1.Role of Adenosine Triphosphate
What is best known about ATP is its role as a universal “fuel” inside living cells. This fuel or energy drives biologic reactions necessary for cells to function. For a cell to function, it must be able to extract and use the chemical energy in organic molecules. When 1 mole (mol) of glucose metabolically breaks down in the presence of oxygen into CO2 and water, 686 kilocalories (kcal) of chemical energy are released. The chemical energy lost by one molecule is transferred to the chemical structure of another molecule by an energy-carrying or energy-transferring molecule, such as ATP. The energy stored in ATP can be used in various energy-requiring reactions and in the process is generally converted to adenosine diphosphate (ADP) and inorganic phosphate (Pi). The energy available as a result of this reaction is about 7 kcal/mol of ATP. The cell uses ATP for muscle contraction and active transport of molecules across cellular membranes. ATP not only stores energy but also transfers it from one molecule to another. Energy stored by carbohydrate, lipid, and protein is catabolized and transferred to ATP.
Emerging understandings are the role of ATP outside cells—as a messenger. In animal studies, using the newly developed ATP probe, ATP has been measured in pericellular spaces. New research is clarifying the role of ATP as an extracellular messenger and its role in many physiologic processes, including inflammation. 2.Lymphocytes, a type of WBC, activate macrophages and initiate specific, protective immune responses against pathogens and cancer. B lymphocytes produce antibodies, and T lymphocytes regulate other immune cells and kill viruses and cancer cells (see Chapter 7). Natural killer (NK) cells, a type of lymphocyte, eliminate virally infected and cancerous cells. NK cells have inhibitory and activating receptors that allow differentiation between infected or tumor cells and normal cells. If the NK cell binds to a target cell through activating receptors, it produces several cytokines and toxic molecules, which, in turn, kill the target cell.
3.Phagocytosis is the ingestion of microbes, foreign particles, or cell fragments 7 (Fig. 6.8). The two most important phagocytes for phagocytizing pathogens or damaged cells are neutrophils and macrophages. Neutrophils circulate in the blood in large numbers and are attracted to the area of injury by chemotactic factors, such as mast cell cytokines, chemokines, and complement. Activated neutrophils and endothelial cells express adhesion molecules, which increase the “stickiness” of the cells, causing these neutrophils to more readily adhere to the endothelial cell wall of the capillaries and venules. This process of increased adhesion is called margination, or pavementing. Neutrophil-endothelial interactions lead to diapedesis, the emigration of the cells through the interendothelial junctions.
4.The human body has several ways to protect itself from injury and infection. Innate immunity includes natural barriers and inflammation. Innate barriers form the first line of defense at the body's surfaces. They serve to prevent damage by the environment and thwart infection by pathogenic microorganisms. If the surface barriers are breached, the second line of defense, the inflammatory response, is activated to protect the body from further injury, fight infection, and promote healing. The third line of defense, adaptive immunity (also known as acquired or specific immunity), is induced through a slower and more specific process and targets particular invaders and diseased tissues for the purpose of eradicating them. Adaptive immunity also involves “memory,” which results in a more rapid response during future exposure to the same invader. Comparisons among defense mechanisms are described in Table 6.1. The information presented in this chapter introduces the components and processes of innate immunity and sets the stage for Chapter 7, which presents an overview of adaptive immunity; Chapter 8, which discusses alterations in immunity; and Chapter 9, which reviews infection. 5.Innate barriers form the first line of defense at the body's surfaces. These barriers can be physical, mechanical, and biochemical. Surface barriers also may house a group of beneficial microorganisms known as the “normal microbiome” that can protect us from pathogenic microorganisms. Physical Barriers The physical barriers offer considerable protection from tissue damage and infection. These barriers comprise tightly associated epithelial cells of the skin and of the linings of the gastrointestinal, genitourinary, and respiratory tracts (Fig. 6.1). When pathogens attempt to penetrate such barriers, they may be removed by mechanical means. Such 135microorganisms may be sloughed off with dead skin cells (which can then be replaced). Epithelial cells of the upper respiratory tract can trap microorganisms through the production of mucus and remove them through the action of hair-like cilia which move the mucus upward where it is expelled through coughing or sneezing. Invading microorganisms can be removed from the gastrointestinal (GI) tract through vomiting or defecation and from the urinary tract through urination. Other protective mechanisms of innate barriers include the relatively low temperature present on the skin and the low pH found in the stomach, both of which inhibit the growth of pathogenic microorganisms. 