KEY TO IMMUNOLOGY CHALLENGE QUESTIONS1-Why is phagocytosis necessary for most of the body's immune responses to be initiated? What are the main phagocytic cells of the body and where are they found?The phagocytic cells process the invading pathogen, placing antigens on their own cell surface. These antigen-bearing cells alone travel to the lymphatic tissues and present the antigens to the T and B lymphocytes. Without processing, the T and B cells normally do not recognize or respond to the antigenic material. Phagocytic cells include macrophages in tissues, monocytes inthe blood, neutrophiles in the blood and tissues. 2-How do natural killer cells and cytotoxic T-cells differ from one another? How are they alike?Both natural killer cells and cytotoxic T-cells recognize abnormal eukaryotic cells (abnormal self or parasitic by the MHC-1 on their surface) and destroy them using perforin to rupture the cell. Natural killer cells, however, roam the body and destroy ANY abnormal cell, while cytotoxicT-cells are produced in large numbers in response to a specific antigen within the cell’s MHC-1, and seek and destroy cells bearing that specific antigen ONLY. Cytotoxic T-cells also secrete cytokines while at the site of infection to increase phagocytic effectiveness.3-Interferon and complement proteins may both be active during infections. Differentiate between where they originate, and their effect on the nearby cells in each case.Interferon is secreted from any type of cell infected by a virus, and is released to provide protection from viral invasion to the immediate neighboring cells as they make anti-viral proteins, AVP, in response to the interferon. Complement proteins, in contrast, are present in the body’s fluids and tissues at all times, although separate from one another. Complement proteins may come together to create a membrane attack complex (MAC), to increase rate of phagocytosis (opsonize), or to stimulate inflammation in two ways: a)when certain abnormal bacterial surface molecules are detected or more commonly b)when antibodies are attacked to abnormal or foreign cells, and complements begin binding to the Fc portion of the antibodies. 4-What special problems do the tuberculosis and gonorrhea pathogens present to the immune system? Which of the two branches of specific immunity are best at destroying them, and why?These two pathogens survive within the cytoplasm of other cells, therefore they are protected from many of the effects of antibodies. Our best defense against them comes in the form of cytotoxic T-cells, which recognize the abnormal self cells harboring the pathogens (by their MHC-1 antigen complex) and destroy them with perforin and granzyme, exposing the pathogens to other mechanisms of killing also. Also, complement may be triggered by antibodies adhering to the surface of the abnormal cell to lyse the cell (MAC). 5-Hypothesize about the consequences of the following abnormalities in the immune response ofan individual: - Inability of the body's cells to form lysosomes o phagocytosis would be inefficient, would not result in antigen on surface, therefore cell mediated and humoral immunity would not be initiated. - Nonfunctional thymuso T-cells produced by bone marrow would not mature. Cell-mediated immunity could not operate, and because of lack of helper T-cells, no humoral immunity would occur also. - B-lymphocytes fail to produce functional clones o plasma cells are not produced, so no antibodies would be produced. - lymphatic vessels blocked by parasitic filarial worm (elephantiasis) o drainage of tissues poor, so few phagocytic cells with antigens would get to lymphnodes. The few cytotoxic T-cells and antibodies made would not be able to pass through lymph vessels easily on their way to the bloodstream and tissues. - leukemia in which bone marrow is unable to produce new white blood cells o white blood cells with short life spans, such as phagocytes would decline first, therefore lowering the cell-mediated and humoral responses. T-cells and B-cells would also decline in number, so that the entire immune system would eventually shut down, leaving the individual vulnerable to any pathogen. 6-Which antibody type(s) would be found in the following locations in the body: - breast milk -IgA (as dimer)- blood stream -IgG, IgM, IgA (as monomer), IgE, (IgD) - tissue fluid -IgG, IgA (as monomer), IgE, (IgD) - fetal tissues (maternal antibodies) -IgG - tissue lining the bronchioles during allergic attack to ragweed -IgE 7-How would antibodies be most likely to destroy the following antigen types: - viral capsid -neutralization - cell wall antigen of gram - bacterium - opsonization, complement activation (all 3 mechanisms), agglutination- flagellar antigen of bacterium - opsonization, agglutination, complement activation (all 3mechanisms)- exotoxin of bacterium -neutralization - cell surface antigen of protozoa -complement activation (MAC and inflammation only), NK activation8-Rank the following cells and defense molecules in the order of appearance in the immune response of an individual confronted with a new antigenic invader. Do a second ranking of the same items during a second exposure to the same invader.HINT: This will make more sense to you if you write them out in the order they are numbered ona separate piece of paper! FIRST EXPOSURE / SECOND EXPOSURE - 4-perforin and granzyme 3 from memory resp., 7 from new- 5-plasma cells 3 from memory B, 6 from new- 5-memory B-cells 2 from previous exp., 6 from new- 2-TH1cells 5- 1-APC cell arrives at lymph node 4- fully loaded mast cells *even with second exposure, probably not enough IgE produced yet to sensitize individual- 6-antibodies 4 from memory, 7 from new- 4-TH2 cells 5- 3-cytotoxic T-cells 2 from memory T, 6 from new- 6-IgM 7 from new- 3-memory T-cells 1 from previous exp., 6 from new- 7-IgG 4 from memory, 7 from new9-Which antibody(s) are: monomers? IgG, IgE, IgD dimers? IgA polymers? Nonepentamers? IgM10-How does IgE differ from other immunoglobulins in terms of what it can bind to? (Hint: whatis bound at each end of the molecule, and compare this to other antibody types)IgE has the ability to bind to mast cells, basophiles and eosinophiles by the Fc portion, during sensitization, and then it also binds to allergens by the Fab portion of the molecule, just like other immunoglobulins, during an allergic reaction (degranulation). Other antibody types use their Fc portion to bind to complement proteins