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Transcript
Anatomy & Physiology
Lecture 22: The Lymphatic
System and Immunity
Lecturer: Dr. Barjis
Room P307
Phone: (718) 260-5285
E-Mail: [email protected]
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
Frederic H. Martini
Fundamentals of
Learning Objectives
• Describe the structure and function of lymphatic
cells, tissues and organs
• List the body’s nonspecific defenses and describe
the components and mechanisms of each
• Define specific resistance and distinguish between
cell-mediated immunity and antibody mediated
immunity
Learning Objectives
• Discuss the role of the T cell, B cell and antibodies
in specific immunity
• Describe the origin, development, activation and
regulation of normal resistance to disease
• Discuss the effects of stress and aging on the
immune system
lymphatic system
• The lymphatic system
• Contains cells, tissues, and organs responsible
for defending the body
• Lymphocytes resist infection and disease by
responding to
• Invading pathogens such as bacteria or viruses
• Abnormal body cells such as cancer cells
• Foreign proteins such as toxins
The Components of the Lymphatic System
The lymphatic system consists of
• Lymph
• Lymphatic vessels
• Lymphoid tissues and organs
• Lymphocytes and supporting phagocytic cells
Functions of lymphatic system
• Primary function is production, maintenance,
and distribution of lymphocytes
• Lymphocytes must:
• Detect where problems exist
• Be able to reach the site of injury or
infection
• Return of fluid and solutes from peripheral tissue
to blood
• Distribution of hormones, nutrients, and waste
product from their tissue of origin to general
circulation.
Lymphatic vessels include
• Lymphatic capillaries
• Small lymphatic vessels
• Major lymph-collecting vessels
Lymphatic Capillaries
Major lymph-collecting vessels
• Superficial and deep lymphatics
• Thoracic duct
• Cisterna chyli
• Right lymphatic duct
The Relationship between the Lymphatic Ducts
and the Venous System
• Most of the lymph
returns to the
venous circulation
by Thoracic duct
The Relationship between the Lymphatic Ducts
and the Venous System
Lymphocytes
• Account for 20-30 % of circulating WBC, but
body contain 10 to the power of 12 lymphocytes
• There are tree classes of lymphocytes
• T (thymus dependent) cells
• B (bone marrow-derived) cells
• NK (natural killer) cells
Lymphocytes
Major types of T cells
• Cytotoxic T cells (TC) – attack foreign cells
• Helper T cells (TH) – activate other T cells and B
cells
• Suppressor T cells (TS) – inhibit the activation of
T and B cells
• TH and TS cells regulates immune response
Lymphocytes
Major types of B cells
• Active B cell differentiates into
• Memory B Cell or
• Plasma B cell
• Plasma B cells synthesize and release
antibody
Lymphocyte production (lymphopoiesis)
• Lymphocyte production and maturation involves
bone marrow, thymus, and peripheral lymphoid
tissue
• B cells and NK cells mature in bone marrow
• T cells mature in the thymus
The Derivation and Distribution of Lymphocytes
Lymphoid tissue
• Connective tissue dominated by lymphocytes
• Lymphoid nodules
• Lymphocytes are packed densely
• Found in the respiratory, digestive, and
urinary tracts
• MALT (mucosa-associated lymphoid tissue)
• Collection of lymphoid tissues linked with the
digestive system
Lymphoid Nodules
Lymphoid organs
Lymphoid organs include: lymphoid nodes,
thymus and spleen
• Lymph nodes – function in the purification of
lymph
The Thymus
• Located behind sternum in anterior mediastinum
• Reaches its maximum size just before puberty
• Consists two lobes
• Divided into of lobules, each with a cortex and medulla
• Lymphocytes in cortex are dividing, when mature
migrate to modula and after 3 weeks enter the blood
• Secretes thymic hormones: thymosins,
thymopoietins, and thymulin
• stimulate stem cell division and T-cell differentiation
The Thymus
The Spleen
• Largest mass of lymphoid tissue
• Cellular components form pulp
• Red pulp contains RBC
• White pulp similar to lymphoid nodules
• Spleen functions include
• Removal of abnormal blood cells and other
blood components
• Storage of iron
• Initiation of the specific immune response
The Spleen
Lymphatic system and body defenses
• Nonspecific defenses
• Do not distinguish one type of pathogen (e.g.
bacteria) from another type
• There are 7 types of non specific defenses
• Specific defenses
• Protect against one particular threats
• Specific defense depend upon the activation of
lymphocytes
Nonspecific Defenses
Physical barriers
• Keep hazardous organisms outside the body
• Includes hair, epithelia, secretions of
integumentary and digestive systems
Nonspecific Defenses
Phagocytes
• Remove cellular debris and respond to invasion
by foreign pathogens
Nonspecific Defenses
Immunological surveillance
• Constant monitoring of normal tissue by NK cells
• NK cells
• Recognize cell surface markers on foreign cells
• Destroy cells with foreign antigens
• Activation of NK cells:
• Recognition of unusual surface proteins
• Rotation of the Golgi toward the target cell and production of
perforins
• Release of perforins by exocytosis
• Interaction of perforins causing cell lysis
Nonspecific Defenses
Immunological Surveillance)
How Natural Killer Cells Kill Cellular Targets
Nonspecific Defenses
Interferons (cytokines)
• Interferons are small proteins that act as
chemical messengers that coordinate defense
• Interferons are released by virally infected cells
and activated lymphocyytes
• Interferons bind to the surface of abnormal cells
and trigger the production of antiviral proteins
that prevents virus proliferation.
