Anatomy & Physiology

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Chapter 22

• Anatomy Physiology
• Fifth Edition
• Seeley/Stephens/Tate
• (c) The McGraw-Hill Companies, Inc.

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The Lymphatic System and Immunity

• The human body recognizes anything other than its
  own as an invader.
• When these foreign bodies are capable of living
  in the human body and are harmful, they are
  called pathogens.
• Plasma contains antibodies against cells other
  than its own. These antibodies are formed when
  the infants are about three months old. Recall
  when the blood types were formed.
• Thus, there is the lymphatic system in the body
  to identify and destroy foreign bodies. (by
  forming antibodies)
• But, how do they distinguish our own from the
  others?
• When the reaction is against each specific
  foreign body, it is called immune response or
  immunity.

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• Organization and Functions of the Lymphatic
  System
• In the lymphatic system there are
• Lymphatic fluid, lymph, that contains lymphocytes
• Vessels that transport lymph
• And sites where large contents of lymphocytes are
  held lymph nodes, spleen, and thymus.
• Functions of the lymphatic system
• The lymph system has three major functions
• 1. Fluid Balance. Circulating blood release about
  30 L of fluid into interstitial space each day.
  Of the 27 L are returned to the circulation. The
  remaining 3L will enter the lymphatic system as
  lymph. The lymph passes through the lymphatic
  system and enter back to the blood vessels. In
  addition to water, lymph contains substances as
  in plasma and substances extracted from cells.
• 2. Fat Absorption. Fats and other substances are
  absorbed from the digestive tract and carried
  through the lymphatic system.
• 3. Defense. Immune system (lymphocytes, B-cells,
  T-cells)

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• Lymphatic Vessels
• Lymphatic vessels are spread out throughout the
  body except in the CNS (Fig 22.1)
• They originate from within lymphocyte producing
  organs and empty into the thoracic duct.
• They contain many lymphatic nodes and nodules.
• Like blood vessels, they have small vessels
  called lymphatic capillaries which lay close to
  the blood capillaries.
• Lymph soluble fluid will be picked up through the
  capillaries and pushed back to larger truck.
• They even have valves to control the flow of
  lymph through very low pressure of fluid.

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• Lymphatic Organs
• Diffuse lymphatic tissue
• Dispersed lymphocytes, macrophages and other
  cells. No clear boundaries. (Fig. 22.2)
• Lymphoid Nodules
• Packed with lymphocytes.
• Flexible in size depending upon the number of
  lymphocytes
• Spread in loose C.T. of the digestive,
  respiratory and urinary systems. Larger patches
  in intestinal system call Peyers patches.
• In lymph nodes they are called follicles, there
  they contain a germinal center, where lymphocytes
  divide.
• Though filled with lymphocytes, lymphoid nodules
  could be infected tonsillitis, appendicitis.

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• Tonsils
• Large groups of lymph nodules and diffuse
  lymphatic tissue located in the oral cavity (Fig.
  22.3)
• Protection against bacteria, etc.. In the nose
  and mouth.
• Three types of tonsils pharyngeal, palatine,
  and lingual
• Enlarged pharyngeal tonsil is called adenoid.
• Lymph Nodes ( Fig. 22.1 and Fig. 22.4)
• Found throughout the body except in the brain.
• They are encapsulation of lymphocytes,
  macrophages and reticular cells with blood
  vessels
• 1-25mm in diameter and are subdivided into two
  regions called, a medulla and cortex.
• Within the cortex germinal centers are found.
  This is where lymphocyte division takes place.
• Act as sieve and removal of 99 of antigens while
  reactivating T- cells and B-cells.

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• The Spleen
• Upper and posterior part of the abdominal
  cavity.
• Largest of the lymphatic tissue, 160g. (Fig.
  22.5)
• Contains two types of lymphatic tissue white
  pulp (arterial supply) and red pulp (venous
  supply).
• The spleen detects and responds to foreign
  substances in the blood, destroys worn-out RBCs
  and acts as a blood reservoir.

