chapter 22: the lymphatic system and immunity 2/18/20091

Chapter 22: The Lymphatic System and Immunity

2/18/2009 1

Three Parts or Sections

I. Lymphatics in general

II. Innate or nonspecific immunity

III. Adaptive or specific/memory immunity

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Immunity or Resistance

Ability to ward off damage or disease through our defenses

2 types of immunity Innate or nonspecific immunity – present at birth

No specific recognition of invaders, no memory component

1st and 2nd line of defenses Adaptive or specific immunity

Specific recognition of invaders with a memory component

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Lack of resistance is also known as: Pathogenic Innate Specific Susceptibility Lymphatic

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I. Lymphatic system structure and function

Consists of lymph, lymphatic vessels, structures and organs containing lymphatic tissue, red bone marrow

Functions of the lymphatic system1. Drain excess interstitial fluid

2. Transport dietary lipid and lipid soluble vitamins (K, E, D, and A)

3. Carry our immune responses

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Which of the following is not a function of the lymphatic and immune system? Draining excess interstitial fluid Maintaining water homeostasis in the body Transporting dietary lipids Carrying out immune responses

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What is the major difference between lymph and interstitial fluid? Composition of electrolytes White blood cells are present in lymph Location Types of proteins present Red blood cells are present in interstitial fluid

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Components of the Lymphatic System

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Lymphatic vessels and lymph circulation

Vessels begin as lymphatic capillaries Closed at one end

Unite to form large lymphatic vessels Resemble veins in structure but thinner walls

and more valves Passes through lymph nodes

Encapsulated organs with aggregates of B and T cells

Lymphatic capillaries are found throughout the body except in avascular tissue, the CNS, portions of the spleen, and red bone marrow.

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Lymphatic capillaries

Slightly large diameter that blood capillaries Unique one-way structure Permits interstitial fluid to flow in but not out Anchoring filaments pull openings wider

when interstitial fluid accumulates Small intestine has lacteal for dietary lipid

uptake Chyle is lymph with lipids

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What causes lymph from the small intestines to appear white? Proteins WBC RBC Lipids Fats

This is known as ________________.

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Lymphatic Capillaries

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Describe how lymphatic capillaries are one-way only vessels.

Ans: The ends of the endothelial cells in the wall of the lymphatic capillary overlap. When pressure is higher in the interstitial fluid than in the lymph, the cells separate slightly allowing interstitial fluid into the vessel. When pressure is greater inside, the cells are tightly packed, not allowing the lymph to cross back into the interstitial fluid.

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Lymph trunks and ducts

Vessels unite to form lymph trunks Principal trunks are the lumbar, intestinal,

bronchomediastinal, subclavian and jugular

Passes from lymph trunks into 2 main channels (thoracic and right lymphatic ducts) before draining into venous blood (subclavian veins)

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Routes for drainage of lymph

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The left subclavian vein receives lymph from Left axillary vein Lumbar trunk Jugular trunk Thoracic duct Right lymphatic duct

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Formation and flow of lymph – Starling’s Law

More fluid filters out of blood capillaries than returns to them by reabsorption

Excess filtered fluid – about 3L/day – drains into lymphatic vessels and become lymph

Important function of lymphatic vessels to return lost plasma proteins to blood stream

Contain valves Same 2 “pumps” aiding venous return also used

Skeletal muscle pump – milking action Respiratory pump – pressure changes during breathing

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What is/are important function(s) of the lymphatics?

1. Drain excess interstitial fluid

2. Transport dietary lipid

3. Carry our immune responses

4. Important function of lymphatic vessels to return lost plasma proteins to blood stream

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How is lymph moved? Valves Skeletal muscle pump Respiratory pump Venoconstriction

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The skeletal muscle and respiratory pumps are used in Lymphatic system Cardiovascular system Immune system Lymphatic and Immune systems only Lymphatic, Immune and Cardiovascular

systems

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Define Starlings Law: More fluid filters out of blood capillaries

than returns to them by reabsorption Excess filtered fluid – about 3L/day –

drains into lymphatic vessels and become lymph

85% of interstitial fluid is reabsorbed by the capillaries.

