lymphatic Flashcards
1
Q
What are the main functions of the lymphatic and immune system?
A
Draining excess interstitial fluid, Transporting dietary lipids
Carrying out immune responses
2
Q
What is the major difference between lymph and interstitial fluid?
A
Location
What mean lack of resistance?
Susceptibility
3
Q
Describe how lymphatic capillaries are one-way only vessels.
A
The ends of the endothelial cells in the wall of the lymphatic capillary overlap. When pressure is higher in the interstitial fluid than in the lymph, the cells separate slightly allowing interstitial fluid into the vessel. When pressure is greater inside, the cells are tightly packed, not allowing the lymph to cross back into the interstitial fluid.
4
Q
What causes lymph from the small intestines to appear white?
A
Lipids
5
Q
List the organs of the immune system
A
Spleen, Lymph node, Lymph nodule, Red bone marrow and Thymus
6
Q
The left subclavian vein and left internal jugular vein receive lymph from what?
A
Thoracic duct
7
Q
What physiological systems use the skeletal muscle and respiratory pumps?
A
Lymphatic, Immune and Cardiovascular systems
8
Q
Which organ produces a hormone that promotes maturation of T cells?
A
Thymus
9
Q
In which part of the thymus are T cells thought to die?
A
Thymic (Hassall’s) corpuscles
10
Q
What are the functions of the spleen?
A
Removal of RBCs
11
Q
What are the physical and/or chemical barriers?
A
Saliva, Urine, Mucus, Stratified squamous epithelium
12
Q
Describe the barriers used in innate defense.
A
Barriers used by the innate defense include epidermis, mucus, hairs, cilia, lacrimal apparatus, saliva, urine, vaginal secretions, sebum, perspiration and gastric juices.
Which cells provides a non-specific cellular disease resistance mechanism?
Macrophages
13
Q
What are immunocompetent cells?
A
When B and T cells are fully developed and mature
14
Q
Genetic recombination generates diversity in what part (s) of the immune system?
A
MHC antigen and antigen receptors
15
Q
Which class of cells includes macrophages, B cells and dendritic cells?
A
Antigen presenting cells
16
Q
To become activated, which of the following requires being bound to a foreign antigen AND simultaneous costimulation?
A
T Cell
17
Q
Which cells display CD4 proteins and interact with MHC Class II antigens?
A
Helper T Cells
18
Q
List the five actions of antibodies.
A
Solution: Antibodies can act as a neutralizing agent, they can immobilize bacteria, agglutinate and precipitate the antigen, activate the complement and enhance phagocytosis.
19
Q
Which class of antibodies is mainly found in sweat, tears, breast milk and GI secretions?
A
IgA
20
Q
Describe the ways to acquire adaptive immunity.
A
Naturally acquired active immunity is acquired following exposure to a microbe, antigen recognition by B and T cells and costimulation leading to formation of antibody-secreting plasma cells, cytotoxic T cells, and B and T memory cells. Naturally acquired passive immunity occurs when IgG antibodies are transferred from mother to fetus across the placental barrier or IgA antibodies are transferred from mother to infant during breast-feeding. Artificially acquired active immunity is acquired via antigens introduced during vaccinations. Artificially acquired passive immunity is acquired via intravenous injection of immunoglobulins.
21
Q
The ability to ward off the pathogens that produce disease is called immunity or resistance. Lack of resistance is called susceptibility. Immunity to disease can be grouped into two broad areas:
A
Innate (nonspecific) immunity) to disease includes defense mechanisms that provide general protection against invasion by a wide range of pathogens.
Adaptive (specific) immunity involves activation of specific lymphocytes that combat a particular pathogen or other foreign substance.
22
Q
The body system that carries out immune responses is
A
the lymphatic system
23
Q
LYMPHATIC SYSTEM STRUCTURE AND FUNCTION
The lymphatic system consists of a fluid called lymph flowing within lymphatic vessels, several structures and organs that contain lymphatic tissue (specialized reticular tissue containing large numbers of lymphocytes), and bone marrow, which is the site of lymphocyte production
Lymph and interstitial fluid are basically the same. Their major difference is location. The lymphatic system functions to:
A
Drain excess interstitial fluid from tissue spaces and return it to the blood, (Left over from what is not reabsorbed during bulk flow).
return leaked plasma proteins to the blood,
Transport lipid and lipid soluble vitamins (ADEK) absorbed from the GIT to the blood,
protect against invasion by nonspecific defenses and specific immune responses.
