MICRO Chapter 26

A. Interferons are small cytokine proteins that are produced by virally infected cells B. Serve as a warning system and prevent viral replication by stimulating the production of antiviral proteins in uninfected cells once they receive the interferon signal from infected cells

Under what conditions are interferons produced, and how do they limit the transmission of viruses from one host cell to another?

The T cell, with its TCR, can recognize peptide only when the peptides are complexed with self proteins called major histocompatibility complex (MHC) proteins, found on host cell surfaces. o All host (nucleated) cells display MHC I proteins that present peptides from viruses and other intracellular pathogens for immune recognition o APCs (macrophages, dendritic cells, and B cells) also display an additional antigen-presenting protein, MHC II. § APCs ingest bacteria, viruses, and other antigenic material by phagocytosis (in macrophages and dendritic cells) or through internalization of molecular antigen bound to a BCR. § After ingestion, the APCs degrade the antigens to small peptides. The MHC proteins inside the APC bind the peptides derived from the digested pathogens. § The MHC-embedded peptides are then transported to the phagocyte surface where the complex is displayed, a process called antigen presentation . o In organ donation, MHC must be of same type to prevent rejection

What are MHCs and why are they important?

A. Complement system is a set of circulating, inactive proteins that are sequentially activated in response to a pathogen. B. The classicalpathway of complement activation is initiated when the complement binds to antibodies that are attached to a pathogen C. C1 cleaves C2 and C4 to form C2a-C4b, otherwise known as C3 convertase. This convertase breaks C3 to C3b, which binds to the target cell and C3a, which diffuses into the surrounding area and serves as a chemoattractant. D. With C3b added, the C3 convertase also binds C5, leading to C5a being released and C5b binding to the cell. This is called membrane attack complex (MAC).

What are complement and the complement pathway?

Mucosa-associated lymphoid tissue (MALT) is a part of the lymphatic system that interacts with antigens and microorganisms that interact with the body through mucous membranes, including those of the gut, genitourinary tract, and bronchial tissues

What are examples of lymphoid tissue?

Once a phagocyte has ingested its target microbe, several processes ensue that bring about the destruction of the microbe. o First, the phagosome must fuse with the lysosome. This process is enabled by microtubules, which facilitate the movement of organelles within cells. § Defective microtubule function would likely prevent the formation of phagolysosomes. Chediak-Higashi is a disease characterized by defective microtubule function and impaired phagocytosis. Infected individuals suffer from repeated infections. o Once phagolysosomes are formed, the next step in phagocytosis is the generation of toxic oxygen products that are lethal to the ingested microbe. § A defect in this process can compromise phagocytosis. Chronic granulomatous disease is an inherited disorder in which the oxidative burst process is defective and phagocytic cells are unable to effectively kill the microbes they phagocytize. This disease is characterized by repeated serious infections. o A third disorder of phagocyte function is myeloperoxidase deficiency. § Phagocytic cells may show an oxidative burst but be unable to produce hypochlorous acid; as a result, the phagocytes' ability to kill the microbes is compromised.

What defects in the phagocyte might cause lack of phagocytosis? Explain.

A. The coating of pathogens with antimicrobial host proteins, such as antibodies or C3b, resulting in enhanced phagocytosis of the target cells. B. Neutralizes pathogens and makes them much more likely to be identified, engulfed, and destroyed by phagocytes. This is because moth pathogens, including neutrophils and macrophages, have antibody receptors (fcR) and C3b receptors (C3R) on their surfaces, which bind antibody and C3b complement protein, respectively.

What is opsonization, and how does opsonization help fight bacterial infections?

a. Phagocytes mediate innate immune responses. Cells of several types that can ingest, kill, and digest microbial pathogens) b. Lymphocytes are additional tyra of immune cells needed for adaptive immunity

What major class of immune cells mediates an innate immune response? What additional type of immune cells is required for an adaptive immune response?

Antibiotic drug treatments nonspecifically killing harmless and even beneficial microbes in the body, smoking, poor diet, intravenous drug use, excessive alcohol consumption, and chronic lack of sleep can all play a role in the outcome of an infectious disease

What other factors may control the outcome of an infectious disease?