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The lymph from the right foot empties into the Left axillary vein Lumbar trunk Jugular trunk Thoracic duct Right lymphatic duct

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Describe how edema can form.

Ans: Edema can form by obstruction to lymph

flow or increased capillary blood pressure causing interstitial fluid to form faster than it is reabsorbed.

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Relationship of the Lymphatic System to the Cardiovascular System

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Lymphatic tissues and organs

2 groups based on function

1. Primary lymphatic organs Sites where stem cells divide and become

immunocompetent Red bone marrow and thymus

2. Secondary lymphatic organs Sites where most immune response occurs Lymph nodes, spleen, lymphatic nodules

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Define primary lymphatic organ: Sites where stem cells divide and become immunocompetent

List primary lymphatic organs: Red bone marrow and thymus

Define secondary lymphatic organ: Sites where most immune response occurs

List secondary lymphatic organs: Lymph nodes, spleen, lymphatic nodules

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Thymus

Thymus Outer cortex composed of large number of T cells

Immature T cells migrate here from red bone marrow where they proliferate and begin to mature - THYMOSIN

Dendritic cells derived from monocytes assist in T cell maturation

Specialized epithelial cells help educate T cells through positive selection – only about 25% survive – HASSALLS CORPUSCLES

Macrophages clear out dead and dying cells Medulla

More mature T cells migrate here from cortex More epithelial cells, dendritic cells and macrophages

Thymus shrinks with age from 70g in infants to 3g in old age

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Thymus

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Which of the below produces the hormone that promotes maturation of T cells? Spleen Lymph node Red bone marrow Thymus Pancreas

What is the hormone?

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In the thymus, where is it speculated that T cells die? Capsule Trabeculae Epithelial cells Hassall’s corpuscles T cells do not die in the thymus

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Lymph nodes

Located along lymphatic vessels Scattered throughout body Stroma – supporting connective tissue

Capsule, trabeculae, reticular fibers and fibroblasts Parenchyma – functional part

Outer cortex – aggregates of B cells called lymphatic nodules (follicles) – site of plasma cell and memory B cell formation

Inner cortex – mainly T cells and dendritic cells Medulla – B cells, antibody producing plasma

cells from cortex, and macrophages; some follicles

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Structure of a Lymph Node

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This portion of the lymph node does not contain any lymphatic nodules. Inner cortex Outer cortex Medulla Sinuses Trabeculae

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Lymph

Lymph flows through a node in 1 direction only Enters through afferent lymphatic vessels Directs lymph inward Lymph enters sinuses (irregular channels) Into medulla Medullary sinuses drain into efferent lymphatic vessels Conveys lymph, antibodies and activated T cells out of the

node Lymph nodes function as a filter

Foreign substances trapped Destroyed by macrophages or immune response of

lymphocytes

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Spleen

Largest single mass of lymphatic tissue in the body

Stroma – capsule, trabeculae, reticular fibers, and fibroblasts

Parenchyma White pulp – lymphatic tissue (lymphocytes

and macrophages) B cells and T cells carry out immune

function Red pulp

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Red Pulp

Red pulp – blood-filled venous sinuses and splenic (Bilroth’s) cords – red blood cells, macrophages, lymphocytes, plasma cells, and granulocytes1. Macrophages remove ruptured, worn out or

defective blood cells

2. Storage of up to 1/3 of body’s platelet supply

3. Production of blood cells during fetal life

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Structure of the Spleen

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Which of the following is a function of the spleen? Removes worn out blood cells Circulates lymph Cleanses interstitial fluid Cleanses lymph Traps microbes with mucus

List the other functions of the spleen. (Don’t forget white pulp!)

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Lymphatic nodules

Not surrounded by a capsule Scattered throughout lamina propria of

mucous membranes lining GI, urinary, reproductive tract

Mucosa-associated lymphatic tissue (MALT)

Most small and solitary Some larger – tonsils, Peyer’s patches,

appendix

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What is a lymphatic nodule? Not surrounded by a capsule

List sites of lymphatic nodules: Scattered throughout lamina propria of mucous

membranes lining GI, urinary, reproductive tract What is MALT?