6.Inflammation is a protective response that supports recovery from injury and disease. Fig. 6.2 summarizes the process. When cellular or tissue damage occurs, inflammatory mediators are released, causing a number of changes in the microcirculation. The ultimate result of these changes is the migration of leukocytes, plasma proteins, and other biochemical mediators from the circulation into the nearby damaged tissue, where they can work together to destroy invaders, limit tissue injury, and promote healing. Uncontrolled or chronic inflammation plays a role in virtually all diseases, including heart and lung disease, cancer, neurodegenerative disorders, and rheumatologic disease. Inflammation is a dynamic process programmed to respond to cellular or tissue damage irrespective of the location or condition of the tissue. There is a rapid initiation of an interactive system of humoral (soluble in the blood) and cellular responses. Inflammation functions to destroy pathogens, trigger the adaptive immune response, limit the extent of tissue damage, and initiate the healing process. 7.Prostaglandins cause increased vascular permeability, neutrophil chemotaxis, and pain. Pain results from direct effects on nerves. They are long-chain, unsaturated fatty acids produced by the action of cyclooxygenase (COX) . COX exists in two different forms: COX-1, which activates platelets and protects the stomach lining, and COX-2, which is associated with inflammation. Particular drugs can have inhibitory effects on one or both COX entities. The inhibition of COX-1 is associated with a number of undesirable side effects. Among the most serious of such side effect involves the GI system, where the use of these agents can result in GI bleeding and ulcers. Aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) inhibit both COX-1 and COX-2. Their use to suppress inflammation is associated with GI tract bleeding. Selective COX-2 inhibitors are available and may offer an improved GI effect profile. However, all COX inhibitors have been associated with an increased risk for cardiovascular disease because of their effects on blood vessels and clotting.
8.Most type III hypersensitivity disease reactions are caused by antigen–antibody (immune) complexes that are formed in the circulation and are deposited in vessel walls or other tissues (Fig. 8.4). The primary difference between type II and type III mechanisms is that in type II hypersensitivity, antibody binds to antigen on the cell surface, whereas in type III, antibody binds to soluble antigen that was released into blood or body fluids. The immune complex is then deposited in the tissues. Type III reactions are not organ specific and most commonly result in a vasculitis in the skin, kidney, or lungs. The harmful effects of immune complex deposition are caused by complement activation and by neutrophils attempting to phagocytose the immune complexes. During the attempted phagocytosis, large quantities of lysosomal enzymes are released into the inflammatory site instead of into phagolysosomes. The attraction of neutrophils and the subsequent release of lysosomal enzymes cause most of the resulting tissue damage.
9.Bradykinin causes dilation of blood vessels. Bradykinin also acts in concert with prostaglandins to induce pain, trigger smooth muscle cell contraction (i.e., bronchoconstriction), and increase vascular permeability.
10.Stages of pressure ulcers. ◦Stage 1. -Non blanchable (the redness does not fade) - The skin is still intact ◦Stage 2. - Partial thickness skin loss - The ulcer is SUPERFICIAL and looks like a blister
◦Stage 3. - Full thickness skin loss - Damage or necrosis of subcutaneous tissue - NO exposed muscle or bone, but the ulcer appears as a deep crater. ◦Stage 4. - Full thickness tissue loss - Tissue necrosis - Damage to muscle, bone

11.Active immunity is the person's OWN body produce antibodies in response to presence of pathogen. Two days to get active immunity is catching the disease a 1st time and vaccinations (of weak/dead pathogen). 12.Cytotoxic T-cells are a type of immune cell. They destroy cells infected with viruses. Another name for cytotoxic T-cells is killer T-cells. Cytotoxic T-cells are one of the three main types of cells developed in your thymus.
