Lymphatics and immune system Flashcards
What are the main functions of the lymphatic system?
Immunity and returning interstitial fluid into the blood stream.
What are the primary lymphoid tissues/organs?
Red bone marrow/thymus (i.e. these are where lymphocytes are formed and mature)
What are the secondary lymphoid tissues and organs?
These are where lymphocytes are activated and cloned.
- lymph nodes
- tonsils
- MALT
- appendix
- spleen
leukocytes can be granular or agranular. List which belong to which category.
Granular:
Neutrophils
Eosinophils
Basophils
Agranular:
Monocytes
lymphocytes
Describe lymphocytes in general
They are slightly larger than RBC’s, differential count 20-40%, They have little cytoplasm and provide defense against specific pathogens or toxins. They can be B-cells, T-cells or natural killer cells.
What is lymph?
Interstitial fluid that has entered the a lymphatic vessel
Lymphatic capillaries are closely associated with what structures in the tissues?
blood capillary networks
How do lymphatic capillaries differ from blood capillaries? (4ways)
- they originate as pockets rather than forming continuous tubes
- they have larger diameters
- have thinner walls
- typically have a flattened or irregular outline in sectional view.
How are the endothelial cells arranged in lymphatic vessels?
overlapping (to form a one way valve) and an incomplete or missing basement membrane
Where are lymphatic vessels found?
Everywhere blood flow is found, EXCEPT: CNS and bone marrow
… and not found where it doesn’t (cornea of the eye)
Do lymphatic vessels have valves?
The larger ones do. at each valve, the lymphatic vessel bulges noticeably, as valves are typically close to one another. Contraction of surrounding skeletal muscle helps move lymph.
How do we classify lymphatic vessels?
Superficial or deep.
Superficial are in the subcutaneous layer deep to skin and in areolar tissues of mucous membranes.
Deep ones run along with deep arteries and veins.
What do we call the convergence of deep and superficial lymphatic vessels?
Their convergence is called a lymphatic trunk
Where to lymphatic trunks empty?
the thoracic duct or the right lymphatic duct
Which trunks empty into the thoracic duct? (3)
- the left bronchomediastinal trunk
- left subclavian trunk
- left jugular trunk
Which trunks empty into the right lymphatic duct?
- right bronchomediastinal trunk
- right subclavian trunk
- right jugular trunk
Where does each lymphatic duct empty?
the right lymphatic duct dumps into the right subclavian vein just lateral to the right internal jugular vein.
The thoracic duct dumps into the left subclavian vein just lateral to the left internal jugular vein.
What is lymphedema?
A blockage of lymphatic drainage, causing an accumulation of toxins and pathogens. If left untreated, it can become permanent.
What are the class of lymphocytes?
- T-cells
- B-cells
- NK cells
What % of lymphocytes are T cells? Describe the three subcategories of T cells.
80%
Cytoxic T cells: attack foreign cells or body cells infected by viruses. They are the primary cells of cell-mediated immunity.
Helper T cells: stimulate the activation and function of both T cells and B cells. With regard to suppressor T cells, the Helper T cells help establish and control the sensitivity of the immune response.
Suppressor T cells: inhibit the activation and function of both T cells and B cells. The interplay between suppressor T cells and Helper T cells helps establish the sensitivity of the immune response.
What % of lymphocytes are B cells? Describe their role in immunity.
10-15%
These become plasma cells when stimulated. Plasma cells produce and secrete antibodies (Ab). They are responsible for antibody mediated immunity.
What % of lymphocytes are NK cells? What is their basic role in immunity?
5-10%
These attack foreign cells, self cells infected with viruses, and cancer cells that appear in normal tissues. Their continuous monitoring of peripheral tissues is called immune surveillance.
lymphocytes are sensitive to what/
Antigens (Ag)
Describe lymphopoeisis
Hematopoietic stem cells in the red bone marrow differentiate into lymphoid stem cells. Some migrate to the thymus (passing the blood/thymus barrier) to become various kinds of T-cells. 98% of those apoptose. The remaining can divide clonally and become involved in cell mediated immunity in peripheral tissues.
Other hemopoietic stem cells become lymphoid stem cells that differentiate into B cells and NK cells. The B cells become involved in antibody mediated immunity while the NK cells become involved in immune surveillance.
All can divide clonally.
Where are lymphocytes found?
lymphatic tissues (lymphoid nodules, MALT, tonsils) Lymphoid organs (lymph nodes, thymus, spleen)
How do we define a lymphoid organ?
They are separated from surrounding tissues with a dense fibrous capsule. These include lymph nodes, thymus, spleen.
Lymphoid tissues are what? and what can they form?
They are connective tissues dominated by lymphocytes. They can form lymphoid nodules
What are lymphoid nodules?
