Ch. 22 - Lymphatic System Flashcards
Leukocytes
white blood cells; formed in red bone marrow. 5 types are neutrophils, eosinophils, basophils, monocytes, and lymphocytes. most are housed in body tissues
monocytes
leukocytes that become macrophages when they leave blood and enter tissue
secondary lymphatic structures
t- and b-lymphocytes, macrophages, dendritic cells, and NK cells housed in lymph nodes, spleen, tonsils, MAL:, lymphatic nodules. Select organs house macrophages; some permanent named for location
dendritic cells are housed in…
epithelial layers of skin and mucosal membranes. dendritic cells are usually derived from monocytes and engulf pathogens and migrate into lymph.
Connective tissue houses…
mast cells. Mast cells are typically close to small blood vessels, and abundant in dermis and mucosa of resp. GI, and uro tracts and in CT of organs.
Cytokines
small proteins that regulate immune activity. they are produced by cells of both innate and adaptive immune system. They are chemical messengers released from one cell that binds to target cells to signal, control development and behavior of immune cells, regulate inflammation, or destroy cells. Can act of cells that release it (autocrine) local cells (paracrine) or distant cells (endocrine)
Innate Immunity
present at birth and protect against a variety of different substances (nonspecific). No prior exposure is necessary and respond immediately to potentially harmful agents. Include barriers like skin and mucosal membranes, and nonspecific cellular and molecular internal defenses.
Adaptive Immunity
acquired/ specific. Response to antigen involves specific T- and B- lymphocytes (a particular cell responds to one specific foreign substance but not another. Takes several days to be effective. 2 branches, cell mediated (t) and humoral (b)
first line of defense (innate immunity)
skin and mucosal membrane
second line of defense (innate immunity)
internal processes of innate immunity such as activities of neutrophils, macrophages, dendritic cells, eosino and basophils, and NK cells. Chemicals such as interferon and complement, and physiological processes such as fever and inflammation
Preventing entry
few microbes can penetrate skin; skin releases antimicrobial substances such as dermicidin, lysozyme, sebum, and defensins. Skin also has nonpathogenic flora of microorganisms that prevents growth of pathogenic ones.
Mucus membranes line body openings and release antimicrobial substances like defensins, lysozymes, and IgA. It is lined by harmless bacteria that suppress growth of virulent types.
Innate immunity cells (nonspecific)
phagocytic cells (includes neutrophils, macrophages, and dendritic cells, basophils and mast cells, NK cells, and Eosinophils
Phagocytic cells
neutrophils, macrophages, dendritic cells
Neutrophils
destroy engulfed particles; intake vesicle fuses with lysosome forming a phagolysosome that digests unwanted substances. Residue is released via exocytosis.
Dendritic Cells
destroy particles and then present fragments. The antigens are presented on dendritic cell surface for T-lymphocytes and is necessary for initiating adaptive immunity.
Macrophages
phagocytotic, makes a phagolysosome within cell. Can perform antigen presentation.
Proinflammatory cells
Basophils and mast cells
Proinflammatory cells
Basophils and mast cells
Basophils and Mast Cells
basophils circulate in blood and mast cells reside in CT, mucosa, and organs. They release granules containing chemicals that increase movement of fluid from blood to injured tissue. They serve as chemotaxic chemicals that attract immune cells (histamine, heparine). Eicosanoids released from cell membrane also increase inflammation.
Chemotaxic Chemicals
chemicals that attract immune cells. Includes histamine that increases vasodilation and capillary permeability and Heparin that acts as an anticoagulant.
Apoptosis-initiating cells
NK cells and eosinophils
NK cells
cells formed in bone marrow, circulate in blood, and accumulate in secondary lymphatic structures. They perform immune surveillance and destroy unhealthy cells (bacteria/virus infested, tumor cells, transplanted) They kill by releasing cytotoxic chemicals Perforin and Granzymes.
Perforin
creates a transmembrane pore in an unwanted cell to later cause apoptosis
Granzymes
enter pore and cause apoptosis of cell (shriveling)
Immune Surveillance
patrol the body, detect unhealthy cells
Eosinophils
attack multicellular parasites They degranulate (release enzymes and other toxic substances that can from transmembrane pores in parasites cells) They participate in immune responses of allergy and asthma, engage in phagocytosis of antigen-antibody complexes.
Recognition of microbes as foreign
foreign microbes are recognized for receptors. pattern recognition receptors (toll-like receptors) on cell surface bind to patterns on microbe surface.