13.Primary lymphoid organs: These organs include the bone marrow and the thymus. They create special immune system cells called lymphocytes. Secondary lymphoid organs: These organs include the lymph nodes, the spleen, the tonsils and certain tissue in various mucous membrane layers in the body (for instance in the bowel).
14.Types of hypersensitivity reactions. Mnemonic: "ACID"
•Type I – Allergic
•Type II – Cytotoxic
•Type III – Immune complex deposition
•Type IV – Delayed
15.Systemic lupus erythematosus (SLE) is the most common, complex, and serious of the autoimmune disorders. SLE is characterized by the production of a large variety of antibodies (autoantibodies) against self-antigens, including nucleic acids, erythrocytes, coagulation proteins, phospholipids, lymphocytes, platelets, and many other self-components. The most characteristic autoantibodies are against nucleic acids (e.g., single-stranded deoxyribonucleic acid [ssDNA], double-stranded DNA [dsDNS]), histones, ribonucleoproteins, and other nuclear materials. The blood normally contains many of these products of cellular turnover and breakdown so that autoantibodies react with the circulating antigen and form circulating immune complexes. The deposition of circulating DNA/anti-DNA complexes in the kidneys can cause severe kidney inflammation. Similar reactions can occur in other systems, such as the brain, heart, spleen, lung, gastrointestinal tract, peritoneum, and skin. Thus some of the symptoms of SLE result from a type III hypersensitivity reaction. Other symptoms are related to type II hypersensitivity reactions and include destruction of red blood cells (anemia), lymphocytes (lymphopenia), and platelets (thrombocytopenia).
16.The Rh blood group is a group of antigens also expressed on red blood cells. This is the most diverse group of red blood cell antigens, consisting of at least 45 separate antigens, although only one is considered of major importance: the D antigen. Individuals who express the D antigen on their red blood cells are Rh positive, whereas individuals who do not express the D antigen are Rh negative. About 85% of North Americans are Rh positive. Rh-negative individuals can make an IgG antibody to the D antigen (anti-D) if exposed to Rh-positive erythrocytes.
17.Cancer is a disease in which abnormal cells divide uncontrollably and invade other tissues. A tumor is a new growth, or neoplasm. Benign tumors are usually encapsulated and well differentiated with well-organized stroma and do not spread to distant locations. They are named for the tissues from which they arise. Benign tumors are noncancerous. Malignant tumors are cancerous. Compared with benign tumors, malignant tumors have more rapid growth rates, specific microscopic alterations (anaplasia, or loss of differentiation, and pleomorphism, or variability in size and shape), absence of normal tissue organization, and no capsule. They invade blood vessels and lymphatics and have distant metastases. The stroma is disorganized with loss of normal tissue structure.
18.Metastasis is the spread of cancer cells from the site of the original tumor to distant tissues and organs through the body. Metastasis is a defining characteristic of cancer and is the major cause of death from 245cancer. Cancer that has not metastasized can often be cured by a combination of surgery, chemotherapy, and radiation. These same therapies are frequently ineffective against cancer that has metastasized. For example, in appropriately treated women with localized low-stage breast cancer, the 5-year survival rate is often greater than 90%. Tragically, less than 30% of women with metastatic breast cancer are still alive 5 years after diagnosis. A growing body of basic and clinical research is defining the biologic principles of metastasis, with the hope that this improved understanding will lead to novel diagnostic approaches and better therapies to prevent and treat metastatic cancers. How do cancer cells develop the ability to metastasize? Metastasis is a highly inefficient process. Cancer cells must surmount multiple physical and physiologic barriers in order to spread, survive, and proliferate in distant locations, and the destination must be receptive to the growth of the cancer. Changes in the tumor microenvironment initiate the metastatic process and may include stromal cell adaptation to increase tumor mass and intratumor hypoxia. As this diversity increases within the changing tumor microenvironment, some cancer cells evolve with multiple new abilities that can facilitate metastasis. The model for transition to metastatic cancer cells is called epithelial-mesenchymal transition.
