A&PI Ch. 21&22 Lymphatic and Immune Systems Flashcards
What are the components of the Lymphatic System?
- collection of organs, capillaries, vessels, and tissues
- contains fluid (lymph) that circulates through the vessels
- contains both lymph nodes and nodules
What are the functions of the Lymphatic System?
- returns excess interstital fluid to the venous system
- absorbs fats from the digestive tract and returns them to the venous system for processing by the liver
- produces and matures many immune cells
- filters microorganisms and foreign substances from lymph and blood
What is lymph?
- fluid that leaves blood capillaries and is not reabsorbed by them
- this interstitial fluid moves into lymphatic capillaries where it is then called lymph
What are the components of lymph?
- water, dissolved solutes, and small amount of protein
- sometimes cell debris, pathogens, or cancer cells
What do lymphatic vessels do?
-begin as fenestrated capillaries, composed of a single layer of endothelium
-lymph is transported through progressively bigger vessels, through lymph nodes, until it reaches the vena cava
-larger lymphatic vessels contain one-way valves and smooth muscle
Lymphatic Trunks are fed by _________ _________.
lymphatic vessels
Jugular trunks drain lymph from _______ and ______.
head, neck
Subclavian trunks drain ______ ______, _______, and _________ ________ _______.
upper limbs, breasts, and superficial thoracic wall
____________ __________ drain deep thoracic structures.
Bronchomediastinal trunks
Intestinal trunks drain most ________ _________.
abdominal structures
________ _______ drain lower limbs, abdominopelvic wall, and pelvic organs.
Lumbar Trunks
Lymphatic ducts are fed by ________ ________.
lymphatic trunks
Lymphatic Ducts
-bring lymph to venous blood circulation
-two types: right lymphatic ducts and thoracic duct
Right Lymphatic Duct
-near right clavicle
-drains right upper quadrant of the body
-delivers lymph to junction of left subclavian and right internal jugular veins
Thoracic Duct
-largest lymphatic vessel
-runs from diaphragm to junction of left subclavian and left jugular veins
-drains lymph from the left side of the head and neck, left upper limb, left side of the thorax, abdomen, and both lower limbs
Primary Lymphoid Structures
-Involved in the formation and maturation of lymphocytes
-Red bone marrow and thymus
Secondary Lymphoid Structures
-house lymphocytes and other immune cells
-sites of immune response initiation
-include lymph nodes, spleen, tonsils, and lymphatic nodules
-include MALT (Mucosa-Associated Lymphoid Tissue)
Bone Marrow is the site of ____________.
leukopoiesis
Leukopoiesis
-begins in the bone marrow
– includes the creation of lymphocytes (B&T)
-maturation may occur in the bone marrow, or continue in another organ, depending on the cell type
-T-lymphocytes migrate to thymus to complete maturation
Tonsils
-lymphatic tissue and organ
-large group of lymphatic nodules in nasopharynx and oral cavity
-provide protection against bacteria and other harmful material
-form a ring around the border between the oral cavity and the pharynx
Tonsil Groups
- Palantine (the “tonsils”)
- Pharyngeal (the “adenoids”)
- Lingual
The Thymus
-lymphatic tissue and organ
-flat, bi-lobed organ located in superior mediastinum above heart
-the thymus quickly starts to atrophy (shrivel) in life after puberty, possibly much earlier
-each lobe is comprised of lobules held together by areolar connective tissue
-site of T cell maturation
What are Lymph Nodes?
follicles consisting of lymphatic and non-lymphatic cells surrounded by a network of lymphatic capillaries
Lymph Nodes
-each is supplied by afferent (more numerous) lymphatic vessels and drained by efferent lymphatic vessels
-Resident Cells include B and T lymphocytes, macrophages, dendritic cells, and reticular cells
What do B and T cells, macrophages, dendritic cells, and reticular cells do in the lymph nodes?
-lymph is monitored for the presence of foreign material
-macrophages remove foreign debris from lymph
-lymphocytes may initiate an immune response (can cause enlarged nodes that can be palpated in the neck and axilla
-lymph exits the node through efferent vessels that may then pass to the neighboring lymph node
True or False? B cell maturation is a feature of the Thymus.