24
Q
Lymphatic Vessels and Lymph Circulation
Lymphatic vessels begin as blind-ended lymph capillaries in tissue spaces between cells
Interstitial fluid drains into lymphatic capillaries, thus forming lymph .
A
Lymph capillaries merge to form larger lymphatic vessels which convey lymph into and out of structures called lymph nodes (Figure 22.1).
Lymph vessels are like veins with thinner walls and more valves. Lymph nodes are encapsulated bean shaped structures that contain lots of T and B cells.
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are found throughout the body and generally follow same route as veins . There are no lymph capillaries in avascular tissue, the central nervous system , portions of the spleen, and red bone marrow.
have a slightly larger diameter than blood capillaries and have overlapping endothelial cells that work as one-way valve for fluid to enter the lymphatic capillary. (The endothelial cells overlap and when pressure is greater in the interstitial fluid than lymph the cells separate and fluid enters through a 1 way swinging door. When pressure inside the vessel exceeds interstitial pressure the cells adhere closely and lymph cannot escape.)
Anchoring filaments are elastic fibers that extend out to attach lymph vessel to surrounding tissues
When there is excess fluid/swelling in the tissue the anchoring filaments are pulled and this helps open up the endothelial spaces in the vessels.
Lymphatic capillaries
A lymphatic capillary in the villus of the small intestine is the lacteal . It functions to transport digested fat from the small intestine into blood. The lymph fluid in lacteals is called chyle . (Called lacteals because the lymph juice (chyle) is milky looking due to the lipids.)
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begins as a dilation called the cisterna chyli) and is the main collecting duct of the lymphatic system.
receives lymph from the left side of the head, neck, and chest, the left upper extremity, and the entire body below the diaphragm.
It drains lymph into venous blood at the junction of the left subclavian vein and the left internal jugular vein.
The thoracic duct
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The right lymphatic duct drains lymph from the upper right side of the body.
It drains lymph into venous blood at the junction of the right subclavian vein and right internal jugular vein.
Right Lymphatic Duct
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Formation and Flow of Lymph
drains into lymph capillaries. (Approx. 3L/day, also pick up any leaked plasma proteins and return to blood).
The passage of lymph is from the blood capillaries (blood) to interstitial spaces (interstitial fluid) to lymph capillaries (lymph) to lymphatic vessels to lymph trunks to the thoracic duct or right lymphatic duct to the junction of the subclavian and internal jugular veins (blood)
Lymph flows as a result of the milking action of skeletal muscle contractions and respiratory movements.
It is also aided by lymphatic vessel valves that prevent backflow of lymph.
Interstitial fluid
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Lymphatic Organs and Tissues:
The primary lymphatic organs are the red bone marrow and the thymus gland that produces B and T cells. These are areas where stem cells divide and become immunocompetent. Pluripotent stem cells in red bone marrow make immunocompetent B cells and pre T cells which then go to thymus to become immunocompetent.
The secondary lymphatic organs are the lymph nodes and spleen. Most immune responses occur in secondary lymphatic organs. The lymphatic nodules (clusters of lymphocytes that stand guard in all mucus membranes) are included as secondary lymphatic organs.
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lies between the sternum and the heart and functions in immunity as the site of T cell maturation. It has 2 lobes separated by a capsule with extensions called trabeculae that divide the lobe into lobules.
The lobules have an outer cortex containing T cells, dendritic cells, epithelial cells, macrophages and is the site for maturation of T cells (with help from dendritic cells). (Only 2% of pre T cells survive maturation and move into the medulla.
Medulla also has thymic corpuscles (Hassall’s) possibly sites of T cell death in medulla).
The thymus gland is large in infants and after puberty much of it is replaced by adipose and areolar connective tissue. Through whole life it will produce some T cells.
