Chapter 14 Host Defense I: learning outcomes

14.11. List the four major categories of nonspecific immunity.

(1) phagocytosis, (2) inflammation, (3) fever, and (4) antimicrobial proteins

red blood cells (erythrocytes)

- originate from stem cell then Erythroblast -function: carry O2 and CO2 -Simple, biconcave sacks of hemoglobin that transport oxygen and carbon dioxide to and from the tissues -Most numerous of all circulating cells -Do not have immune function Contains whole blood, serum

3. Edema and Pus formation

-Scab -neutrophils -pus -Fibrous exudate

1. Injury/immediate actions

-bacteria in wound -Mast cells release chemical mediators -vasoconstriction

2. Vascular reactions

-clot -bacteria -neutrophil -seepage of plasma and migration of WBC's out of the blood vessels -vasodilation

Mast cells

-orginate from stem cell then Myeloblast function: specialized tissue cell similar to Basophils that trigger local inflammatory reactions and are responsible for many allergic symptoms -contains whole blood and lymph

Eosinophils

-orginate from stem cell then Myleoblast -function: active in worm and fungal infections, allergy and inflammatory reactions (Granulocyte) -Granules contain peroxidase, lysozyme, and other digestive enzymes, toxic proteins, inflammatory chemicals Attack and destroy large eukaryotic pathogens -contains whole blood and lymph

Macrophages

-orginate from stem cells then Monoblast then Monocyte function: largest phagocytes that ingest and kill foregin cells; strategic participants in certain immune reactions -is a granulocytes -Monocytes that have left blood circulation Long-lived and able to multiply -Specific and nonspecific killing functions / Phagocytosis -contains whole blood and lymph

lymphocytes

-orgniate from lymphoid stem cell >lymphoblast function: primary cell involved specific immune reactions of foreign matter contains whole blood and lymph

T cell

-orgniate from lymphoid stem cell. Lymphoblast>lymphocyte function: perform a number of specific cellular immune responses such as assisting B cells and killing foreign cells (cell-mediated immunity) -is a granulocytes -Cell-mediated immunity: A wide spectrum of immune functions Modulate immune functions and kill foreign cells -contains whole blood and lymph

Natural killer cell

-orgniate from lymphoid stem cell> Lymphoblast > function: related to T cells but displaying no antigen specifity , these cells are active against cancerous and virally infected cells -is a granulocytes -contains whole blood and lymph

Platelets

-orgniate from stem cell then Megakaryoblast > Megakaryocyte function: Involved in blood clotting, inflammation response, and recognition and destruction of blood-borne bacteria -Sticky cell fragments circulating in blood -Not whole cells -Function in hemostasis (plugging broken blood vessels) and releasing chemicals that act in blood clotting and inflammation -contain: whole blood and lymph

Monocytes

-orgniate from stem cell then Monoblast - blood phagocytes that rapidly leave the circulation; mature into macrophages and dendritic cells -is a granulocytes -Discharged by bone marrow into the bloodstream -Specific and nonspecific killing functions / Phagocytosis -contains whole blood and lymph

B cell

-originate from Lymphoid stem cell >Lymphoblast >lymphocyte function: differentiate into plasma cells and form antibodies (Humerol immunity) -is a granulocytes -Form plasma cells that produce antibodies Antibodies: large protein molecules that interlock with antigen and participate in their destruction -Antibody-mediated immunity -contains whole blood and lymph

Dendritic cell

-originate from stem cell then Monoblast then Monocyte -function: relatives of macrophages that reside throughout tissues and mononuclear phagocyte system; responsible for processing foreign matter and presenting it to lymphocytes -is a granulocytes -Move from the blood to lymphoid tissues where they trap pathogens -Specific and nonspecific killing functions / Phagocytosis -contains whole blood and lymph

Basophil

-originate from stem cell then Myeloblast function: in inflammatory events (Granulocyte) -Make up less than 0.5% of circulating WBCs -contains whole blood and lymph

Neutrophil

-originate from stem cell then Myloblast -function: phagocytes in blood: active engulfers and killers of bacteria (Granulocyte) -55 to 90% of circulating leukocytes -contains whole blood and lymph

