Lymphatic

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Lymphatic Immune System

• Dr. Michael P. Gillespie

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Important Terminology

• Pathogens disease producing microbes such as
  bacteria and viruses.
• Resistance the ability to ward off damage or
  disease through our defenses.
• Susceptibility our lack of resistance or
  vulnerability.

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Types Of Resistance

• Nonspecific resistance innate defenses.
• Present at birth.
• Provides immediate, but general protection
  against invaders.
• Mechanical and chemical barriers of the skin and
  mucous membranes (1st line of defense).
• Acidity of the gastric juice.

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Types Of Resistance

• Specific resistance immunity.
• Develops in response to contact with a particular
  invader.
• Occurs more slowly than nonspecific resistance.
• Involves activation of specific lymphocytes.
• The lymphatic and immune system is responsible
  for this kind of resistance.

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Components

• Lymph fluid.
• Lymphatic vessels.
• Various structures containing lymphatic tissue.
• Red bone marrow stem cells develop into
  lymphocytes (among other types) here.

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Lymph Fluid

• A clear liquid.
• Blood plasma filters through the capillaries into
  the interstitial fluid.
• After interstitial fluid passes into lymphatic
  vessels it is called lymph.

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Lymphocytes In The Immune Response

• B cells.
• T cells.

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Functions Of Lymphatic Immune System

• 1. Draining excess interstitial fluid.
• 2. Transporting dietary lipids and lipid soluble
  vitamins (A, D, E, and K).
• 3. Carry out immune responses.
• Lymphocytes, aided by macrophages, recognize
  foreign cells, microbes, toxins, and cancer
  cells.
• T cells destroy the intruders.
• B cells produce antibodies that recognize foreign
  cells.

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Lymphatic Vessels Circulation

• Lymphatic vessels begin as lymphatic capillaries.
• Lymphatic capillaries unite to form larger
  lymphatic vessels.
• Lymphatic vessels are similar to veins, but have
  thinner walls and more veins.
• Lymph flows through lymph nodes (masses of B
  cells and T cells).

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Lymphatic Vessels Circulation

• In the skin, lymphatic vessels generally follow
  veins.
• Lymphatic vessels of the viscera generally follow
  arteries.
• Avascular tissues lack lymphatic capillaries
  (cartilage, epidermis, cornea of the eye).
• The CNS, portions of the spleen, and bone marrow
  also lack lymphatic capillaries.

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Lymphatic Capillaries

• Slightly larger than blood capillaries.
• Permit fluid to flow into them, but not out.
• Lacteals specialized lymphatic capillaries in
  the small intestine that carry dietary lipids.
  Lymph here appears white due to the lipids and is
  referred to as chyle.

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Lymph Trunks Ducts

• Lymph vessels merge and unite to form trunks.
• Principal trunks
• Lumbar, intestinal, bronchomediastinal,
  subclavian, and jugular trunks.
• Lymph passes from lymph trunks into two main
  channels, the thoracic duct and the right
  lymphatic duct.

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Thoracic (Left Lymphatic) Duct

• Begins as a dilation of the cisterna chyli
  anterior to the 2nd lumbar vertebra.
• Receives lymph from the left side of the head,
  neck and chest, left upper limb, and the entire
  body inferior to the ribs.

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Thoracic (Left Lymphatic) Duct

• Drains into the left subclavian vein.
• Drains the following trunks
• Right and left lumbar trunks.
• Intestinal trunk.
• Left jugular trunk.
• Left subclavian trunk.
• Left bronchomediatinal trunk.

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Right Lymphatic Duct

• Drains lymph from the upper right side of the
  body into venous blood via the right subclavian
  vein.
• Drains lymph from the following trunks
• Right jugular trunk.
• Right subclavian trunk.
• Right bronchomediastinal trunk.

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Formation Flow Of Lymph

• Many components of blood plasma freely flow
  through the capillaries to form interstitial
  fluid.
• More fluid filters out of blood capillaries than
  is reabsorbed by them (about 3 liters more).

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Formation Flow Of Lymph

• The excess fluid drains into lymphatic
  capillaries and becomes lymph.
• Lymph returns plasma proteins to the blood (they
  cannot be reabsorbed by the blood capillaries).
• Lymphatic vessels have valves to ensure one way
  flow.

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Sequence Of Fluid Flow

• Blood capillaries (blood) gt interstitial spaces
  (interstitial fluid) gt lymphatic capillaries
  (lymph) gt lymphatic vessels (lymph) gt lymphatic
  ducts (lymph) gt subclavian veins (blood).

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Pumps To Return Lymph

• Skeletal muscle pump.
• Respiratory pump.