The thymus gland
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are encapsulated oval structures located along lymphatic lymphatic vessels.There are approximately 600 throughout the body.
They contain T cells, macrophages, follicular dendritic cells, and B cells.
The capsule surrounding lymph nodes extends projections (trabeculae) into the node to divide it into compartment.
Medulla contains B cells, macrophages, and antibody producing plasma cells
Foreign substances filtered by the lymph nodes are trapped by nodal reticular fibers.
Macrophages then destroy some foreign substances by phagocytosis and lymphocytes bring about the destruction of others by immune responses.
Lymph nodes are the site of proliferation of plasma cells and T cells.
Lymph nodes
Lymph enters nodes through afferent lymphatic vessels, is filtered to remove damaged cells and microorganisms, and exits through efferent lymphatic vessels. (The route of the lymph in a lymph node is as follow: Afferent vessels – subcapsular sinus – trabecular sinus – medullary sinus – efferent vessels)
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The parenchyma (functional part) of node has a cortex and medulle.
Outer cortex has lymphatic follicles which are aggregates of B cells and have germinal centers.
Inner cortex consists of T cells, and dendritic cells which present antigen and cause T cells to proliferate and migrate to area of infection.
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is the largest mass of lymphatic tissue in the body and is found in the left hypochondriac region between the fundus of the stomach and the diaphragm
Spleen
| Spleen has a hilum where splenic artery, splenic vein, efferent lymph vessels pass.
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is lymphatic tissue arranged around the central arteries (branches of splenic artery).
Its T lymphocytes directly attack and destroy antigens in blood.
Its B lymphocytes develop into antibody producing plasma cells, and the antibodies inactivate antigens in blood.
Macrophages destroy antigens in blood by phagosytosis.
The white pulp
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consists of venous sinuses filled with blood and splenic cords (Billroth’s) consisting of RBCs, macrophages, lymphocytes, plasma cells, and granulocytes.
Macrophages remove worn-out or defective RBCs, WBCs, and platelets.
The spleen stores blood platelets in the red pulp.
The spleen is often damaged in abdominal trauma. A splenectomy may be required to prevent excessive bleeding].
The red pulp
| [The red pulp is involved in the production of blood cells during the second trimester of pregnancy.
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are oval-shaped concentrations of lymphatic tissue which are not surrounded by a capsule. They are scattered throughout the lamina propria of mucus membranes lining the GI tract, respiratory airways, urinary tract, and reproductive tract. This is the ______
Tonsils are multiple aggregations of large lymphatic nodules embedded in a mucous membrane at the junction of the oral cavity and the pharynx. They include the pharyngeal (adenoid), palatine (most commonly removed), and lingual tonsils
They are situated strategically to protect against invasion of foreign substances and participate in immune responses by producing lymphocytes and antibodies.
Lymphatic nodules
mucosa-associated lymphatic tissue (MALT).
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are lymphatic nodules in the ileum of the small intestine.
Peyer’s patches
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INNATE (NONSPECIFIC) IMMUNITY
First Line of Defense: Skin and Mucous Membrane
Nonspecific immunity refers to a wide variety of body responses against a wide range of pathogens (disease producing organisms) and their toxins. It is present at birth and responds in the same way regardless of the type of invader.
Mechanical protection includes:
Intact epidermis layer of the skin which provides a very effective barrier to the entrance of microbes and because our skin cells shed, they take microbes away with them, (Intact skin is very difficult for bacteria to penetrate.)
Mucous membranes line body cavities and secrete mucus to moisten the cavity surface and trap microbes, (The mucous membrane of the nose has hairs that help trap and filter dust and microbes.
Cilia in the upper respiratory tract wave to help propel microbes trapped in mucus toward the pharynx where they can be coughed or sneezed out or swallowed to the stomach where gastric juices destroy microbes.
-Lacrimal apparatus in the orbital cavity produces and drains away tears in response to irritants to dilute and wash away microbes. Tears contain lysozyme that can break down bacterial cell walls.