Antigen

What term is used to describe the unique molecules found on the surface of different pathogens?

a. All blood cells come from stem cells in bone marrow. b. Cytokines and chemokines are soluble proteins that influence many aspects of immune cell differentiation

Where do all blood cells originate? What determines what they differentiate into?

Phagocyte

a cell that engulfs foreign particles, and can ingest, kill, and digest most pathogens

Plasma cell

a differentiated B cell that produces soluble antibodies

Major Histocompatibility Complex (MHC)

a genetic region that encodes several proteins important for antigen processing and presentation. MHC I proteins are expressed on all cells. MHC II proteins are expressed only on antigen-presenting cells

Macrophage

a large leukocyte found in tissues that has phagocytic and antigen-presenting capabilities

granulocyte

a leukocyte derived from a myeloid precursor that contains cytoplasmic granules consisting of toxins or enzymes that are released to destroy target cells.

Neutrophil

a leukocyte exhibiting phagocytic properties, a granular cytoplasm (granulocyte), and a multilobed nucleus; also called polymorphonuclear leukocyte or PMN

B cell

a lymphocyte that has immunoglobulin surface receptors, produces immunoglobulin, and may present antigens to T cells

Chemokine

a lymphocyte that has immunoglobulin surface receptors, produces immunoglobulin, and may present antigens to T cells

T cell

a lymphocyte that interacts with antigens through a T cell receptor for antigen; T cells are divided into functional subsets including Tc (T-cytotoxic) cells and Th (T-helper) cells. Th cells are further subdivided into Th1 (inflammatory) cells and Th2 cells, which aid B cells in antibody formation

Antigen-presenting cells (APCs)

a macrophage, dendritic cell, or B cell that takes up and processes antigen and presents it to T-helper cells

antigen

a molecule that interacts with specific components of the immune system

Inflammation

a nonspecific reaction to noxious stimuli such as toxins and pathogens, characterized by redness (erythema), swelling (edema), pain, and heat (fever), usually localized at the site of infection

Leukocyte

a nucleated cell in blood; also called a white blood cell

Mucosa-associated lymphoid tissue (MALT)

a part of the lymphatic system that interacts with antigens and microorganisms that enter the body through mucous membranes, including those of the gut, the genitourinary tract, and bronchial tissues

dendritic cells

a phagocytic antigen-presenting cell found in various body tissues; transports antigen to secondary lymphoid organs

Stem cell

a progenitor cell that can develop into other cell types

Complement system

a series of proteins that react sequentially with antibody-antigen complexes, mannose-binding lectin, or alternative activation pathway proteins to amplify or potentiate target cell destruction

Immunoglobulin

a soluble protein produced by B cells and plasma cells that interacts with antigen; also called antibody

antibody

a soluble protein produced by B cells and plasma cells that interacts with antigen; also called immunoglobulin

cytokine

a soluble protein produced by a leukocyte or damaged body cell; modulates an immune response

Natural killer (NK cells)

a specialized lymphocyte that recognizes and destroys infected host cells or cancer cells in a nonspecific manner

Lymphocytes

a subset of nucleated cells in blood involved in the adaptive immune response

fever

an increase in body temperature resulting from infection or the presence of toxins in the body

Phagosome

an intracytoplasmic vacuole containing engulfed materials, especially pathogens or foreign particles

interferons

cytokine proteins produced by virus-infected cells that induce signal transduction in nearby cells, resulting in transcription of antiviral genes and expression of antiviral proteins

lypmh nodes

organs that contain lymphocytes and phagocytes arranged to encounter microorganisms and antigens as they travel through the lymphatic circulation

Invasion

the ability of a pathogen to enter into host cells or tissues, spread, and cause disease

Immunity

the ability of an organism to resist infection

Specificity

the ability of the immune response to interact with particular antigens

Memory cell

the ability to rapidly produce large quantities of specific immune cells or antibodies after subsequent exposure to a previously encountered antigen

adaptive immunity

the acquired ability to recognize and destroy a particular pathogen or its products, dependent on previous exposure to the pathogen or its products

Pathogens do not easily infect tissues that have a well established normal microbiota because the harmless microbes limit available nutrients and sites for infection by the pathogens

Although technically not part of the immune system, nonpathogenic normal microbiota plays a major role in preventing disease. Describe this role.

