1) Small organs associated with lymphatic vessels are termed ________.
A) lymph follicles
B) lymph nodes
C) axillary nodes
D) cisterna chyli
b
2) Which of the following would not be classified as a lymphatic structure?
A) pancreas
B) spleen
C) tonsils
D) Peyer's patches of the intestine
a
3) The distal portion of the small intestine contains clumps of lymph follicles called ________.
A) islets of Langerhans
B) Peyer's patches
C) rugae
D) villi
b
4) Both lymph and venous blood flow are heavily dependent on ________.
A) the pumping action of the heart
B) skeletal muscle contractions and differences in thoracic pressures due to respiratory movement
C) contraction of the vessels themselves
D) two-way
b
5) The thymus is most active during ________.
A) fetal development
B) childhood
C) middle age
D) old age
b
6) Which lymphatic structure drains lymph from the right upper limb and the right side of the head and thorax?
A) lumbar trunk
B) thoracic duct
C) right lymphatic duct
D) cisterna chyli
c
7) What effect does age have on the size of the thymus?
A) The size of the thymus increases continuously from birth to death.
B) The size of the thymus decreases continuously from birth to death.
C) The thymus is not affected by age.
D) The thymus initial
d
8) The lymphatic capillaries are ________.
A) more permeable than blood capillaries
B) less permeable than blood capillaries
C) equally permeable to blood capillaries
D) completely impermeable
a
9) Antibodies that act against a particular foreign substance are released by ________.
A) T lymphocytes
B) plasma cells
C) lymph nodes
D) medullary cords
B
10) Lymph leaves a lymph node via ________.
A) efferent lymphatic vessels
B) afferent lymphatic vessels
C) the cortical sinus
D) the subscapular sinus
A
11) By secreting hormones, the thymus causes what cells to become immunocompetent?
A) basophils
B) lymphocytes
C) macrophages
D) monocytes
B
12) Functions of the spleen include all of those below except ________.
A) removal of old or defective blood cells from the blood
B) crypts that trap bacteria
C) storage of blood platelets
D) storage of iron
B
13) When the lymphatics are blocked due to tumors, the result is ________.
A) shrinkage of tissues distal to the blockage due to inadequate delivery of lymph
B) severe localized edema distal to the blockage
C) increased pressure in the lymphatics proximal
B
14) Select the correct statement about lymph transport.
A) Under normal conditions, lymph vessels are very high-pressure conduits.
B) Lymph transport is faster than that occurring in veins.
C) Lymph transport is only necessary when illness causes tissue s
D
15) Select the correct statement about lymphocytes.
A) The two main types are T cells and macrophages.
B) B cells produce plasma cells, which secrete antibodies into the blood.
C) T cells are the precursors of B cells.
D) T cells are the only form of lymp
B
16) Select the correct statement about lymphoid tissue.
A) Once a lymphocyte enters the lymphoid tissue, it resides there permanently.
B) Lymphoid macrophages secrete antibodies into the blood.
C) Lymphoid tissue is predominantly reticular connective tiss
C
17) A ring of lymphoid tissue that appears as a swelling of the mucosa in the oral cavity is called a(n) ________.
A) tonsil
B) thymus
C) Peyer's patch
D) appendix
A
18) Which is not a mucosa-associated lymphatic tissue?
A) tonsil
B) thymus
C) Peyer's patch
D) appendix
B
19) Peyer's patches are found in the ________.
A) stomach
B) small intestine
C) large intestine
D) spleen
B
20) Lymph collecting or pooling from the lower extremities would first pool in the ________ before moving on up.
A) thoracic duct
B) inguinal nodes
C) cisterna chyli
D) azygos
C
21) What is a bubo?
A) a wall in a lymph node
B) a lobe of the spleen
C) an infected Peyer's patch
D) an infected lymph node
D
22) What is the function of a Hassall's corpuscle?
A) It increases the surface area of the thymic cortex.
B) It assists in the production of lymphocytes.
C) It forms the blood-thymus barrier.
D) It has no known significant function.
D
23) Particularly large clusters of lymph nodes occur in all of the following locations except the ________.
A) inguinal region
B) cervical region
C) axillary region
D) lower extremities
D
24) Digestive tract-associated lymphatic tissue includes all of the following except ________.
A) Peyer's patches
B) palatine tonsils
C) lingual tonsils
D) islets of Langerhans
D
25) Functions of the lymphatic system include ________.
A) transport of excess tissue fluid to the blood vascular system
B) transport of red blood cells to the blood vascular system
C) maintenance of blood pressure in the venous circulation
D) excretion o
A
26) The tonsils located at the base of the tongue are the ________.
A) lingual tonsils
B) palatine tonsils
C) pharyngeal tonsils
D) Peyer's tonsils
A
27) Which of the following is not a normal component of lymph?
A) water
B) plasma proteins
C) red blood cells
D) ions
C
28) A sentinel node is ________.
A) a lymph node found in the intestinal lamina propria
B) the first node at the junction of all the lumbar trunks
C) a small node in the spleen
D) the first node to receive lymph from an area suspected to be cancerous
D
1) Peyer's patches are clusters of lymphoid tissue found primarily in the large intestine.