Antimicrobial Proteins
molecules that function against microbes. Includes interferons and complement systems
Interferons
class of cytokines that nonspecifically impedes viral spread.
IFN-alpha and IFN-beta
produced by leukocytes and virus-infected cells; they bind to neighboring cells and prevent their infection and trigger synthesis of enzymes that destroy viral nucleic acids (inhibits synthesis of viral protein)
IFN-g
produced by t-lymphocytes and NK cells. Stimulates macrophages to destroy virus-infected cells
Complement System
group of over 30 plasma proteins. work along with complement antibodies. Identified with letter C and # (C2). Synthesized by liver, continuously released in inactive form. Activation occurs by enzyme cascade.
Complement Activation Pathways
Classical pathway: antibody attaches to foreign substance, then complement binds to antibody.
Alternative Pathway: Complement binds to polysaccharides of bacterial or fungal cell wall, especially potent against bacterial infections.
Opsonization
complement protein (opsonin) binds to pathogen, enhances likelihood of phagocytosis of pathogenic cell.
Inflammation
is enhanced by complement. Activates mast cells and basophils; attracts neutrophils and macrophages. Nonspecific response to ward off unwanted substances
Cytolysis
complement triggers splitting of target cell. Complement proteins form Membrane attack complex (MAC) that creates channel in target cell’s membrane causing lysis.
Elimination of Immune complexes
complement links antigen-antibody complexes to erythrocytes and they move to liver and spleen where they are stripped off.
Events of inflammation
- Release of chemicals to cause
- vascular changes like
- Recruitment of leukocytes that release cytokines stimulating leukopoiesis in marrow
- Delivery of Plasma Proteins
Inflammation step one: Release of Chemicals
Injured tissue, basophils, mast cells, and infectious organisms release chemicals such as histamine, leukotrienes, prostaglandins, chemotactic factors that initiate vascular response
Inflammation step two: Vascular changes
vasodilation, increased capillary permeability, increased endothelial expression of molecules for leukocyte adhesion.
Inflammation step three: Recruitment of leukocytes
Leukocytes release cytokines stimulating leukopoiesis in marrow and macrophages may release pyrogens. Recruits through three processes…
Margination: adherence of leukocytes to endothelial CAMs
Diapedesis: cells escape blood vessel wall
Chemotaxis: leukocytes migrate toward chemicals released from damaged, dead, or pathogenic cells.
Pyrogens
fever-inducing molecules released by macrophages
Inflammation step four: Delivery of plasma proteins to site
certain proteins are brought to infection site immunoglobins, complement, clotting proteins, and kinins
Clotting proteins
form clots that wall off microbes
Kinins
stimulate pain receptors, increase capillary permeability, increase production of CAMs by capillary cells. Kinins are produced from inactive kininogens and include bradykinin
Effects of inflammation
- fluid (exudate) moves from blood to injured or infected area
- fluid, proteins, immune cells eliminate pathogens
- vasodilation increased bloodflow
- contraction of vessel cells increases capillary permeability
- loss of plasma proteins decreases capillary osmotic pressure which decreases fluid reabsorption into blood. This extra fluid is taken up b lymphatic capillaries in the area (washing)
Washing
extra fluid from inflammation site is taken up by lymphatic capillaries that carries away debris for lymph node to monitor contents
How long does inflammatory response last
within 72 hrs inflammatory response slows and tissue repair begins as fibroblasts form new CT. Macrophages eat bacteria, neutrophils begin to die and host cells are damaged.
exudate
fluid, protein, and immune cell matrix that leaves blood towards infected tissue
Cardinal signs of inflammation
Redness: from increased blood flow
Heat: from increased blood flow and metabolic activity
Swelling: from increased fluid loss from capillaries
Pain: from stimulation of pain receptors due to compression from fluid or chemical irritants (kinins, prostaglandins, microbial secretions)
Loss of function: from pain and swelling in severe cases
Fever (pyrexia)
nonspecific internal defense; temp. is 1 degree Celsius or more from normal.
Events of fever and stages
pyrogens circulate through blood and target hypothalamus, which releases prostaglandin E2 raising temp. 3 stages, onset, stadium, defervescence.
Onset: temp. begins to rise. Hypothalamus stimulates constriction of dermal blood vessels and shivering generates more heat.
Stadium: elevated temp. maintained. Metabolic rate increases to promote elimination of harmful substances. Liver and spleen bind zinc and iron thereby slowing microbial reproduction.
