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05 B215 Lymphatic

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Daniel Howell

on 9 November 2018

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Transcript of 05 B215 Lymphatic

The Lymphatic 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
Components of the Lymphatic System
Components of the Lymphatic System
Organization of the Lymphatic System
The Lymphatic System Consists of...
1. Lymph - similar to blood plasma but fewer proteins
2. Lymphatic vessels and capillaries
3. Lymphoid tissues and organs





4. Lymphocytes and supporting phagocytic cells
Function of the Lymphatic System
To rid the body of pathogens and infected or dead body cells
Produce, maintain, and distribute lymphocytes, the cells of the lymphatic system

Lymphocytes must:
Detect when and where problems exist
Migrate to the site of injury or infection
Assist removal of pathogens & debris
Lymphatic Vessels
Lymphatic capillaries
Small lymphatic vessels
Major lymph-collecting vessels
Histology of Lymphatic Vessels
Like veins
lymphatic vessels are under very low pressure

lymphatic vessels contain valves to keep fluid flowing in the right direction
Superficial and deep lymphatics
Right lymphatic duct
Cisterna chyli
Thoracic duct (left lymphatic duct)
Major Lymphatic Vessels
Lymphatics of the Female Breast
Numerous small lymphatic vessels drain the breasts

Mammary lymphatic nodes chain adjacent to the sternum
Highly developed lymphatics protect mother and baby during breast-feeding
Lymphocytes
Lymphocytes account for 20-30% of circulating WBCs
Most lymphocytes are NOT in circulating blood, but in the lymphatic vessels or other tissues
Lymphocytes are “wanderers” in the body
Total number of lymphocytes: ~10
Lifespan: 4 – 20 years (assists in immune “memory”)
12
Three Classes of Lymphocytes
B (bone marroww-derived) cells - 15%
produce antibodies that bind to antigens (antibody-mediated or humoral immunity

T (thymus-derived) cells - 80%
cytotoxic T cells (Tc) - attack foreign cells or infected body cells (cell-mediated immunity)
helper T cells (Th) - Stimulate T and B cells
suppressor T cells (Ts) - inhibit T and B cells

NK (natural killer) cells - 5%
attach foreign cells, infected or cancerous body cells
Lymphocyte Production: Lymphopoiesis
Involves bone marrow, thymus, and peripheral lymphoid tissue
B cells and NK cells mature in bone marrow
T cells mature in the thymus
Lymphoid Tissue
Connective tissue dominated by lymphocytes
Lymphoid nodules




MALT (mucosa-associated lymphoid tissue)
Lymphocytes densely packed in areolar tissue
Found in the respiratory, digestive, and urinary tracts
Tonsils = large nodules in the walls of the pharynx
Collection of lymphoid tissues linked with the mucous membranes
Tonsils
Peyer's Patches (“tonsils in your gut”)
Appendix
MALT
MALT: Peyer's Patches
MALT protects the body from intestinal bacteria (10x more bacteria than body cells)
MALT: Tonsils
Tonsils protect the body from airborne pathogens
Lymphoid Nodules: Lymph Nodes
Lymph nodes – function in the purification of lymph
Lymph node vessels



Lymph node structure
Afferent vessels – carry lymph to nodes
Efferent vessels – carry lymph from nodes
1 – 25 mm in size
Deep cortex dominated by T cells
Outer cortex & medulla dominated by B cells
Hilus = blood vessels & efferent vessel
Location of Lymph Nodes
Located behind sternum in anterior mediastinum
Fibrous outer capsule divides thymus into 2 lobes



Cortical lymphocytes surrounded by reticular epithelial cells (maintain blood–thymus barrier)
Lymphoid Organs: The Thymus
Lobes divided into lobules, each with a cortex and medulla
Reticular epithelial cells secrete thymic hormones: thymosin, thymopoietin, and thymulin (collectively called “thymosins”
Lymphoid Organs: 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 & other blood components (blood filter)
Storage of iron
Initiation of the specific immune response
The spleen does for blood what lymph nodes do for lymph.
Lymphatic System & Body Defenses
Types of Nonspecific Defenses
Nonspecific (nonadaptive)
Defenses
1. Physical barriers
2. Phagocytes
3. Immunological surveillance
4. Interferons
5. Complement system
6. Inflammatory response
7. Fever
Nonspecific Defenses: 1 - Physical Barriers
Keep hazardous organisms outside the body
Includes hair, epithelia, secretions of integumentary and digestive systems
Nonspecific Defenses: 2 - Phagocytes
Remove cellular debris and respond to invasion by foreign pathogens