FALSE
2) The lymphatics function to absorb the excess protein-containing interstitial fluid and return it to the bloodstream
TRUE
3) Lymph always flows away from the heart
FALSE
Lymphatic capillaries are permeable to proteins
TRUE
Digested fats are absorbed from the intestine by the lymph capillaries.
TRUE
Chyle is delivered to the blood via the lymphatic system
TRUE
All lymphoid organs develop from mesoderm
FALSE
About 3 liters of fluid are lost to the tissue spaces every 24 hours and are returned to the bloodstream as lymph
TRUE
Because lymph vessels are very low-pressure conduits, movements of adjacent tissues are important in propelling lymph through the lymphatics
TRUE
Lymphoid tissue is mainly reticular connective tissue
TRUE
) Lymphocytes reside temporarily in lymphoid tissue, then move to other parts of the body.
TRUE
All the lymphoid organs are well developed before birth
FALSE
An infected lymph gland is called a bubo
TRUE
The largest lymphatic vessels are called lacteals
FALSE
The cisterna chyli collects lymph from the lumbar trunks draining the upper limbs and from the intestinal trunk draining the digestive organs
FALSE
) If even a small part of the spleen is left in a ten-year-old child, it will most likely regenerate itself
TRUE
The thymus lacks T cells
FALSE
Immune System
Population of cells that inhabit all of our organs and defend the body from agents of disease; not an organ system
Lymphatic System
Population of cells especially concentrated in the true organ system
Fluid Recovery, Immunity, Lipid Absorption
3 Functions of the Lymphatic System
Lacteals
Lymphatic vessels in the small intestine that absorb dietary lipids that are not absorbed by the blood capillaries
Lymph
Clear, colorless fluid, similar to plasma, but much less protein; recovered fluid of the lymphatic system
Lymphatic Vessels
Transport the lymph from interstial spaces (tissues) to the bloodstream
Nodes, Tonsils, Thymus, Spleen
4 Major Lymphatic Organs
Lymphatic Capillaries - Collecting Vessels - 6 Lymphatic Trunks - 2 Collecting Ducts - Subclavian Veins
Route of Lymph Flow
Cisterna Chyli
Sac in the abdomen that receives lymph; Begins thoracic duct
Thoracic Duct
Left collecting duct that empties into the left subclavian vein
Lymphatic Duct
Right collecting duct that empties into the right subclavian vein
Low Pressure
Causes lymph to flow at a slower speed than venous blood
Exercise
Can significantly increase lymphatic return
Skeletal Muscle Pump
Aids the flow of lymph
NK Cells, T Cells, B Cells, Macrophages, Dendritic Cells, Reticular Cells
6 Types of Lymphatic Cells
Natural Killer Cells
Large lymphocytes that attack and destroy bacteria, transplanted tissue, host cells infected with viruses or have turned cancerous; Responsible for immune surveillance
T Lymphocytes
Lymphatic cells that mature in the thymus and become immunocompetent
B Lymphocytes
Lymphatic cells that when activated causes proliferation and differentiation into plasma cells that produce antibodies
Macrophages
Develop from monocytes; Phagocytize tissue debris, dead neutrophils, bacteria, and other foreign matter; Antigen Presenting Cells
Dendritic Cells
Branched, mobile APCs found in the epidermis, mucous membranes, and lymphatic organs; Alert immune system to pathogens that have breached their surface
Reticular Cells
Branched stationary cells that contribute to the stroma of a lymphatic organ; Act as APCs in the thymus
Lymphatic (Lymphoid) Tissue
Aggregations of lymphocytes in the connective tissues of mucous membranes and various organs
Diffuse Lymphatic Tissue
Lymphocytes are scattered, rather than densely clustered in mucous membranes and connective tissue of many organs; Found in respiratory, digestive mucosa, urinary, and reproductive tracts; Associated with MALT
MALT
Found in digestive layers; Associated with diffuse lymphatic tissue
Lymphatic Nodules
Dense masses of lymphocytes and macrophages that congregate in response to pathogens
Peyer Patches
Dense clusters in the ileum, the distal portion of the small intestine
Primary Lymphatic Organs
Sites where T and B cells become immunocompetent
Red Bone Marrow, Thymus
2 Primary Lymphatic Organs
Immunocompetent
Able to recognize and respond to antigens
Secondary Lymphatic Organs
Immunocompetent cells populate these tissues
Lymph Nodes, Tonsils, Spleen
3 Secondary Lymphatic Organs
Red Bone Marrow
Lymphatic organ involved in hemopoiesis and immunity
Thymus
Member of the endocrine, lymphatic, and immune systems; Houses developing T cells; Goes through involution; Location where T cells become immunocompetent
Lymph Nodes
Most numerous lymphatic organs; Cleanses the lymph and act as a site of T and B cells activation
Tonsils
Patches of lymphatic tissue located at the entrance to the pharynx
Tonsilar Crypts
Deep pits of the tonsils lined with lymphatic nodules where pathogens enter in and encounter lymphocytes
Palatine, Lingual, Pharyngeal (Adenoid)
3 Main Sets of Tonsils
Palatine Tonsils
Pair of tonsils at posterior margin of oral cavity (most often infected) - visible to naked eye
Lingual Tonsils
Pair of tonsils at the root of the tongue
Pharyngeal (Adenoid) Tonsil