Opsonization

the deposition of antibody or complement protein on the surface of a pathogen or other antigen that results in enhanced phagocytosis

Monocytes

Circulating phagocyte that contains many lysosomes and can differentiate into a macrophage or dendritic cell

Plasma

the liquid portion of the blood containing proteins and other solutes

Serum

the liquid portion of the blood with clotting proteins removed

Innate immunity

the noninducible ability to recognize and destroy an individual pathogen or its products that does not rely on previous exposure to a pathogen or its products

Phagocytosis

the process of engulfing and killing foreign particles and cells

a. Most pathogens must adhere and infect at the site of exposure to initiate infection. However, the microorganism cannot colonize unless the host site isn't compatible with the pathogen's nutritional and metabolic needs. Different pathogens invade different tissues. Some pathogens also interact exclusively with members of a few closely related host species because the host share tissue-specific receptors a. Tetanus will not thrive in the intestines, just salmonella b. Shigella will not live in a puncture wound c. HIV only infects humans and closest primate relatives because of HIV-binding cell surface proteins CXCRH (present on T-lymphocytes) and CCR5 (present on macrophages)

Describe host tissue specificity for pathogens?

A. Phagocyte inhibition a.Some pathogens have mechanisms for neutralizing toxic phagocyte products, for killing the phagocyte, or for avoiding phagocytosis. 1. Mycobacteria tuberculosis produces cerotenerds to neutralize singlet oxygen and has a waxy cell wall that absorbs free radicals. This pathogen lives and divides within the phagocytes. 2. Some pathogens, such as streptococcus pyogenes produce leukocidins, which kill white blood cells, dead WBCs are found in pus 3. Lastly, some pathogens contain a capsule, which makes it difficult for the phagocyte to engulf them. Host antibodies can counteract this which is why pneumococcal vaccines are effective in preventing pneumonias caused by streptococcus pneumoniae. 4. Also produces M protein which alters surface pathogen and inhibits phagocytosis

Describe several reasons why phagocytes are not always effective at removing pathogens from the body.

a. Leukocytes are formed by stem cells in bone marrow which then is released into blood circulation. Once a leukocyte has traveled in the blood long enough to reach a capillary it passes to and from the blood and into the lymphocyte system via lymphatic capillaries and then into the lymph nodes. The leukocyte travels in the lymphatic system until it is needed and is then released back into the blood via extravasation (diapedesis)

Describe the circulation of a leukocyte from the blood to the lymph and back to the blood.

A. The innate PRRs on macrophages and other tissue cells at the site of infection engage the pathogens PAMPs. This activates local cells to produce and release mediators including cytokines and chemokines that interact with receptors on other cells, such as neutrophils. B. The chemokines and cytokines mediators released by injured cells and phagocytes contribute to inflammation. a. These cytokines increase vascular permeability, causing swelling (edema), reddening (erythema), and local heating associated with inflammation. b. The pressure associated with swelling also serves to force fluids away from blood vessels and into the lymphatic system, simultaneously helping to strengthen the immune response and prevent the spread of pathogens to the bloodstream. C. The two main causes of inflammation are injury and infection a. Local tissue macrophages secrete a chemokine called CXCL8 which activates neutrophils to migrate along the chemokine gradient toward the source of CXCL8, where they begin to ingest and kill the pathogen b. Macrophages and other cells at the sight of infection produce proinflammatory cytokines including interleukin-1 (IL-1), IL-6 and tumor necrosis factor X (TNF-x)

Describe the inflammation reaction. What are some causes of inflammation?

If pathogens were not phagocytized by the phagocytes, we wouldn't be able to present their antigens to T cells, and then to B cells, so that plasma cells could make the antibodies to destroy the pathogens. We also wouldn't be able to kill pathogens through phagocytosis, so the pathogens would increase in the body, and damage it to a point of death. · One could not survive in a college campus because the close contact in this environment leads to high exposure and transfer of potential pathogens. The inability to rid these pathogens leads to too many infections, which would be fatal.