They are densely packed lymphocytes in an area of areolar tissue. The boundaries are indistinct (lacking a capsule)
If lymphoid nodules aggregate, what do we call those?
aggregated lymphoid nodules or Peyer’s patches.
Describe the structure of aggregated lymphoid nodules
They have a germinal center which contains dividing lymphocytes atop the underlying connective tissue. The germinal center is almost completely enclosed in mucous membrane wall of the intestine.
Describe MALT and where they are found
These are lymphoid tissues that protect epithelia in the digestive, respiratory, urinary, and reproductive tracts.
Disorders of MALT tissues include? (2)
tonsilitis and appendicitis
Tonsils are what?
Large lymphoid nodules in the walls of the pharynx. They begin to atrophy after puberty. The nasopharyngeal lymphoid nodule is called an adenoid. These used to be routinely removed in the mid 1900’s.
What are lymph nodes?
These are small lymphoid organs, about 1 inch max in diameter. They detect pathogens before they reach vital organs. They remove about 99% of pathogens and stimulate the immune response.
Describe the 6 fold path of lymph flow through a lymph node.
1) AFFERENT LYMPHATICS carry lymph to the lymph node from peripheral tissues
2) Lymph encounters DENDRITIC CELLS in the sub capsular space. These are involved in the initiation of the immune response. Some of these migrate to a lymph node bearing Ag’s from peripheral tissues.
3) Lymph then flows into the OUTER CORTEX, which contains B cells within germinal centers
4) Lymph flows through lymph sinuses in the DEEP CORTEX which is dominated by T-cells.
5) Lymph continues into the MEDULLARY SINUS, which contains B cells and plasma cells.
6)EFFERENT LYMPHATICS leave the lymph node at the hilum on the opposite end from the afferent ones. These vessels head toward venous circulation.
ADODME is Padme Amidala’s little lymphy brother.
Thymus is where lymphocytes do what?
Develop and mature
The involution of the thymus corresponds to what?
increased susceptibility to disease
Describe thymic epithelial cells
These are around blood vessels of cortex and form the blood thymus barrier. They are also around lymphocyte clusters to regulate T cell development and function.
Describe the thymic corpuscle
These mature after 3 weeks. T cells travel to medulla where they can enter blood stream or lymphatic vessel.
Describe T cell maturation process in thymus
The immature T-cells are tested for their binding affinity for self Ag (MHC-1, MHC-2). They are signaled to undergo apoptosis if they either bind too tightly or not well enough. The ones who make it are considered naive mature T lymphocytes and leave to blood or lymph. They have either CD4 or CD8 receptors AND a T cell receptor. These start out under the sub capsular region when immature and proceed inward during the maturation process (toward the medulla).
What is the largest lymph organ?
The spleen
What are the 3 main functions of the spleen?
- Removing abnormal blood cells and other blood components by phagocytosis
- Storing iron recycled from RBC’s
- Initiating immune responses by B cells and T cells in response to Ag’s in circulating blood.
Describe the structure of the spleen
The spleen is surrounded by a capsule containing collagen and elastic fibers. The cellular components within make up the pulp. The red pulp contains large quantities of RBC’s, whereas white pulp resembles lymphoid nodules and contains lymphocytes.
Describe blood flow through the spleen
The TRABECULAR ARTERIES are branches of the splenic artery. Their little branches, called central arteries are surrounded by white pulp.
CAPILLARIES discharge the bold into reticular tissue of red pulp, which contains free and fixed macrophages.
Then blood flows into SINUSOIDS whose walls contain fixed macrophages.
Blood collects into small veins that merge to form TRABECULAR VEINS.
TCST: Tammy cock sucks Tommy.
What is the negative consequence of a splenectomy
increased susceptibility to bacterial infections.
What are the 7 components of innate immunity?
- physical barriers
- phagocytes
- immune surveillance
- interferons
- complement
- inflammation
- fever
What is the difference between the innate and adaptive immune system branches?
Innate: doesn’t distinguish one type of threat from another. present at birth, nonspecific resistance.
Adaptive: protects against specific threats, ineffective against others. It depends on what lymphocytes are encountering.
Give examples of physical barriers
These can be components of the integument or epithelial linings.
Integument: glands and ducts secrete oils and sweat which flush the surface of skin to wash away microorganisms and also can contain chemical agents which may be bactericidal. Also, enzymes and antibodies. Hair protects against abrasion and insects.
Epithelia lining body openings have MALT, produce mucous to trap pathogens, glandular secretions wash stuff away. Enzymes, antibodies, and low pH increase effectiveness.
How do phagocytes offer protection in innate immunity?
They patrol peripheral tissues and clean up debris. They also respond to foreign substances and pathogens. They move by chemotaxis. They can leave tissues by diapedesis. Phagocytic cells include: neutrophils, eosinophils, and macrophages (derived from monocytes). Macrophages can be fixed or free.