Single tonsil on the wall of the nasopharynx; Intercepts inhaled pathogens
Spleen
The body's largest lymphatic organ; Functions in blood production in the fetus, as a blood reservoir, in RBC disposal, and monitors blood for foreign antigens; Highly vascular and vulnerable to trauma and infection
Red Pulp
Sinuses of the spleen filled with erythrocytes
White Pulp
Lymphocytes, macrophages surrounding small branches of splenic artery
Pathogens
Environmental agents capable of producing disease
External Barriers
Make up the first line of defense against pathogens
Second Line of Defense
Nonspecific defense mechanisms; Leukocytes and macrophages, antimicrobial proteins (lysozymes), immune surveillance, inflammation, stomach acid, and fever
Third Line of Defense
The immune system; results from prior exposure, defeats specific pathogen, and leaves the body a 'memory' of it so it can defeat it faster in the future (vaccine)
Nonspecific Resistance
Guards equally against a broad range of pathogens; effectiveness does not depend on prior exposure (first and second lines of defense)
Immunity
Specific defense because it results from prior exposure to a pathogen; usually provides future protection only against that particular one (vaccine)
Acid Mantle
Thin film of lactic acid from sweat which inhibits bacterial growth
Lysozyme
Enzyme that destroys bacterial cell walls
Phagocytes
Phagocytic cells with voracious appetite for foreign matter
Neutrophils
Highly mobile phagocytes that water in connective tissue killing bacteria; Create a killing zone by degranulation and respiratory burst
Degranulation
Lysosomes discharge contents into tissue fluid
Respiratory Burst
Neutrophils rapidly absorb oxygen and creates toxic chemicals
Eosinophils
Phagocytes that stand guard against parasites and allergens; Limit action of histamine and other inflammatory chemicals; Found in mucous membranes
Basophils
Phagocytes that secrete histamine and heparin
Histamine
Vasodilator secreted by basophils
Heparin
Inhibits the formation of clots; Anticoagulant secreted by basophils
Leukotrienes
Activate and attract neutrophils and eosinophils
Lymphocytes
T cells, B cells, and NK cells
Monocytes
Emigrate from the blood into the connective tissue and transform into macrophages
Interferons, Complement System
Two Families of Antimicrobial Proteins
Interferons
Secreted by certain cells infected by viruses; Alert neighboring cells (NK cells and macrophages) and protect them from becoming infected
Complement System
A group of 30 or more globular proteins that make powerful contributions to both nonspecific resistance and specific immunity
Classical, Alternative, Lectin
3 Routes of Complement Activation
Classical Pathway
Route of the complement activation that requires an antibody molecule to get started; Part of specific immunity
Alternative Pathway, Lectin Pathway
Routes of the complement activation that are nonspecific and do not require an antibody
Inflammation, Immune Clearance, Phagocytosis, Cytolysis
4 Mechanisms of Action of Complement Proteins
Immune Clearance
Macrophages of the liver and spleen strip off and destroy the Ag-Ab complexes leaving RBCs unharmed (clearing foreign antigens from the bloodstream)
Opsonization
Coats microbial cells and serves as binding sites for phagocyte attachment (aids in phagocytosis by making the foreign cell more appetizing)
Cytolysis
Mechanism of complement system that forms a hole in the target cell, electrolytes leak out, water flows in rapidly and the cell ruptures
Immune Surveillance
Process in which natural killer cells release perforins that form a hole in the target cells plasma membrane and secrete granzymes that induce apoptosis
Perforins
Proteins that polymerize a ring and create a hole in the plasma membrane of a target cell
Granzymes
Degrading enzymes that induce apoptosis
Fever
An abnormally elevation of body temperature; Stimulates neurons in the hypothalamus that raises the set point for body temperature
Pyrogens
Fever producing agents
Onset, Stadium, Defervescence
3 Stages of Fever
Inflammation
Local defensive response to tissue injury of any kind, including trauma and infection
Redness, Swelling, Heat, Pain
4 Cardinal Signs of Inflammation
Cytokines
Class of chemicals that regulate inflammation and immunity
Mobilization, Containment, Tissue Cleanup
3 Stages of Inflammation
Margination
Adhesion of the leukocytes to the vessel wall; Occurs during inflammation
Diapedesis (Emigration)
Leukocytes squeeze through gaps in the endothelial cells and enter tissue fluid; Occurs during inflammation
Specificity, Memory
2 Characteristics that Distinguish Immunity from Nonspecific Resistance
Cellular, Humoral
2 Types of Immunity
Natural Active Immunity
Production of one's own antibodies or T cells as a result of infection or natural exposure to an antigen
Artificial Active Immunity
Production of one's own antibodies or T cells as a result of vaccination against disease
Natural Passive Immunity
Temporary immunity that results from antibodies produced by another person; Fetus acquires antibodies from mother through placenta
Artificial Passive Immunity