Saliva works much the same way as tears to continually wash your mouth. It also contains lysozyme as does perspiration, nasal secretions, tissue fluids.
Urine flow cleans out the urethra, (Drink lots of water when bladder infection so you pee more!).
Defecation, vomiting, vaginal secretions also may be considered mechanical processes that expel microbes.
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is localized on the skin, in loose connective tissue, stomach, and vagina.
The sebaceous glands in the skin produce sebum that adds a protective film to the skin barrier. Sebum also inhibits growth of some types of bacteria and fungi because of its low PH due to the presence of unsaturated fatty acids and lactic acid.
Lysozyme is an enzyme component of sweat that also has antimicrobial properties.
Gastric juice contains HCL that renders the stomach nearly sterile because its low pH (1.5-3.0) kills many bacteria and destroys most of their toxins.
Vaginal secretions also are slightly acidic discourage bacterial growth.
Chemical protection-First Line of Defense: Skin and Mucous Membrane
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involves internal antimicrobial substances, phagocytic and natural killer cells, inflammation , and fever.
Lymphocytes, macrophages, and fibroblasts infected with viruses produce proteins called interferons (IFNs). Once produced and released from virus-infected cells, IFN diffuses to uninfected neighboring cells and binds to surface receptors, inducing uninfected cells to synthesize antiviral proteins that interfere with or inhibit viral replication. IFNs also enhance the activity of phagocytes and natural killer (NK) cells, inhibit cell growth, and suppress tumor formation.
A group of about 30 proteins present in blood plasma and on cell membranes comprises the complement system when activated, these proteins “complement” or enhance certain immune, allergic, and inflammatory reactions.
Iron-binding proteins inhibit the growth of certain bacteria by reducing the amount of available iron, e.g. transferrin (in blood and tissue fluid), lactoferrin (in milk, saliva and mucus), ferretin (in liver, spleen and red bone marrow), and hemoglobin (in RBCs)
Second Line of Defense: Internal Defenses
The second line of defense
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The second line of defense
Antimicrobial Substances : There are four main types including:
interferons, complement, iron-binding proteins, and antimicrobial proteins.
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are short peptides that have a broad spectrum of antimicrobial activity, e.g dermicidin (produced by sweat glands ), defensins and cathelicidins (produced by neutrophils, macrophages and epithelia), and thrombocidin (produced by platelets )
Antimicrobial proteins (AMPs)
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are lymphocytes that lack the membrane molecules that identify T and B cells.
They have the ability to kill a wide variety of infectious microbes or certain tumor cells.
Phagocytes are cells specialized to perform phagocytosis and include neutrophils and macrophages
Wandering macrophages migrate to the area of infection.
Fixed macrophages stay in specific tissues.(They are included: Histiocytes in connective tissue, Kupffer cells in the liver, alveolar in the lungs, microglia in nervous system, tissue macrophages in spleen, lymph nodes, red bone marrow)
Natural Killer Cells and Phagocytes
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Natural killer (NK) cells
NK cells attack body cells that display abnormal or unusual plasma membrane proteins.
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NK cells bind to a target cell and release granules that contain toxic substances such as perforins (punch holes in target cells’ membranes which causes them to burst) or granzymes that destroy the target cell (by forcing it to undergo apoptosis – self destruction).
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occurs when cells are damaged by microbes, physical agents, or chemical agents.
is usually characterized by four symptoms: redness, pain, heat, and swelling. Loss of function may be a fifth symptom, depending on the site and extent of the injury. ( goal of inflammation is to dispose of microbes/toxins at the site of injury, prevent spread to other tissues
Inflammation
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The three basic stages of inflammation
1. vasodilation & increased permeability of blood vessels, 2. phagocyte migration
3. tissue repair
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and increased permeability of vessels = more substances ( antibodies , clotting factors) are able to pass from the blood and more blood is able to flow through the damaged area. Substances that contribute to inflammation are:
-Histamines are released from mast cells causing vasodilation and increased permeability of vessels,
- Kinins are polypeptides that induce vasodilation , increase permeability, act as chemotaxic agents (bradykinin),
- Prostaglandins are lipids released by damaged cells and intensify effects of histamine and kinins. They also stimulate emigration of phagocytes through capillary walls,
- Leukotrienes are produced by basophils and mast cells and cause increased permeability, act as chemotaxic agents, and help with adherence of phagocytes to pathogens,
- Complements stimulate histamine release, attract neutrophils, promote phagocytosis, some destroy bacteria.
