11
Non-Specific Host Defenses and Host Systems
16-1. Which exists before one encounters an infectious agent?
A. large amounts of specific antibody
B. vigorous, specific, cell-mediated immunity
C. innate immunity
D. specific adaptive immunity
E. specific acquired immunity
16-2. Which body site is protected by a sheet of keratinized cells and acidic secretions produced by normal microflora and associated glands?
A. respiratory tract
B. skin
C. eye
D. gastrointestinal tract
E. genitourinary tract
16-3. Of the cell types listed below, which are "professional phagocytes?"
A. erythrocytes and platelets
B. lymphocytes
C. T cells and B cells
D. neutrophils and macrophages
E. endothelial cells and epithelial cells
16-4. A patient has extensive, severe burns over most of his upper body. What defense mechanism has he lost?
A. confluent barrier of cells with normal flora
B. lysozyme
C. mucus secreting cells and ciliated epithelium
D. inflammatory response and phagocytosis
E. flushing action of tears
16-5. Which of the cells listed below is found in highest number in the blood of normal humans?
A. lymphocyte
B. basophil
C. eosinophil
D. monocyte
E. neutrophil
16-6. In the bone marrow of normal humans one can detect stem cells and neutrophils.
A. true
B. false
16-7. Factors that improve the efficiency of ingestion during phagocytosis are called:
A. lysosomes
B. phagosomes
C. phagolysosomes
D. opsonins
E. cytokines
16-8. Which of the following should not be considered a primary part of innate immunity?
A. lysozyme
B. specific IgG
C. the normal bacterial flora
D. skin
E. mucus on membranes
16-9. A mucociliary escalator functions to:
A. trap and sweep pathogens into the urine
B. kill via lysozyme activity
C. harbor normal flora that discourage pathogens from colonizing
D. produce fatty acids with a low pH that kills microbes
E. trap and sweep microbes from the bronchi back up to the throat to be swallowed
16-10. Which of the following bacterial cell structures is most likely to inhibit phagocytosis of bacterial cells by human neutrophils?
A. ribosomes
B. flagella
C. capsule
D. sex pili
E. cell membrane
16-11. Which of the following parts of the bacterium Streptococcus pneumoniae (the pneumococcus) is noted for its ability to protect the pneumococcus from being ingested by human phagocytic cells such as neutrophils?
A. cell wall
B. flagella
C. capsule
D. cell membrane
E. chromosome
16-12. Which is part of the "first line of defense" (innate immunity)?
A. skin
B. mucus blanket
C. lysozyme
D. low pH of the stomach
E. all of the above
16-13. Which total leukocyte (white blood cell) count would be considered normal?
A. 500 cells/mm3
B. 100 cells/mm3
C. 100,000 cells/mm3
D. 1,000,000 cells/mm3
E. 7,000 cells/mm3
16-14. Which cell listed below is a professional phagocytic cell?
A. erythrocyte
B. platelet
C. lymphocyte
D. neutrophil
E. epithelial cell
16-15. When a patient's chest x-ray reveals granulomas, this is an indication of chronic inflammation of lung tissue:
A. true
B. false
16-16. Neutrophils are found only in the circulating blood, never in other tissues.
A. true
B. false
16-17. The proper term to describe a person having very low numbers of the leukocyte that is normally the predominant circulating leukocyte is:
A. lymphopenic
B. lymphocytotic
C. neutropenic
D. neutrophilic
E. anemic
16-18. Which of the white blood cells (leukocytes) listed below is found in lowest number in the blood of normal humans?
A. lymphocyte
B. basophil
C. eosinophil
D. monocyte
E. neutrophil
16-19. A woman has been taking excessive amounts of antacids for heartburn. These tablets are very alkaline. Which defense mechanisms might be altered by her actions?
A. mucociliary escalator
B. lysozyme
C. flushing action of urine
D. skin pH
E. pH of stomach
16-20. The proper term to describe a person having abnormally high numbers of the leukocyte that is normally the predominant circulating blood leukocyte is:
A. lymphcytotic
B. neutropenic
C. anemic
D. thrombocytopenic
E. neutrophilic
16-21. Fever is caused by endogenous pyrogens stimulated by a cytokine response triggered by exogenous pyrogens.
A. true
B. false
16-22. Nonspecific host defenses include chemical substances such as:
A. antibodies
B. penicillin
C. lysozyme
D. A and C
E. B and C
16-23. Complement is a host defense which:
A. functions in two pathways
B. consists of proteins found in blood
C. is rapid and non-specific
D. promotes opsonization
E. all of the above
16-24. In immune cytolysis, neutrophils cause formation of lesions in the plasma membranes of the infectious agent and causes lysis.