Mucosa-associated lymphatic tissue (MALT) List the large or prominent lymphatic

nodules: Some larger – tonsils, Peyer’s patches, appendix

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II. Innate immunity

First line of defenses: Skin and mucous membranes Provide both physical and chemical barriers Physical barriers

Epidermis – closely packed, keratinized cells Periodic shedding

Mucous membranes Mucus traps microbes and foreign substances

Nose hairs trap and filter Cilia of upper respiratory tract propel trapped particles

up and out

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Innate Immunity

Fluids Lacrimal apparatus of eye

Washing action of tears Lysozyme breaks down bacterial cell walls – also present

in saliva, perspiration, nasal secretions, and tissue fluids Saliva washes mouth Urine cleanses urinary system Vaginal secretions, defecation and vomiting

Chemicals Sebaceous (oil) glands secrete sebum – protective film,

acid Perspiration, gastric juice, vaginal secretions – all acidic

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Second line of defenses: Internal defenses

Antimicrobial substances

1. Interferons Produced by lymphocytes, macrophages, and fibroblasts

infected by viruses Prevents replication in neighboring uninfected cells

2. Complement Proteins in blood plasma and plasma membranes “complement” or enhance certain immune reactions Causes cytolysis of microbes, promotes phagocytosis,

contributes to inflammation

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These anti-microbial substances promote cytolysis, phagocytosis and inflammation. Transferrins Perforins Complement proteins Defensins Interferons

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Which of these does NOT provide a physical or chemical barrier? Macrophages Saliva Urine Mucus Stratified squamous epithelium

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Describe the barriers used in innate defense. Ans: Barriers used by the innate defense

include epidermis, mucus, hairs, cilia, lacrimal apparatus, saliva, urine, vaginal secretions, sebum, perspiration and gastric juices.

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These anti-microbial substances will diffuse to uninfected cells and reduce production of viral proteins. Transferrins Perforins Complement proteins Defensins Interferons

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Internal Defenses

3. Iron-binding proteins Inhibit growth of bacteria by reducing available

iron

4. Antimicrobial proteins (AMPs) Short peptides that have a broad spectrum of

antimicrobial activity Can attract dendritic cells and mast cells that

participate in immune responses

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Internal Defenses

Natural Killer (NK) cells Lymphocyte but not a B or T cell Ability to kill wide variety of infected body cells and

certain tumor cells Attack any body cell displaying abnormal or unusual

plasma membrane proteins Can release perforin (makes perforations) or granzymes

(induce apoptosis) Phagocytes

Neutrophils and macrophages (from monocytes) Migrate to infected area 5 steps in phagocytosis

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1 MicrobeCHEMOTAXIS

Phagocyte

Phases of phagocytosis

1


MicrobeCHEMOTAXIS

Pseudopod

Phagocyte

ADHERENCE2

1 MicrobeCHEMOTAXIS

Lysosome

Pseudopod

Phagocyte

ADHERENCE INGESTION2 3


1 MicrobeCHEMOTAXIS

Lysosome

Digestiveenzymes

Pseudopod

Phagocyte

ADHERENCE INGESTION

Plasmamembrane

DIGESTION

2 3

4


1 MicrobeCHEMOTAXIS

Lysosome

Digestiveenzymes

Pseudopod

Phagocyte

ADHERENCE INGESTION

Plasmamembrane

DIGESTION

KILLINGResidual body(indigestiblematerial)

Digested microbein phagolysosome

2 3

4

5


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Phagocytosis of a microbe

These are mainly used to kill infectious microbes and tumor cells. Natural killer cells Perforins platelets Mucus Antimicrobial proteins

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Which of these provides a non-specific cellular disease resistance mechanism? Macrophages T lymphocytes B lymphocytes Memory B cells Stratified squamous epithelium

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Inflammation

Nonspecific, defensive response of body to tissue damage

4 signs and symptoms – redness, pain, heat and swelling

Attempt to dispose of microbes, prevent spread, and prepare site for tissue repair

3 basic stages1. Vasodilation and increased blood vessel

permeability

2. Emigration

3. Tissue repair

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Vasodilation and increased permeability of blood vessels

Increased diameter of arterioles allows more blood flow through area bringing supplies and removing debris