Vasodilation
Swelling is a result of the increased amount of fluid moving from the plasma to tissues.
Heat is due to increased dilation and permeability and increased metabolic reactions.
Altered function is usually associated with restriction to movement as a result of swelling and pain.
Redness (Erythma) is due to the increased amount of blood and increased metabolic reactions.
Pain results from injury to neurons, toxic chemicals released from microbes, kinins, prostaglandins, pressure from edema.
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– phagocytes arrive on the scene within an hour of the start of inflamation. Neutrophils predominate at first but die off quite quickly so monocytes ( wandering macrophages) take over and also clean up the dying neutrophils.
[After phagocytes engulf damaged tissue and microbes, they eventually die, forming a pocket of dead phagocytes and damaged tissue and fluid called pus. Pus must drain out of the body or it accumulates in a confined space, causing an abscess. (Clinical Application)]
Emigration of phagocytes
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is usually caused by infection from bacteria (and their toxins) and viruses. The high body temperature inhibits some microbial growth and speed up body reactions that aid repair.
is caused when the thermostat in the hypothalamus is reset. This will result from bacterial toxins and viruses. A fever intensifies the effects of interferons, inhibits growth of microbes, speeds repair reactions
Fever
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is the ability of the body to defend itself against specific invading agents. Antigens (Ags) are substances recognized as foreign by the immune responses. The distinguishing properties of immunity are specificity and memory.
The branch of science that deals with the responses of the body when challenged by antigens is called immunology.
Adaptive (specific) Immunity
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Maturation of T Cells and B Cells
Cells that develop the ability to carry out immune responses (immunocompetence) are T and B lymphocytes.
Both T cells and B cells derive from stem cells in bone marrow (Figure 22.11).
B cells complete their development in bone marrow (Figure 22.11).
T cells develop from pre-T cells that migrate to the thymus. Most T cells develop before puberty but do continue to mature and leave the thymus throughout life.
Before T cells leave the thymus or B cells leave bone marrow, they acquire several distinctive surface proteins; some function as antigen receptors, molecules capable of recognizing specific antigens (Figure 22.12).
T cells exit the thymus as either helper T cells known as CD4 T cells or cytotoxic T cells or CD8 T cells. (this means that in the plasma membrane of these cells in addition to antigen receptors there are proteins known as CD4 & CD8)
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Types of adaptive immunity
refers to destruction of antigens by T cells. It is particularly effective against intracellular pathogens, such as fungi, parasites, and viruses; some cancer cells; and foreign tissue transplants. CMI always involves cells attacking cells. Cytotoxic T cells attack the invaders.
Cell-mediated immunity (CMI)
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Types of adaptive immunity
refers to destruction of antigens by antibodies. It works mainly against antigens dissolved in body fluids and extracellular pathogens (primarily bacteria) that multiply in body fluids but rarely enter body cells.
B cells transform into plasma cells which synthesize/secrete antibodies (Ads) or immunoglobulins. Often a pathogen provokes both types of immune response.
Helper T cells aid both cell-mediated and antibody-mediated immune responses.
Antibody-mediated (humoral) immunity (AMI)
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is the process by which a lymphocyte ( T cells, cytotoxic T cells and B cells) proliferation and differentiate (forms more highly specialized cells) in response to a specific antigen. (Fig. 22.11)
A clone is a population of identical cells that can recognize the same specific antigen as the original lymphocyte.
Clonal selection
Clonal selection of lymphocytes occurs in the secondary lymphatic organs and tissues. During the first exposure to an antigen, there are only a few lymphocytes that can recognize that antigen. The clonal selection helps the body to make thousands of lymphocytes to respond to that antigen in the future exposure.
During Clonal selection the lymphocytes give rise to effector and memory cells.