A. true
B. false
Leukocyte lineage: All blood cells arise from a bone marrow cell called the pluripotent stem cell, which is capable both of proliferation to make more of itself and differentiation into the various types of white blood cells (leukocytes) as well red blood cells (erythrocytes). When the stem cell differentiates it first commits itself to being either lymphoid or myeloid. The lymphoid pathway gives rise to B lymphocytes (which ultimately differentiate into plasma cells that secrete antibody) and T lymphocytes (which further differentiate into CD4+ cytokine-secreting "helper" T cells, and CD8+ killer or "cytotoxic" T cells). The myeloid pathway gives rise to the erythrocytes, megakaryocytes (that become platelets), basophils, mast cells, eosinophils, and myelomonocytic precursor cells that eventually differentiate into monocytes (macrophages) and neutrophils. The precise lineage of natural killer cells and dendritic cells is not well understood. Various cytokines drive cells to differentiate into the different types of leukocytes.
Cytokines drive hematopoiesis
Hematopoiesis, the generation of blood cells, is regulated by a complex network of cytokines. See the diagram in Figure 3-2 in your textbook; Table 3-1 from your textbook is condensed below. The principle is simple even if the process is not. If the cytokine binds to the progenitor (precursor) cell and stimulates that cell, then the cell will differentiate into a more mature form of leukocyte. Notice that some cytokines stimulate several different progenitor cells, whereas other cytokines act only on one or two progenitors. Most progenitors need combinations of cytokines to fully differentiate.
TARGET CELL / STIMULATING CYTOKINESPluripotent stem cell / IL3, GM-CSF
Myeloid stem cell / IL3, IL6, GM-CSF
Myelomonocytic progenitor / IL3, GM-CSF, G-CSF, M-CSF
Monocyte progenitor / IL3, GM-CSF, M-CSF
Neutrophil progenitor / IL3, IL8, GM-CSF, G-CSF
Eosinophil progenitor / IL3, IL5, GM-CSF
Basophil progenitor / IL4, GM-CSF
Mast cell / IL3, IL4, IL9, IL10, GM-CSF
Megakaryocyte / IL3, GM-CSF, EPO
Erthroid progenitor / IL3, GM-CSF, EPO
B lymphocyte progenitor / IL4, IL7
T lymphocyte progenitor / IL7
Morphology of cells: Different leukocytes are often distinguished by their staining characteristics. The acidic stain eosin is negatively charged and binds to positively charged molecules; the basic dye methylene blue is positively charged and binds to negatively charged molecules. Giemsa stain, a mixture of eosin and methylene blue, is used to stain leukocytes. Granulocytes (neutrophils, eosinophils, basophils, and mast cells) in particular can be distinguished by the color and staining intensity of their granules.
Cell Type / Giemsa StainingEosinophil / granules stain red
Basophil / granules stain deep blue
Neutrophil / granules stain light purple
Mast cells / granules stain deep blue
The shape of the nucleus also differentiates different type of cells. Polymorphonuclear cells (neutrophils, eosinophils, and basophils) have nuclei that are highly variable in shape and appear to be segmented like links of sausage. Mononuclear cells have nuclei that are either kidney shaped (monocytes, mast cells) or round (lymphocytes). The amount of cytoplasm also distinguishes different cells; for example, monocytes have an abundance of cytoplasm as do the granulocytes. Resting (unactivated) lymphocytes are the smallest intact leukocyte, measuring about 6 microns in diameter, with only a small amount of cytoplasm (most of the cell volume is occupied by the nucleus). Activated lymphocytes (lymphoblasts) are ~15 microns in diameter and have more abundant cytoplasm. For comparison, the granulocytes are ~12-15 microns in diameter, and activated macrophages in tissues can grow to ~50 microns in diameter.
Surface markers are molecules found on the plasma membranes of some but not all cells and can be used to identify the different cell types. Examples of surface markers are receptors for antibody, complement receptors, and CD molecules. Macrophages, for example, have a receptor with high affinity for the IgG class of antibody, as well as two types of low affinity receptors; granulocytes have only the low affinity receptors. Basophils and mast cells have high afffinity receptors for the IgE class of antibody. Lymphocytes can be distinguished because B cells (until they terminally differentiate into plasma cells) bear antibodies as surface markers; this a unique marker, no other cell produces antibodies. T cells do not have antibodies but instead have T cell antigen receptors and associated CD3 molecules, which serve as unique markers.