FALSE; T cell maturation is a feature of the Thymus
The Spleen
-lymphatic tissue and organ
-filters the blood, stores erythrocytes, removes defective erythrocytes/ platelets, recycles iron
-contains red pulp and white pulp
White Pulp
lymphocytes and macrophages
Red Pulp
addition of erythrocytes and platelets
Innate Immunity
provided by multiple components that protect against a wide array of substances
What does Innate Immunity include?
-skin and mucosal membranes (prevent entry)
-nonspecific internal defenses
Nonspecific internal defenses (part of Innate Immunity)
-most immune cells (e.g. macrophages, NK cells)
-chemicals (e.g. interferon, complement)
-physiologic responses (e.g. inflammation, fever)
Adaptive Immunity
provided by lymphocytes that are activated to replicate and respond when replicated by a specific antigen
What does adaptive immunity include?
- T-lymphocytes (cell-mediated immunity)
- B-lymphocytes (antibody-mediated immunity)
B-lymphocytes (antibody-mediated immunity)
plasma cells (synthesize and release antibodies)
How do innate and adaptive immunity differ?
- cells involved
- specificity of cell response
- mechanisms of eliminating harmful substances
-amount of time for response
-
How do you to compare innate and adaptive immunity?
work together in body defenses
Innate Immunity Specifics
- present at birth
- protects against variety of different substances (nonspecific: neds no prior exposure to the substance)
- responds immediately to potentially harmful agents
- includes barriers of skin and mucosal membranes, nonspecific cellular and molecular internal defenses
Adaptive Immunity Specifics
- acquired/ specific immunity
-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
Innate Immunity External physical barriers
- Skin
- Mucosal Membranes
- Tears
- Saliva
- Stomach Acid
- Sebum
Chemicals, proteins, and cells Internal physical barriers
- Histamine
- Complement
- Neutrophils
- Eosinophils
- Basophils
- NK cells
- Macrophages
Stereotype response
fever and inflammation
What are the features of the skin?
- first line of defense against foreign threats
-Epidermis: waterproof, chemically resistance to bacterial enzymes
-Glands: maintain surface pH of 3-5, blocking the growth of most microorganisms
-mucosal membranes contain anti-pathologic substances (lysozymes)
Second Line of Defense: nonspecific internal defenses
-if pathogens pass the first line of defense, the second line of defense (nonspecific internal defenses) is initiated
Nonspecific Internal Defenses
- selected immune cells
- antimicrobial proteins
- inflammation
- fever
What are the 3 phagocytic cells?
- neutrophils
- macrophages
- dendritic cells
What do phagocytic cells do?
-non-specific internal defenses
-engulf unwanted substances by phagocytosis
Neutrophils and Macrophages function
destroy engulfed particles
Neutrophils
-most numerous leukocyte
-first responder to site of injury
-act as weaker macrophages
-intake vesicle fuses with lysosome forming phagolysosome
-digestive enzymes break down the unwanted substances
-degraded residue is released by exocytosis
Dendritic Cells
-destroy particles
-present fragments
-antigens are presented on dendritic cell surface to T-lymphocytes
-necessary for initiating adaptive immunity
Macrophages
also perform antigen presentation
What are the two proinflammatory cells?
- basophils
- mast cells
- eicosanoids
-non-specific internal defenses
Basophils and Mast Cells
-promote inflammation
Basophils
Mast Cells
-reside in connective tissue, mucosa, and internal organs
-release granules containing chemicals
Granules that contain chemicals
-increase movement of fluid from blood to injured tissue
-serve as chemotaxis chemicals (attract immune cells)
-Histamine increases vasodilation and capillary permeability
-Heparin acts as an anticoagulant
Eicosanoids
-released from their plasma membrane
-also increase inflammation
What is the Apoptosis inducing cell?
NK (Natural Killer) cells
NK (Natural Killer) Cells
-destroy unhealthy/unwanted cells
-form in bine marrow
-circulate in blood
-accumulate in secondary lymphoid structures
–perform immune surveillance- patrol the body, detect unhealthy cells
-destroy virus-infected cells, bacteria-infected cells, tumor cells, cells of transplanted tissue
-kill by releasing cytotoxic chemicals
What are the two cytotoxic chemicals?
