the lymphatic system. what exactly is this system? which organs are involved? what is the function...
TRANSCRIPT
THE LYMPHATIC SYSTEM
What exactly is this System?
• Which organs are involved?
• What is the function of the Lymphatic System?
• How does it work?
Jobs of Lymphatic System: Lymphatic System which consists of vessels and
organs plays two vital roles in our lives:
1) The vessels essentially maintain interstitial fluid levels by carrying excess fluids as well as any plasma proteins, back into the CVS.
2) The organs, house critical immune cells such as lymphocytes which carryout our body defense against infection and disease as well as offer ACQUIRED IMMUNITY .
Lymphatic Characteristics
• Lymph – excess tissue fluid carried by lymphatic vessels ( general definition)
• Properties of lymphatic vessels– One way system toward the heart– No pump– Lymph moves toward the heart
• Milking action of skeletal muscle• Rhythmic contraction of smooth muscle in vessel
walls
Composition of Lymph
• Lymph is usually a clear, colorless fluid, similar to blood plasma but low is protein
• Its composition varies from place to place; after a meal, for example, lymph draining from the small intestine, takes on a milky appearance, due to lipid content.
• Lymph may contain macrophages, viruses, bacteria, cellular debris and even traveling cancer cells.
EDEMA• Edema is the excess
accumulation of fluids in tissue spaces. This can retard normal exchange of nutrients and metabolites. Filtration of the extracellular fluid exceeds drainage. Anything that causes increased capillary pressure, such as decreased plasma protein, increased capillary permeability or lymphatic blockage, can result in swelling and congestion of the extravascular compartment.
Lymphatic Vessels
• Lymph Capillaries– Walls overlap to form flap-like minivalves– Fluid leaks into lymph capillaries– Capillaries are anchored to connective tissue by
filaments– Higher pressure on the inside closes minivalves
What Type of Vessels Make up the Lymphatic System?
• The vessels are called lymphatics. • They are thin-walled and are analogous to veins.• Small lymphatics are similar to capillaries only more
porous; Larger vessels are called collecting vessels: both have valves.
• 2 large Ducts: Right LYMPHATIC DUCT and THORACIC DUCT (BOTH EMPTY INTO THE RT AND LT SUBCLAVIAN VEINS)
• Lymph flows only TO THE HEART (ONE WAY).• This is a low-pressure, pumpless system. Lymph
moves via skeletal muscles and pressure changes in thorax during breathing only.
Lymph Carries …
• Harmful materials that enter lymph vessels– Bacteria– Viruses– Cancer cells– Cell debris
Lymph Nodes
• Then Lymph Nodes take the germ-filled lymph and
• Filter lymph before it is returned to the blood
• Defense cells within lymph nodes– Macrophages – engulf and destroy foreign substances
– Lymphocytes – provide immune response to antigens
Where are these lymph nodes?
The Lymphatic System
• Consists of two semi-independent parts– Lymphatic vessels– Lymphoid tissues and organs
• Lymphatic system functions– Transport fluids back to the blood– Play essential roles in body defense and
resistance to disease
Lymphatic Organs:• A Lymph Node- Important lymphocytes of the
immune response are matured here. • Spleen: DESTROYS RBCs and Resevoir of Blood;
IT IS THE LARGEST Lymph organ and it filter blood of bacteria and antigen-filled cells.
• Thymus Gland-produces hormone, thymosin, functions in programing lymphocytes T and B cells; T-cells matured here ( become immunocompetent)
• Tonsils-Traps bacteria and other microbes in throat.• Peyer’s Patch-capture and destroy bacteria in
intestine, thereby preventing them from penetrating the intestinal wall.
Lymph Node Structure
• Most are kidney-shaped, less than 1 inch long• Cortex
– Outer part– Contains follicles – collections of
lymphocytes• Medulla
– Inner part– Contains phagocytic macrophages
Anatomy of a Lymph Node
• Fluid enters afferent vessels
• Exists efferent vessels• Germinal center of
follicle – These enlarge during time of plasma cell production (B Cells)
• Medulla- Phagocytes are located here
SPLEEN• Filters blood of bacteria, viruses and other debris • Destroys worn out blood cells. It then returns (or
recycles) some of the breakdown products of RBCs to the liver ..for example Fe, so that more RBCs can be made .The unusable portion of worn-out blood is excreted in bile.
• Another function: Stores platelets and acts as a blood reservoir.
• Lymphocytes are produced; RBCs also made in fetus only.
Body’s Defense System:
Physical and Chemical
Skin - largest organ of the body• Skin Flora• Sweat and Sebum
Mucous membranes on inside:• in gut• in lungs
Tear ducts
Immune System•Inflammatory response•Immune response
Leukocytes
White blood cells, also called leukocytes, are continuously made in the bone marrow White Blood Cells.