Temporary immunity that results from the injection of immune serum from another person or animal; Antivenum for a snake bite
Antigen
Any molecule that triggers an immune response; Complex molecule with structures unique to the individual
Epitopes
Certain regions of an antigen molecule that stimulate immune responses
Clonal Deletion, Anergy
2 Forms of Negative Selection
Clonal Deletion
Self-reactive T cells die and macrophages phagocytize them (Negative Selection)
Anergy
Self-reactive T cells remain alive but unresponsive (Negative Selection)
Positive Selection
2% of T cells that pass the test multiply to form clones of identical T cells programmed to respond to a specific antigen
MHC Proteins
Act as cell 'identification tags' that label every cell of your body as belonging to you
Cellular Immunity
A form of specific defense in which the T lymphocytes directly attack and destroy diseased or foreign cells, and the immune system remembers the antigens and prevents them from causing disease in the future
Cytotoxic, Helper, Regulatory, Memory
4 Classes of T Cells Involved in Cellular Immunity
Cytotoxic T Cells
Killer T cells, carry out attack on enemy cells
Helper T Cells
Help promote cytotoxic T cell and B cell action and nonspecific resistance
Regulatory T Cells
Inhibit multiplication and cytokine secretion by other T cells; Limit immune response
Memory Cells
Responsible for memory in cellular immunity for future exposure to an antigen
Recognition, Attack, Memory
3 Stages of Both Cellular and Humoral Immunity
Recognition
Phase of immunity that includes antigen presentation and T cell activation
Attack
Phase of immunity in which the helper T cells secrete interleukins that attract neutrophils, NK cells, and macrophages; Cytotoxic cells deliver a lethal hit of toxic chemicals
Costimulation
The double checking of the T ell to see if it is really bound to a foreign antigen
Memory
Phase of immunity in which some cytotoxic and helper T cells develop a recall so as to issue a quick attack upon re-exposure to the same pathogen later in life
Humoral Immunity
Indirect method of specific immunity in which B lymphocytes produce antibodies that bind to antigens and tag them for destruction by other means
Immunoglobulin
A defensive gamma globulin found in the blood-plasma, tissue fluids, body secretions, and some leukocyte membranes; Antibody
Antibody Monomer
Basic structural unit of an antibody; Composed of four polypeptide chains: two larger heavy chains and two light chains
IgA
Monomer in plasma; Provides passive immunity to newborns
IgD
Monomer which functions in B cell activation
IgE
Monomer that stimulates the release of histamine and other chemical mediators of inflammation
IgG
Monomer that constitutes 80% of circulating antibodies
IgM
Largest antibodies; Secreted in primary immune response, agglutination, and complement fixation
Lymphatic System
Resistance to disease and has two intrinsic systems:
� Innate (nonspecific) defense system
� Adaptive (specific) defense system
Innate Defense System
Two lines of defense
� First line of defense is external body membranes (skin and mucosae)
� Second line of defense is antimicrobial proteins, phagocytes, and other cells by: Inhibit spread of invaders
Inflammation is its most important
mechanism
Adaptive Defense System
Third line of defense attacks particular
foreign substances by:
Takes longer to react than the innate system and innate and adaptive defenses are deeply intertwined.
Surface Barriers
Part of internal defense by the Skin, mucous membranes, and their secretions by physical barrier to most microorganisms, keratin is resistant to weak acids and bases, bacterial enzymes, and toxins and mucosae provide similar mechanical barriers plus Prote
Respiratory System Modifications
Mucus-coated hairs in the nose and cilia of upper respiratory tract sweep dust- and bacteria-laden mucus from lower respiratory passages.
Internal Defenses: Cells and Chemicals
Necessary if microorganisms invade deeper tissues by:
� Phagocytes
� Natural killer (NK) cells
� Inflammatory response (macrophages, mast cells, WBCs, and inflammatory chemicals)
� Antimicrobial proteins (interferons and complement proteins)
� Fever
Phagocytes: Macrophages
Develop from monocytes to become the chief phagocytic cells
Free macrophages wander through tissue spaces
� E.g., alveolar macrophages
Fixed macrophages are permanent
residents of some organs
� E.g., Kupffer cells (liver) and microglia (brain)
Neutrophils
Become phagocytic on encountering infectious material in tissues.
Adherence of Phagocyte to Pathogen
Facilitated by opsonization�coating of pathogen by complement proteins or antibodies.
Destruction of Pathogens
Acidification and digestion by lysosomal
enzymes by:
� Respiratory burst
� Release of cell-killing free radicals
� Activation of additional enzymes
� Oxidizing chemicals (e.g. H2O2)
� Defensins (in neutrophils)
Natural Killer (NK) Cells
Large granular lymphocytes, target cells that lack "self" cell-surface
receptors, induce apoptosis in cancer cells and virus- infected cells, and secrete potent chemicals that enhance the inflammatory response.
