21-1

Maintain fluid balance Protect body from infection and disease

21-2

Immunity fluids from all capillary beds are filtered immune cells stand ready to respond to foreign cells or

chemicals encountered Lipid absorption

Lacteals in small intestine absorb dietary lipids Fluid recovery

absorbs plasma proteins and fluid (2 to 4 L/day) from tissues and returns it to the bloodstream interference with lymphatic drainage leads to severe edema

Lymph is a clear, colorless fluid, similar to plasma but much less protein

Lymphatic capillaries are closed at one end and much ‘leakier’ than blood capillaries

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21-4

Larger lymphatics have 3 layers tunica interna: endothelium

and valves tunica media: elastic fibers,

smooth muscle tunica externa: thin outer

layer

Valves

21-5

Lymphatic capillaries Collecting vessels: course through many lymph nodes Lymphatic trunks: drain major portions of body Collecting ducts :

right lymphatic duct – receives lymph from R arm, R side of head and thorax; empties into R subclavian vein

thoracic duct - larger and longer, begins as a prominent sac in abdomen called the cisterna chyli; receives lymph from below diaphragm, L arm, L side of head, neck and thorax; empties into L subclavian vein

course through many lymph nodes

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21-7

21-8

Lymph flows at low pressure and speed Moved along by rhythmic contractions of lymphatic

vessels Flow aided by skeletal muscle pump (like veins) Thoracic pump aids flow from abdominal to thoracic

cavity (also like veins) Valves prevent backward flow The rapidly flowing blood in subclavian veins draws

lymph into the vascular system Exercise significantly increases lymphatic return

21-9

Natural killer (NK) cells can find and destroy tumor cells

T lymphocytes (mature in thymus)

B lymphocytes (mature in bone marrow) activation makes cells that produce antibodies

Antigen Presenting Cells - APCs macrophages (from monocytes)

dendritic cells (in epidermis, mucous membranes and lymphatic organs)

21-10

Diffuse lymphatic tissue lymphocytes in mucous membranes and connective

tissues of many organs Mucosa-Associated Lymphatic Tissue (MALT): prevalent

in passages open to exterior Lymphatic nodules

dense oval masses of lymphocytes, congregate in response to pathogens

Peyer patches: more permanent congregation, clusters found at junction of small to large intestine

21-11

At well defined sites; have connective tissue capsules Primary lymphatic organs

site where T and B cells become immunocompetent red bone marrow and thymus

Secondary lymphatic organs immunocompetent cells populate these tissues lymph nodes, tonsils, and spleen

21-12

Lymph nodes – are the only organs that filter lymph Fewer efferent vessels, slows flow through node Lymph nodes are divided into compartments containing

stroma (reticular CT) and parenchyma (lymphocytes and APCs)

Lymph nodes are subdivided into cortex and medulla reticular cells, macrophages phagocytize foreign matter lymphocytes respond to antigens lymphatic nodules-germinal centers for B cell activation

21-13

Fig. 21.12 a and b

21-14

Collective term for all lymph node diseases Lymphadenitis

swollen, painful node responding to foreign antigen Lymph nodes are common sites for metastatic

cancer swollen, firm and usually painless

21-15

Palatine tonsils pair at posterior margin of oral cavity most often infected

Lingual tonsils pair at root of tongue

Pharyngeal tonsil (adenoid) single tonsil on wall of pharynx

Very large in babies. Begins to involute at about 14 years T lymphocytes mature here. Secretes thymopoietin, thymulin and thymosins.

21-16

Parenchyma appears in fresh specimens as red pulp: sinuses filled with erythrocytes white pulp: lymphocytes, macrophages

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21-18

Why is the ‘white pulp’ blue?

Functions blood reservoir RBC disposal immune reactions: filters blood, quick to detect antigens

Your immune system’s structure and function is much like that of an earth army fighting alien invaders.

It is there in times of peace and in times of war.

To distinguish ‘self’ from ‘non-self’ to destroy ‘non-self’

The fortifications

The human body’s first line of defense is a set of physical barriers and chemical agents that prevent foreign invaders from getting inside.