There are a variety of leukocytes and they are all derived from hematopoietic stem cells. Leukocytes specific for immunity are called lymphocytes
Your Immune SystemLevels of Immunity:
• First Line of Defense PHYSICAL BARRIERS
The Skin, Mucus Membranes
and Cilia
• Inflammation Innate Responses
Phagocytes plus other WBCs
• Adaptive Immune Response Cells with “memory” of past infections are released to defend invaders.
White blood cells - from bone marrowThree groups of white blood cells are important 1. Macrophages: "big eaters" - phagocytic cells
Two types of Lymphocytes2. T cells3. B cells
Innate and Acquired Immune Responses
Breaking the Barriers: Portals of Entry
• Skin
• Mucus membranes line your gastrointestinal tract, genitourinary tract, respiratory tract and your eyes.
• Microbes can gain entrance past these portals of entrance when you: breath, touch your eyes(if your fingers are contaminated), touch your genitals, or ingest microbes. Of course if you get a splinter or cut in skin, microbes then gain entrance.
Inflammatory Response
• When cells are injured they release inflammatory chemicals called histamines and Kinins
• Causes blood vessels to dilate and capillaries to become leaky.
• Activates pain receptors.• Attracts phagocytes and lymphocytes
(neutrophiles) to area. • Inflammatory response does 3 things: 1.
Prevents spread of damaging agents to nearby tissue 2. Disposes of pathogens and 3. Sets the stage for healing.
Inflammatory Response
•Tissue invaded locally•Release of histamines•Dilate blood vessels•Swelling •Fluid from capillaries•Increased heat•Redness •Macrophages move in
……..INFLAMMATION!
Containment and Destruction of Pathogens
• Fibrinogen now in tissue clots, trapping pathogens
• Heparin prevents clotting at site of injury
– pathogens are in a fluid pocket surrounded by clot
• Chemotaxis– leukocytes are attracted to chemotactic chemicals
• Neutrophils are quickest to respond – phagocytosis – respiratory burst– secrete cytokines for recruitment of macrophages and neutrophils– macrophages and T cells secrete colony-stimulating factor to
stimulate leukopoiesis ( to produce more WBC from Stems)
Tissue Repair
• Blood platelets and endothelial cells in injured area secrete a cytokine, PDGF, that stimulates fibroblasts to multiply and synthesize collagen
• Facilitated by hyperemia that provides materials needed and heat that increases metabolism
• Fibrin clot may provide a scaffold for repair• Pain limits use of body part allowing for repair
Lymphocytes Found At Site of Infection (Innate Response)
• Macrophages- are large phagocytic cells that act as scavengers devouring pathogens and worn-out cells.
• Neutrophils-the first cells at the site of inflammation. They destroy invaders by the use of digestive enzymes.( These are also phagocytes)
• Dendritic Cells-eat pathogens and activate other immune cells. Dendritic cells take pieces of “chewed”pathogens and “present” them.
• Natural Killer Cells-kill virus-infected cells and cancerous cells.
What’s The Difference between the Innate and Acquired?
• Acquired Immunity is
1. antigen specific
2. Systemic
3. Has Memory (recognizes previous encountered pathogens)
• Local Infection- The pathogen has caused an infection of tissues at surface of skin or mucous membranes.
• Systemic infection- From the skin or mucous membranes the pathogen enters either the bloodstream or lymphatic system…hence the name systemic
Where Are T Cells And B Cell Made?
During a systemic infection the acquired immune response will:
• Recognize specific antigens
• Make specific ..antibodies and killer T Cell
• Then have memory of thess antibodies and T cells for ….a future encounter.
Where Do We Get the names T and B?
T stands for Thymus-dependent
B stands for Bursa of Fabricius in which they were first discovered.
Where Do Lymphocytes Originate?
• All Lymphocytes originate in the RED BONE MARROW called hematoblasts in a process called hematopeiosis.
• Whether or not it becomes a B cell or a T cell depends on WHERE it become IMMUNOCOMPETENT (Capable of responding to a specific antigen)
• Certain lymphocytes migrate to Thymus (these will become T cells as they undergo a maturation process under the direction of the hormone Thymosin.
What About B Cell Immunocompetence?
• B Cells actually mature and gain their immunocompetence in the BONE MARROW. ( we do not know much about their cues)
• In the Lymph nodes the B- cells transform into plasma cells which produce antibodies.