Defervescence: temp. returns to normal. Hypothalamus no longer stimulated by pyrogens, so less prostaglandin. Hypothalmus stimulates mechanisms to release heat (vasodilation, sweating)
Benefits of fever
Inhibits reproduction of bacteria/viruses
Promotes interferon activity
Increases activity of adaptive immunity
Accelerates tissue repair
Increases CAMs of endothelium of capillaries in lymph nodes
Risks of high fever
considered 103 in kids, slightly lower in adults. high fever changes metabolic pathways and denatures proteins, possible seizures and irreversible brain damage at greater than 106, death likely at 109
Pus
contains destroyed pathogens, dead leukocytes, macrophages, and cellular debris removed by lymphatic system or through skin. If not cleared it may for an abscess.
Abscess
pus walled off with collagen fibers, usually requires surgical intervention.
Chronic Inflammation
inflammation for longer than 2 weeks. Characterized by macrophages and lymphocytes (not neutrophils) can occur from overuse injuries, autoimmune, or when acute inflammation cant eliminate pathogen. Can lead to tissue destruction and scar tissue formation.
Cell-mediated immunity
involving t-lymphocytes
Humoral immunity
involving b-lymphocytes, plasma cells, and antibodies
Antigens
pathogens are detected by lymphocytes because they contain antigens. Antigens are usually a protein or polysaccharide. (bacterial toxins, tumor antigens, protein capsid of viruses, cell wall of bacteria).
Foreign antigens
differ from human body’s molecules, bind to body’s immune components
Self-antigens
body’s own molecules, typically do not bind immune components.
Autoimmune disorders
system reacts to self-antigens as if foreign
Antigenic determinant
also known as epitope. Specific site on antigen recognized by immune system and each has a different shape; can have multiple determinants
Method of Lymphocyte contact with antigen
B-lymphocytes make direct contact with antigen. T-lymphocytes have antigen presented by another cell. T-lymphocyte coreceptors (CD ) facilitate the interaction
T-lymphocyte subtypes
helper t-lymphocytes are CD4+ cells: assist in cell-mediated, humoral, and innate immunity (activate NK cells and macrophages)
Cytotoxic t-lymphocytes are CD8+ cells: release chemicals that destroy other cells.
Other types include memory t-cells and regulatory t-cells
Antigen presentation
cells display antigen on plasma membrane so t-cells can recognize it. all nucleated cells do this. Two categories of cells present antigens: antigen presenting cells and all other nucleated cells.
Antigen-presenting cells (APCs)
immune cells that present to BOTH helper t and cytotoxic t cells. Includes: dendritic cells, macrophages, and b-cells. Requires attachment of antigen to major histocompatibility complex (MHC).
Major histocompatibility complex
group of transmembrane proteins. MHC I is found on all nucleated cells and MHC II is found on APCs (along w/ MHC I)
Synthesis and Display of MHC class I molecules
MHC I molecules are glycoproteins that have a genetically determined structure that is unique to the individual. Continuously synthesized by rough ER and inserted into cell membrane. It displays fragments of proteins that were bound to rough ER. If those fragments are endogenous proteins, immune system ignores them, if from infectious agent, immune system considers them non self and communicates to cytotoxic t-cells that the cell should be destroyed.
Display of MHC class II molecules
glycoproteins synthesized in rough ER and sent to membrane. Exogenous antigens are brought into cell via endocytosis and phagosome merges with lysosome within cell forming phagolysosome. Substance is digested into peptide fragments. Those fragments are loaded onto MHC class II molecules within vesicle and vesicle merges with plasma membrane. Provides means of communicating with helper T’s
Organ Transplants
Individuals are tested prior to donation for MHC antigens and ABO group. No 2 individuals have the exact same MHC. Components of innate and adaptive immune system attempt to destroy transplanted tissue so recipients immune system must be suppressed.
3 main events in the life of a lymphocyte
Formation of lymphocytes: occurs in primary lymphatic structures, and they become able to recognize one specific foreign antigen
Activation of lymphocyte: exposed to antigen and become activated in secondary lymphatic structures and replicate.
Effector response: t cells move to site of infection and b cells stay in secondary lymphatic structures (as plasma cells) where they synthesize antibodies that are transported to infection to eliminate antigen.
Formation of T-lymphocytes
originate in red bone marrow and migrate to thymus as pre-T-lymphocytes to complete maturation. Initially have both CD4 and CD8 proteins and produce unique TCR receptors randomly. The TCRs are tested to see if it can bind to MHC with antigen and whether it binds to only foreign antigens.