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Edema Lymph Flow

• Edema excessive accumulation of interstitial
  fluid.
• Edema can be caused by obstruction of lymph flow
  due to an infected lymph node or blocked
  lymphatic vessel.
• Increased capillary blood pressure can cause
  edema by producing accumulation of interstitial
  fluid faster than it can flow into the lymphatic
  vessels.

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Elephantiasis
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Lymphatic Organs Tissues

• Primary lymphatic organs sites where stem cells
  divide and become immunocompetent.
• Red bone marrow.
• Thymus.

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Lymphatic Organs Tissues

• Secondary lymphatic organs sites where most
  immune responses occur.
• Lymph nodes.
• Spleen.
• Lymphatic nodules (follicles) these are tissues
  not organs because they lack a capsule.

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Thymus

• A bilobed organ located in the mediastinum
  between the sternum and the aorta.
• The cortex consists of T cells.

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Thymus

• Pre-t cells migrate from the bone marrow and
  mature into T cells here.
• The medulla consists of more mature T cells and
  macrophages.
• The thymus is large in an infant, but begins to
  atrophy after puberty.

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Lymph Nodes

• Located along the lymphatic vessels.
• There are about 600 bean shaped lymph nodes.
• They are scattered throughout the body, but
  usually occur in groups.

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Lymph Nodes

• The outer cortex contains aggregates of B cells
  called lymphatic nodules (follicles).
• When B cells encounter a foreign antigen, they
  develop into antibody producing plasma cells or
  into memory B cells (which persist to recognize
  the foreign antigen in the future).

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Lymph Nodes

• The inner cortex contains primarily T cells,
  which proliferate when exposed to a foreign
  antigen. They then migrate to areas of the body
  with antigenic activity.
• The medulla contains B cells, antibody-producing
  plasma cells, and macrophages.

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Lymph Flow

• Lymph flows through the node in only one
  direction.
• Afferent (to carry toward) vessels carry lymph to
  the node.
• Efferent (to carry away) vessels carry lymp away
  from the node.

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Lymph Nodes

• Lymph nodes serve to filter lymph.
• Foreign substances are trapped within the
  reticular fibers.
• Macrophages destroy foreign substances by
  phagocytosis.
• Lymphocytes destroy substances via other immune
  responses.

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Metastasis

• Metastasis is the spread of disease from one part
  of the body to another.
• The blood vessels and lymph nodes serve as routes
  for metastasis.

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Metastasis

• Cancer cells may travel through the lymphatic
  vessels and lodge in a lymph node.
• Cancerous lymph nodes feel enlarged, firm,
  non-tender, and fixed to underlying structures.
• Lymph nodes enlarged due to infection are soft,
  movable, and very tender.

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Spleen

• The spleen is the single largest mass of
  lymphatic tissue.
• It is located in the left hypochondriac region
  between the stomach and the diaphragm.

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Spleen

• B cells and T cells carry out immune functions in
  a similar fashion to lymph nodes.
• Macrophages destroy blood born pathogens by
  phagocytosis.
• Blood cell related functions
• Removal of worn out or defective RBCs by
  macrophages.
• Storage of platelets (1/3).
• Hemopoiesis (production of RBCs) during fetal
  life.

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Ruptured Spleen

• The spleen is the most often damaged organ in
  cases of abdominal trauma.
• Blows to the left inferior chest can fracture
  ribs and rupture the spleen.
• Intraperitoneal hemmorrhage and shock follow.

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Ruptured Spleen

• Splenectomy (removal of the spleen) is needed to
  prevent death due to bleeding.
• The red bone marrow and liver take over many of
  the functions of the spleen However, immune
  functions are decreased.

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Ruptured Spleen

• Sepsis (blood infection) is more likely to occur
  due to loss of the filtering and phagocytosis of
  the spleen.
• These patient must take antibiotics prior to any
  invasive procedures to reduce the risk of sepsis.

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Lymphatic Nodules

• Lymphatic nodules are egg-shaped masses of
  lymphatic tissue that are not surrounded by a
  capsule.
• The are scattered through mucous membranes of the
  GI, urinary, reproductive, and respiratory
  systems.

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Lymphatic Nodules

• They are referred to as mucosa-associated
  lymphatic tissue (MALT).
• Large aggregations of these nodules are referred
  to as tonsils (5 of them).
• A single pharyngeal tonsil (adenoid), 2 palatine
  tonsils, 2 lingual tonsils.

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Development Of Lymphatic Tissues

• Lymphatic vessels develop from lymph sacs that
  are derived from mesoderm.
• The jugular lymph sacs appear first, then the
  retroperitoneal lymph sac, then the cysterna
  chyli, and finally the posterior lymph sacs.