Move by diapedesis (squeezing through blood vessels)
Exhibit chemotaxis
Monocyte
Fixed & free macrophages
Microphages – Neutrophils and eosinophils
Nonspecific Defenses: 3 - Immunological Surveillance
Constant monitoring of tissues by NK cells
NK cells


NK cell activation
Recognize cell surface markers on abnormal cells
Destroy cells with abnormal antigens
Recognition of unusual surface proteins
Rotation of the Golgi toward the target cell and production of perforins
Release of perforins by exocytosis, causing cell lysis
Nonspecific Defenses: 4 - Interferons
Small proteins released by virally infected cells
Trigger the production of antiviral proteins
Three major types of interferons:
Alpha– produced by leukocytes, attract/stimulate NK cells
Beta– secreted by fibroblasts, cause inflammation
Gamma – secreted by T cells & NK cells, stimulate macrophage activity
Nonspecific Defenses: 5 - Complement System
Cascade of ~11 complement proteins found in blood plasma
Destroy membranes of target cells
Stimulate inflammation
Attract phagocytes
Enhance phagocytosis
Nonspecific Defenses: 6 - Inflammation
Localized tissue response to injury



Effects of inflammation include
mast cells (ie, basophils) release histamine & heparin
produces swelling, redness, heat, pain
Temporary repair of injury
Slowing the spread of pathogens
Mobilization of local, regional and systemic defenses
Nonspecific Defenses: 7 - Fever
Maintenance of a body temperature above 37.2C (99F)
Pyrogens reset the hypothalamic thermostat and raise body temperature
Pathogens, toxins, antigen-antibody complexes can act as pyrogens
Specific (Adaptive) Defenses
Forms of Immunity
Properties 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
An Overview of the Immune Response
Major Types of T cells
An antigen enters the body

Antigen engulfed by phagocytes

Phagocytes activate T cells

Some T cells stimulate B cells

B cells mature & produce antibody

Antibody binds to antigen

Other T cells attack & destroy antibody-coated antigens
T Cells & Cell-mediated Immunity
Cytotoxic T cells (Tc) – attack foreign or infected cells (cell-mediated immunity)


Suppressor T cells (Ts) – inhibit the activation of T and B cells

Helper T cells (Th) – activate Tc cells and B cells
Antigen Presentation
T cells recognize antigens only when antigens are bound to glycoproteins in somatic (body) cell membranes (ie, they are not activated by free antigens)

When an antigen-glycoprotein combination appears on a cell membrane, this is
antigen presentation

The presenting glycoproteins are called MHC proteins (Major Histocompatibility Complex)

The presenting cells are 1) infected cells or 2) antigen-presenting cells (APC)

T-cells sensitive to the antigen are activated upon contact with presented antigen-MHC complex
Two Classes of MHC Proteins
Class I MHC
– found on all nucleated cells
Tells T cells, “I’m an abnormal (cancerous/infected) cell – kill me!”


Class II MHC
– found on antigen presenting cells (APC) and lymphocytes
Tells T cells, “The foreign cell (bacteria/virus) possessing this antigen is dangerous – find it and kill it!”
Antigens & Class I MHC Proteins
"I'm sick! Kill me!"
Antigens & Class II MHC Proteins
"Kill the foreign cell possessing this antigen!"
T cells respond to antigens bound to either class I or class II MHC proteins
T cell response is called
antigen recognition

Antigen recognition is dependent upon a class of membrane proteins called CD markers in T cells
T cells with CD8 markers respond to antigens presented by class I MHC proteins (“destroy sick body cells”)
cytotoxic T cells (Tc) and suppressor T cells (Ts)

T cells with CD4 markers respond to antigens presented by class II MHC proteins (“destroy invading foreigners”)
helper T cells (Th cells)
Activation of CD8 T cells by Antigen-MHC I Complex
Antigen Recognition & Activation of Tc Cells
Activation of CD4 T Cells by Antigen-MHC II Complex
Antigen Recognition & Activation of Th Cells
Activation of Sensatized B Cells
Activated Th cell activates sensitized B cell.

