1. Third Line of Defense Antibodies and the Cell Mediated Immune System

2. Lesson Objectives: – Define specific immunity and its role in protecting host functions. – Describe the roles of the humoral branch and the cell mediated branch of the immune system. – List the properties of antigens. – Compare the structure and function of the 5-clases of antibodies. – State the origin and function of B cells and T cells. – Explain the role of the antigen presenting cells. – Describe the interleukins that control the formation of antibodies and activation of T cells. – Briefly describe the cell mediated immune response to immunogenic stimulation (including the types and functions of interferon). – Contrast the 4-types of acquired immunity.

3. Some vocabulary first: Third Line of Defense: a host reaction to non-self that is induced but specific to the molecular composition of the non- self. Antibody: a protein produced by B lymphocytes that specifically bonds to molecules on/of non-self. Antigen: the non-self molecules that bond to a host’s antibodies. Humoral response: The part of the Third Line of Defense that involves dissolved chemicals (usually proteins and polypeptides) in the blood. Cell mediated response: The part of the Third Line that involves stimulation of specific cells (usually T lymphocytes).

4. The star of the show for the Third Line: LYMPHOCYTES Lymphocytes--~15-40 % of white blood cells. They are formed in bone marrow. Three types: B Lymphocytes: mature in bone marrow. These produce all antibodies. T Lymphocytes: mature in the thymus gland. Involved in presentation of antigen, cell mediated immunity, and assist B lymphocytes. Natural killer cells: cell mediated, target cancer cells.

5. Development of an antibody response Scenario: Timmy, 8 year old boy in the woods gets bit by a baby rattlesnake. The boy is near death, but survives, requiring three months of recuperation. Two years later, another rattlesnake bite. Temporary paralysis of the right leg, two weeks of convalescence. Six months later: another bite, this time from an adult rattlesnake. Timmy is limping badly for a week. Over the next several years, Timmy is bitten by rattlesnakes near his home. Never sustains any more discomfort than the occasional heavy bleeding episode. Timmy is immune to rattlesnake venom.

6. Bill Haast, born Dec 30, 1910, died June 15, 2011. Bitten by venemous snakes and lizards 172 times. For Mr. Haast, snake venom was an antigen. His body mounted an immune response that involved both humoral immunity and cell mediated immunity.

7. I. Antigen and antigen presentation Antigens are any molecules that stimulate an immune response. An immune response involves two features: - specificity (one antigen always creates the same response) - memory (that antigen creates the response every time the host is exposed) Not every molecule is an antigen: Antigens are usually - large molecules - have molecular variety (are not repeats of the same molecule)

8. Molecules that make effective antigens: Proteins Polypeptides Complex polysaccharides (multiple kinds of sugars) Glycoproteins, lipoproteins (e.g. peptidoglycan, exotoxins, viral capsids, bacterial flagella, fimbriae)

9. Molecules that do not make effective antigens (they don’t elicit a strong immune response): Simple sugars (too small) DNA or RNA (regular repeats) Polysaccharides (e.g. starch, glycogen) (regular repeats) Antigen presentation: After various phagocytic cells have ingested non-self entities, the antigens on non-self are bound to proteins on antigen presenting cells (APC). Examples of APCs are macrophages, B lymphocytes, and dendritic cells (another macrophage).

10. Antigen presenting cell Antigen Class II MHC protein MHC proteins (MHC = Major Histocompatibility Complex are the proteins in the host that make immune cells what they are. Class I MHC: These are on all nucleated host cells (not RBCs). They identify a cell as “self.” Cells with the wrong Class I MHC proteins are non-self and must be destroyed. Class II MHC: These are only on APCs. These are proteins involved with presenting antigen on the surface of APCs.

11. II. T lymphocytes (T cells) attack Once an antigen has been presented, T cells and B cells (lymphocytes) go into action. They each respond to different types of antigens. T cells: Generally target eukaryotes, virally infected cells, intracellular pathogens (e.g. tuberculosis). Four types of T cells work here:

12. T Cell nameSurface ReceptorsFunction T helper (T h )CD4Release Interleukin 2, which allows B and T cells to mature, stimulates B cells to produce antibodies. Other cytokines (chemicals that act on cells) stimulate antibody diversity. T regulatory (T r )CD4Reduce the immune response of B and T cells. Prevents hypersensitivity (over-identification of non-self, like allergy) and auto-immunity (immune response where self is incorrectly identified as non-self). T memory (T m )CD4Formed at the same time as other types of T cells. T memory cells are long lived, and upon attack by the same antigen, reproduce to provide T h and T c cells for future pathogen attacks. T cytotoxic (T c )CD8These cells kill things. Dead.

13. A non-specific piece of the Third Line of Defense: Natural Killer cells and interferon Viral infection of cells causes certain cells to produce a protein called interferon. Interferon is produced early in viral infection, so it is considered part of the Second Line of Defense. Three types of interferon, based on their origin: α interferon: produced by most white blood cells. β interferon: produced by fibroblasts and epithelial cells. γ interferon: produced by lymphocytes

14. Functions of interferons Interferon is produced by the cell in response to viral infection or cancerous transformation. Exact mechanisms of action are not clear, but interferons seem to stimulate immune cells (T cells and Natural killer cells) to attack infected or cancerous cells. Natural Killer cells: lymphocytes which non- specifically attack cancer cells and virally infected cells.