Inflammatory Response
Triggered whenever body tissues are injured or infected, prevents the spread of damaging agents, disposes of cell debris and pathogens, sets the stage for repair, Cardinal signs of acute inflammation:
1. Redness
2. Heat
3. Swelling
4. Pain
(And sometimes
Toll-Like Receptors (TLR)
Macrophages and epithelial cells of boundary tissues bear this and recognize specific classes of infecting microbes
by activated this trigger the release of cytokines that promote inflammation.
Inflammatory Mediators
� Histamine (from mast cells)
� Blood proteins
� Kinins, prostaglandins (PGs), leukotrienes, and complement
Released by injured tissue, phagocytes, lymphocytes, basophils, and mast cells.
Inflammatory Chemicals
This cause:
� Dilation of arterioles, resulting in hyperemia
� Increased permeability of local capillaries and edema (leakage of exudate)
Exudate contains proteins, clotting factors, and antibodies.
Edema
Moves foreign material into lymphatic vessels and delivers clotting proteins to form a scaffold for repair and to isolate the area.
Phagocyte Mobilization
Neutrophils, then phagocytes flood to inflamed sites.
Leukocytes
Neutrophils enter blood from bone marrow.
Margination
Neutrophils cling to capillary wall, clinging of phagocytic cells to inner wall of capillaries.
Diapedesis
Neutrophils flatten and squeeze out of capillaries, phagocytes squeeze through the capillary endothelium.
Chemotaxis
Neutrophils follow chemical trail, white blood cells migrate to the site of tissue damage.
Interferons (IFNs)
Complement proteins that attack microorganisms directly and hinder microorganisms' ability to reproduce, Viral-infected cells are activated to
secrete this by enter neighboring cells, neighboring cells produce antiviral proteins that block viral reproduct
Gamma (?)
Lymphocyte produce this.
Alpha (?) Interferon
Most other WBC's produce this.
Beta (?) Interferon
Fibroblasts produce this.
Complement
~20 blood proteins that circulate in an inactive form, include C1-C9, factors B, D, and P, and regulatory proteins, major mechanism for destroying foreign substances, amplifies all aspects of the inflammatory response, kills bacteria and certain other cel
Classical Pathway
Antibodies bind to invading organisms and C1 binds to the antigen-antibody complexes (complement fixation).
Alternate Pathway
Triggered when activated C3, B, D, and P interact on the surface of microorganisms.
Complement Activation
Each pathway involves activation of proteins in an orderly sequence, each step catalyzes the next, both pathways converge on C3, which cleaves into C3a and C3b, enhances inflammation, promotes phagocytosis, causes cell lysis, C3b initiates formation of a
Fever
Systemic response to invading microorganisms, leukocytes and macrophages exposed to foreign substances secrete pyrogens, reset the body's thermostat upward, high fevers are dangerous because heat denatures enzymes, benefits of moderate fever, causes the l
Adaptive Immune System
Protects against infectious agents and abnormal body cells, amplifies the inflammatory response, activates complement, and specific defense.
Adaptive Immune Response
Is specific, systemic, and has memory.
Antigens
Substances that can mobilize the adaptive defenses and provoke an immune response and most are large, complex molecules not normally found in the body (nonself).
Immunogenicity
Ability to stimulate proliferation of specific lymphocytes and antibodies.
Reactivity
Ability to react with products of activated lymphocytes and antibodies released.
Haptens (Incomplete Antigens)
Small molecules (peptides, nucleotides, and hormones), not immunogenic by themselves, are immunogenic when attached to body proteins, cause the immune system to mount a harmful attack.
Ex: Poison ivy, animal dander, detergents, and cosmetics.
Antigenic Determinants
Certain parts of an entire antigen that are immunogenic and antibodies and lymphocyte receptors bind to them.
Most naturally occurring antigens have numerous antigenic determinants that:
Mobilize several different lymphocyte populations, form different ki
Self-Antigens: MHC Proteins
Protein molecules (self-antigens) on the surface of cells, antigenic to others in transfusions or grafts (example: MHC proteins) coded for by genes of the major histocompatibility complex (MHC) and are unique to an individual.
Class I MHC Proteins
Found on virtually all body cells (except RBC)
Class II MHC Proteins
Found on certain cells in the immune response, antigen-presenting cells.
B Lymphocytes
(B Cells) Humoral Immunity in Red Bone
T Lymphocytes
(T Cells) Cell-Mediated Immunity in Thymus
Antigen-Presenting Cells (APCs)
Do not respond to specific antigens and play essential auxiliary roles in immunity.
Immunocompetence
Able to recognize and bind to a specific antigen.
Self-Tolerance
Unresponsive to self antigens and property of lymphocytes that prevents them from attacking the body's own cells.
Naive (Unexposed)
B and T cells are exported to lymph nodes, spleen, and other lymphoid organs.
T Cells
Mature in the thymus under negative and positive selection pressures, positive selection, selects T cells capable of binding to self-MHC proteins (MHC restriction), negative selection, prompts apoptosis of T cells that bind to self-antigens displayed by s
B Cells
Mature in red bone marrow, Self-reactive B cells, are eliminated by apoptosis (clonal deletion) or undergo receptor editing - rearrangement of their receptors are inactivated (anergy) if they escape from the bone marrow, involved in adaptive immunity.