Thymic Selection
eliminates 98% of T-cells produced. Includes positive and negative selection.
Positive selection of T-cells
selects for the ability of t-cells to bind thymic epithelial cells with MHC molecules
Negative selection of T-cells
Tests ability of lymphocyte to not bind to self-antigens (self-tolerance). Occurs in primary lymphatic structures, specifically called central tolerance. Thymic dendritic cells present self-antigens and t-cells that bind to them are destroyed.
T-lymphocyte differentiation
Helper t-lymphocytes lose CD8 and cytotoxic lose CD4
Naïve T-lymphocyte
not yet exposed to antigens they recognize
Regulatory T-lymphocytes (tregs)
CD4+ cells formed from t-cells that bind to self-antigens to inhibit the immune response.
Clonal selection of lymphocytes
forming clones in response to an antigen. All formed cells have the same t-cell receptors or BCR. that matches a specific antigen.
Antigen challenge
first encounter between antigen and lymphocyte. Usually occurs in secondary lymphatic structures. Antigen in blood is taken to spleen, antigen penetrating skin is transported to lymph node, and resp., GI, & uro. tracts in tonsils or MALT
Activation of helper T-lymphocytes: First signal
First signal: direct contact with MHC molecule of antigen presenting cell. APC presents exogenous antigen with MHC class II molecules in secondary lymphatic. structures. Specific t-cell receptor site of t-cell binds to antigen peptide fragment and interaction is stabilized by CD4 molecule of helper t. If it doesn’t recognize antigen as foreign, it disengages quickly, if it recognizes antigen contact lasts several hours.
Second signal: other receptors of APC and t-cell interact. Helper t-cell secretes interleukin-2, stimulating itself. helper t-cells proliferate clones with same TCR and some clones become activated helper t-cells that produce IL-2 and some become memory helper t-cells available for future encounters. Lack of a second signal results in helper t-cells becoming tregs.
Activation of cytotoxic t-lymphocytes
First signal: direct contact b/w TCR of cytotoxic t-cell and peptide fragment with MCH I molecule on APC of infected cell. This is stabilized by CD8 of cytotoxic t-cell.
Second signal: IL-2 released from helper t-cells binds to and stimulates cytotoxic T-cells. Activated cytotoxic t-cells proliferate and differentiate into activated or memory cytotoxic T-cells.
Activation of B-lymphocytes
B-cells can respond to antigens outside of cells.
First signal: intact antigen binds to b-cell receptor, cross-linking 2 BCRs. Stimulated B-cell engulfs, processes, and presents antigen to helper t-cell for recognition
Second signal: activated helper t-cell releases IL-4, stimulating B-cell to proliferate and differentiate into plasma cells that produce antibodies or memory b-cells that retain BCRs and activate with reexposure to same antigen (much longer lifespan than plasma cells). In some cases activation occurs without t-cells but production of antibodies and memory b-cells require helper t-cell involvement in activation.
Lymphocyte recirculation
after a time, a lymphocyte exits secondary lymphatic structure and circulates blood and lymph for several days and some are delivered to secondary lymphatic structures. Makes it more likely that a lymphocyte will encounter a specific antigen
Effector response
mechanisms used by lymphocyte to eliminate antigen. Each lymphocyte has its own. Helper t releases IL-2 and other cytokines, Cytotoxic use apoptosis and plasma cells produce antibodies.
Effector response of Helper T-lymphocytes
after exposure to antigen in sec. lymphatic structure, activated and memory helper t-cells migrate to infection site and continually release cytokines to regulate other immune cells. Help active b and cytotoxic cells and stimulate innate immune system cells.
Effector response of Cytotoxic t-cells
migrate to infection site after exposure to antigen and destroy cells that display that antigen by releasing granules containing perforin and granzymes to induce apoptosis. Because this works against antigens associated with cells, the system is called cell-mediated immunity.
perforin
cytotoxic chemical that forms channel in target cell membrane
granzymes
enter channels in cell and induce apoptosis
Effector Response of B-lymphocytes
most activated b-lymphocytes become plasma cells that remain in lymph nodes. They synthesize and release millions of antibodies during 5-day lifespan. Antibodies circulate through lymph and blood until encountering antigen
Antibody titer
circulating blood concentration of antibody against a specific antigen. Help measures immunological memory
Antibodies
immunoglobulin (Ig) proteins produced against a specific antigen. Antibodies tag pathogens for destruction by immune cells and are good defense against viruses, bacteria, toxins, and yeast. Soluble antigens are combatted by humoral immunity. Has a y-shaped structure. Each “arm” contains antigen binding sites.
