The First Line of Defence – Skin and Mucous Membranes

1. 10.1 – The Body’s Lines of Defence • The First Line of Defence – Skin and Mucous Membranes • as well as a physical barrier, skin secretes acids (pH 3-5) • lysozymes (antimicrobial enzymes) are secreted in sweat, tears, saliva, and mucous • mucous-covered cilia lining repiratory tract sweep foreign particles out • HCl and proteases destroy food-borne pathogens in stomach

2. The Second Line of Defence – White Blood Cells • nucleated WBC (leucocytes)are produced in the bone marrow and destroy pathogens by phagocytosis • digestion of pathogens releases chemical messengers which reset the thermostat in the hypothalamus to 40oC to create unfavourable conditions for pathogens to proliferate • most granulocytes are neutrophils which are drawn to an injury by chemotaxis, squeeze out between cells of capillaries and destroy both the pathogen and itself by phagocytosis and release of lysozyme, resulting in pus • agranulocytes are modified in the lymph nodes into lymphocytes and monocytes • monocytes migrate from the blood into tissues where they develop into macrophages that engulf pathogens by amoeboid pseudopods • B lymphocytes produce antibodies specific to antigens of pathogens

3. Nonspecific (Inflammatory) Response • an inflammatory response is a nonspecific immune response resulting in swelling, redness, heat, and pain (see Fig. 3, P. 463 and “Inflammatory response to infection” animation) • chemicals released by pathogens cause the release of histamines and prostaglandins which increase blood flow and permeability of capillaries • chemicals released by injured cells attract leucocytes •  Nelson CD Inflammatory Response Animation •  Section 10.1 Questions – P. 465, #2-5

4. 10.2 - THE IMMUNE RESPONSE • some macrophages reside permanently in brain, lung, kidney, liver, and connective tissue • others reside in lymphatic tissue (i.e. spleen, lymph nodes) to trap and filter pathogens in the blood The Lymphatic Organs

5. marker proteins (antigens = antibody generators) on pathogens activate one of about 20 antimicrobial plasma proteins (complement proteins) to aggregate and initiate an attack • (see Fig. 2, P. 467) •  first group forms an immobilizing coat •  second group creates pores through which water can enter to burst the cell  third group attaches to membrane, reducing solubility and attracting leucocytes for phagocytosis

6. Cell-Mediated Immune Response • when a pathogen is encountered for the first time, it is engulfed by a macrophage, antigens are displayed on the surface, and lymphokines are secreted  matching receptor sites of a helper T cell bind to antigen, release of IL-1 (pink) activates helper T lymphocytes,causing them to replicate and release IL-2 which stimulates other helper Ts and search-and-destroy cytotoxic killer T cells to create clones • helper Ts secrete BCGF which stimulate B lymphocytes to divide • BCDF cause some B cells to differentiate into super-antibody-producing plasma B cells  Nelson CD Cell-Mediated Immune Response Animation

7. Humoral (Antibody-Mediated) Response • when a previously-encountered pathogen is engulfed by a macrophage, a memory B cell with matching receptors binds to antigen • B cell engulfs pathogen, displays antigen-MHC complex on surface • attracts T cells activated by encounter with macrophage displaying pathogen antigen • T cells secrete BCGF and BCDF for the rapid production of antibodies • antibodies lock onto several pathogen antigens, immobilizing them and making them conspicuous

8. Antigen-Antibody Reactions • each antibody is similar in shape, variations existing only at the edge of each arm • antigen markers are complementary and therefore specific to a particular pathogen • antigen-antibody complex is conspicuous, more easily engulfed by wandering macrophages  Nelson CD Humeral Immune Response Animation

9. 10.3 - IMMUNE SYSTEM MALFUNCTIONS Inappropriate/Exaggerated Immune Responses – Allergies • harmless foreign bodies are mistaken for harmful invaders (i.e. dust, ragweed pollen, leaf moulds) • resulting nonspecific immune response causes swelling of tissue, secretion of mucous, and constriction of air passages • anaphylactic reactions result from severe food allergies (i.e. peanuts, shellfish, eggs, berries, milk) as well as drugs and vaccines, accompanied by swelling, hives, and itching • symptoms including weakness, sweating, breathing difficulty, nausea, diarrhea, blood pressure drop can combine to be life-threatening • precautions include an epipen containing epinephrine (adrenaline) which speeds the processing of allergens, and antihistamines

10. The Classical Allergic Reaction • classical allergic reactions are dependent upon previous exposure and sensitization to specific allergens that result in the development of antigen specific IgE antibodies  occur when allergens bind and crosslink IgE antibodies present on the cell membranes of mast cell and basophils, triggering the release of numerous mediators of inflammation • histamine increases capillary permeability, allowing proteins and macrophages to attack “invaders” • change in osmotic pressure reduces water absorption into capillaries, resulting in tissue swelling

11. Attacks of the Immune System on “Self” – Autoimmune Diseases • renegade lymphocytes treat the body’s cells as aliens and produce antibodies to attach to their membranes • rheumatoid arthritis is an immune response mounted against bones and connective tissues around the joints • rheumatic fever results from an exaggerated immune response which scars the heart • type I diabetes results from an immune response against -cells on islets of Langerhans • lupus results from the accumulation of antigen-antibody complexes in blood vessels, joints, kidneys, and skin

12. multiple sclerosis results from an attack on the myelin sheath of nerve cells

13. normally, renegade lymphocytes are held in check by suppressor T cells •  drugs or serious infection can weaken suppressor T cells •  supressor T’s decline with age •  defective supressor T’s can be innate • artificial immune suppressor drugs can reduce intensity of attack by renegades •  Section 10.3 Questions – P. 475, #1-5