Describe the potential problems that would arise if a person had an acquired inability to phagocytose pathogens. Could the person survive in a normal environment such as a college campus?

a. Phagocytes will enguld pathogens upon recognition of their pathogen-associated molecular patterns (PAMPs), ehich are structually repeating subunits common to broadly related groups of infectious agents, by their toll-like receptors (TLRs), which are one of a family of oattern recognition receptors (PRR) on phagocytes b. Once engulfed, the pathogen will be pinched while enclosed a membrane bound vesicle called a phagosome. The phagosome will move into the cytoplasm and fuses with a lyozyme to form a phagolysozyme. c. The toxic chemicals and enzymes withing the phagolysozyme combine to kill and digest the engulfed microbial cell. --> The toxic compiounds include: 1. Hydrogen peroxide 2. Superoxide anions 3. Hydroxyl radicals 4. Sunglet oxygen 5. Hypochlorus acid 6. Nitric oxide

Describe the process of phagocytosis. What types of cells are phagocytic? Phagocytosis

A. Innate Immunity o Also known as natural or native immunity o Includes natural barriers (physical, mechanical, and biochemical) and inflammation o Forms the first line of defense at the body's surface and are in place at birth B. Adaptive Immunity o Also known as acquired or specific immunity o Induced in a relatively slow and specific process-targets particular invading microorganisms for the purpose of eradicating them o Involves "memory", which results in a more rapid response during future exposure to the same microorganism C. Neither is more important than the other; and we couldn't survive without an innate or adaptive immune response because we could not fight off infections.

Describe the relative importance of innate immunity compared to adaptive immunity. Is one more important than the other? Can we survive in a normal environment without immunity?

A. Targets of natural killer cells a. Intracellular pathogens (viruses) b. Cancer cells c. Recognition mechanisms 1. Recognize and destroy pathogen-infected or tumor cells by using a two receptor system. The molecular targets of NK cells are MHCI receptors on the surface of others. As NK cells circulate and interact with other cells in the body, they use special MHCI receptors on their surfaces, to recognize MHCI proteins on normal, healthy cells. Binding of the MHCI recognition receptors on NK cells to MHCI on other cells deactivate the NK cell, turning off the perforin and granzyme killing mechanisms. In addition to a deficiency of MHCI proteins, pathogen-infected or tumor cells frequently express stress proteins on their surfaces NK cells have complementary receptors for many of these stress proteins. Especially in the absence of the MHCI interactions, the stress receptors on NK cells engage stress proteins on the target cell. B. Targets of Cytotoxic T-cells b. Infected cells 1. In cells that have been infected by viruses or other intracellular pathogens, MHCI proteins display peptides derived from the infectious agent, signaling a T-cytotoxic cell i. Granzyme- an enzyme that induces programed cell death (apoptosis) ii. Perferin- chemically and functionally similar to C9, it pokes holes in (perforates) the target membrane iii. T-cells- originate in bone marrow, but nature in the thymus

Identify and compare the targets and the recognition mechanisms used by T-cytotoxic cells and NK cells.

A. Physical barriers a. Tight junctions between epithelial cells in all body tissues that inhibit invasion and infection b. Mucosal surfaces have mucus that traps microorganisms, pollen, and other foreign agents c. Epithelial cells underlying mucous layers have cilia on their surfaces that expel pathogens B. Chemical barriers a. Sebaceous glands in the skin secrete fatty acids and lactic acids, lowering the acidity of the skin to pH 5 which inhibits colonization of many pathogens b. Pathogens that are ingested are usually destroyed by stomach acids, but if they make it through they have to deal with the microbiota in the small and large intestines c. Defensins are produced in the skin, lungs, and gut which enhances resistance to infection and invasion d. The lumen of the kidney, eye, respiratory system, and the cervical mucosa are constantly bathed with tears mucus, or other secretions that contain lysozyme (enzyme that can kill bacteria by ingesting the cell wall) C. Physical barriers can be compromised by thinning of the skin, atrophy of the vaginal wall, and loss of cilia in the respiratory tract. Chemical barriers can be compromised by the atrophy of the glands that secrete mucus, tears, and other things

Identify physical and chemical barrier to pathogens. How might these barriers be compromised?

A. Septic shock symptoms a. Body wide inflammatory event b. Massive eflux of fluids from central vascular tissue causing a loss of systemic blood pressure and the influx of fluid from vascular tissue into extravascular space B. Localized inflammation

Identify the major symptoms of localized inflammation and of septic shock

Mast cell

tissue cells adjoining blood vessels throughout the body that contain granules with inflammatory mediators