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Antigens (Nonself) Any substance capable of exciting the immune
system and provoking an immune response
Examples of common antigens
Foreign proteins
Nucleic acids
Large carbohydrates
Some lipids
Pollen grains
Microorganisms
MEMORY• Some B and T cells have what is called “memory”.
Memory Cells have the ability to divide on short notice to produce more of all of the T and B cells. This is the basis of acquired immunity. After the initial response, some of Bs and Ts which were amplified in response to antigen ARE RESERVED and circulate in lymphatic system..for years or even life. If same antigen enters body again immune response will take place RAPIDLY and without full-blown illness.
What is an APC?• Antigen Presenting Cell (APC)
• Antigen-something,usually a protein or bacteria that is recognized by the body as foreign.
• APC can be dendritic cells or macrophages; they ingest pathogens and place pieces of them ( antigens) on their cell membranes so that they can trigger a response from helper T cells.
The Acquired or Humoral Immune Response.
• How are Antibodies Formed?
• Where are they formed?
• What other form of “help” aids the acquired immune response?
• What are the steps?
• Which cells are involved?
Major Histocompatibility Complex Proteins
These are proteins called HLAs or human leukocyte antigens. Expressed from genes located on a region on chromosome 6.
There are 2 Classes: MHC I and MHC II.MHC I : These surface proteins (antigens) are
recognized by , and bind to, CD8 receptors found on KILLER T cells.
MHC II: These surface proteins (antigens) are recognized by, and bind to, CD4 receptors found only on HELPER T cells.
Target Cell w/ MHC-I
• This cell has MHC-I on its plasma membrane
• It was derived from a protein from a bacteria or virus that phagacytized.
• The protein was processed by ER (follow Arrows)
• A CD8 receptor will bind to this complex ..Killer T
Antigen Processing
Acquired Immune Response
Four Phases:
1) Recognition of Invading Pathogen
2) Amplification (Clonal Selection)
3) Attack
4) Slowdown
“RAAS”
Phase I; Recognition• Dendritic Cells and Macrophages are drawn to
site of injury; have consumed pathogen and PRESENTED their ANTIGENs on outside of cell surface. This is read by Helper T-Cells.
• Antigen- a marker on the surface of a foreign substance that immune system cells recognize as non-self and trigger the immune response.
• Helper T-Cells (CD4 cells) which activate killer T cells (CD8 cells) activate B-cell and their maturation to plasma cells. Plasma cells are the active form of B cells. They make specific antibodies.
Role of Helper T Cells
Helper T response needs APC. Dendritic Cells detect antigen and act as APCs.
• Helper Ts (CD4s) can then trigger clonal selection of Killer Ts.
• Helper T also trigger clonal selection of B cells.
• Clonal selection is amplification.
CD4 or CD8
• Helper Ts are CD4
• Killer Ts are CD8
Phase II: Clonal Selection
• Helper T cells (CD4 cells)- multiply rapidly and trigger the production of killer T cells and B cells in the spleen and lymph nodes.
• Cytokines, chemical messengers secreted by the lymphocytes, help regulate and coordinate the immune response; interleukins and interferons.
Phase II : CLONAL SELECTION (AMPLIFICATION)
• Helper T cells (CD4 cells)- multiply rapidly and trigger the production of killer T cells (CD8) and B cells in the spleen and lymph nodes.
• Cytokines, chemical messengers secreted by the lymphocytes, help regulate and coordinate the immune response; interleukins and interferons.
PHASE III: ATTACK•Killer T cells strike at foreign cells and body cells that have been invaded and infected,APCs- identifying them by the antigens displayed on their cell surfaces. They puncture cells to sacrifice. Macrophages clean up-Cell-Mediated Immune Response
•B Cells do it DIFFERENTLY: Stimulated to multiply by helper T cells, they produce large quantities of antibodies. (Y-shaped proteins that bind to specific antigen bearing targets and mark them for destruction by macrophages). This is called the ANTIBODY-MEDIATED IMMUNE RESPONSE
Phase IV: SLOW DOWN
• The danger is over. The suppressor T cells halt the immune response by secreting chemicals that suppress killer T and B cells.
• Dead Cells filtered by the lymphatic system ( i.e. spleen) and excreted.
INCUBATION
• This is when viruses or bacteria are multiplying.
• You don’t have symptoms yet, although you may be weak.
• Your immune system has recognized enemy and is in stages 2 o3. YOU are very CONTAGIOUS!!!!
Another B cell T cell Difference:
• Antibodies can only affect the OUTSIDE of cell DIRECTLY or must use Indirect means ( others such as macrophages) to get inside cell) that is IF the microbe is inside.
• Killer Ts: Lyse cell to get INFECTED cell.