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Nonspecific Resistance Innate Defenses

• Present at birth.
• Offer immediate protection against a wide variety
  of pathogens and foreign substances.

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Nonspecific Resistance Innate Defenses

• First line of defense skin and mucous
  membranes.
• Epidermis.
• Mucous membranes, mucus, hairs, cilia.
• Lacrimal apparatus manufactures and drains tears.
• Saliva washes microbes from the teeth.
• Flow of urine retards microbial colonization.
• Vaginal secretions move microbes out of the body.
• Defecation and vomiting expel microbes.
• Sebaceous glands secrete sebum which forms a
  protective film.
• Perspiration flushes microbes and contains
  lysozyme.
• Acid gastric juice destroys microbes.

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Nonspecific Resistance Innate Defenses

• Second line of defense internal defenses.
• Antimicrobial proteins.
• Interferons (IFNs) and transferrins inhibit
  bacterial growth and replication.
• Natural killer cells and phagocytes.
• Inflammation.
• Redness, pain, heat, swelling.
• Emigration of phagocytes.
• Fever.
• Inhibits the growth of microbes and speeds up
  body reactions that aid repair.

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Specific Resistance Immunity

• Specific resistance or immunity is the ability of
  the body to defend itself against specific
  invading agents such as bacteria, toxins,
  viruses, and foreign tissues.

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Specific Resistance Immunity

• Antigens (Ags) are substances that are recognized
  as foreign and provoke immune responses.
• 2 properties distinguish immunity from
  nonspecific defenses
• 1. Specificity.
• 2. Memory.

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Immunocompetence

• Immunocompetence is the ability to carry out
  immune responses.
• Lymphocytes called B cells and T cells carry out
  immune responses.

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Immunocompetence

• Both of these types of cells develop from the
  primary lymphatic organs (red bone marrow and
  thymus).
• B cells mature in the bone marrow.
• Pre-t cells from the bone marrow migrate to the
  thymus where they mature.

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Types Of Immune Responses

• Cell-mediated immune responses.
• T cells become cytotoxic T cells that attack the
  invading antigen directly.
• Antibody-mediated immune responses.
• B cells secrete antibodies (abs) or
  immunoglobulins. Antibodies bind to and
  inactivate specific antigens.

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Immune Response Invader Types

• Cell-mediated immunity is effective against
• 1. Intracellular pathogens that reside within
  host cells.
• Fungi, parasites, and viruses.
• 2. Some cancer cells.
• Foreign tissue transplants.
• Antibody-mediated immunity is effective against
• 1. Antigens present in body fluids.
• 2. Extracellular pathogens in body fluids
  (bacteria).
• Most pathogens elicit both responses.

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Characteristics Of Antigens

• Immunogenicity the ability to provoke an immune
  response by stimulating the production of
  specific antibodies.
• Reactivity the ability of an antigen to react
  with specific antibodies.
• Epitopes the small parts of antigen molecules
  that initiate immune responses.
• Entire microbes or parts of microbes may act as
  antigens.

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Routes Of Antigens Into Lymphatic Tissue

• Most antigens that enter the bloodstream are
  trapped as they flow through the spleen.
• Antigens that penetrate the skin enter lymphatic
  vessels and lodge in lymph nodes.
• Antigens that penetrate mucous membranes are
  entrapped by mucosa-associated lymphatic tissue.

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Hapten

• A hapten is a smaller substance that has
  reactivity, but lacks immunogenicity.
• It can only stimulate an immune response if it is
  attached to a larger carrier molecule.
• Poison ivy is an example of a hapten.

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Major Histocompatibility Complex (MHC)

• The major histocompatibility complex (MHC)
  antigens are self antigens.
• The MHC are located in the plasma membrane of
  body cells.
• Unless you have an identical twin, your MHC
  antigens are unique.
• These are responsible for identifying a foreign
  antigen as not self.

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Histocompatibility Testing

• The more similar the MHC antigens, the greater
  the histocompatibility.
• Greater histocompatibility leads to a lower
  likelihood that the organ or tissue will be
  rejected.

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Processing Presenting An Antigen

• B cells recognize and bind to foreign antigens
  However, T cells only recognize fragments of
  antigenic compounds that are presented with the
  MHC.

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Processing Of Exogenous Antigens

• Exogenous antigens are outside of body cells.
• Ingestion of the antigen by the
  antigen-presenting cells (APCs).

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Processing Of Exogenous Antigens

• Digestion of the antigen into peptide fragments.
• Antigen fragments fuse to MHC-II complexes, which
  are then inserted into the plasma membrane of the
  APC.
• The APCs then migrate to lymphatic tissue where
  they present the antigen fragment-MHC-ii
  complex to T cells to inform them to attack.