The effector cells including the active helper T cells, active cytotoxic T cells and plasma cells eventually die after the immune response has been completed.
The memory cells including the memory helper T cells, memory cytotoxic T cells and memory B cells will proliferate during the second exposure to the same antigen. They will vigorously attack to the antigen and will destroy them before any sign or symptoms of disease can occur
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are chemical substances that are recognized as foreign by antigen receptors when introduced into the body.
are both immunogenic (ability to provoke an immune response by stimulating the production of specific antibodies and/or T cel and reactive (ability of antigen to react with the specific antibodies/cells it provoked).
Antigens (antibody generators)
An antigen that gets past the nonspecific defenses can get into lymphatic tissue by entering an injured blood vessel and being carried to the spleen, penetrating the skin and entering lymph vessels leading to lymph nodes, or penetrating mucous membranes and lodging in mucosa-associated lymphoid tissue (MALT).
Antigens are large, complex molecules. They are most often proteins, but sometimes are nucleoproteins, lipoproteins, glycoproteins, and certain large polysaccharides.
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Specific portions of antigen molecule
called antigenic determinants, or epitopes, trigger immune responses
Antigen receptors exhibit great diversity due to genetic recombination. (The human immune system can recognize and bind to at least 1 billion different epitopes. Before the antigen even enters the body T and B cells that are able to recognize and respond to the antigen are waiting.)
Genetic recombination = gene segments are put together in different combinations as the lymphocytes are developing in red bone marrow and thymus.
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are tiny substances that have no immunogenicity on their own but can stimulate an immune response if attached to a larger carrier molecule
Haptens
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are unique to each person’s body cells. These transmembrane glygoproteins are also called human leukocyte antigens (HLA) because they were first identified on WBC. ( self antigen)
These self-antigens aid in the detection of foreign invaders.
Major histocompatibility complex (MHC) antigens
All cells except red blood cells display MHC class I antigens. Some cells also display MHC class II antigens.
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Pathways of Antigen Processing
For an immune response to occur, B and T cells must recognize that a foreign antigen is present.
B cells can recognize and bind to antigens in extracellular fluid, blood plasma , and lumph.
T cells, however, can only recognize fragments of antigenic proteins that first have been processed and presented in association with MHC (self-antigen).
Antigen processing breaks down antigen proteins into protein fragments and binds them to the MHC molecule. The antigen-MHC complex is “presented” by inserting into the plasma membrane of a cell. The T cells will ignore the antigen-MHC complex if the peptide fragment comes from a self-protein, but will cause an immune response to occur if it is a foreign protein.
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Processing of Exogenous Antigens
Cells called ____process exogenous antigens (antigens formed outside the body) and present them together with MHC class II molecules to T cells. After processing and presenting antigen, APCs migrate to lymph nodes via lymph vessels.
antigen-presenting cells (APCs)
APCs include macrophages, B cells, and dendritic cells. APCs are located in skin, mucus membranes of respiratory tract, GIT, urinary, reproductive and lymph nodes.
The presentation of exogenous antigens together with MHCII molecules on antigen presenting cells alerts T cells that “intruders are present”.
Ingestion of antigen = APCs ingest antigen by phagocytosis /endocytosis
Digestion of antigen into peptide fragments + phagosome/endosome digestive enzymes split antigens into short peptide fragments.
Synthesis of MHC II molecules = APC synthesizes MHC II molecules and packages them into vesicles.
Fusion of vesicles = antigen peptide fragments in their vesicles merge with MHC II vesicles.
Binding of peptide fragments to MHC II molecules.
Insertion of antigen-MHC II complex into plasma membrane = exocytosis of combined vesicle allows the complex to be inserted into the plasma membrane.
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5 Processing of Endogenous Antigens
Endogenous antigens are synthesized within the body and include viral proteins or proteins produced by cancer cells.
Most of the cells of the body can process endogenous antigens.