4. resolution/scar formation

-scar -lymohocytes -macrophges

14.15. Discuss the Classical pathway of complement activation.

1. C1 becomes activated when it bind to an antigen antibody complex 2. the activated C1 than cleaves C2 into C2a and C2b and C4 into C4a and C4b 3. C2b and C4b combine to form a protase C3 convertase 4. C3 convertase than cleaves C3 into C3a and C3b 5.C3a is involved in stimulating inflammation 6.C3b reacts with complemnet components to form more C3 convertase to form more C3a and C3b (C3 b also attaches to surfaces of microorganisms, phagocytes have a binding site , coating of bacteria to make them more suspetible to phagocytosis is called opsonization) 7. properdin and C3 convertase results in formationof C5 convertase which cleaves C5 into C5a and C5b 8.C5a inhances inflammation and acts as a chemo attractnt for phagocytes, 9.C5b reacts with other complent components including C6, C7, C8, C9 to form a membrane attack complex this stcuture forms a hole in the cell membrane and causes cells to lyse

14.16. Name three types of antimicrobial proteins and describe how they target microorganisms.

1. Interferon - Small protein produced naturally by certain WBCs and tissue cells Used in therapy against certain viral infections and cancer Involved in defenses against other microbes and in immune regulation and intercommunication (Three major types are interferons alpha and beta, products of many cells, including lymphocytes, fibroblasts, and macrophages; and interferon gamma, a product of T cells. Interferons are also a type of cytokine) (degrade the viral nucleic acid, either by degradeding mRNA , stopping viral replication) 2.Complement- In immunology, serum protein components that act in a definite sequence when set in motion either by an antigen-antibody complex or by factors of the alternative (properdin) pathway. - consists of over 30 blood proteins that work together to destroy bacteria and certain viruses. complement cascade includes the four stages of initiation, amplification and cascade, polymerization, and membrane attack: This complex can digest holes in the cell membranes of bacteria, cells, and enveloped viruses, thereby destroying them. 3.Antimicrobial Peptides- (AMPs) Short protein molecules found in epithelial cells; have the ability to kill bacteria. -have only recently been appreciated. They are short proteins—of between 12 and 50 amino acids—that have the capability of inserting themselves into bacterial membranes (figure 14.22). Through this mechanism and others, they kill the microbes. They have names like bacteriocins, defensin, magainins, and protegrins.

14.09. Name six types of blood cells that function in nonspecific immunity, and specify the most important function of each.

1. Neutrophils: 55 to 90% of circulating leukocytes Production of toxic chemicals and phagocytosis (bacterial infection) 2. Eosinophils: Granules contain peroxidase, lysozyme, and other digestive enzymes, toxic proteins, inflammatory chemicals Attack and destroy large eukaryotic pathogens(non-phagocytic killing) 3.Basophils: Make up less than 0.5% of circulating WBCs Share morphological and functional characteristics of mast cells(histamine rich , allergy and inflammation) 4.Lymphocytes: are the key cells of the third line of defense—the specific immune response. When stimulated by foreign substances (antigens), lymphocytes are transformed into activated cells that neutralize and destroy those foreign substances. B-lymphocyte A white blood cell that gives rise to plasma cells and antibodies. T-lymphocyte- A white blood cell that is processed in the thymus and is involved in cell-mediated immunity.(cytotoxcity) 5.Monocytes- Monocytes are discharged by the bone marrow into the bloodstream, where they live as phagocytes for a few days. Later, they leave the circulation to undergo final differentiation into macrophages. Unlike many other WBCs, the monocyte series is relatively long-lived and retains an ability to multiply. (Monocyte>(blood flow). reside in tissue/organ Macrophages kill by phagocysis) ) Also include dendritic cell- A large, antigen-processing cell characterized by long, branchlike extensions of the cell membrane. 6. natural killer (NK) cells: Cells that are derived directly from lymphoid stem cells that do not have specific antigen receptors and directly attack and kill virus-infected and cancer cells.(non-phagoyctic killing)

14.02. Identify three components of the first line of defense.

1. The skin The outermost layer (stratum corneum) of the skin is composed of epithelial cells that have become compacted, cemented together, and impregnated with an insoluble protein—keratin. The result is a thick, tough layer that is highly impervious and waterproof. Few pathogens can penetrate this unbroken barrier, especially in regions such as the soles of the feet or the palms of the hands, where the stratum corneum is much thicker than on other parts of the body 2. The mucous membranes of the digestive, urinary, and respiratory tracts and of the eye are moist and permeable Blinking and tear production (lacrimation) flush the eye's surface with tears and rid it of irritants. The constant flow of saliva helps carry microbes into the harsh conditions of the stomach. Vomiting and defecation also evacuate noxious substances or microorganisms from the body. 3. The respiratory tract Nasal hair traps larger particles. The copious flow of mucus and fluids that occurs in allergy and colds exerts a flushing action. In the respiratory tree (primarily the trachea and bronchi), a ciliated epithelium (called the ciliary escalator) conveys foreign particles entrapped in mucus toward the pharynx to be removed - Irritation of the nasal passage reflexively initiates a sneeze, which expels a large volume of air and fluids at high velocity. Similarly, the acute sensitivity of the bronchi, trachea, and larynx to foreign matter triggers coughing, which ejects irritants.