Variable region of an antibody
located at the ends of antibody arms and contain antigen-binding site. Binds antigens through weak intermolecular forces such as hydrogen and ionic bonds or hydrophobic interaction.
Constant region of an antibody
contains the Fc region, which determines antibody’s biological function. Same in structure for antibodies of a given class (IgG, IgM, etc.)
Five major classes of immunoglobulins
IgG, IgM, IgA, IgD, IgE
Neutralization
antibody physically covers antigenic determinant of pathogen making it ineffective in establishing infection. (cover region of virus used to bind to other cells)
Agglutination
antibody cross-links antigens of foreign cells causing clumping. This is especially effective against bacteria.
Precipitation
antibody cross-links circulating antigens to form an antigen-antibody complex that becomes insoluble and precipitates out of body fluids. Precipitated complexes are engulfed by phagocytes
Complement fixation
Fc region of IgG and IgM can bind complement for activation
Opsonization
Fc region of certain antibody classes make it more likely target cells will be seen by phagocytic cells. Some phagocytes have receptors for these Fc regions and binds to and engulfs antigen and antibody.
Activation of NK cells
Fc region of some antibodies (IgG) trigger NK cells to release cytotoxins. This destroys abnormal cells through antibody-dependent cell-mediated cytotoxicity.
IgG
makes up 75-85% of antibodies in blood. The predominant antibody in other fluids like lymph and CSF. Can participate in all types of antibody actions and can cross placenta and cause hemolytic disease of newborn.
IgM
mostly found in blood. Normally has pentamer structure and most effective at agglutination and binding complement. Responsible for rejection of mismatched transfusions
IgA
found in areas exposed to environment such as mucus, saliva, tears, and breastmilk. Protects resp. and GI tract. Helps prevent pathogens adhering to and penetrating epithelium; especially good at agglutination.
IgD
functions as antigen-specific b-lymphocytes ready for activation. Identifies when immature B-lymphocytes are ready for activation.
IgE
usually formed in response to parasites and in allergic reactions. Otherwise low rates of synthesis, causes release of products from basophils and mast cells. attracts eosinophils.
class switching
when a plasma cell changes the type of antibody it produces. requires contact between helper t-cell and plasma cell. T-cell must release specific cytokines to specify antibody class that will be formed.
Immunological Memory
Activation leads to formation of many memory cells. With subsequent antigen exposure, memory cells contact with antigen more rapidly producing a powerful secondary response before symptoms develop. Vaccines help develop memory.
Initial exposure and the primary response vs. subsequent exposures and secondary response
Primary response is antibody production to initial exposure to an infection. It has a lag or latent phase of 3-6 days where there are no detectable antibodies. Includes detection, activation, proliferation and differentiation. Antibodies are then produce by plasma cells (IgM and then IgG) within 1-2 weeks.
Secondary response: second exposure to an infection. The lag phase is much shorter and antibody levels rise rapidly with a large proportion of IgG antibodies
Active Immunity
results from direct encounter with pathogen. can occur naturally by direct exposure to antigen or artificially through vaccine. Memory cells against specific antigen are formed
Passive Immunity
obtained from another individual. Can occur naturally via transfer of antibodies from mother to fetus or artificially when serum transferred from one person to another (antibodies to snake venom). Neither form of passive immunity produces memory cells.
Vaccinations
weakened or dead microorganism or component that stimulates immune system to develop memory b-lymphocytes to cause a secondary response if later exposed. Immune system response predominantly from the humoral branch. May provide lifelong immunity or require booster shots.
Hypersensitivities
abnormal and exaggerated response of immune system to antigen.
Acute hypersensitivities
occur within seconds. Involves cell-mediated immunity. Exaggerated response of immune system to a noninfectious substance or allergen. May cause multiple symptoms like labored breathing (allergic asthma) and red welts (hives)
Subacute hypersensitivities
occur within 1-3 hrs. Involves cell-mediated immunity.
Delayed hypersensitivities
occurs within 1-3 days. Involves cell-mediated immunity
anaphylactic shock
severe allergy, can be lethal.
AIDS
acquired immunodeficiency syndrome. Result of human immunodeficiency virus (HIV). It infects and destroys helper t-cells. Resides in body fluids of infected individuals and can be transmitted through breastfeeding, intercourse, and needle sharing. Given a diagnosis of AIDS when helper t-cells are below 200 cells per cubic mm. Death usually from opportunistic infections or cancer.