T-Cell Lysis
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
T Cell Clones Suppressor T cells
Release chemicals to suppress the activity of T and B cells
Stop the immune response to prevent uncontrolled activity
A few members of each clone are memory cells
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Secondary Response Memory cells are
long-lived
A second exposure causes a rapid response
The secondary response is stronger and longer lasting
Figure 12.13
Humoral Immune Response
Figure 12.12
Whenever its…PHAGOCYTOSIS
Antibodies (Immunoglobulins) (Igs)
• Soluble proteins secreted by B cells (plasma cells)
• Carried in blood plasma
• Capable of binding specifically to an antigen
Figure 12.15a
A Plasma Cell
Structure of an Antibody• 4 amino acid chains linked together via
S-S bonds• 2 heavy chains, 2 light chains• Each of the heavy and light chains have
a both a constant and variable portion.• The variable region forms the antigen-
binding site and make each antibody unique.
• There are 2 antigen binding sites.• The binding sites will bind, not to the
entire antigen BUT to specific portions called antigenic determinant sites.
• This will be the antigen-antibody complex
Antibody Matches Antigenic Determinant
The Formation of Antibody-Antigen Complex May Cause Elimination of
Antigen in Several Ways: 2 are
1. Neutralization- Virus or bacteria can’t attract due to antibodies have bound to their receptors.
2. Precipitation and Agglutination. The formation of insoluble complexes due to binding of antibody-antigen determinant (precipitation) (which also form bridges), causes clumping of cells which we call it agglutination. Basically, the microbes are immobilized.
Agglutination and Precipitation
Where Do B Cells Mature?What happens after this?
• In The Lymph Nodes by a maturation process prompted by CD4 (helper T cells).
• B cells transform into a PLASMA cells.
• Plasma Cells produce ANTIBODIES. Antibodies are also called IMMUNOGLOBULINS. There are 5 classes of antibodies; IgD, IgM, IgG, IgA and IgE.” MADGE”
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Antibody Classes Antibodies of each class have slightly
different roles
Five major immunoglobulin classes
IgM – can fix complement
IgA – found mainly in mucus
IgD – important in activation of B cell
IgG – can cross the placental barrier
IgE – involved in allergies
Antibody Classes
• By amino acid sequences of C region of antibody• IgA: monomer in plasma; dimer in mucus, saliva, tears,
milk, intestinal secretions, prevents adherence to epithelia
• IgD: monomer; B cell membrane antigen receptor
• IgE: monomer; on mast cells; stimulates release of histamines, attracts eosinophils; immediate hypersensitivity reactions
• IgG: monomer; 80% circulating, crosses placenta to fetus, 2 immune response, complement fixation
• IgM: pentamer, 10% in plasma, 1 immune response, agglutination, complement fixation
How Do Antibodies Work?
How Do Natural Killer Cells “Kill”?
• These are lymphocytes that do not use phagocytosis
• They emit chemicals called porifins which are directed at selected “bad” cells.
• The target cell’s membrane as a consequence will disintingrate..bye…bye.
What is COMPLEMENT?• About 20 proteins by themselves are INERT.• However, when attached or “FIXED” to a
pathogen or antigen become ACTIVATED---Complement FixationMAC
• MAC=membrane attack complexes: these produce lesions or holes in forgein cells surface and amplify inflammatory response
Vaccines• Vaccine development is based on acquired immunity. 2 BASIC
TYPES:
1. TO CONFER ACTIVE IMMUNITY : a. Weakened microbes(measles, mumps, rubella) b. Killed pathogens that still retain surface antigens so they can stimulated antibody production
2. PASSIVE IMMUNITY: Give just the antibodies. In this case a person has already been exposed to pathogen; needs antibodies fast. OR person is traveling abroad and doesn’t have time to wait for “lag period” for antibodies to build. Doctor gives patient a shot of gammaglobulin which is a “mixed bag” of antibodies which will last a couple of weeks and then disintegrate.
Active Immunity
• Your B cells encounter antigens and produce antibodies
• Active immunity can be naturally or artificially acquired
Figure 12.14
Allergies
• Allergies are a hypersensitivity of the immune system. They are abnormal. Allergens are what we prompt an allergic response.
• Histamine is released by Mast cells in in a allergic response. Histamine causes blood vessels to dilate and leak causing runny nose, mucus. .
MAST CELLS
• Mast Cells are produced in the bone marrow but migrate to, and are found mostly in, the connective tissue.
• Mast cells play a key role in the inflammatory process.
• When activated, a mast cell rapidly releases its characteristic granules and various hormonal mediators( histamine is one) into the interstitium. Mast cells can be stimulated to degranulate by direct injury.[
The Mast Cell
•Allergen binds to IgE on Mast
•Granules release histamine et al.