Antigen Receptor Diversity
Lymphocytes make up to a billion different types of antigen receptors is coded for by ~25,000 genes, gene segments are shuffled by somatic recombination, genes determine which foreign substances the immune system will recognize and resist.
Antigen-Presenting Cells (APCs)
Engulf antigens, present fragments of antigens to be recognized by T cells.
Major types:
Dendritic cells in connective tissues and epidermis, macrophages in connective tissues and lymphoid, organs, and B cells.
Present Antigen and Activate T Cells
Macrophages mostly remain fixed in the lymphoid organs dendritic cells internalize pathogens and enter lymphatics to present the antigens to T cells in lymphoid organs.
Activated T Cells
Release chemicals that:
Prod macrophages to become insatiable phagocytes and to secrete bactericidal chemicals.
Antigen Challenge
First encounter between an antigen and a
naive immunocompetent lymphocyte
plus usually occurs in the spleen or a lymph node.
Lymphocyte is a B Cell
The antigen provokes a humoral immune
response and antibodies are produced.
Red Bone Marrow and place where T and B Cells are born at
A.
Thymus and is immunocompetent with T Cells
B.
Bone Marrow and is immunocompetent with B Cells
C.
Lymph Nodes and help with clone selection and with both B and T cells
D.
Capillaries and Recirculate
E.
Clonal Selection
1. B cell is activated when antigens bind to its surface receptors and cross-link them
2. Receptor-mediated endocytosis of cross- linked antigen-receptor complexes occurs
3. Stimulated B cell grows to form a clone of identical cells bearing the same antig
Fate of Clone Cells
Most clone cells become plasma cells that secrete specific antibodies at the rate of 2,000 molecules per second for four to five days.
Secreted antibodies by: circulate in blood or lymph, bind to free antigens, and mark the antigens for destruction.
Clone Cells that do not become plasma cells
Become memory cells that provide immunological memory and mount an immediate response to future exposures of the same antigen.
Primary Immune Response
Occurs on the first exposure to a specific
antigen, lag period: three to six days, peak levels of plasma antibody are reached in 10 days, antibody levels then decline.
Secondary Immune Response
Occurs on re-exposure to the same antigen, sensitized memory cells respond within hours, antibody levels peak in two to three days at much higher levels, antibodies bind with greater affinity, antibody level can remain high for weeks to months plus last l
Active Humoral Immunity
Occurs when B cells encounter antigens and produce specific antibodies against them.
Active Naturally Acquired
Response to a bacterial or viral infection.
Active Artificially Acquired
Response to a vaccine of dead or attenuated pathogens.
Vaccines
Spare us the symptoms of the primary response,
provide antigenic determinants that are immunogenic and reactive, target only one type of helper T cell, so fail to fully establish cellular immunological memory.
Passive Naturally Acquired
Antibodies delivered to a fetus via the placenta or to infant through milk.
Passive Artificially Acquired
Injection of serum, such as gamma globulin and protection is immediate but ends when antibodies naturally degrade in the body.
Immunoglobulins
Gamma globulin portion of blood, protein secreted by plasma cells and capable of binding specifically with antigen detected by B cells.
T or Y Shaped Monomer
Of 4 looping linked polypeptide chains, two identical heavy chains and two identical light chains and variable regions of each arm combine to form two identical antigen-binding sites.
Constant Region
Of stem determines: the antibody class, cells and chemical that the antibody can bind to, and how the antibody class functions in antigen elimination.
Antigen-Binding Site
A.
Heavy Chain
B.
Light Chain
C.
Hinge Region
D.
Stem Region
E.
IgD
Monomer attached to the surface of B cells and functions as a B cell receptor, and pump plus antigen receptor found on B cells.
IgM
A pentamer; first antibody released, potent agglutinating agent, readily fixes and activates complement, largest, medics of the first responders.
IgA
Monomer or dimer; in mucus and other
secretions, helps prevent entry of pathogens, and in all body fluids.
IgG
Monomer; 75-85% of antibodies in plasma, from secondary and late primary responses, crosses the placental barrier, abundant, and cross placenta barrier plus most abundant class of antibodies.
IgE
Monomer active in some allergies and
parasitic infections and causes mast cells and basophils to release histamine.
Generating Antibody Diversity
Billions of antibodies result from somatic recombination of gene segments, hypervariable regions of some genes increase antibody variation through somatic mutations, and each plasma cell can switch the type of H chain produced, making an antibody of a dif
Antibody Targets
Antibodies inactivate and tag antigens, form antigen-antibody (immune) complexes, defensive mechanisms used by antibodies, neutralization and agglutination (the two most important), and precipitation and complement fixation.
Neutralization
Simplest mechanism, antibodies block specific sites on viruses or bacterial exotoxins, prevent these antigens from binding to receptors on tissue cells, and antigen-antibody complexes undergo phagocytosis.
Agglutination
Antibodies bind the same determinant on more than one cell-bound antigen and cross-linked antigen-antibody complexes agglutinate.