1. Digestion of antigen into peptide fragments inside the infected cell.
2. Synthesis of MHC-I molecules inside the infected cell.
3. Binding of peptide fragments to MHC-I molecules.
4. Packing of antigen -– MHC-I molecules into vesicle.
5. Insertion of antigen—MHC-I complexes into the plasma membrane, where it alerts T cells.
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are small protein hormones needed for many normal cell functions such as cell growth and differentiation.
Cytokines
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an antigen is recognized (bound), a small number of specific T cells proliferate and differentiate into a clone of effector cells, and the antigen (intruder) is eliminated.
Effector cells derived from clonal selection are a population of identical cells that can recognize the same antigen and carry out some aspect of the immune attack.
cell-mediated immune response,
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Activation of T Cells
T - cell receptors (TCR) recognize antigen fragments associated with MHC molecules on the surface of a body cell.
Antigen recognition by a TCR with CD4 or CD8 protein is the 1st signal in the activation of a T cell.
Activation of T cells requires constimulation
Recognition and binding without costimulation results in a prolonged state of inactivity (anergy).
(Like starting car and letting it idle until it runs out of gas).
When T cell receives both signals it becomes activated and subsequently undergoes clonal selection.
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Only a few T cells will have receptors that will recognize and bind to any one antigen. The CD4/CD8 proteins help with the binding process and are called
coreceptors.
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_____ by cytokines (interleukin-1/IL-1 and interleukin-2/IL-2), or by pairs of plasma membrane molecules, one on the surface of the T cell and a second on the surface of an antigen-presenting cell(APC).
Costimulation
| Costimulation is believed to prevent accidental immune responses (need to have clutch in or in park to start car).
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Activation and Clonal Selection of Helper Cells
Helper T (TH) cells, or CD4 T cells, display CD4 protein, recognize antigen fragments associated with MHC-II molecules, and secrete several cytokines.
The most important, interleukin-2, is needed for all immune responses and is the main trigger for T cell proliferation and also acts as a costimulatory for helper T cells or cytotoxic T cells. It enhances activation and proliferation of T cells, B cells, NK cells.
Costimulation for the TH cells is provided by molecules from the APC interacting with the T cell to activate it.
Within hours the activated helper T cells will have cloned and started secreting cytokines (IL-2).
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Activation and Clonal Selection of Cytotoxic T Cells
Cytotoxic T (TC) cells, or CD8 cells, develop from T cells that display CD8 protein and recognize antigen fragments associated with MHC-I molecules.
TC cells only become activated by costimulators produced by helper T cells (mainly IL-2).
Cytotoxic T response requires presentation of antigen associated with both MHC I and MHC II.
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are the result of the clonal selection of the activated cytotoxic T cells. They would proliferate and differentiate into more active cytotoxic T cells and more memory cytotoxic T cells if the same antigen enters the body at the future time.
Memory cytotoxic T cells
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Elimination of Invaders
Cytotoxic T cells fight foreign invaders by killing the target cell (the cell that bears the same antigen that stimulated activation or proliferation of their progenitor cells) without damaging the cytotoxic T cells itself
To do this the TC cells leave secondary lymphatic organs and tissues and migrate out to seek and destroy infected target cells, cancer cells, transplanted cells.
When cytotoxic T cells encounter a cell displaying a microbial antigen, they can release granzymes to trigger apoptosis (Figure 22.15a). When the infected cell bursts open, the microbes are released. The microbe is then destroyed by phagocytes.
Cytotoxic T cells can also bind to infected cells and release perforin and granulysin. Perforin causes cytolysis while granulysin destroys the microbe.
Cytotoxic T cells can also release lyphotoxin which activates damaging enzymes within the target cell (target cell DNA fragmentation).
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is carried out by cytotoxic T cells with help from macrophages and natural killer cells.
They recognize tumor antigens displayed on the surface of cancerous cells and destroy the tumor cell.
The immune system can recognize proteins in transplanted organs as foreign and mount a graft rejection.
Success of a proposed organ or tissue transplant depends on histocompatibility. Tissue typing (histocompatibility testing) is done before any organ transplant.
Organ transplant recipients also receive immunosuppresive drugs.
Immunological surveillance
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Activation, Proliferation, and Differentiation of B Cells
During activation of a B cell, an antigen binds to antigen receptors on the cell surface
B cell antigen receptors are chemically similar to the antibodies that will eventually be secreted by their progeny.