- Perforin: creates a transmembrane pore in unwanted cell
- Granzymes: enter pore and cause apoptosis of cell
Apoptosis
cell death that causes shriveling rather than lysis
Eosinophils
-non-specific internal defenses
-attack multicellular parasites
-degranulate, release enzymes and other toxic substances
–can release proteins that form transmembrane pores in parasite’s cells
-participate in immune responses of allergy and asthma
-cells of innate immune system recognize microbes as foreign because of receptors
–pattern recognition receptors (toll-like receptors) on cell surface bind to patterns on microbe surface
Antimicrobial Proteins
-nonspecific internal defenses
-molecules that function against microbes
Interferons
-nonspecific internal defenses
-a class of cytokines that nonspepcifically interferes with spread of intracellular pathogens (for example, viruses, intracellular bacteria)
Types of Interferons
IFN-alpha and IFN-beta: produced by leukocytes and virus-infected cells
-bind to neighboring cells and prevent their infection
–trigger synthesis of enzymes that destroy viral nucleic acids, inhibit synthesis of viral proteins
-stimulate NK cells to destroy virus-infected cells
Types of Interferons (2)
IFN-gamma: produced by T-lymphocytes and NK cells
-stimulates macrophages to destroy virus-infected cells
__________ affect both the innate and adaptive immune systems.
Cytokines
Cytokines
- small proteins that regulate immune activity
- act in an autocrine, paracrine, and endocrine manner
- produced by a broad range of immune cells
- overproduction of cytokines can lead to sickness and death
Complement System
- proteins involved in innate immunity
- group of over 30 plasma proteins
- work along with (“complement”) antibodies
- identified with letter “C” and number (for example, C2)
- synthesized by liver, continuously released in inactive form
– activation occurs by enzyme cascade - complement activation follows pathogen entry
Classical Pathway
antibody attaches to foreign substance, then complement binds to antibody
Alternative Pathway
complement binds to polysaccharides of bacterial or fungal cell wall
Lectin Pathway
initiated when mannose-binding lectin binds to mannose (sugar (rare for humans))
Non-specific internal defenses: Inflammation
-an immediate response to ward off unwanted substances
-local, nonspecific response of vascularized tissue to injury, infection
-major response of innate immunity
Events of inflammation
-injured tissue, basophils, mast cells, and infectious organisms release chemicals that initiate response
-released chemicals cause vascular changes
-recruitment of leukocytes
Vascular changes
-vasodilation
-increased capillary permeability
–increased endothelial expression of molecules for..
-leukocyte adhesion
–recruitment of leukocytes
Recruitment of Leukocytes
-Diapedesis
-Chemotaxis
Diapedesis
cells escape blood vessel walls
Chemotaxis
leukocytes migrate toward chemicals released from damaged, dead, or pathogenic cells
Effects of Inflammation
- fluid (exudate) moves from blood to injured or infected area
– fluid, protein, immune cells to eliminate pathogens, promote healing
– vasodilation brings more blood to that area
– contraction of vessel endothelial cells opens grasp between them, increasing capillary permeability
– loss of plasma proteins decreases capillary osmotic pressure, thus decreasing fluid reabsorbtion into blood
– extra fluid is taken up by lymphatic capillaries in the area (“washing”)
—carries away debris and allows lymph node monitoring of its contents - Within 72 hours, inflammatory response slows
– macrophages eat bacteria, damaged host cells, dying neutrophils
– tissue repair begins as fibroblasts form new connective tissue
Cardinal signs of inflammation
- redness from increased blood flow
- heat from increased blood flow and increased metabolic activity within the area
- swelling from increase in fluid loss from capillaries
-pain from stimulation of pain receptors (nociceptors)
– due to compression (extra fluid) and chemical irritants (kinins, prostaglandins, microbial secretions) - loss of function from pain and swelling in severe cases
– duration of acute inflammation: about 8 to 10 days - Chronic inflammation has detrimental effects (cancer)
Fever
- also called pyrexia
- abnormal body temperature elevation
–1 degree more than the normal (37 degrees C)
–results from release of pyrogens (ex. IL-1) from immune cells or infectious agents
Events of Fever
- pyrogens circulate through blood and target the hypothalamus
-in response, hypothalamus releases prostaglandins
-hypothalmus raises the temperature set point, leading to fever
What are the benefits of fever?
-it inhibits the production of bacteria and viruses
-promotes interferon activity
-stimulates capillary permeability
-increases activity of adaptive immunity
-accelerates tissue repair
What are the risks of a high fever?