Example: clumping of mismatched blood cells
Precipitation
Soluble molecules are cross-linked and complexes precipitate and are subject to
phagocytosis.
Complement Fixation and Activation
Main antibody defense against cellular antigens, several antibodies bind close together on a cellular antigen, their complement-binding sites trigger complement fixation into the cell's surface, complement triggers cell lysis, activated complement functio
Monoclonal Antibodies
Commercially prepared pure antibody, produced by hybridomas, cell hybrids: fusion of a tumor cell and a B cell, proliferate indefinitely and have the ability to
produce a single type of antibody; used in research, clinical testing, and cancer treatment.
Cell-Mediated Immune Response
T cells provide defense against intracellular antigens, two types of surface receptors of T cells, T cell antigen receptors:
� Cell differentiation glycoproteins
� CD4 or CD8
� Play a role in T cell interactions with other
cells
CD4
Cells become helper T cells (TH) when activated.
CD8
Cells become cytotoxic T cells (TC) that destroy cells harboring foreign antigens.
Other Type of T Cells
Regulatory T cells (TREG) and memory T cells.
Antibodies of the Humoral Response
The simplest ammunition of the immune
response
Targets:
Bacteria and molecules in extracellular environments (body secretions, tissue fluid, blood, and lymph).
T Cells of the Cell-Mediated Response
Recognize and respond only to processed fragments of antigen displayed on the surface of body cells
Targets
� Body cells infected by viruses or bacteria
� Abnormal or cancerous cells
� Cells of infused or transplanted foreign tissue
Immunocompetent T Cells
Are activated when their surface receptors bind to a recognized antigen (nonself)
T cells must simultaneously recognize, nonself (the antigen), self (an MHC protein of a body cell).
Both Types of MHC Proteins
Synthesized at the ER and bind to peptide fragments.
Class I MHC Proteins
Displayed by all cells except RBCs, bind with fragment of a protein synthesized in the cell (endogenous antigen), endogenous antigen is a self-antigen in a normal cell; a nonself antigen in an infected or abnormal cell, informs cytotoxic T cells of the pr
Class II MHC Proteins
Dsplayed by APCs (dendritic cells, macrophages and B cells), bind with fragments of exogenous antigens that have been engulfed and broken down in a phagolysosome, and recognized by helper T cells.
T Cell Activation
APCs (most often a dendritic cell) migrate to lymph nodes and other lymphoid tissues to present their antigens to T cells
T cell activation is a two-step process:
1. Antigen binding
2. Co-stimulation
T Cell Activation: Antigen Binding
CD4 and CD8 cells bind to different classes of MHC proteins (MHC restriction), CD4 cells bind to antigen linked to class II MHC proteins of APCs, CD8 cells are activated by antigen fragments linked to class I MHC of APCs, TCR that recognizes the nonself-s
Dendritic Cells
Are able to obtain other cells' endogenous antigens by
� Engulfing dying virus-infected or tumor cells
� Importing antigens through temporary gap
junctions with infected cells
They then display the endogenous antigens on both class I and class II MHCs.
T Cell Activation: Co-Stimulation
Requires T cell binding to other surface receptors on an APC, dendritic cells and macrophages produce surface B7 proteins when innate defenses are mobilized, and B7 binding with a CD28 receptor on a T cell is a crucial co-stimulatory signal.
Without Co-Stimulation
Anergy occurs by T cells because:
� Become tolerant to that antigen
� Are unable to divide
� Do not secrete cytokines
T Cells that are Activated
Enlarge, proliferate, and form clones plus differentiate and perform functions according to their T cell class.
Primary T Cells
Response peaks within a week, T cell apoptosis occurs between days 7 and
30, effector activity wanes as the amount of antigen declines, benefit of apoptosis: activated T cells are a hazard, memory T cells remain and mediate secondary responses.
Cytokines
Mediate cell development, differentiation, and responses in the immune system plus include interleukins and interferons.
Interleukin 1
(IL-1) released by macrophages
co-stimulates bound T cells to:
� Release interleukin 2 (IL-2)
� Synthesize more IL-2 receptors
Interleukin 2
IL-2 is a key growth factor, acting on cells that release it and other T cells:
Encourages activated T cells to divide rapidly, used therapeutically to treat melanoma and kidney cancers, and other cytokines amplify and regulate innate and adaptive respons
Roles of Helper T(TH) Cells
� Play a central role in the adaptive immune response, once primed by APC presentation of antigen, they:
� Help activate T and B cells
� Induce T and B cell proliferation
�Activate macrophages and recruit other immune cells
� Without TH, there is no immun
Helper T Cells
� Interact directly with B cells displaying antigen fragments bound to MHC II receptors
� Stimulate B cells to divide more rapidly and begin antibody formation
� B cells may be activated without TH cells by binding to T cell-independent antigens
� Most an
Roles of Cytotoxic T(TC) Cells
� Directly attack and kill other cells
� Activated TC cells circulate in blood and lymph and lymphoid organs in search of body cells displaying antigen they recognize
Targets:
� Virus-infected cells
� Cells with intracellular bacteria or parasites
� Cance
Cytotoxic T Cells
Bind to a self-nonself complex and can destroy all infected or abnormal cells.