Processing: Some antigen is taken into the B cell, broken down into peptide fragments and combined with the MHC-II self-antigen, and moved to the B cell surface.
B cells can respond to unprocessed antigen but the reaction is more intense when they process it first.
Helper T cells recognize the antigen-MHC-II combination and deliver the Costimulation (IL-2) needed for B cell proliferation and differentiation.
Some activated B cells become antibody-secretion plasma cells. Others become memory B cells.
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is a protein that can combine specifically with the antigenic determinant ( epitope ) on the antigen that triggered its production.
antibody
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Antibody Structure - known as immunoglobulins
Antibodies consist of heavy and light chain and variable and constant portions (Figure 22.17).
Most antibodies contain 4 polypeptide chains: 2 heavy chains with short CHO chains attached, 2 light chains (about half the number of aa’s that the heavy chains have).
Antibodies are Y or T-shaped with arm regions and a heavy stem region (both heavy chains).
The tips of the heavy and light chains have variable regions that are different for every type of antibody and this is the area that recognizes and attaches the antibody to the specific antigen for which it was produced. Y arms and flexibility allow the antibody to bind to 2 epitopes at the same time on the surface of the microbe.
The rest of the antibody is the constant region and is responsible for the type of antibody-antigen reaction that occurs and gives us the 5 classes of immunoglobulins: IgG, IgA, IgM, IgD, and IgE. Table 22.3 summarizes the structures and functions of these five classes of antibodies.
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The functions of antibodies include:
neutralizing antigen by neutralizing bacterial toxins and preventing attachment of viruses to body cells,
immobilization of bacteria so that if antigen is on the cilia/flagella for a motile bacteria the antibody will bind at that site immobilizing the bacteria and limiting their ability to spread to nearby tissues,
agglutination and precipitation of antigen because one antigen binding site on an antibody may bind to an epitope on one microbe while the other ABS may bind to the epitope on another microbe causing microbes to clump together which makes it easier for phagocytes to ingest the invaders,
activation of complement,
enhancing phagocytosis because the stem portion kind of waves like a flag to attract phagocytes,
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is due to the presence of long-lived antibodies and very long-lived lymphocytes that arise during proliferation and differentiation of antigen-stimulated B and T cells.
immunological memory
Immunization against certain microbes is possible because memory B cells and memory T cells remain after the primary response to an antigen (Figure 22.19).
The secondary response (immunological memory) provides protection should the same microbe enter the body again. There is rapid proliferation of memory cells, resulting in a far greater antibody titer (amount of antibody in serum) than during a primary response.
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SELF-RECOGNIZITON AND SELF-TOLERANCE
T cells undergo both positive and negative selection to ensure that they can recognize self-MHC antigens (self-recognition) and that they do not react to other self-proteins ( self-tolerance). Negative selection involves both deletion and anergy (Figure 22.20).
Pre-T cells in the thymus develop the ability for self-recognition via positive selection where the TCR will interact with MHC proteins on cells in the cortex of the thymus and these cells will survive because they are now able to recognize MHC. If they are unable to interact with the thymus cells and don’t learn how to recognize self MHC they will die.
Negative selection happens when T cells interact with the dendritic cells in the junction of the medulla and cortex of the thymus. T cells that recognize and bind to self peptides are eliminated or inactivated. Only 1-5% of immature T cells will survive this process.
If they encounter an unfamiliar self protein once mature they will either become anergic or deleted (apoptosis).
B cells develop tolerance through deletion and anergy
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STRESS AND IMMUNITY
The field of psychoneuroimmunology (PNI) deals with common pathways that link the nervous, endocrine, and immune systems.
PNI has shown that thoughts, feelings, moods, and beliefs influence the level of health and the course of a disease.
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AGING AND THE IMMUNE SYSTEM
With advancing age, the immune system functions less effectively. Individuals become more susceptible to infections and malignancies, response to vaccines is decreased, and more autoantibodies are produced.
Cellular and humoral responses also diminish.