Activated B cells release antibodies

Abundance of antibodies circulate in blood and lymph, binding to antigen (i.e., tags bacteria)
Summary of Pathways to T Cell Activation
B Cells & Antibody-mediated Immunity
B Cell Sensitization & Activation
Inactive B cells carry antibodies on cell membrane
If the antibody contacts & binds to its specific antigen, the B cell will be sensitized
Sensitized B cells endocytose antigen-antibody complex, then subsequently display the antigen on Class II MHC proteins
Sensitized B cells are activated by helper T cells activated by the same antigen
Activated B cells differentiate into Memory B Cells or Plasma cells
Plasma cells synthesize and release antibody
The Sensitization & Activation of B Cells
B cells sensitized by binding to free antigen in the body

Engulfs antigen and presents it on MHC II complex

B cell with presented antigen activated by Th cell
Antibody (Immunoglobin) Structure
Antibodies are Y-shaped proteins consisting of:

2 heavy chains and 2 light chains (4 polypeptides)
Each chain has a constant region and a variable region
A portion of the variable region constitutes the antigen binding site
Antibody (Immunoglobin) Structure
Heavy chains
IgG
IgE
IgD
IgM
IgA
IgE
Accelerates local inflammation

binds to mast cells & basophils; stimulates release of histamine & heparin
IgD
Found on the surface of B cells

Involved in the activation of B cells
IgG
Resistance against many viruses, bacteria and bacterial toxins

Largest, most diverse group of antibodies (80% of total Abs)

Freely cross the placenta to provide passive immunity to fetus

Anti-D antibodies (sensitive to Rh antigen)
Antibody Specificity
Depends on the structure of the variable region (parts from both heavy & light chains)

Antigens interact with antibodies like substrates interact with enzymes
Antibody Diversity
Normal adult produces ~100 million unique antibodies!

Since the human genome only contains ~50,000 genes, how can we make 100 million unique proteins?

Recall: "one gene = one protein"
Antibody Diversity
Antibody Actions
Neutralization
Agglutination and precipitation
Activate complement
Opsinization (attract phagocytes by coating antigen with antibodies)
Stimulate basophils & mast cells (inflammation)
Prevent adhesion to body (epithileal) surfaces
Primary & Secondary Immune Response
Primary Response:
Takes about 2 weeks to fully develop
IgM first to appear, then IgG
Primary & Secondary Immune Response
Secondary response
occurs from 2nd exposure to an antigen

made possible by long-living memory B cells

Rapid increase in IgG

Maximum antibody titer much higher than primary response
Development of the Immune Response
Normal & Abnormal Resistance
Immunological competence = The ability to demonstrate an immune response after exposure to an antigen

Fetuses receive immunity from the maternal bloodstream

Infants acquire immunity following exposure
Immune Disorders & Diseases
Autoimmune disorders
Immune response mistakenly targets normal cells
examples: Type I diabetes & Rheumatoid arthritis

Immunodeficiency diseases
Immune system does not develop properly or is blocked
examples: AIDS & SCID
SCID = severe combined immunodeficiency disease (now can be cured by gene therapy)
Allergies
Inappropriate or excessive immune response to allergens (harmless antigens)

Type I allergies (Immediate hypersensitivity) are the most common
Symptoms may be reduced by administration of antihistamines
Mechanism of Anaphylaxis
Anaphylaxis
Circulating allergen affects mast cells body-wide

anaphylactic shock may cause circulatory collapse (systemic vasodilation) and death

may be triggered by ingested antigens (like peanuts) or bee stings

treated by injection with epinephrine (why?)
Lymphatic System Diseases
Lymphatic System Diseases
Lymphomas



Elephantiasis
Cancers involving lymphocytes
Hodgkins & non-Hodgkins types (43 different types)
Severe lymphodema caused by a parasitic roundworm infection
Affects limbs, breasts or external genitalia
Affected areas may become immensely swollen & distended
Elephantiasis
Elephantiasis
Fevers may contribute to Specific Immune Response as well.
Repasky et al. Journal of Leukocyte Biology (2011)
These cells are activated by high temperature (fever)
Answer: Gene Fragment Rearrangements
Clonal Selection & Immunity
Lymphocytes and
Lymphoid Tissues
1. Non-specific defenses
Does not distinguish one type of threat from another
Seven types

2. Specific Defenses
Protect against particular threats
Depends upon activation of lymphocytes
1. Innate immunity
genetically determined
present at birth

2. Acquired immunity
not present at birth
achieved by exposure to antigen
Active immunity
natural v induced
Passive immunity
natural v induced
T Cell Responses
Daniel Howell, Ph.D.
Liberty University

lymph nodes
thymus
spleen
MALT
Elephantiasis
Interferons warn neighboring cells of a virus in the tissue
cytotoxic and memory T cells activated quickly

Tc cells destroy infected cells using
perforins
cytokines
lymphotoxins

Suppressor T cells activated slowly
Antigen presented by APC cell activates Th cell

Active Th cells
release cytokines
activate sensitized B cells
IgM
First type secreted after antigen arrives

anti-A, anti-B in blood are IgM

Cannot cross the placenta
IgA
Primarily in glandular secretions (tears, saliva, mucus)
BIOL 215
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