Describe the role of NK cells in innate immunity
These destroy abnormal cells in peripheral tissues and perform immune surveillance. They recognize tumor specific antigens to destroy cancer cells.
How do NK cells destroy abnormal cells?
They recognize and adhere to them. Then the golgi moves toward the adhered surface. Secretory vesicles with perforin bud out and are released to diffuse across the narrow gap separating the NK cell from the abnormal one. The perforin makes pores on the target cell and it disintegrates.
What is immunological escape?
This is the process of cancer cells sometimes avoiding the detection of NK cells. If the cells within a primary tumor grow rapidly, and if the tumor has a surrounding capsule, the cells may not evoke a response from NK cells. As malignent tumor cells begin invading surrounding tissues, they can usually be detected by NK cells, but… sometimes a daughter cell will be produced that doesn’t display tumor specific antigen or that secretes chemicals that destroy NK cells. Such a cell will survive and be free to grown and divide. These can move throughout the body and establish potentially lethal secondary tumors.
How does the interferon response work?
Cytokines are released by activated lymphocytes and macrophages and cells infected with viruses. These cytokines bind receptors on nearby cells (second messenger system) which trigger the production of antiviral proteins in the cytoplasm. Some of the cytokines (interferon gamma) stimulates macrophage activity.
Why would interferon beta be used to treat MS?
Interferon beta diverts your immune cells, macrophages in this instance. Preoccupies them from attacking the myelination of axons.
Very generally, how does the complement system aid in innate immunity?
It complements the adaptive immune system, but it is dependent on antibodies. There are 30+ proteins involved in multiple cascades. There are two complement pathways, the classical and alternative pathways, both of which end with a lysed pathogen.
Describe the classical pathway of the complement system
Antibodies must first attach to the surface of a bacterial cell wall. Then our complement protein attaches for the activation of a cascade of reactions ending in three things: histamine release, enhanced phagocytosis, and pore formation (and subsequent lysis of bacterial cell).
Describe the alternative pathway of the complement system
This pathway begins when several complement proteins, notably properdin interact in the plasma. This is triggered by exposure to foreign substances such as the capsule of a bacterium (or endotoxins, yeast cell walls, aggregated immunoglobulins, snake venom). The end result is the attachment of an activated complement protein to the bacterial cell wall.
What are some complement disorders?
Acute proliferative glomerulonephritis, hereditary angioedema, lupus
What are the signs of inflammation?
what is it caused by?
localized redness, swelling, heat, pain
tissue injury, whether pathogens, impact, abrasion, chemicals, etc.
Explain the process of inflammation
- Tissue damage results in chemical change in interstitial fluid.
- This activates mast cells to release histamine and heparin.
- Release of these substances attracts phagocytes, especially neutrophils, which clean up debris and stimulate fibroblasts. Also, the histamine and heparin cause redness, swelling, heat and pain by dilating blood vessels, increasing blood vessel permeability (this can encourage clot formation). The phagocytes attracted in turn release cytokines to activate other specific defenses.
- Finally, tissues are repaired by pathogen removal, clot erosion, and scar tissue formation.
What are some of the interstitial fluid changes that activate mast cells for the inflammatory response?
Prostaglandins
Proteins
Potassium ions
Foreign proteins/pathogens
How is fever an innate immune response?
This is a body temperature greater than 99 degrees Fahrenheit. It inhibits some viruses and bacteria, but ups our metabolism by 10%/degree to speed up defenses and repair of tissue.
What are pyrogens?
They are fever inducing proteins. They can be endogenous (made by our own cells, ex. cytokines) or exogenous (made by bacteria, ex. LPS) Pyrogens cause the hypothalamus to “reset” the body’s thermostat to a higher temperature, producing a fever.
What type of innate defense protects us against
- viruses
- Mosquito
- cancerous cells
- bacteria
- spread of infection
- physical barriers, mucous, interferon, fever, NK cells
- inflammation, physical barriers, phagocytes
- NK cells
- physical barriers, phagocytes, immune surveillance, complement system, inflammation response, fever, interferon for an intracellular bacterium
- All of the above prevent spread of infection, interferon is useful here, as well as the complement system’s anaphlatoxins.
Adaptive immunity is subdivided into two categories. What are they and what cells mediate them?
Cell mediated (T cells) and antibody mediated (B cells)
What are the four properties of adaptive immunity?
Specificity: lymphocyte binds 1 antigen
Versatility: millions of lymphocytes waiting for activation
Immunologic memory: each division makes a memory cell and an activated lymphocyte
Tolerance: distinguish self from non-self
Describe MHC proteins
These are genetically determined glycoproteins present on the surface of cells. MHC class 1 proteins are present on all nucleated cells MHC class 2 proteins are present on all antigen presenting cells and lymphocytes.
