chapter 21 Q&A

.

Chapter 21 The Lymphatic and Immune Systems

A. Topics

1) The Lymphatic System

2) Three Lines of Defense

1) External Barriers (nonspecific)

2) Other nonspecific resistance mechanisms

3) Immunity (specific resistance)

B. Lecture Outline

1) The Lymphatic System (Figs. 21.1, 21.3)

a. 3 functions:

• Fluid recovery: 15% (2 to 4 L/day) of the water and about half of the plasma proteins enter the vein-like vessels of the lymphatic system and then are returned to the blood

• Immunity: As the fluid is recovered, it is inspected in the lymphatic system for disease agents. Excess filtered fluid picks up foreign cells and chemicals from the tissues

• Lipid absorption: Lacteals in small intestine absorb dietary lipids that are not absorbed by the blood capillaries

b. Components:

Lymph: The recovered fluid that is usually clear and colorless. It is similar to blood plasma, but is low in protein. Lymph can also carry hormones, cellular debris, travelling cancer cells, and foreign invaders like viruses and bacteria, as well as immune cells to fight these invaders.

Lymphatic vessels: Transport the lymph (Fig. 21.3, 21.4, 21.5, 21.6, 21.12). These begin with lymphatic capillaries, which converge into larger collecting vessels. At intervals, the collecting vessels empty into lymph nodes, where the lymph is monitored for foreign invaders. Bacteria are killed by macrophages and other immune cells turn on other aspects of immune system. It leaves the other side of the node and travels on, often going through multiple nodes before re-entering the bloodstream. Six lymphatic trunks drain major portions of body and empty into 2 collecting ducts. Right lymphatic duct receives lymph from right arm, right side of head and thorax; empties into right subclavian vein. Thoracic duct is larger and longer, begins as a prominent sac in abdomen called the cisterna chyli; receives lymph from below diaphragm, left arm, left side of head, neck, and thorax; empties into left subclavian vein.

Lymphatic organs:

Primary lymphatic organs: red bone marrow (Fig. 21.9) and thymus (Fig. 21.10).

• Red bone marrow: Soft, loosely organized, highly vascular material that is involved in hemopoiesis (produces all classes of formed elements of the blood – gets its red color from RBCs) and immunity.

• Thymus: Bilobed organ located in superior mediastinum between the sternum and aortic arch. This is the site where T and B cells become immunocompetent (able to recognize and respond to antigens)

Secondary lymphatic organs: Lymph nodes (Fig. 21.1, 21.12), tonsils (Fig. 21.13), and spleen (Fig. 21.14). Immunocompetent cells migrate to these organs only after they mature in the primary lymphatic organs.

• Lymph node: Most numerous lymphatic organs (450 in typical young adult). The lymph node is a bottleneck that slows down lymph flow and allows for cleansing of foreign matter. Macrophages and reticular cells remove about 99% of impurities before the lymph leaves the node. Because the lymph travels through multiple lymph nodes, it is thoroughly cleansed before it re-enters the bloodstream. Lymph nodes are also a site of T and B cell activation.

• Tonsils: Patches of lymphatic tissue located at the entrance to the pharynx, where they guard against ingested or inhaled pathogens. Each is covered with epithelium and have deep pits: tonsillar crypts lined with lymphatic nodules

• Spleen: The body’s largest lymphatic organ, measuring up to 12 cm long and weighing up to 160 grams (about the size of an apple). Functions include:

o Blood production in fetus

o Blood reservoir

o “Erythrocyte graveyard”: RBC disposal

o White pulp monitors blood for foreign antigens

Lymphatic tissues: Composed of aggregates of lymphocytes and macrophages that populate many organs in the body. The simplest form is diffuse lymphatic tissue, in which lymphocytes are scattered throughout the tissue. This is particularly prevalent in body passages that are open to the exterior (where foreign invaders can enter), like the respiratory, urinary and reproductive tracts. In some places, the lymphocytes and macrophages clump together to form clusters or nodules. We see this in the small intestine (Peyer’s patches – see Fig. 21.8).

2) Three Lines of Defense

The first 2 are examples of Nonspecific Resistance that are effective against a broad range of pathogens. Their effectiveness does not depend on prior exposure. The third line of defense defeats a pathogen and leaves the body with a “memory” of it so it can defeat it faster in the future. This is Specific Resistance because it results from prior exposure to a pathogen. Usually provides future protection only against that particular one.

a. First Line of Defense: External Barriers (Nonspecific Resistance)

Skin: Mechanical (via keratin) and Chemical (skin is coated with antimicrobial chemicals such as defensins and lactic acid.) Lactic acid makes up the acid mantle, which is generated by sweat and inhibits bacterial growth. Sweat also contains an antibacterial peptide called dermicidin. Keratinocytes, neutrophils, and macrophages produce defensins and cathelicidins that destroy bacteria, viruses and fungi.