Nonspecific Defenses
Complement system
• There are 11 plasma complement proteins (C)
• They are activated by:
• Classical pathway
• In Classical pathway compliment binds to Ab molecule,
• Alternative pathway
• In alternative pathway compliment binds to bacterial cell
• Both pathways trigger:
• Chain of reaction and result attraction of phagocytes,
• Stimulation of phagocitic activity,
• Promotion of inflammation and
• Result puncture of bacterial cell
Nonspecific Defenses
Inflammation
• Localized tissue response to injury producing
• Swelling
• Redness
• Heat
• Pain
• Effects of inflammation include
• Temporary repair of injury
• Slowing the spread of pathogens
Nonspecific Defenses
Inflammatory Response
Nonspecific Defenses
Fever
• Maintenance of a body temperature above 37.2oC
(99oF)
• High temperature may inhibit some viruses and
bacterial activities.
• It increases metabolism (1°C increase in
temperature would increase metabolism by 10%)
• Pyrogens reset the hypothalamic thermostat and
raise body temperature
• Pyrogen secretion is stimulated by Ag,
macrophages
Specific Defenses
• Act on specific Ag only
• T-Cells are responsible for cell mediated
immunity (cellular immunity) – defense against
abnormal cells and pathogens inside cells
• B-cells provide Ab-mediated immunity (also
called humoral immunity) – defense against Ags
and pathogens in body fluid
Specific Defenses
Forms of immunity
• Innate immunity
• Genetically determined
• Present at birth
• Acquired immunity
• Not present at birth
• Achieved by exposure to antigen
• Acquired immunity can be
• Active immunity
• Passive immunity
Types of Immunity
Properties/characteristics of immunity
• Specificity – activated by and responds to a
specific antigen
• Versatility – is ready to confront any antigen at
any time
• Memory – “remembers” any antigen it has
encountered
• Tolerance – responds to foreign substances but
ignores normal tissues
The immune system response
• Antigen triggers an immune response
• Activates T cells and B cells
• T cells are activated after phagocytes exposed
to antigen
• T cells attack the antigen and stimulate B cells
• Activated B cells mature and produce antibody
• Antibody attacks antigen
T cell activation
• T cells recognize Ag-glycoprotein complex in cell
membrane
• Glycoproteins are synthesized in the region called
Major Histocompatibility Complex (MHC)- so
they are known as MHC proteins
• Each individual have different MHC proteins
• There are 2 classes of MHC proteins:
• MHC class I
• MHC class II
MHC classes
• Class I – found on all nucleated cells
• They are synthesized, and transported to
membrane by vesicles of golgi apparatus
• As they are formed, they pick up small peptides
from the cytoplasm and take them to membrane
• If the peptides that are picked up by MHC
proteins are self (belong to the body), T-cells will
ignore them,
• If the peptides that are picked up by the MHC
proteins are none self (do not belong to the body
i.e. if they are antigens) then T-cell becomes
activated anddestroy the abnormal cell.
Antigens and MHC Proteins
MHC classes
• Class II – found on antigen presenting cells and
lymphocytes
• Phagocitic cells engulf pathogen
• Once the pathogen is inside the phagocitic cell,
lysosome action breaks down the pathogen into
fragments (Ag)
• Endoplasmic reticulum produces MHC II
proteins
• Ag fragments will bound to MHC ll proteins and
will be presented on the cell membrane
• MHC II and Antigen complex on the surface of
membrane will activate T cells
Antigens and MHC Proteins
B cells and Antibody Mediated Response
• B cells produce specific Ab
• There are millions of B-cells - each with specific
Ab on its membrane
• When B- cells are activated they can produce up
to 100 million Ab per hour
Antibodies structure
• Antibodies are Y-shaped proteins consisting of:
• Two parallel polypeptide chains
• Heavy chains and light chains
• Constant region and variable region
• Antigen binding site
Antibody Structure
Antibody Structure
Actions of antibodies include:
• Neutralization
• Agglutination and precipitation
• Activation of complement
• Attraction of phagocytes
• Opsinization
• Stimulation of inflammation
• Prevention of adhesion
Classes of Antibodies (immunoglobins)
• IgG – resistance against many viruses, bacteria
and bacterial toxins
• IgE – accelerates local inflammation and
responsible for allergic reaction
• IgD – found on the surface of B cells
• IgM – first type secreted after antigen arrives
• IgA – primarily found in glandular sec
Primary and secondary antibody response
• Primary response
• Takes about two weeks to develop
• Produced by plasma cells
• Secondary response
• Rapid increase in IgG
• Maximum antibody titer app
Aging and the Immune Response
With age
• Immune system becomes less effective
• Increased susceptibility to infection
• Immune surveillance declines
You should now be familiar with:
• The structure and function of lymphatic cells,
tissues and organs
• The body’s nonspecific defenses and the
components and mechanisms of each
• Specific resistance, cell-mediated immunity and
antibody mediated immunity
• The role of the T cell, B cell and antibodies in
specific immunity
• The origin, development, activation and
regulation of normal resistance to disease
• The effects of stress and aging on the immune
system