Increased permeability means substances normally retained in the blood are permitted to pass out – antibodies and clotting factors

Histamine, kinins, prostaglandins (PGs), leukotrienes (LTs), complement

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Emigration of phagocytes

Depends on chemotaxis Neutrophils predominate in early stages but

die off quickly Monocytes transform into macrophages

More potent than neutrophils Pus – pocket of dead phagocytes and

damaged tissue

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Which of the following is NOT a sign of inflammation? Redness Pain Heat Mucus production Swelling

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Which of the following intensifies the effect of interferons and promotes the rate of repair? Complement proteins Perforin Fever Macrophages Natural killer cells

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Which of the below do NOT induce vasodilation and permeability (increased fluid flow to an infection site. Histamines Kinins Perforin Leukotrienes Complement

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III. Adaptive immunity

Ability of the body to defend itself against specific invading agents

Antigens (Ags) – substances recognized as foreign and provoking an immune response

Distinguished from innate immunity by Specificity Memory

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This induces production of a specific antibody. Phagocytosis Antigen Antibody Defensin Imunnoglobulin

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2 types of adaptive immunity

Cell-mediated Cytotoxic T cells ( CD 8 or T8) directly attack

invading antigens Particularly effective against intracellular pathogens,

some cancer cells and foreign tissue transplants

Antibody-mediated B cells transform into plasma cells making antibodies

(Abs) or immunoglobulins Works against extracellular pathogens in fluids outside cells

Helper T cells ( CD4 or T4) aid in both types 2 types of immunity work together

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Maturation of T cells and B cells

Both develop from pluripotent stem cells originating in red bone marrow B cells complete their development in red bone

marrow T cells develop from pre-T cells that migrate from

red bone marrow to the thymus Helper T cells (CD4 T cells) and cytotoxic T cells

(CD8 T cells) Immunocompetence – ability to carry out

adaptive immune response Have antigen receptors to identify specific antigen

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When B and T cells are fully developed and mature, they are known to be Immunocompetent Pluripotent stem cells Primary lymphatic cells Specifically promoted Germ cells

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Cell-mediated and antibody-mediated immunity

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Clonal selection

Process by which a lymphocyte proliferates and differentiates in response to a specific antigen Clone – population of identical cells all recognizing the

same antigen as original cell

Lymphocyte undergoes clonal selection to produce Effector cell – active helper T cell, active cytotoxic T cell,

plasma cell, die after immune response Memory cell – do not participate in initial immune

response, respond to 2nd invasion by proliferating and differentiating into more effector and memory cells, long life spans

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Antigens Antigens have 2

characteristics Immunogenicity – ability to

provoke immune response Reactivity – ability of

antigen to react specifically with antibodies it provoked

Entire microbes may act as antigen

Typically, just certain small parts of large antigen molecule triggers response (epitope or antigenic determinant)

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This can only stimulate an immune response if attached to a large carrier molecule. Epitope Antigen Hapten MHC CD8

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Diversity of antigen receptors Human immune system able to recognize and

bind to at least a billion different epitopes Result of genetic recombination – shuffling and

rearranging of a few hundred versions of several small gene segments

Major Histocompatibility Complex Antigens MHC or human leukocyte antigens (HLA) Normal function to help T cells recognize foreign or self Class I MHC (MHC-I) – built into all body cells except RBCs Class II MHC (MHC-II) – only on antigen presenting cells

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Pathways of antigen processing

B cells can recognize and bind to antigens T cells must be presented with processed

antigens Antigenic proteins are broken down into peptide

fragments and associated with MHC molecules Antigen presentation – antigen-MHC complex

inserted into plasma membrane Pathway depends on whether antigen is outside or

inside body cells

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Which of the following is responsible for diversity in the immune system? Antigen receptors MHC Hapten MHC and antigen receptors Epitopes

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Exogenous and Endogenous Antigens Exogenous antigens – present in fluid

outside body cells Antigen-presenting cells (APCs) include

dendritic cells, macrophages and B cells Ingest antigen, process, place next to MHC-II

molecule in plasma membrane, and present to T cells

Endogenous antigens – antigens inside body cells Infected cell displays antigen next to MHC-I