1. List and describe the basic steps of phagocytosis.

1. chemotaxis by phagocyte 2. adhesion of bacteria 3.engulfment into phagocytic vacuole 4. Phagosome 5.Phagolysosome formation 6. killing and destruction of bacterial cells 7.release of residual debris

14.12. Summarize the steps in phagocytosis, and describe the roles of PAMPs in this process.

1. chemotaxis by phagocyte 2. adhesion of bacteria 3.engulfment into phagocytic vacuole 4. Phagosome 5.Phagolysosome formation 6. killing and destruction of bacterial cells 7.release of residual debris Role of of PAMPs(Pathogen-associated molecular patterns (PAMPs): -Recognized by phagocytes and other defensive cells -Serve as signal molecules on the surfaces of microbes ex; Peptidoglycan Lipopolysaccharide Double-stranded RNA found in viruses

2. What are the five symptoms of inflammation?

1. rubor 2. calor 3. tumor 4.dolor 5. loss of function

1. Describe the three responsibilities of a healthy immune system.

1.surveillance of the body, 2.recognition of foreign material, and 3.destruction of entities deemed to be foreign

14.05. Name four body compartments that participate in immunity.

1.the mononuclear phagocyte system, 2.the spaces surrounding tissue cells that contain extracellular fluid (ECF), 3.the bloodstream, and 4.the lymphatic system.

granulocytes

A mature leukocyte that contains noticeable granules in a Wright stain. Examples: neutrophils, eosinophils, and basophils.

14.14. Discuss the mechanism of fever and its role in nonspecific immunity.

Fever is initiated when substances called pyrogens reset the hypothalamic thermostat to a higher setting.This change signals the musculature to increase heat production and peripheral arterioles to decrease heat loss through vasoconstriction. Fevers range in severity from low-grade (37.7°C to 38.3°C, or 100°F to 101°F) to moderate (38.8°C to 39.4°C, or 102°F to 103°F) to high (40.0°C to 41.1°C, or 104°F to 106°F) -Fever inhibits multiplication of temperature-sensitive microorganisms such as the poliovirus, cold viruses, herpes zoster virus, systemic and subcutaneous fungal pathogens, Mycobacterium species, and the syphilis spirochete. -Fever impedes the nutrition of bacteria by reducing the availability of iron. It has been demonstrated that during fever, macrophages stop releasing their iron stores, which slows down several enzymatic reactions needed for bacterial growth. -Fever increases metabolism and stimulates immune reactions and naturally protective physiological processes. It speeds up hematopoiesis, phagocytosis, and specific immune reactions. It increases the ability of specific lymphocytes to home in on sites of infection.

14.01. Summarize the three lines of host defenses.

First line of defense: Barriers that block invasion at the portal of entry Does not involve recognition of foreign substances General in action Second line of defense: Nonspecific Internalized system of protective cells Inflammation and phagocytosis The second line of defense is a cellular and chemical system that comes immediately into play if infectious agents make it past the surface defenses. These include phagocytosis, inflammation, fever, and antimicrobial proteins Third line of defense: Acquired on an individual basis as each foreign substance is encountered by lymphocytes Reaction with each microbe produces unique protective substances and cells that can come into play if the microbe is encountered again Provides long-term immunity The third line of defense Includes specific host defenses that must be developed uniquely for each microbe through the action of specialized white blood cells. These B cells and T cells develop actively through an infection or passively through maternal antibodies.