Lethal Hit- Tc cell releases perforins and granzymes by exocytosis, perforins create pores through which granzymes enter the target cell, granzymes stimulate apoptosis
� In som
Natural Killer Cells
Recognize other signs of abnormality:
� Lack of class I MHC
� Antibody coating a target cell
� Different surface marker on stressed cells
� Use the same key mechanisms as Tc cells for killing their target cells
Regulatory T (TReg) Cells
Dampen the immune response by direct contact or by inhibitory cytokines and important in preventing autoimmune reactions.
Autografts
From one body site to another in
the same person.
Isografts
Between identical twins.
Allografts
Between individuals who are not identical twins.
Xenografts
From another animal species.
Prevention of Rejection
� Depends on the similarity of the tissues
� Patient is treated with immunosuppressive
therapy
� Corticosteroid drugs to suppress inflammation
� Antiproliferative drugs
� Immunosuppressant drugs
� Many of these have severe side effects
Immunodeficiencies
Congenital and acquired conditions that cause immune cells, phagocytes, or complement to behave abnormally.
Severe Combined Immunodeficiency (SCID) Syndrome
� Genetic defect
� Marked deficit in B and T cells
� Abnormalities in interleukin receptors
� Defective adenosine deaminase (ADA) enzyme
� Metabolites lethal to T cells accumulate
� This is fatal if untreated; treatment is with bone marrow transplants
Hodgkin's Disease
� An acquired immunodeficiency
� Cancer of the B cells
� Leads to immunodeficiency by depressing lymph node cells
Acquired Immune Deficiency Syndrome (AIDS)
� Cripples the immune system by interfering with the activity of helper T cells
� Characterized by severe weight loss, night sweats, and swollen lymph nodes
� Opportunistic infections occur, including pneumocystis pneumonia and Kaposi's sarcoma
Human Immunodeficiency Virus (HIV)
AIDS is caused by this transmitted via body fluids�blood, semen, and vaginal secretions
� HIV enters the body via
� Blood transfusions
� Blood-contaminated needles
� Sexual intercourse and oral sex
� HIV
� Destroys TH cells
� Depresses cell-mediated immun
Making of AIDS
� HIV multiplies in lymph nodes throughout the asymptomatic period
� Symptoms appear in a few months to 10 years
� HIV-coated glycoprotein complex attaches to the
CD4 receptor
� HIV enters the cell and uses reverse transcriptase to produce DNA from viral
Autoimmune Diseases
� Immune system loses the ability to distinguish self from foreign
� Production of autoantibodies and sensitized TC cells that destroy body tissues
� Examples include multiple sclerosis, myasthenia gravis, Graves' disease, type I diabetes mellitus, system
Mechanisms of Autoimmune Diseases
1. Foreign antigens may resemble self-antigens and antibodies against the foreign antigen may cross- react with self-antigen.
2. New self-antigens may appear, generated by Gene mutations
Changes in self-antigens by hapten attachment or as a result of infe
Hypersensitivities
� Immune responses to a perceived (otherwise harmless) threat
� Causes tissue damage
� Different types are distinguished by
� Their time course
� Whether antibodies or T cells are involved
� Antibodies cause immediate and subacute
hypersensitivities
� T c
Acute (Type I) Reactions
� Hypersensitivities (allergies) begin in seconds after contact with allergen
� Initial contact is asymptomatic but sensitizes the person
� Reaction may be local or systemic
� The mechanism involves IL-4 secreted by T cells
� IL-4 stimulates B cells to pr
Subacute Hypersensitivities
Caused by IgM and IgG transferred via blood plasma or serum and slow onset (1-3 hours) and long duration (10-15 hours).
Cytoxic (Type II) Reactions
�Antibodies bind to antigens on specific body cells, stimulating phagocytosis and complement-mediated lysis of the cellular antigens
�Example:mismatched blood transfusion reaction
Immune Complex (Type III) Hypersensitivity
� Antigens are widely distributed through the
body or blood
� Insoluble antigen-antibody complexes form
� Complexes cannot be cleared from a particular area of the body
� Intense inflammation, local cell lysis, and death may result
� Example: systemic lup
Delayed Hypersensitivities
� Slow onset (one to three days)
� Mechanism depends on helper T cells
� Cytokine-activated macrophages and cytotoxic T cells cause damage
� Example: allergic contact dermatitis (e.g., poison ivy)
Bacterial Infection
Increase in Neutrophil
Peyer's Patches
Small intestine (end part of ilium).
Lacteal
Fats absorbed in lymph capillaries.
Chyle
Delivered to blood via lymphatic system.
3 Liters
Lost to tissues every 24 hours returned to the bloodstream.
Tissue Injury
First Step in Inflammation
Leukocytosis
An increase in the number of white blood cells that are in circulation.
Humoral Immunity
Provided by antibodies
Bone Marrow
Where self-reactive B cells are eliminated at.
Rheumatoid Arthritis
Autoimmune Disorder
Immediate Hypersensitivity
Allergy