•Allergic attack occurs
•Common allergens are:
•Animal dander
•Pollen
•Dust
Sensitization
• This is when you are initially exposed to an allergen, the time your B cells are producing antibodies ( IgEs) against it. You have no symptoms at this time.
• However, as the IgEs will bind to Mast cells, the next time you are exposed you will have allergic symptoms as allergen will bind to IgE and mast cell will release histamines and other chemical. It is these chemicals that induce the symptoms of an allergic response.
PASSIVE IMMUNITY
• Colostrum- “ Mother’s first milk” is rich is IgA antibodies and gives baby passive immunity for months.
Passive Immunity
• Antibodies are obtained from someone else– Conferred naturally from a mother to her fetus– Conferred artificially from immune serum or
gamma globulin
• Immunological memory does not occur
• Protection provided by “borrowed antibodies”
Anaphalactic Shock
• This is a severe widespread acute hypersensitivity that occurs when an allergen such as bee venom or penicillin is introduced to bloodstream of allergic people.
• Symptoms: Brochoconstriction, dyspnea, widespread vasodilation,circulatory shock sometimes sudden death
• Remedy: Shot of epinephrine
• DISORDERS of the IMMUNE SYSTEM
Immunodeficiency Diseases
• Severe Combined Immunodeficiency Disease – hereditary lack of
T and B cells– vulnerability to
opportunistic infection
• AIDS– HIV structure (next slide)– invades helper T cells, macrophages and
dendritic cells by “tricking” them to internalize viruses by receptor mediated endocytosis
– reverse transcriptase (retrovirus), uses viral RNA as template to synthesize DNA, new DNA inserted into host cell DNA, may be dormant for months to years
Immunodeficiency Diseases
HIV/ AIDS
• This disease involves destruction of the CD4 cells.
• Virus (HIV) (Not Lack of Self ANTIGEN), that causes AIDS is a retrovirus
• Use of antivirals only is the way this virus is being treated.
• Why isn’t a vaccine available?
HIV Structure
AIDS• Signs and symptoms
– early symptoms: flulike chills and fever– progresses to night sweats, fatigue, headache,
extreme weight loss, lymphadenitis– normal TH count is 600 to 1,200 cells/L of blood
but in AIDS it is < 200 cells/L • person susceptible to opportunistic infections
(Toxoplasma, Pneumocystitis, herpes simplex virus, CMV or TB)
– thrush: white patches on mucous membranes
– Kaposi sarcoma: cancer originates in endothelial cells of blood vessels causes purple lesions in skin
How Does an HIV Person Know When He or She Has AIDS?
There are 2 Indicators that AIDS has arrived:
1. Your CD4 T cell count has become severely reduced. Usually once you are HIV positive, this cell is monitored.
2. The person develops an infection known as an AIDS indicator. These are infections that people with normal immune systems usually resist. i.e. pnemonocystisis carnii.
Kaposi Sarcoma
HIV Transmission• Through blood, semen, vaginal secretions, breast
milk, or across the placenta
• Most common means of transmission– sexual intercourse (vaginal, anal, oral)– contaminated blood products– contaminated needles
• Not transmitted by casual contact
• Undamaged latex condom is an effective barrier to HIV, especially with spermicide nonoxynol-9
Disorders of Immunity: Autoimmune Diseases
• The immune system does not distinguish between self and nonself.
• The body produces antibodies and sensitized T lymphocytes that attack its own tissues.
Disorders of Immunity: Autoimmune Diseases
• Examples of autoimmune diseases– Multiple sclerosis – white matter of brain and spinal
cord are destroyed
– Myasthenia gravis – impairs communication between nerves and skeletal muscles
– Juvenile diabetes – destroys pancreatic beta cells that produce insulin
– Rheumatoid arthritis – destroys joints
Mechanisms of Self-Tolerance
Why we don’t attack our own cells:
• SUPRESSOR T CELLS – create “self-antigen” a surface protein that makes all of your proteins recognizable as a ”self”. This protein must be continuously made throughout your life. If you stop producing it you get an autoimmune disease, one being rheumatoid arthritis.
Rheumatoid Arthritis
An autoimmune disease that affects the joints, destroying the cartilage with an inflammatory reaction and causing pain and the severe deformities seen here. Occurs when selected tissues do not recognize their “self antigen”.
Systematic Lupus
• Inflammatory connective tissue autoimmune disease . A variety of autoantibodies damage tissue. Cause unknown. Disease affect women 8x more than men. Butterfly rash characterizes this disease. Severe pain accompanies this disease.