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This class of cells includes macrophages, B cells and dendritic cells. Antigen presenting cells Primary lymphocytes T cells RBC Epitope cells

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Phagocytosis orendocytosis ofantigen

APCs present exogenous antigens in association with MHC-II molecules

Antigen-presentingcell (APC)

MHC-IIself-antigen

Antigenpeptidefragments

Key:

Exogenousantigen

1 Phagocytosis orendocytosis ofantigen

Digestion ofantigen intopeptide fragments

Phagosomeor endosome



MHC-IIself-antigen


Key:

1

2

Exogenousantigen






Synthesis of MHC-II molecules

MHC-IIself-antigen


Key:

Endoplasmicreticulum

1

3

2

Exogenousantigen






Packaging of MHC-IImolecules into a vesicle


MHC-IIself-antigen


Key:


1

4

3

2

Exogenousantigen






Vesicles containing antigenpeptide fragments andMHC-II molecules fuse



MHC-IIself-antigen


Key:


1

5

4

3

2

Exogenousantigen



Antigen peptidefragments bind toMHC-II molecules







MHC-IIself-antigen


Key:


1

5

6

4

3

2

Exogenousantigen



Antigen peptidefragments bind toMHC-II molecules







MHC-IIself-antigen


Key:


Vesicle undergoesexocytosis andantigen–MHC-IIcomplexes are insertedinto plasma membrane

1

5

6

7

4

3

2

Exogenousantigen

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Exogenous Antigens

Endogenous Antigens

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Cell-mediated immunity Activation of T cells

First signal in activation T-cell receptors (TCRs) recognize and bind to a specific

foreign antigen fragments that are presented in antigen-MHC complexes

CD4 and CD8 proteins are coreceptors Second signal required for activation

Costimulation – 20 known substances (cytokines, plasma membrane molecules)

May prevent immune response from occurring accidentally Anergy – recognition without costimulation (in both B and T

cells) leads to prolonged state of inactivity

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This can only become activated when bound to a foreign antigen and simultaneously receiving costimulation. B Cell T Cell Interferon MHC Antigen presenting cell

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Activation and clonal selection of helper T cells

Most that display CD4 develop into helper T cells (CD4 T cells)

Recognize exogenous antigen fragments associated with MHC-II molecules on the surface of an APC

After activation undergoes clonal selection Makes active helper T cells and memory helper T cells Active helper T cells secrete variety of cytokines

Interleukin-2 (IL-2) needed for virtually all immune responses

Memory helper T cells are not active cells – can quickly proliferate and differentiate if the antigen appears again

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These display CD 4 in their membrane and are associated with MHC class II molecules. Cytotoxic T cells Helper T Cells Memory T Cells MHC B cells

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Activation and clonal selection of a helper T cell

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Activation and clonal selection of cytotoxic T cells

Most that display CD8 develop into cytotoxic T cells (CD8 T cells)

Recognize antigens combined with MHC-I Maximal activation also requires presentation of

antigen with MHC-II to cause helper T cells to produce IL-2

Undergoes clonal selection Active cytotoxic T cells attack body cells Memory cytotoxic T cells do not attack but wait for

a antigen to appear again

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Activation and clonal selection of a cytoxic T cell

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Elimination of invaders Cytotoxic T cells migrate to seek out and destroy

infected target cells Kill like natural killer cells Major difference is T cells have specific receptor

for particular microbe while NK cells destroy a wide variety of microbe-infected cells

2 ways to kill cells Granzymes cause apoptosis Perforin and/ or granulysin causes cytolysis

Immunological surveillance Tumor antigens displayed on cancerous cells targeted by

cytotoxic T cells, macrophages and natural killer cells

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Activity of cytoxic T cells

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Antibody-mediated immunity

Activation and clonal selection of B cells During activation, antigen binds to B cell receptor (BCRs) Can respond to unprocessed antigen Response much more intense when B cell processes

antigen Antigen taken into B cell, combined with MHC-II, moved to

plasma membrane, helper T cell binds and delivers costimulation (interleukin-2 and other cytokines)

B cell undergoes clonal selection Plasma cells secrete antibodies Memory B cells do not secrete antibodies but wait for

reappearance of antigen

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Activation and clonal selection of B cells