-there are changes in the metabolic pathways and denaturation of proteins which causes irreversible brain damage at body temperature greater than 106 degrees F
-death is likely if body temperature is greater than 108 degrees F (109 degrees F)
What constitutes as a high-grade fever?
103-104 degrees F
What constitutes as a dangerous high-grade fever?
over 104 degrees F
What innate cell type is typically the first responder at the sight of infection?
neutrophils (most common and phagocytic)
Adaptive Immunity
- involves specific lymphocyte responses to an antigen
– contact with antigen causes lymphocyte proliferation
– immune response consists of lymphocytes and their products
– longer response time than innate immunity
— since it takes days to develop, adaptive immunity is considered the thrid line of body’s defense - Two branches of adaptive immunity
What are the two branches of adaptive immunity?
- Cell mediated immunity (involving T-lymphocytes)
- Antibody- mediated immunity (involving B-lymphocytes, plasma cells, and antibodies)
T- Lymphocyte
-one of the two branches of adaptive immunity
-effective against antigen within cells; requires antigen- presenting cells
Cells formed following stimulation of T-lymphocytes
Cytotoxic t-lymphocyte and helper t-lymphocyte
Effector Response of T-lymphocyte
- Cytotoxic T-lymphocyte; destroys cells through apoptosis
- Helper T-lymphocyte; releases molecules (e.g. interleukins) that regulate the immune system
B-Lymphocyte
effective against antigen outside cells; does not require antigen- presenting cell
Cells formed following stimulation of B-lymphocytes
plasma cells
Effector Response of B-lymphocyte
produce antibodies
Lymphocyte Classification
-contain a single, large nucleus, a small amount of cytoplasm, and a wide range of proteins expressed on their surface
-B lymphocytes: develop in bone marrow
-T lymphocytes: begin development in bone marrow but complete it in the thymus
– classified by surface proteins referred to as Cluster of Differentiation (CD) markers
Cytotoxic T- lymphocytes
-CD8+ cells (circle shaped)
-release chemicals that destroy other cells
Helper T- lymphocytes
-CD4+ cells (hook shaped)
-assist (“help”) in cell mediated, antibody-mediated, and innate immunity
– for ex. activate NK cells and macrophages
Types of T Cells
-lymphocyte
-Cytotoxic T cells (Tc)
-Memory T cells (Tm)
-Regulatory T cells (Tr)
-Other T cell types
Cytotoxic T cells (Tc)
- designed to destroy virus-infected and tumor cells
- releases perforin, granzymes and granulysin
- expresses CD8 on its surface
Memory T cells (Tm)
carry the memory of antigen exposure after the antigen has left the body
Regulatory T cells (Tr)
- maintain immunological tolerance
- block T cell-mediated immune responses at the end of the response window
Other T cell types
Natural killer T cells, helper T cells, etc
Types of B cells
- Memory B cells
- Plasma B cells
Memory B cells
-carry the memory of previous exposure to antigen
-generated after exposure to antigen by cytokine signaling
Plasma B cells
-long-lived, non-proliferating antibody-secreting cells
-arise after exposure to antigen
Features of Antigens
- pathogens are detected by lymphocytes because they contain antigens
- any molecule has the ability to act as an antigen, but some are more potent than others
–proteins are the most potent, followed by sugars
Antigen definition
anything that can bind to a t-lymphocyte it antibody
Common Antigens
- Components of bacteria
- Viruses
- Pollen
- Animal Dander
- Food
- Drugs
Foreign Antigens
-differ from human body’s molecules
- binds body’s immune components
Self- Antigens
-body’s own molecules
-typically do not bind immune components
-the immune system is generally able to distinguish
- however, in autoimmune disorders, the system reacts to self-antigens as if foreign
What does MHC stand for?
Major Histocompatibility Complex
What is MHC good for?