19.Adjuvant chemotherapy is given after surgical excision of a cancer with the goal of eliminating micrometastases. Neoadjuvant chemotherapy is given before localized (surgical or radiation) treatment of a cancer. As with induction chemotherapy, the effectiveness, or lack thereof, of neoadjuvant therapy can be measured (for example, with follow-up scans). Neoadjuvant therapy can shrink a cancer so that surgery may spare more normal tissue. For example, in the bone cancer osteogenic sarcoma, neoadjuvant therapy often converts a large tumor mass into a much smaller mass, allowing the surgeon to perform a limb-sparing excision rather than an amputation.
20.Cancer arises from a complicated and interacting web of multiple etiologies. Avoiding high-risk behaviors and exposure to individual carcinogens will prevent many types of cancers. Risk factors for cancer include lifestyle behaviors (smoking, alcohol intake, diet), lack of physical exercise and obesity, certain infections, environmental factors (exposure to sunlight or ionizing radiation), occupational exposure to carcinogens, and certain medications.
21.Wilms tumor is a rare kidney cancer that mainly affects children. Also known as nephroblastoma, it's the most common cancer of the kidneys in children. Wilms tumor most often affects children ages 3 to 4. It becomes much less common after age 5, but it can affect older children and even adults.
22.Human immunodeficiency virus (HIV) infects and destroys the CD4-positive (CD4+) Th cells, which are necessary for the development of both B cells (humoral immunity) and cytotoxic T cells (cellular immunity). There are two types of HIV: HIV-1 (the most common [95% of HIV infections]) and HIV-2 (less common and less infectious). The discussion in this section is related to HIV-1 and will be referred to as “HIV.” HIV suppresses the immune response against itself and secondarily creates a generalized immune deficiency by suppressing the development of immune responses against other pathogens and opportunistic microorganisms. Acquired immunodeficiency syndrome (AIDS) is the most advanced stage of HIV infection.
23.Colon cancer cells often have the hypermethylation in the promoter region of the MLH1 gene that encodes a protein that repairs DNA 70damage. When MLH1 becomes inactive, DNA damage accumulates, giving rise to colon tumors. 1 , 2 Abnormal methylation of tumor-suppressor genes also is common in Barrett esophagus, a condition in which the lining of the esophagus is replaced by abnormal cells.
24.Leukemia is a broad term for cancers of the blood cells. The type of leukemia depends on the type of blood cell that becomes cancer and whether it grows quickly or slowly. Leukemia occurs most often in adults older than 55, but it is also the most common cancer in children younger than 15.