Natural history: The most abundant leukocyte in blood is the neutrophil (50-70% of all leukocytes), followed by lymphocytes (20-40%), monocytes (1-6%), eosinophils (1-3%), and basophils (~0.5%). In contrast, neutrophils are the most short-lived. They spend ~1/2 day in the blood and about 1-3 days in tissues before they die by apoptosis. The life span of eosinophils is longer (1-2 weeks), and macrophages in tissues (which come from the monocytes in blood) may live many months. Lymphocytes that are unstimulated may live weeks whereas antigen-stimulated lymphocytes that have become memory cells may survive for years.
In the blood there are almost five times as many T lymphocytes as B lymphocytes. Mature T lymphocytes are typically either CD4+ or CD8+ (that is, they bear on their cell surfaces either the CD4 molecule or the CD8 molecule). In blood, the CD4+:CD8+ ratio is ~2:1.
Functions:
Phagocytosis: Neutrophils and monocytes/macrophages are very effective in undergoing phagocytosis. Eosinophils are poorly phagocytic in the sense that they do not readily engulf particles such as bacteria and yeast, but they can adhere to and degranulate on large parasites such as worms. Phagocytosis is a form of defense that the body can launch immediately upon invasion by pathogens.
Inflammation: Most aspects of inflammation are initiated or mediated by granulocytes and monocytes/macrophages. They secrete cytokines that act on blood vessels (to cause vessel dilation and the leakage of fluid and cells), muscles (mainly to cause contraction), and the nervous system (to cause fever, lethargy, loss of consciousness).
A form of inflammation is the allergic reaction known as immediate hypersensitivity. This type of allergy is mediated by mast cells and basophils when the IgE class of antibody binds to IgE receptors on the cells and also binds to allergens (antigens). The cells release chemicals that cause sneezing, shortness of breath, watery eyes, etc., which are associated with allergies such as hay fever. Although allergies would seem to have no benefit for defense against disease, these same inflammatory mechanisms participate in the fight against parasites, which is a serious health problem in some developing countries.
Cytotoxicity: In addition to phagocytosis, macrophages, natural killer cells, and T lymphocytes can undergo the process of cytotoxicity. The invading organism (cell) is not engulfed, rather, the cytotoxic cells attach to the invading cell and either release cytokines or use membrane proteins to signal the invading cell to die. (There are various forms of cytotoxicity that will be discussed later in the semester.)
Cytokine secretion: Although most cells are capable of secreting some chemicals, the cells best known for cytokine secretion are the macrophages and the CD4+ T lymphocytes. Because the cytokines then direct the action of other cell types, macrophages and CD4+ T lymphocytes are central to the regulation of immunity.
Antigen presentation: Unlike B lymphocytes, T lymphocytes cannot bind antigen directly but require that the antigen be processed and presented as small fragments on surface proteins (major histocompatibility complex, MHC) molecules. Most cells in the body can present antigen fragments to CD8+ T cells, but only certain cells (macrophages, dendritic cells, and B cells) are routinely able to present antigen to CD4+ T cells.
Antibody production: Antibody production is the task of B cells. When B cells start making antibodies the antibody molecules are located in the plasma membrane of the cells. When the B cells terminally differentiate into plasma cells the antibodies that are produced are not found in the membrane but rather are secreted, eventually to appear in the blood and the fluid that baths the tissues.
Other cells in the immune system:
Natural killer (NK) cells are cells with the morphology of large granular lymphocytes. They are a heterogenous group of cells and thus it is difficult to trace a clear genealogy for them. NK are defined more by function than structure. Their function is to kill abnormal cells without first being activated by antigen. Unlike cytotoxic T lymphocytes, NK cells are not antigen specific and they do not require presentation of antigen fragments on MHC molecules; in fact, the presence of MHC molecules on the target cell (the one to be killed) usually inhibits natural killing. NK cells also have a rather restricted range of targets that they can kill. If NK cells are exposed to certain cytokines they become more effective and promiscuous killers. These cells are called Lymphokine-Activated Killer (LAK) cells.
Dendritic cells are so named because of long extensions of cytoplasm that extend like tentacles from the main cell body. They are exceptionally efficient at processing and presenting antigen to CD4+ T lymphocytes. Dendritic cells are found in the many organs and tissues that house lymphocytes.
PLEASE TAKE THIS SELF TEST NOW.
There are 10 questions below. Use this exercise to test your knowledge and reveal areas that you may need to review.
1. The pluripotent stem cell
a. is found in the bone marrow
b. can differentiate to give rise to any leukocyte
c. can proliferate to make more of itself
d. all of the above
e. a, b, but not c
f. a, c, but not b
2. Which cytokine(s) is/are more active in myeloid rather than lymphoid differentiation?
a. IL3
b. IL7
c. GM-CSF
d. all of the above
e. a, b, but not c
f. a, c, but not b
3. A cytokine only affects nearby cells, not the cell producing it.