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• Thymus Gland
• On top of the heart
• T-cells mature here
• Becomes large during the first or second year.
• Intrinsic size is largest at puberty and then
  decreases.
• Produces lymphocytes which then move to other
  lymphatic tissues.
• Blood-thymic barrier - reticular cells wrap
  around capillaries and prevent large molecules
  from entering the cortex of the thymus.

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• Immunity
• How the human body defends itself against damage
  from foreign substances such as microorganisms
  and harmful chemical as toxins.
• Innate (non-specific) and adaptive (specific)
  immunity. These two types are distinguished by
  the way they respond to specific stimulations and
  how they memorize the events.
• Specificity. Innate immunity can act against
  bacteria in genera. (no memory)
• Memory. Adaptive immunity can distinguish among
  different kinds of bacteria and generally get
  more sensitive with each new encounter.

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• Innate Immunity
• Mechanical Mechanism
• Physical barriers, such as the skin and membranes
• Chemical Mediators (Table 22.1)
• Molecules which contribute to develop immunity.
• Kill bacteria lysozyme and sebum mucus
• Others histamine and kinins by vasodilation
  interferon production, etc..
• Complement
• Is a group of approximately 20 proteins that
  makes up approximately 10 of the globulin part
  of serum. They are a group of proteins activated
  in the form of a cascade and provide protection
  by attacking the bacterial membrane. They attach
  to and form holes in the membranes. The proteins
  can also attach to bacteria membrane and
  stimulate macrophages to phagocytize the bacteria.

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• Interferons proteins that protect the body
  against viral infection and possibly cancer.
• Cells for Innate Immunity
• Review the major functions of, neutrophils,
  monocytes, macrophages, basophils, mast cells,
  eosinophils, and natural killer cells. (Table
  22.2)
• Inflammatory Response
• Tissue damage caused by bacteria or others may
  induce inflammation of tissue as it releases
  histamine, prostaglandins, kinins, etc
• Vasodilation attracts chemotatic phagocytes and
  other leukocytes to the region as well as
  fibrinogen to form fibrin in order to localize
  damage.

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• Adaptive Immunity
• Substances to stimulate adaptive immunity are
  antigens, of which molecule weights could be as
  large as 10,000 or more. (produce antibodies)
• Haptens are small molecules capable of combining
  with larger molecules to stimulate adaptive
  immunity response.
• Two type of antigens foreign antigens (allergen)
  are from outside of the body, and self antigens
  (auto-immune) are molecules of its own body.
• For example. Allergic reaction is by foreign
  antigens, while autoimmune disease is from self
  antigens.

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• Immunity has been divided into two types humoral
  (body fluid) immunity and cell mediated immunity.
• Specificity recognition of antigen
• The specificity is established because of the
  specific receptors located on the surface of T
  and B cells.
• Versatility there are many antigens.
• And there are many different forms of lymphocytes
  that are made against them.
• Memory the adaptive immune system has a memory.
  With the presence of the foreign body,
  lymphocytes responding to it begin to initiate
  cell divisions.
• The presence of antigen leads to the formation of
  active and memory cells.
• The active cells respond to antigens, while the
  memory cells wait until the next onslaught.
• In this manner, the second response to the same
  antigen will be fast.

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• Lymphocytes
• 25 of circulating white cells.
• The majority of lymphocytes are in peripheral
  tissues.
• Types of lymphocytes
• We have already seen that there are three types
  of lymphocytes. (Fig. 22.9)
• T cells 80 of circulating lymphocytes (cell
  mediated immunity)
• B cells 10-15 , plasma cells produce antibodies
  (immunoglobulins) and react antigenic pathogens.
  ( antibody-mediated immunity)
• Natural killer cell the remainder they attack
  foreign cells, normal cells infected with viruses
  and cancer cells. They immunologically survey
  peripheral tissues.