25.Basal cell carcinoma (BCC) : cancer in the lower part of the epidermis or outer layer of the skin. commonly occurs on the head and neck. The incidence of basal cell carcinoma and squamous cell carcinoma is strongly correlated with lifetime sunlight exposure (i.e., photocarcinogenesis). Specific patterns of sunlight exposure, intermittent or chronic, confer different host effects. Intense intermittent recreational sun exposure has been associated with melanoma and BCC. 26.Infection with certain viruses, bacteria, and parasites are an important contributor to cancer worldwide. The most notable infections implicated in new cancer cases include Epstein-Barr virus (EBV), Helicobacter pylori, hepatitis B and C viruses (HBV and HCV), and human papillomavirus (HPV). H. pylori is the cause of about 75% of stomach cancers. EBV is linked to nasopharyngeal carcinoma, Hodgkin lymphoma, diffuse large B-cell lymphoma, Burkitt lymphoma, EBV-associated malignant B-cell lymphoma, other lymphomas, and gastric. 27.Mast cells are significant and potent activators of the inflammatory response. They have abundant granules containing biochemical mediators, which are released in instances of tissue injury (Fig. 6.6). They also can be activated by components of the complement cascade and by immunoglobulin E (IgE) antibodies produced in allergies. Located in connective tissue and close to vessels, they can be found near the body's surfaces (skin, GI, and respiratory tract linings). A variety of stimuli associated with tissue injury can induce inflammation by triggering the release of potent soluble substances from mast cells. These substances are released in two ways: 1. Degranulation—release of the contents of mast cell granules. 2. Synthesis—the new production and release of mediators in response to a stimulus. 28.1. Cancer is a disease in which abnormal cells divide uncontrollably and invade other tissues. A tumor is a new growth, or neoplasm. 2. Benign tumors are usually encapsulated and well differentiated with well-organized stroma and do not spread to distant locations. They are named for the tissues from which they arise. Benign tumors are noncancerous. 3. Malignant tumors are cancerous. Compared with benign tumors, malignant tumors have more rapid growth rates, specific microscopic alterations (anaplasia, or loss of differentiation, and pleomorphism, or variability in size and shape), absence of normal tissue organization, and no capsule. They invade blood vessels and lymphatics and have distant metastases. The stroma is disorganized with loss of normal tissue structure. 4. Cancers are named for the cell type from which they originate. Carcinomas arise from epithelial tissue, lymphomas are cancers of lymphatic tissue, and leukemias are cancers of blood-forming cells. 5. Carcinoma in situ (CIS) refers to noninvasive epithelial tumors of glandular or squamous cell origin. These early–stage cancers are localized to the epithelium and have not penetrated the local basement membrane.
29.1. The diagnosis of cancer requires a biopsy and examination of tumor tissue by a pathologist. Cancer classification is established by a variety of tests. 2. Tumor staging involves the size of the tumor, the degree to which it has locally invaded, and the extent to which it has spread. A standard scheme for staging is the T (tumor spread), N (node involvement), and M (metastasis) system. 3. Tumor markers are substances (i.e., hormones, enzymes, genes, antigens, antibodies) found in cancer cells and in blood, spinal fluid, or urine. They are used to screen and identify individuals at high risk for cancer, to help diagnose specific types of tumors, and to follow the clinical course of cancer. To date, no tumor marker has proven satisfactory to screen populations of healthy individuals for cancer. 4. The classification, and hence the treatment decisions, of cancers was originally based on gross and light microscopic appearance, and is now commonly accompanied by immunohistochemical analysis of protein expression. Increasingly, this is supplemented by a more extensive molecular analysis of the tumors. 5. Cancer is treated routinely with surgery, radiation therapy, chemotherapy, and combinations of these modalities. However, cancer therapy is rapidly evolving, and genetic anaolysis may help determine appropriate therapies. 6. Surgical therapy is used for nonmetastatic disease (in which cure is possible by removing the tumor) and as a palliative measure to alleviate symptoms. 7. Ionizing radiation causes cell damage; therefore the goal of radiation therapy is to damage the tumor without causing excessive toxicity or damage to nondiseased structures. 8. The theoretic basis of chemotherapy is the vulnerability of tumor cells in various stages of the cell cycle. Modern chemotherapy uses combinations of drugs with different targets and different toxicities. 9. Induction chemotherapy seeks to cause shrinkage or disappearance of tumors. Adjuvant chemotherapy is given after surgical excision of a cancer with the goal of eliminating micrometastases. Neoadjuvant chemotherapy is given before localized (surgical or radiation) treatment of a cancer to shrink a cancer so that surgery may spare more normal tissue. 10. Immunotherapy attempts to modify the immune system from a cancer-protective state to a destructive condition. 11. Future treatment of tumors will, most likely, use a careful histologic and genetic analysis of individual cancers that prescribes a combination of tumor-targeting drugs to simultaneously disrupt multiple hallmarks of that particular cancer.