-they are crucial proteins that help display antigens
- it is the critical means through which cells communicate about what is self versus non-self
MHCI
- expressed on the surface of all cells, except erythrocytes
- docks with CD8 protein on the surface of Tc cells
-display fragments of proteins
If fragments are from _________ _______, immune system recognizes them as “self” and ignores them.
endogenous proteins
If fragments are from an infectious agent, __________ __________ considers the antigen “nonself”.
immune system; it then communicates to cytotoxic t-cells that they should destroy the cell
MHCII
-only expressed on macrophages, B cells, and dendritic cells
-docks with CD4 protein on the surface of Th cells
-antigens that have been phagocytized bind to MHC II proteins, flag helper T cells
-interaction leads to clonal growth of Th cells resulting in stimulating other immune system cells to respond to antigen
Positive and Negative selection of Lymphocytes
the precursor to both B cells and T cells generate cell-surface receptors with up to 10^14 different versions of each receptor generated through DNA recombination
Positive Selection
ensures lymphocytes are able to respond to antigen
Negative Selection
removes lymphocytes that bind strongly to self-antigens
Outcomes of Negative Selection of Lymphocytes
-Receptor Editing
- Anergy
-Apoptosis
-Ignorance
Receptor Editing
change the lymphocyte receptor so it no longer recognizes self antigens (foreign)
Anergy
change the lymphocyte so it is no longer capable of an immune response (neutralize)
Apoptosis
clonal deletion and cell death
Ignorance
continue maturation (autoimmune disease)
_________ selection ensures lymphocytes are able to respond to antigen, and ________ selection removes those that respond to self-antigen.
Positive, Negative
What does Ig stand for?
Immunoglobulin
Antibodies (Immunoglobulin)
(Ig) proteins produced against a particular antigen
- antibodies “tag” pathogens for destruction by immune cells
- good defense against viruses, bacteria, toxins, yeast spores
– soluble antigens are combated by “humoral immunity”
Structure of Ig
- Y-shaped, soluble proteins
- composed of four polypeptide chains
– two identical heavy chains and two identical light chains - flexibility at hinge region of two heavy chains
- two important functional areas, variable and constant regions
Variable Regions
- located at the ends of the antibody “arms”
– contain antigen-binding site (most antibodies have two sites) - Bind antigens through weak intermolecular forces
– hydrogen bonds, ionic bonds, and hydrophobic interactions
Constant Regions
- contains the Fc region (stalk), which determines biological function
- same in structure for antibodies of a given class
- 5 major classes; IgG, IgM, IgA, IgD, IgE
Functions of Antibodies in Adaptive Immunity
- Antigen Neutralization
- Antigen Agglutination
- Antigen Precipitation
- Complement Activation
- Lymphocyte Recruitment and Activation
Antigen Neutralization
covering and blocking the surface of the antigen
Antigen Agglutination
clumping of antigens into larger complexes more readily recognized by macrophages
Antigen Precipitation
bringing antigens out of solution, making them more easily recognized by macrophages
Complement Activation
through Fc region; leading to cell lysis and attraction of other leukocytes
Lymphocyte Recruitment and Activation
no further description
IgG Class
-makes up 75-85% of antibodies in blood
-also predominant antibody in other fluids (ex. Lymph and CSF)
-can participate in all types of antibody actions
-can cross placenta and cause hemolytic disease in newborns (baby seen as foreign because of blood type)
- Y-shaped
- serum levels (mg/ml) 0.5 to 9
- half-life (days) 23 (secondary exposure response)
IgM Class
-found mostly in blood
-most effective at agglutination and binding complement
-responsible for rejection of mismatched transfusions
- circular shaped
- serum levels (mg/ml) 1.5
-generates 1st exposure response
IgA Class
- found in areas exposed to environment
- especially good at agglutination
- produced in mucus, saliva, tears, and breastmilk
- helps prevent pathogens adhering to and penetrating epithelium
- linear shaped
IgD Class
- functions as antigen-specific B-lymphocyte receptor
- identifies when immature B-lymphocytes ready for activation
- Y-shaped
IgE Class
- usually formed in response to parasites and in allergic reactions
- otherwise low rate of synthesis
- causes release of products from basophils and mast cells
- attracts eosinophils
- Y-shaped
Primary Versus Secondary Antibody Responses
-Primary phase begins with IgM
- Secondary phase begins with IgG
- differences are due to presence of memory B cells in secondary response
- antibodies are more rapidly produced in secondary response
Which antibody stays the longest in the body?
IgG
Causes of Autoimmune Diseases
unknown, but may include molecular mimicry, triggering of an immune response that bypasses Th cell involvement, or a deficiency in Tr cells
Treatments of Autoimmune Diseases
immunosuppressive drugs, removal of thymus, plasmapheresis