An outer layer of intact skin

Hair in the nostrils Mucous membranes Cilia

Tears Sweat Mucous Oils Acid in stomach Urine

The soldiers and their weapons

Non-specific (innate) Neutrophils

Make antibodies Macrophages Natural Killer Cells

Specific (adaptive) Lymphocytes

B cells make antibodies T cells help them

Only vertebrates can do this!!

If something gets past the external barriers, the second line of defense are ‘innate’ immune defenses, primarily white blood cells.

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Nonspecific defenses - broadly effective, no prior exposure first line of defense

external barriers second line of defense – innate immune system

phagocytic cells, antimicrobial proteins, inflammation and fever

Specific defense - results from prior exposure, protects against only a particular pathogen third line of defense – adaptive immune system

21-28

Phagocytize bacteria These are most likely to dramatically increase in

numbers during bacterial infection Create a killing zone

degranulation antimicrobial proteins are discharged into tissue fluid

respiratory burst toxic chemicals are created (O2

.-, H2O2)

How do they distinguish

self from non-self?

21-29

Phagocytize antigen-antibody complexes Antiparasitic effects Promote action of basophils, mast cells Enzymes block excess inflammation, limit action of

histamine

21-30

Aid mobility and action of WBC’s by release of histamine (vasodilator)

blood flow to infected tissue heparin (anticoagulant)

prevents immobilization of phagocytes

The rarest WBCs in

human blood

21-31

Circulating precursors to macrophages Specialized macrophage-like cells are found in specific

localities Dendritic cells

epidermis, oral mucosa, esophagus, vagina, and lymphatic organs Microglia (CNS) Alveolar macrophages (lungs) Kupffer cells (liver)

21-32

There are 3 types but they look identical under a microscope!

Act to destroy cancer cells Kill virus-infected cells Make antibodies The lymphocytes circulating in human

blood are 80% T cells 15% B cells 5% NK cells

These are the cells that confer immunity

through a vaccination!

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Interferons Made by cells when they are invaded by a virus Induce neighbor cells to activate anti-viral defenses Can stimulate destruction of some cancer cells

Complement system More than 20 different proteins Are activated by the presence of pathogens

(like a booby trap)

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Mechanisms of action enhanced inflammation phagocytosis

promoted by opsonization cytolysis

membrane attack complex forms on target cell immune clearance

RBCs carry Ag-Ab complexes to macrophages in liver and spleen

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NK cells (Natural Killer Cells) destroy bacteria, cells infected by viruses,

and cancer cells also destroy transplanted cells

Redness & heat hyperemia

Pain Swelling Purulence

Neutrophils

Macrophages!

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Three major processes1. mobilization of body defenses2. containment and destruction of pathogens3. tissue clean-up and repair

21-39

Kinins, histamine, and leukotrienes are secreted by damaged cells stimulates vasodilation that leads to hyperemia

causes redness and heat local metabolic rate, promotes cell multiplication and

healing dilutes toxins, provides O2, nutrients, waste removal

stimulates permeability of blood capillaries allows blood cells, plasma proteins (antibodies,

complement proteins, fibrinogen) into tissue

21-40

Leukocyte Deployment margination

selectins cause leukocytes to adhere to blood vessel walls

diapedesis (emigration) leukocytes squeeze

between endothelial cells into tissue space

21-41

Chemotaxis leukocytes are attracted to chemotactic chemicals

Neutrophils are quickest to respond phagocytosis respiratory burst secrete cytokines for recruitment of macrophages and

neutrophils macrophages and T cells secrete colony-stimulating factor

to stimulate leukopoiesis

Total WBC: 4,500 - 10,000 Bands or stabs: 3 - 5 % Granulocytes

Neutrophils (or segs): 50 - 70% relative value (2500-7000 absolute value)

Eosinophils: 1 - 3% relative value (100-300 absolute value) Basophils: 0.4% - 1% relative value (40-100 absolute value)

Agranulocytes (or mononuclears) Lymphocytes: 25 - 35% relative value (1700-3500 absolute

value) Moncytes: 4 - 6% relative value (200-600 absolute value)

Defense mechanism: does more good than harm promotes interferon activity accelerating metabolic rate and tissue repair inhibiting pathogen reproduction

A cytokine named interleukin 1 called a pyrogen secreted by macrophages stimulates anterior hypothalamus to secrete PGE2 Prosatglandin E2 resets the body’s thermostat higher> 105F may cause delirium, 111F- 115F, coma-death

21-44

What if your patient is shivering with a normal or very slightly raised temp?