What triggers antigen presentation by Class 1 MHC? How does this process work?
A viral or bacterial infection of a cell results in the appearance of abnormal peptides in the cytoplasm. Newly synthesized Class 1 MHC proteins being synthesized at the ER bind these and then pop up to the plasma membrane with the abnormal peptides.
What triggers Ag presentation by Class 2 MHC? How does this process work?
First the cell phagocytizes the extracellular pathogen, and fuses it with a lysosome. This makes Ag fragments. The ER produces Class 2 MHC proteins and Ag fragments find to them to get displayed on the surface.
CD8 markers interact with which class of MHC? What about CD4?
CD8/Class 1
CD4/Class 2
CD8 T Cells are responsible for what kind of adaptive immunity?
cell-mediated immunity
CD4 T cells are responsible for what kind of adaptive immunity?
antibody mediated immunity
What three kinds of T cells result from activation of a CD8 T-cell? Describe how CD8 T cells respond to antigens presented by class 1 MHC proteins.
Cytotoxic T cells, Memory T cells and Suppressor T cells.
See pages 768 and 769 for answers.
How long does cell mediated immunity take?
about 2 days on first exposure to the pathogen, but much faster upon second exposure.
Describe how CD4 T-cells respond to antigens presented by class 2 MHC proteins.
See pages 770 and 771 for the answers.
What do plasma B cells do?
Secrete antibodies, up to 100 million of them per hour.
Describe an antibody’s structure, in general
It has heavy chain and a light chain. The center is held together by a disulfide bond. The tips of the fork of the Y form Ag binding sites. These are also roughly where the variable segments are. There are also binding sites for complement activation and attachment of the antibody to other cells.
What is a complete antigen? Partial antigen?
Complete has at least two antigenic determinant sites, one for each of the Ag binding site on an Ab. Partial antigens (haptens) can function as complete antigens if they attach to a carrier molecule. The antibodies produced will attack both the happen and the carrier molecule. If the carrier molecule is normally present in the tissues, Ab’s may begin attacking normal cells-> the basis for a drug reaction.
What are the 5 classes of Ab’s?
IgG's IgE's IgD's IgM's IgA's
Gladys eats dead men’s arms.
Describe IgG’s
These make up 80% of our Ab’s
They give us resistance to viruses, bacteria, and bacterial toxins
Describe IgE’s
These attach to basophils and mast cells
Describe IgD’s
These attach to the surface of B-cells. They bind Ag in extracellular fluid. They play a role in B-cell sensitization.
Describe IgM’s
These are the first Ab secreted when an Ag is encountered. They are responsible for agglutination seen when blood typing.
Describe IgA’s
These are found in glandular secretions. They identify pathogens before they get into internal tissues.
What is the difference between a primary antibody response and a secondary antibody response?
In a primary response, the IgM’s are the first on the scene, with peak production seen at about a week and a half. IgM’s are made by the end of the first week, with production peaking at two weeks.
In a secondary response, IgG’s are mass produced immediately, with production peaking by day 2. IgM’s also respond. Overall this response is much faster and stronger.
Give 7 mechanisms antibodies use to destroy their targets
- Neutralization (If Ab’s bind sites the pathogens use to bind their targets, they neutralize on the surface of the target)
- Prevention of pathogen adhesion (here they are dissolved in tears, saliva, etc, and they are in the way of the epithelial tissue)
- activation of complement
- opsonization
- stimulation of inflammation
- precipitation/agglutination
- attraction of phagocytes
What are allergies?
inappropriate or excessive immune response
Describe sensitization that occurs during first exposure to an allergen
The initial exposure leads to the production of large quantities of IgE antibodies. These attach to mast cells and basophils.
What happens in a subsequent exposure to an allergen?
The allergen binding to the IgE associated with a mast cell or basophil correlates with a mass release of histamines, leukotriense, and other chemicals that cause inflammation
Give three examples of misdirected immune response
autoimmune disorders
graft rejection
allergies
Three examples of autoimmune disorders
Type 1 diabetes
rheumatoid arthritis
Thyroiditis (Ab’s against thyroglobulin)
EBV and some influenza proteins are similar to myelin. Why could this be problematic?
Our body is making Ab’s against those proteins, could be a cause of MS.
What are 4 possible reasons for inadequate immune responses
- Embryonic development issue
- viruses
- Radiation or drugs
- Age
Why does immune response diminish with age?
T and B cells become less responsive with age. We have a slower and smaller immune response. Thymus shrinks, and we have increased risk of both infection and cancer.
What are the challenges in developing vaccines?
High mutation rate
Virus targets immune system
Multiple serotypes
Costs and time involved in development
Vaccine safety concerns
What is an adjuvant? What are their side effects?
A substance that enhances the body’s immune response to an antigen
fever, pain at injection site
