Immunoglobulin Classes • IgG / Monomer • IgM / Pentamer • IgA / Dimer • IgD / Monomer • IgE / Monomer

46. 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)

47. Y Y Y IgM Y Y • 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

49. Y Y IgA • 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.

50. 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%