Mucus Membranes: Digestive, respiratory, urinary, and reproductive tracts are open to the exterior and protected by mucous membranes. Mucus physically traps microbes. Lysozyme is an enzyme destroys bacterial cell walls

b. Second Line of Defense: Other Types of Nonspecific Resistance

We can divide these into 3 categories: Protective Cells, Protective Proteins, and Protective Processes.

1. Protective Cells

• Leukocytes and Macrophages:

5 types of leukocytes (explained in detail on p. 823)

Type of Leukocyte Function

Neutrophils Wander in connective tissue killing bacteria. Catalyzes a reaction called a “respiratory burst” – the production of toxic chemicals such as hydrogen peroxide and hypochlorite. These bactericidal chemicals create a “killing zone” which effectively kills more bacteria than the neutrophil could via phagocytosis.

Eosinophils • Found especially in the mucous membranes and stand guard against parasites, allergens (allergy-causing agents), and other pathogens

• Kill tapeworms and roundworms by producing superoxide, hydrogen peroxide, and toxic proteins

• Promote action of basophils and mast cells

• Phagocytize antigen–antibody complexes

• Limit action of histamine and other inflammatory chemicals

Basophils Secrete chemicals (leukotrienes) that aid mobility and action of neutrophils and eosinophils

• Histamine: a vasodilator, which increases blood flow (speeds delivery of leukocytes to the area)

• Heparin: inhibits clot formation (which would impede leukocyte mobility)

Lymphocytes Circulating blood contains

80% T cells

15% B cells

5% NK cells

Many diverse functions, including Immune surveillance and specific immunity

Monocytes Monocytes emigrate from the blood into the connective tissue and transform into macrophages. Macrophages phagocytize pathogens, dead neutrophils, dead cells; also present antigens to activate other immune cells

• Natural Killer (NK) Cells perform Immune Surveillance (Fig. 21.17): Natural killer (NK) cells attack and destroy bacteria, cells of transplanted organs, cells infected with viruses, and cancer cells.

2. Protective Proteins (Antimicrobial Proteins)

• Interferons: secreted by certain cells infected by viruses. Alert neighboring cells and protect them from becoming infected. Interferons bind to surface receptors and activate second-messenger systems that lead to synthesis of dozens of antiviral proteins that defend against virus infection. They also activate NK cells and macrophages that destroy infected cells before they can liberate a swarm of newly replicated viruses.

• Complement: a group of 30 or more globular proteins synthesized by the liver and circulate in the blood in an inactive form. Inactive proteins are called “C(+number like 3)” – when activated, break into smaller pieces like “C3b”, etc.

Activated complement brings about four methods of pathogen destruction:

• Inflammation

• Immune clearance

• Phagocytosis

• Cytolysis

3. Protective Processes

• Fever (Fig. 21.18): An abnormal elevation of body temperature that promotes interferon activity, elevates metabolic rate and accelerates tissue repair, and inhibits reproduction of bacteria and viruses. Endogenous and Exogenous pyrogens stimulate neurons in the anterior hypothalamus to secrete prostaglandin E2 (PGE2). PGE2 in turn raises the hypothalamic set point for body temperature. Aspirin and ibuprofen reduce fever by inhibiting prostaglandin synthesis.

• Inflammation (Fig. 21.19): local defensive response to tissue injury of any kind, including trauma and infection. 4 cardinal signs: redness, swelling, heat, pain

Three major processes of inflammation are:

Mobilization of Body Defenses Containment & Destruction of Pathogen Tissue Cleanup & Repair

• Release of inflammatory chemicals produces local vasodilation. This results in Hyperemia ( blood flow)

• The capillary endothelial cells secrete cell-adhesion molecules, Selectins, that aid in the recruitment of leukocytes. Selectins make the vessel wall sticky and snag leukocytes. The adhesion of leukocytes to the vessel wall is called MARGINATION

• The leukocytes then crawl through the gaps in the vessel walls (this is called DIAPEDESIS)

• Chemotaxis: Release of cytokines that acts as chemical guides to bring Neutrophils to the area

• Phagocytosis of bacteria by neutrophils

• Recruitment of more neutrophils & macrophages

• Neutrophilia (5,000 cells/μL to 25,000 cells/μL in bacterial infection), Eosinophilia (elevated eosinophil count in allergy or parasitic infection)

• Fibrinogen (Forms a sticky mesh that contains the pathogens)

• Heparin (prevents clotting at site of injury)

• Monocytes (the primary agents of tissue cleanup and repair) arrive within 8-12 hours and become macrophages

• Macrophages engulf and destroy bacteria, damaged host cells, and dead and dying neutrophils via Phagocytosis

• Pus: accumulation of dead macrophages & neutrophils, bacteria, other cellular debris, and tissue fluid to form a pool of yellowish fluid

• Edema: forces open valves of lymphatic capillaries, promoting lymphatic drainage

• Hyperemia: delivers oxygen, amino acids, and other necessities for protein synthesis

• Heat increases metabolic rate, speeds mitosis, and tissue repair

• Pain: makes us limit the use of a body part so it has a chance to rest and heal

• New tissue growth: Platelet-derived growth factor secreted by blood platelets and endothelial cells in injured area. This growth factor stimulates fibroblasts to multiply and synthesize collagen

c. Third Line of Defense: Immunity (Specific)

Defeats a pathogen, and leaves the body with a “memory” of it so it can defeat it faster in the future. 2 distinguishing characteristics:

Specificity: immunity directed against a particular pathogen

Memory: when re-exposed to the same pathogen, the body reacts so quickly that there is no noticeable illness. The reaction for nonspecific responses takes just as long on re-exposure as the first exposure.