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• Cytotoxic T cells attack foreign cells or cells
  infected with viruses. Provide cell-mediated
  immunity.
• Helper T cells stimulate the activities of T
  cells and B cells.
• Suppressor T cells inhibit T cells and B cells.

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• Origin and development of lymphocytes
• Lymphocytes travel around the entire body and
  have significantly long life span.
• 80 survive up to 4 years and some to 20 years.
• As we have seen lymphocytes are made in the red
  bone marrow and some continue to develop in the
  thymus. (Fig. 22.9)
• Pre-B cells and pre-T cells are in the red bone
  marrow. Pre-B cells mature in the red bone marrow
  into B cells. T cells mature in the thymus.

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• A positive selection process keep cells capable
  of immune response. Those which are incapable
  will die.
• Each group of B or T cells capable of responding
  to a specific antigen is a clone
• Each clone is capable of responding to a
  particular antigen and there are many different
  clones.
• When the clones respond to self-antigens,
  negative selection eliminates such clones.
• Most of this process occurs during prenatal
  development, but continues throughout life.

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• Activation of Lymphocyte
• Lymphocytes are made in response to a specific
  antigen and in a large quantity.
• Antigenic Determinants and Antigens Receptors
• An antigen may have many antigenic determinants
  (epitopes) (Fig. 22.10) to which lymphocytes can
  respond.
• Each antigenic determinate can activate a
  specific lymphocyte. Thus is possible that an
  antigen with many epitopes can activate many
  different (clones) lymphocytes.
• Each lymphocyte from the same clone will have the
  same antigen receptor.
• For example, a t cell receptor has a variable and
  constant regions. (Fig. 22.11). The variable
  region will have specific antigen binding sites.
  Thus a clone of T cells can bind a specific
  antigenic determinant. The other T cells within
  the same clone could have different antigen
  binding sites.
• The B-cell receptor is similar, but larger.

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• Major Histocompatibility Complex Antigens
• Some are direct, but most lymphocyte activation
  involves glycoproteins on the surface of cells
  called MHC molecules. All cell membranes have
  MHCgt
• MHC class I molecules (Fig. 22.12a)
• On nucleated cells, foreign or self proteins are
  fragmented in the nucleated cells and become
  antigens.
• They combine with MHC class I molecule in the
  cell and the complex are transported on the
  surface of the cell.
• At the surface of the cell membrane, the foreign
  antigen/MHC I complex will attract T cells and
  the cell will be destroyed. (cell mediated
  immunity), while self antigen/MHC I will not.

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• MHC class II Molecules (Fig 22.12b)
• The more complex and advanced lymphocytes
  stimulation use MHC II molecules.
• These molecules are found in antigen-presenting
  cells, such as B cells, macrophages, monocytes
  and dendritic cells.
• Antigen-presenting cells phagocytically ingest
  unprocessed antigens, process them and let them
  combine with MCH II molecules.
• the complex will be presented on the surface of
  the cells.
• They stimulate the other (lymphocytes) immune
  cells to divide and to cause the destruction of
  the antigen.

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• Costimulation
• In addition to the interaction between the
  presented MHC II/ antigen and antigen receptor,
  costimulation, with cytokinins for example, is
  needed (Fig.22 13a)
• Another costimulation (Fig. 23. 13b) is achieved
  cross linking two cells with other molecules such
  as CD4, B7, CD28, etc.
• Other example of cytokinins are listed in Table
  22.4. Note interferons and interleukins.
• Helper T Cells
• Enhances more production of T and B cells
• On activation helper T cells produce a variety of
  cytokins that coordinated specific and
  nonspecific defenses and stimulate cell mediated
  immunity.
• Study Fig. 22.14 and 22.15 to find how
  proliferation of helper T cell can be achieved.
• In short, with the help of cytokinins, such as
  interleukins, the number of helper T cells
  increase and thus stimulate B cells or effector T
  cells, which release perforin, produces hole in
  infected cells.