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Processing Of Endogenous Antigens

• Endogenous antigens are inside of body cells.
• The MHC-I complex binds with the antigen
  fragments inside infected cells.
• The new antigen fragment-MHC-i complex moves to
  the plasma membrane of the cell for
  presentation.

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Cytokines

• Cytokines are small protein hormones that
  stimulate or inhibit many normal cell functions,
  such as cell growth and differentiation.
• Cytokine therapy is the use of cytokines to treat
  medical conditions.
• Interferons were the first cytokines to be
  effective against human cancer.

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Cell-mediated Immunity

• A cell-mediated immune response begins with the
  activation of a small number of T cells by a
  specific antigen.
• Once a T cell has been activated, it undergoes
  proliferation and differentiation into effector
  cells.
• Effector cells recognize and attack the specific
  antigen.

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Types Of T Cells

• Helper T (TH) cells CD4 resting (inactive)
  TH cells recognize antigen fragments associated
  with MHC-II molecules. When activated, they
  secrete a variety of cytokines that attack the
  invaders.

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Types Of T Cells

• Cytotoxic T (TC) cells CD8 recognize foreign
  antigens associated with MHC-I molecules. They
  are capable of lysing affected cells.
• Memory T cells these cells remain from a
  proliferated clone after a cell-mediated
  response. This allows for a swifter response
  with subsequent infection.

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Elimination Of Invaders

• Cytotoxic T cells are the soldiers that battle
  with foreign invaders.
• Cytotoxic T cells use 2 killing mechanisms
• Perforin forms holes in the plasma membrane of
  the target cell, which allows extracellular fluid
  to flow in causing the cell to burst (cytolysis).
• Lymphotoxin is secreted, which activates enzymes
  within the target cell. These enzymes cause the
  targets DNA to fragment and the cell dies.

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Graft Rejection

• Organ transplantation involves the replacement of
  an injured or diseased organ with an organ
  donated by another individual..
• Usually, the immune system recognizes the
  proteins of the transplanted organ as foreign and
  mounts immune responses against them.
• This process is known as graft rejection.

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Graft Rejection

• The more closely matched the histocompatibility,
  the less likely the organ is to be rejected.
• Organ recipients receive immunosuppresive drugs
  to reduce the risk of rejection.
• This increases the risk of infection by some
  diseases.

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Antibody-mediated Immunity

• Cytotoxic T cells leave lymphatic tissue to
  search out and destroy a foreign antigen
  However, B cells stay put.
• When B cells are exposed to a foreign antigen,
  they differentiate into plasma cells that secrete
  specific antibodies, which circulate through
  lymph and blood to reach the site of invasion.

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Activation, Proliferation, Differentiation Of B
Cells

• Antigens bind to B cell receptors, which
  activates them.
• B cells enlarge, divide, and differentiate into
  plasma cells which secrete antibodies.
• Some B cells do not differentiate, but remain as
  B memory cells.
• Antibodies enter circulation and form
  antigen-antibody complexes with the antigen that
  initiated their production.

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Antibodies

• Antibodies (Ab) combine specifically with the
  antigen that initiated their production.

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Antibody Actions

• Neutralizing antigen blocks or neutralizing
  some bacterial toxins and prevents bacterial
  attachment to cells.
• Immobilizing bacteria some form against cilia
  or flagella.

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Antibody Actions

• Agglutinating and precipitating antigen cause
  agglutination (clumping together) of pathogens
  for easier phagocytosis and precipitation.
• Activating complement.
• Enhancing phagocytosis attracts phagocytes.

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Complement System

• The complement system is a defensive system
  consisting of plasma proteins that attack and
  destroy microbes.
• This system leads to the following events
  inflammation, enhancement of phagocytosis, and
  bursting of microbes.

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Complement System

• Inflammation increases the permeability of blood
  capillaries allow WBCs to emigrate into affected
  tissues.
• Opsonization complement fragment c3b binds to
  the surface of the microbe and interacts with
  receptors on phagocytes.
• Cytolysis complement proteins form a membrane
  attack complex (MAC) that inserts on the membrane
  and forms large holes.

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Immunological Memory

• The immune system can remember specific antigens
  that have triggered immune responses, either
  through antibodies, or long lasting lymphocytes.
• Immune responses are much quicker and more
  intense after a second exposure.
• The antibody titer can be utilized to measure
  immunological memory.
• Memory cells may remain for decades.

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Self-recognition Self-tolerance

• To function properly T cells must
• Recognize your own major histocompatibility
  complex (MHC) proteins (self-recognition).
• They must lack reactivity to peptide fragments
  from your own proteins (self-tolerance).