14.13. Outline the steps in inflammation.

Following an injury, some of the earliest changes occur in the vasculature (arterioles, capillaries, venules) in the vicinity of the damaged tissue. These changes are controlled by nervous stimulation, chemical mediators, and cytokines released by blood cells, tissue cells, and platelets in the injured area. Some mediators are vasoactive—that is, they affect the endothelial cells and smooth muscle cells of blood vessels; others are chemotactic factors, also called chemokines, that affect white blood cells. Inflammatory mediators cause fever, stimulate lymphocytes, prevent virus spread, and cause allergic symptoms (table 14.1). Inflammatory mediators, which are chemicals released by host cells, contribute to nonspecific and specific responses. There are very many of them (see table 14.1), and they might be called chemokines or cytokines. They are absolutely critical to our defenses. Y is followed in quick succession by the opposite reaction, vasodilation. The overall effect of vasodilation is to increase the flow of blood into the area, which facilitates the influx of immune components and causes redness and warmth. In order for WBCs to leave the blood vessels and enter the tissues, they adhere to the inner walls of the smaller blood vessels. From this position, they are poised to migrate out of the blood into the tissue spaces by a process called diapedesis diapedesis The migration of intact blood cells between endothelial cells of a blood vessel such as a venule. Another factor in the migratory habits of these WBCs is chemotaxis, defined as the tendency of cells to migrate in response to a specific chemical stimulus given off at a site of injury or infection Phagocytes migrate into a region of inflammation with a deliberate sense of direction, attracted by a gradient of stimulant products from the parasite and host tissue at the site of injury. The endpoint function of the white blood cells is the phagocytosis of microbes or other invading substances. Sometimes a mild inflammation can be resolved by edema and phagocytosis. Inflammatory reactions that are more long-lived attract a collection of monocytes, lymphocytes, and macrophages to the reaction site. Clearance of pus, cellular debris, dead neutrophils, and damaged tissue is performed by macrophages, the only cells that can engulf and dispose of such large masses. At the same time, B lymphocytes react with foreign molecules and cells by producing specific antimicrobial proteins (antibodies), and T lymphocytes kill intruders directly. Late in the process, the tissue is completely repaired, if possible, or replaced by connective tissue in the form of a scar

4. Tears and saliva contain _________ that hydrolyzes the peptidoglycan of bacterial cell walls.

Lysozyme

4. Describe the function of the following cells: Neutrophils Eosinophils T-lymphocytes B-lymphocytes

Neutrophils- 55 to 90% of circulating leukocytes Production of toxic chemicals and phagocytosis Eosinophils -Granules contain peroxidase, lysozyme, and other digestive enzymes, toxic proteins, inflammatory chemicals Attack and destroy large eukaryotic pathogens(non-phagocytocis) T-lymphocytes- Cell-mediated immunity: A wide spectrum of immune functions Modulate immune functions and kill foreign cells(cytotoxicty) B-lymphocytes- Antibody-mediated immunity Also called humoral immunity Form plasma cells that produce antibodies Antibodies: large protein molecules that interlock with antigen and participate in their destruction

agranulocytes

One form of leukocyte (white blood cell) having globular, nonlobed nuclei and lacking prominent cytoplasmic granules. example: monocytes and lymphocytes

3. ____________ ____________ creates unfavorable environments for pathogens for competing for nutrients and altering pH.

Resident Microbiota

14.10. Describe the major roles of T and B lymphocytes.

T lymphocytes (T cells)-A white blood cell that is processed in the thymus and is involved in cell-mediated immunity. B lymphocytes (B cells)- A white blood cell that gives rise to plasma cells and antibodies.

Chemotaxis

Tendency of WBCs to migrate in response to a specific chemical stimulus given off at a site of injury or infection Cells swarm from body compartments to the site of infection and remain there to perform general and specific immune functions

14.06. List the components of the mononuclear phagocyte system.

The MPS consists of -the thymus, where important white blood cells mature; -lymph nodes; - tonsils; -spleen; and -lymphoid tissue in the mucosa of the gut and -respiratory tract, where most of the MPS "action" takes place.

Diapedesis

The migration of intact blood cells between endothelial cells of a blood vessel such as a venule. (Movement of white blood cells from the bloodstream into the tissues)

1. Describe the mononuclear phagocyte system.

The tissues of the body are permeated by a support network of connective tissue fibers, the reticular system, which originates in the cellular basal lamina, interconnects nearby cells, and meshes with the massive connective tissue network surrounding all organs. This network, called the mononuclear phagocyte system (MPS) (figure 14.6), is critical to immune function because it provides a passageway within and between tissues and organs. The MPS consists of the thymus, where important white blood cells mature; lymph nodes; tonsils; spleen; and lymphoid tissue in the mucosa of the gut and respiratory tract, where most of the MPS "action" takes place

2. True/False: Cells marked as "self" are not marked for destruction by the immune system.

True

Serotonin

a mediator produced by platelets and intestinal cells, causes smooth muscle contraction, inhibits gastric secretion, and acts as a neurotransmitter.