• Two types of immunity:

1. Humoral (antibody-mediated) immunity: mediated by B cells

B lymphocytes create and release antibodies that do not directly destroy a pathogen, but tag them for destruction by other mechanisms. Therefore humoral immunity is an indirect form of attack. Can only work against the extracellular stage of infectious microorganisms. Can’t “see” pathogens once they invade the body cells. But this is where the next form of immunity comes in.

Works in 3 stages (Fig. 21.35):

Recognize: Immunocompetent B cell has thousands of surface receptors for one antigen. Activation begins when an antigen (Ag) binds to several of these receptors, links them together, and is taken into the cell. B cell digests the antigen and links some of the epitopes to its MHC-II proteins (MHC = major histocompatibility proteins – identification tags that distinguish “self” from others). Displays these on the cell surface. Usually B cell response goes no further unless a helper T cell binds to this Ag–MHCP complex. Bound TH cell secretes interleukins that activate B cell. This triggers clonal selection -- B cell mitosis gives rise to an entire battalion of identical B cells programmed against the same antigen. Most differentiate into plasma cells (larger than B cells and contain an abundance of rough ER). Secrete antibodies at a rate of 2,000 molecules per second during their life span of 4 to 5 days.

React: Antibodies travel through the body in the blood or other body fluids. Antibodies bind to antigen, render it harmless, “tag it” for destruction.

Remember: Other B cells differentiate into memory cells. These cells can mount a very quick secondary response (“anamnestic” response) if we are ever re-exposed the same antigen (Fig. 21.29).

2. Cellular (cell-mediated) immunity: mediated by T cells

T Lymphocytes directly attack and destroy foreign cells or diseased host cells. This is the means of ridding the body of pathogens that reside inside human cells, where they are inaccessible to antibodies. It kills cells that harbor them.

Works in 3 stages (Fig. 21.22):

Recognize: The recognition phase has 2 aspects:

Antigen presentation: An Antigen-Presenting Cell (APC) encounters and processes an antigen. The APC will digest the antigen and display the epitopes in the grooves of the MHC protein. The APC migrates to nearest lymph node and displays it to the T cells. When T cells encounter a displayed antigen on the MHC protein, they initiate the immune response.

T Cell activation: Begins when TC or TH cell binds to a MHCP displaying an epitope that the T cell is programmed to recognize. But before it can go any further, the T cell must also bind to another APC protein, called the “costimulation” protein (T cell must check twice to see if it is really bound to a foreign antigen). Successful costimulation will trigger clonal selection. Activated T cell undergoes repeated mitosis. Some cells of the clone become effector cells and carry out the attack (“react” stage). Other cells become memory cells (“remember” stage).

React: Helper and cytotoxic T cells play different roles in the attack phase (Fig. 21.22):

Cytotoxic T (TC) cells are the only T cells that directly attack other cells. When TC cell recognizes a complex of antigen and MHC-I protein on a diseased or foreign cell, it “docks” on that cell. Directs a “lethal hit” against the pathogen by releasing several chemicals (perforin, granzymes, interferons, tumor necrosis factor).

Helper T (TH) cells secrete interleukins that exert three effects:

• Attract neutrophils and NK cells

• Attract macrophages, stimulate their phagocytic activity, and inhibit them from leaving the area

• Stimulate T and B cell mitosis and maturation

Helper T cells are necessary for most immune responses – they play a central role in both cellular and humoral immunity.

Remember: Memory cells are long-lived and more numerous than naive T cells. They take fewer steps to be activated, so they respond more rapidly. They generate the “T cell recall response” - upon re-exposure to same pathogen later in life, memory cells launch a quick attack so that no noticeable illness occurs. The person is immune to the disease.

Both types of immunity (humoral and cellular) are complementary – one works against disease-producing agents before they infect cells, the other works on infected cells. So humoral and cellular immunity will often work on the same pathogen at different stages of its life cycle in the body.

You should know the following Clinical Concepts:

• Lymphadenitis

• Lymphadenopathy

• Relationship between Lymph nodes and metastatic cancer

• Tonsilitis

• Reye Syndrome

• Hypersensitivity

• Severe combined immunodeficiency Disease (SCID)

• Acquired Immunodeficiency Syndrome (AIDS)