21-45

Depends on lymphocytes Specificity and memory Cellular immunity: cell-mediated (T cells) Humoral immunity: antibody mediated (B cells)

This is the half of the immune system that

confers immunity through a vaccination!

21-46

Active immunity produces memory cells Natural – you catch the measles Artificial – you’re vaccinated for the measles

Passive immunity is not long lasting Natural - fetus acquires antibodies from mother Natural – nursing child gets antibodies from colostrum Artificial - treatment for snakebite or tetanus

21-47

Trigger an immune response Complex molecules

> 10,000 amu, unique structures proteins, polysaccharides, glycoproteins, glycolipids

21-48

Stem cells in red bone marrow Mature in thymus

Immature T cells must be able to recognize signals from other parts of the immune system

If they don’t – they are destroyed

Immature T cells must not recognize proteins on your tissue cells as ‘foreign’

If they do – they are destroyedOnly 2% of

immature T cells survive these steps

that are called ‘selection’

21-50

Stem cells in red bone marrow Mature in thymus Circulate through blood and lymph Naïve T cells colonize lymph nodes, Peyer’s patches,

tonsils, spleen

21-51

Sites of development bone marrow

B cells also undergo selection (just not in the thymus) Self-tolerant B cells form B cell clones

each cell in a clone has the same antigen receptors

DCs and macrophages (some B cells) display antigens to T cells

21-53

T cells attack foreign cells and diseased host cells; memory of Ag

Three classes of T cells:1. Cytotoxic T cells (Tc cells) carry out attack

2. Helper T cells: help promote Tc cell and B cell action

3. Memory T cells: provide immunity from future exposure to antigen

T Cells must be activated by APCs before they go to work.

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Cytotoxic T cells directly attack enemy cells Lethal hit mechanism

docks on cell with antigen-MHC-I protein complex1. releases perforin, granzymes - kills target cell2. interferons - decrease viral replication and activates

macrophages3. tumor necrosis factor: kills cancer cells

21-56

Cytotoxic T cell binding to cancer cell

21-57

Memory T cells following clonal selection some T cells become memory

cells long-lived; in higher numbers than naïve cells

T cell recall response upon reexposure to same pathogen, memory cells launch

a quick attack

21-58

Helper T cells (TH cells) have been informed of the invader by APCs

Helper T cells (TH cells) stimulate the B cells that have the right ‘weapon’ for this disease

The B cells turn into Plasma cells Plasma cells make antibodies that circulate in the

blood and can incapacitate the pathogen Memory

some B cells differentiate into memory cells

21-59

ALL antibodies are proteins!

IgG is Y-shaped.

80% of your circulating antibody is IgG.

There are other classes of Ig Antibody and immunoglobulin are synonyms

Antibodies are the most

important component of

humoral immunity!

21-61

Immune system capable of as many as 1 trillion different antibodies

Somatic recombination DNA segments shuffled and form new combinations of

base sequences to produce antibody genes Somatic hypermutation

B cells in lymph nodules rapidly mutate creating new sequences

21-62

Neutralization antibodies mask pathogenic region of antigen

Complement fixation antigen binds to IgM or IgG, antibody changes shape, initiates

complement binding; primary defense against foreign cells, bacteria

Agglutination antibody has 2-10 binding sites; binds to multiple enemy cells

immobilizing them Precipitation

antibody binds antigen molecules (not cells); creates antigen-antibody complex that precipitates, phagocytized by eosinophil

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21-65

Excessive immune reaction against antigens that most people tolerate - allergens

Type I Antibody mediated (IgE), acute reaction Asthma, Hay fever, Anaphylaxis

Type II Antibody mediated (IgG, IgM), subacute Type III Antibody mediated (IgG, IgM), subacute

glomerulonephritis, systemic lupus Type IV Cell mediated, delayed (12 to 72 hrs)

TB test Poison ivy

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Failure of self tolerance cross-reactivity abnormal exposure of self-antigens changes in structure of self-antigens

Production of autoantibodies

21-67

Severe Combined Immunodeficiency Disease (SCID) hereditary lack of T and

B cells vulnerability to

opportunistic infection currently treatable with

gene therapy