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• Inhibition of lymphocytes
• Inhibition of lymphocytes proliferation against
  its own self-antigen is achieved by tolerance.
• Deletion of self-reactive lymphocytes
• During prenatal development when immature
  lymphocytes are exposed to the self antigens,
  they die. Thus, no lymphocytes which respond to
  the self antigen will be found as the subject
  matures.
• Preventing activation of lymphocytes
• By lack of costimulation
• Activation of suppresser T cell.
• This is not well understood. The suppressor T
  cells release suppressive cytokins.

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• Antibody-mediated Immunity
• When exposed to an antigen, the body activates B
  cells and produces antibodies.
• the antibodies are found in body fluids thus
  respond to extracellular antigens.
• Antibodies
• Antibodies are produced in B cells in response to
  an antigen and are found in plasma.
• Plasma proteins have four major components
  albumin, alpha, beta and gamma globulins.
• Antibodies are found in gamma globulins group,
  thus sometimes are called gamma globulins or
  immunoglobulins (Ig).
• There are five types (Table 22.5)
• IgG, IgM, IgA, IgE, and IgD

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• They all consist of four peptides. (Fig 22.16)
  connected with disulfide bonds and have a
  constant region and a antigen binding variable
  region.
• The constant region may attach to cells, such as
  macrophages, basophils, etc..
• Effects of Antibodies
• The function of antibody is to find antigen and
  destroy it.
• Neutralization, agglutination and precipitation,
  activation of complement. Attraction of
  phagocytes, enhancement of phagocytes, and
  stimulation of inflammation.
• Antibodies can counteract the action of antigens
  in several ways (Fig. 22.17)
• Upon binding with an antigen, the antibody
  inactivates the antigen.
• Inactivation may lead to co-precipitation of
  antigen and antibodies.
• Binding of two may stimulate phagocytic
  activities and the release of inflammation
  chemicals.

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• Antibody production
• The primary Response
• The first encounter with an antigen, an B cell
  divides and differentiate leading to antibodies
  production (Fig. 22.18a).
• Antibodies, IgM and IgD, are on the surface of B
  cells.
• B cells, which are small lymphocytes, activated
  by antigen starts cell divisions.
• Some become large plasma cells, which produce
  antibodies and other become small memory B cells.
• The primary process takes 1-14 days, the antigen
  may cause tissue damage during this period.

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• The secondary or memory response
• When the immune system is exposed to the same
  antigen after the primary response
• The memory cells quickly divide to produce plasma
  cells and large quantity of antibody is released,
  providing immune protection.
• the response is quick, hours to a few days, and
  the the quantity of antibody production is large.
• Good defense against the disease.
• The memory cells, which may survive for years,
  are also formed.

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• Cell-mediated Immunity
• It is done by T cells and is against the
  intracellular attack, microorganism, virus,
  because antigens in cells are presented.
• Activation of T cells to antigens is regulated by
  antigen-presenting cells and helper T cells like.
  B cells, activated T cells produce cytotoxic T
  cells and memory T cells (Fig 22.19)
• Cytotoxic T cells
• They lyse cells and produce cytokines that
  produce inflammation and phagocytosis.\
• Viral antigens, tumors antigens and foreign
  antigens on the surface of cell are the
  stimulants to cytotoxic T cells.
• Released cytokins may recruit macrophages for
  phagocytosis and inflammation.

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• Immune Disorders
• Autoimmune disorders
• Identify own body cells as antigens, such as
  rheumatoid arthritis.
• Some viruses, measles and influenza, have a
  sequence similar to those of myelin proteins.
  Thus, antibodies which attack viruses may also
  attack myelin sheath.
• Unusual types of MHV proteins.
• Allergies
• Excessive immune response to antigens.
• Immune interactions

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The End.