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Antibodies (Ab)

Can combine specifically with epitope of the antigen that triggered its production

Belong to group of glycoproteins called globulins Ab are immunoglobulins (Igs)

4 polypeptide chains – 2 heavy (H) chains, 2 light (L) chains

Hinge region – antibody can be T shape or Y shape Variable (V) region at tips of each H and L chain

2 antigen-binding sites - bivalent Constant (C) region – remainder of H and L chain

Same in each 5 classes – determines type of reaction

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Chemical structure of the immunoglobin (IgG) class of antibody

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Click to edit Master title style22_table_03

Antibody actions

Neutralizing antigen Immobilizing bacteria Agglutinating and precipitating antigen Enhancing phagocytosis Activating complement

Defensive system of over 30 proteins Destroy microbes by causing phagocytosis, cytolysis, and

inflammation Acts in a cascade – one reaction triggers another Activate C3 C3 then begins cascade that brings about phagocytosis,

cytolysis, and inflammation

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Immunological memory

Thousands of memory cells exist after initial encounter with an antigen

Next time antigen appears can proliferate and differentiate within hours

Antibody titer measure of immunological memory Amount of Ab in serum

Primary response Secondary response faster

and stronger

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List the five actions of antibodies.

Ans: Antibodies can act as a neutralizing agent, they can immobilize bacteria, agglutinate and precipitate the antigen, activate the complement and enhance phagocytosis.

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This class of antibodies is mainly found in sweat, tears, breast milk and GI secretions. IgG IgA IgM IgD IgE

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This will lead to inflammation, enhancement of phagocytosis and bursting of microbes. Classical complement system Alternative complement system Apoptosis Classical and Alternative complement systems Hapten activation

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This action makes microbes more susceptible to phagocytosis. Opsonization Cytolysis Inflammation Complement Hybridoma

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Self-recognition and self-tolerance Your T cells must have

Self-recognition – be able to recognize your own MHC Self-tolerance – lack reactivity to peptide fragments from

your own proteins Pre-T cells in thymus develop self-recognition via

positive selection – cells that can’t recognize your own MHC undergo apoptosis

Self-tolerance occurs through negative selection in which T and B cells that recognize self peptide fragments are eliminated Deletion – undergo apoptosis Anergy – remain alive but are unresponsive

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This is a self-responsive cell that is inactive. Deleted cell Hybridoma cell Epitopic cell Anergy cell Natural killer cell

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This is characterized by the inability of the immune system to protect the body from a pathogen. immunodeficiency diseases allergy autoimmune disease transplantations graft

A natural exposure to an infectious agent leads to: A. Passive immunity B. Active immunity Both a and b None of the above

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This class of antibodies is produced after an initial exposure to antigens. IgA IgE IgM IgD IgG

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Of the following which is considered the body’s second major defense. Mucous cells Germ cells Lymphocytes Natural killer cells None of the above

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An acute allergic response can lead to: transplantation retroviruses anaphylactic shock passive immunity active immunity

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This is a small hormone that can stimulate or inhibit many normal cell functions. Enzyme Kinins Cytokine MHC Leukocyte

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DISORDERS: HOMEOSTATIC IMBALANCES Discuss AIDS in terms of epidemiology,

pathogenesis of the HIV virus, signs and symptoms, progression to AIDS, and treatment.

Discuss the basic types of allergic reactions. Discuss the causes and symptoms of infectious

mononucleosis. Discuss the causes and treatments of

autoimmune diseases. Discuss the two basic types of lymphomas. Discuss the causes and treatments of systemic

lupus erythematosus.

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End of Chapter 22

Copyright 2009 John Wiley & Sons, Inc.All rights reserved. Reproduction or translation of this work beyond that permitted in section 117 of the 1976 United States Copyright Act without express permission of the copyright owner is unlawful. Request for further information should be addressed to the Permission Department, John Wiley & Sons, Inc. The purchaser may make back-up copies for his/her own use only and not for distribution or resale. The Publishers assumes no responsibility for errors, omissions, or damages caused by the use of theses programs or from the use of the information herein.

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chapter 22: the lymphatic system and immunity 2/18/20091

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