Interleukin (IL) 1

a product of macrophages and dendritic cells that has many of the same biological activities as TNF, such as inducing fever and activating certain white blood cells.

Bradykinin

a vasoactive amine from the blood or tissues, stimulates smooth muscle contraction and increases vascular permeability, mucus production, and pain. It is particularly active in allergic reactions.

Histamine

a vasoactive mediator produced by mast cells and basophils, causes vasodilation, increased vascular permeability, and mucus production. It functions primarily in inflammation and allergy.

Exudate

blood-borne components that escape into extracellular space

3. _________ is the tendency of white blood cells to migrate in response to a specific chemical stimulus.

chemotaxis

2. A thick layer ___________ in the nasal and of respiratory passages traps bacteria

cilia

4. True/False: Fever should always be treated.

false

2. True/False: Lymph is propelled through the body by the actions of smooth muscles.

false( Lymph is only transported through the contraction of skeletal muscles)

4. True/False: Nonself cells such as food or commensal organisms are attacked by the immune system.

false, (Nonself proteins that are not harmful—such as those found in food we ingest and on commensal microorganisms—are generally recognized as such and the immune system is signaled to not react.)

Mature white blood cells (leukocytes) include

granulocytes, agranulocytes , mast cells, dendritic cells, macrophages, natural killer cells, and gamma-delta T cells.

6. the three pathways of complement activation are known as the ___________ , ___________ , _______________ pathways.

intertin, alternative , classic

1. the skin produces_________ to create a waterproof barrier to microbes.

keratin

Edema

local swelling and firmness due to accumulation of exudate into the tissues

14.04. Define marker, and discuss its importance in the second and third lines of defense.

markers- Any trait or factor of a cell, virus, or molecule that makes it distinct and recognizable. Example: a genetic marker. These markers, which generally consist of proteins and/or sugars, can be thought of as the cellular equivalent of facial characteristics in humans and allow the cells of the immune system to identify whether or not a newly discovered cell poses a threat. While cells deemed to be self are left alone, cells and other objects designated as foreign are marked for destruction by a number of methods, the most common of which is phagocytosis. There is a middle ground as well. Nonself proteins that are not harmful—such as those found in food we ingest and on commensal microorganisms—are generally recognized as such and the immune system is signaled to not react. .

14.03. Discuss the role of normal biota as a first-line defense mechanism.

normal biota provide microbial antagonism, which can block the access of pathogens to epithelial surfaces and can create an unfavorable environment for pathogens by competing for limited nutrients or by altering the local pH.

Interferons (IFN)

produced by leukocytes, fibroblasts, and other cells, inhibit virus replication and cell division and increase the action of certain lymphocytes that kill other cells.

Prostaglandins

produced by most body cells; complex chemical mediators that can have opposing effects (e.g., dilation or constriction of blood vessels) and are powerful stimulants of inflammation and pain.

3. Markers are composed of __________ or __________ or both.

protein and sugar

5. the low pH in the ________ and ________ prevents the growth of microbes.

skin and vagina

3. The ________ processes worn-out red blood cells and filters pathogens from the blood.

spleen

14.07. Fully describe the structure and function of the lymphatic system.

structure: The lymphatic system is a compartmentalized network of vessels, cells, and specialized accessory organs It begins in the farthest reaches of the tissues as tiny capillaries that transport fluid (lymph) through an increasingly larger tributary system of vessels and filters (lymph nodes), and it leads to major vessels that drain back into the regular circulatory system function: 1. to provide an auxiliary route for the return of extracellular fluid to the circulatory system proper; 2. to act as a "drain-off" system for the inflammatory response; and 3. to provide surveillance, recognition, and protection against foreign materials through a system of lymphocytes, phagocytes, and antibodies.

5. Interferon is produced in response to infection by a ______________.

virus

14.08. Differentiate between whole blood, plasma, and serum.

whole blood- A liquid connective tissue consisting of blood cells suspended in plasma. plasma- The carrier fluid element of blood. . The main component of this fluid is water (92%), and the remainder consists of proteins such as albumin and globulins (including antibodies); other immunochemicals; fibrinogen and other clotting factors; hormones; nutrients (glucose, amino acids, fatty acids); ions (sodium, potassium, calcium, magnesium, chloride, phosphate, bicarbonate); dissolved gases (O2 and CO2); and waste products (urea). serum- The clear fluid expressed from clotted blood that contains dissolved nutrients, antibodies, and hormones but not cells or clotting factors.