30.Virtually all cervical cancer is caused by infection with specific types of HPV, which infects basal skin cells and commonly causes warts. There are more than 120 HPV types, but only about 40 can infect human mucosal tissue, and only a few (HPV-16, -18, -31, and -45) are associated with the highest risk for developing cervical, anogenital, and penile cancer. Most HPV infection is handled effectively and rapidly by the immune system and does not cause cancer. Cancer is more common in people with prolonged infection with HPV (a decade or more), during which the viral DNA becomes integrated into the genomic DNA of the infected basal cell of the cervix and directs the persistent production of viral oncogenes. Early oncogenic HPV infection is readily detected by the Papanicolaou (Pap) test, an examination of cervical epithelial scrapings. Early detection of atypical cells in a Pap test alerts health care providers to the possibility of cervical carcinoma in situ, which can be effectively treated. The Pap test is probably the most effective cancer-screening test developed to date. For women age 30 to 65 years old, additional testing for HPV infection of cervical cells (HPV test) should be added.
31.Bacteria have been around for a long, long time. They can live independently of a host (unlike viruses) and don’t change their genetic structure quickly or easily. As a result, vaccines against bacteria are much more efficient. Because these bacterial vaccines don’t change, we have a lot more data about them. They’ve been more or less perfected and don’t need to be altered. Unlike bacteria, viruses are not considered to be alive in their own right. Viruses require a host. They’re not as hardy as bacteria, but they are constantly — and rapidly — mutating their genetic material in order to survive. Thus, viral vaccines have to be changed and updated to meet and vanquish mutated viruses. As a result, you have to get vaccinated more frequently, and with updated vaccines. Until COVID, the primary viral vaccine was for influenza. 32.Humoral Immunity (Antibodies) 1. The humoral immune response consists of molecules (antibodies) produced by B cells. B cells are lymphocytes. 2. Antibodies are plasma glycoproteins that can be classified by chemical structure and biologic activity as immunoglobulin G (IgG), IgM, IgA, IgE, or IgD. 3. A typical antibody molecule is constructed of two identical heavy chains and two identical light chains (either κ or λ) and has two Fab portions that bind antigen and an Fc portion that interacts with complement or receptors on cells. 4. The protective effects of antibodies may be direct through the action of antibody alone or indirect requiring activation of other components of the innate immune response 5. IgE is a special class of antibody produced against environmental antigens that are the primary cause of common allergies. It also protects the individual from infection by large parasitic worms (helminths). 6. The secretory immune system protects the external surfaces of the body through secretion of antibodies in bodily secretions, such as tears, sweat, saliva, mucus, and breast milk. IgA is the dominant secretory immunoglobulin.

33.Peanut allergy affects as many as 2% of children in the United States and is the leading cause of death related to food-induced anaphylaxis. For many years, parents were advised to avoid exposing infants to peanuts in an effort to reduce the likelihood of sensitization to peanut allergens. However, peanuts are contained in many processed foods and often contaminate food processing machines used to make other food products, so it is difficult for an individual to avoid accidental exposure. A study published in 2015 found that exposure to peanut butter in the first year of life creates tolerance to peanut allergens, resulting in a 70% reduction in the risk for later peanut allergy. Later studies demonstrated that mothers who consumed peanuts while breast feeding and then introduced peanuts into their infant's diets during the first year of life further reduced the risk of future allergy. It is postulated that peanut antigens are delivered to the infant along with maternal immunoglobulins and immune cells, cytokines, and microbiota, which prime the infant immune system to develop tolerance. Guidelines published in 2017 recommend that infants 4 to 6 months of age should be given age-appropriate peanut-containing foods (along with other solid foods). In high-risk children (history of severe eczema or egg allergy) peanuts should be administered only after testing for peanut-specific IgE levels or performing skin-prick tests with peanut allergen. If strong sensitivity to peanuts is found on these tests, peanut exposure should occur under supervision of a specialist.