Chapter 22

The Lymphatic and Immune Systems

The Lymphatic System Basic organization

Lymph fluid in lymph vessels Structures, organs w/ lymph tissue, red

bone marrow Functions

drain interstitial fluid and proteins transport dietary fats protect against invasion

resistance - fight off disease nonspecific resistance - general protection against

disease immunity - specific protection

susceptibility - lack of resistance

Lymphatic Vessels Lymphatic capillaries

Blind ended vessels between cells, larger than blood capillaries

Not in avascular tissues, CNS, splenic pulp, bone marrow

Lymphatic Capillaries Structure/Function regulates fluid flow

Anchoring filaments - from lymphatic endothelium attach to surrounding tissues

Endothelial cells overlap high hydrostatic fluid pressure separates cells, fluid into caps hydrostatic fluid pressure in cap prevents fluid movement out

The Lymphatic System Lymph flow follows

venous circulation Lymph vessels have

same organization as vascular tree

Smaller vessels drain into larger vessels

The Lymphatic System (cont.) Lymph returns

to venous blood through R,L lymphatic ducts

Enter at internal jugular and subclavian veins

The Lymphatic System Lymph ducts

Right lymphatic duct

about ½ inch long drains lymph from

upper right side of body

Thoracic (left) duct main collecting

duct of lymph system

38-45 cm long drains 75% of body begins as a dilation

known as cisterna chyli located anterior to lumbar disk #2

The Lymphatic System Flow of Lymph

More fluid out of blood capillaries by filtration than returns by absorption - Starling’s Law

3Ll day of lymph fluid Proteins from blood returned by lymphatics Lymph flow by muscle pump, respiratory pump,

valves

Lymphatic Tissue - General 1º lymphatic organs - site of B and T

cell production bone marrow - produces B cells, pre-T

cells thymus gland - migrate to thymus gland

2 º lymphatic organs site of most immune responses lymph nodes, spleen – surrounded by

connective tissue capsule lymphatic nodules – not surrounded by

capsule

Thymus Gland Thymus Gland

Between sternum, heart 2 lobes Atrophies w/ age

Structure/Function Outer cortex

pre-T cells migrate to thymus

proliferation Maturation

dendritic cells macrophages

Inner medulla – more of the same

Lymph Node Structure oval, bean shaped

structures along lymph vessels

may be deep or superficial scattered throughout body

concentrated in mammary glands, axillae, groin

filter lymph fluid

Lymph Nodes

Lymph Nodes Connective tissue

capsule w/ trabeculae extending into cortex

Stroma -supportive network of reticular fibers, fibroblasts

Lymph Nodes

Cortex

Medulla

Parenchyma Outer cortex -

lymphatic nodules inner germinal

center site of B-cell proliferation

Site of B-cell maturation and plasma cell formation

Inner medulla - medullary cords of lymphycytes, macrophages, plasma cells

Node fluid flow Enter cortex through

afferent vessels Filter, remove damaged

cells, microorganisms, foreign substances by reticular fibers

macrophages phagocytize some, lymphocytes destroy others

exit medulla from hilus by efferent vessels

Metastasis cancer cells from tumor trapped in lymph nodes

Lymphatic Tissue - Specific

Lymph Nodes Histology

Lymphatic Tissue - Specific Spleen

largest mass of lymphoid tissue in body

Left side of body between stomach/diaphragm

thick fibrous capsule w/ artery, vein, efferent lymph vessel organ function:

immune function removal of worn

out, damaged RBC’s

storage of platelets

production of RBC’s during fetal life

Lymphatic Tissue - Specific Lymphatic nodules

(tonsils) oval-shaped non-

encapsulated groups of lymphatic tissue

scattered in mucous membranes, GI tract, respiratory tract, urinary tract, reproductive tract

protect against invasion of inhaled or ingested foreign substances

Nonspecific Resistance to Disease Summarized in Table 22.1 Surface Barrier – Skin and mucosa Internal Defenses

1) Antimicrobial proteins2) Natural killer cells and Phagocytosis3) Inflammation4) Fever

Nonspecific Resistance to Disease Surface Barrier – Skin and mucosa

Mechanical protection intact epidermis mucous membranes

line body cavities, mucus prevents drying, traps foreign bodies

nose hairs, respiratory tract cilia lacrimal apparatus saliva - dilute microbes, wash them from teeth

surface urine flow, vaginal secretions – flow and pH help

kill microorganisms defecation and vomiting - expel microbes

Nonspecific Resistance to Disease Surface Barrier – Skin and mucosa

Chemical protection Skin

sebum (unsaturated FA’s) forms layer, prevents bacterial growth

perspiration has fatty acids, lo pH lysozyme - enzyme breaks down bacterial walls gastric juice - stomach nearly sterile due to lo pH,

2ish

Nonspecific Resistance to Disease1) Antimicrobial substances produced

against pathogens that penetrate 1º defense

A. Interferons Released from infected cells Stimulate production of antiviral proteins from

neighboring cells

B. Complement system 20 plasma and cell membrane proteins Function to complement (enhance) certain

immune, allergic and inflammatory systems

C. Transferrins – inhabit bacterial growth by binding iron

Nonspecific Resistance to Disease

2) Natural killer (NK) cells and phagocytosis

NK nonspecific killers that respond before immune

system is activated ability to kill virus infected body cells and some

tumor cells by poking holes in cells and stimulating cell death

Nonspecific Resistance to Disease2) Natural killer (NK) cells and phagocytosis

Phagocytosis ingestion of microbes or foreign material by phagocytes 2 kinds of phagocytosis - neutrophils and macrophages steps

chemotaxis adherence ingestion digestion killing

Nonspecific Resistance to Disease3) Inflammation 4 symptoms:

Redness Pain Heat Swelling

3 steps in process1. Vasodilation/increased

vessel permeability2. Phagocyte migration3. Tissue repair

Nonspecific Resistance to Disease Step 1. Vasodilation

and increased vessel permeability Release of factors from

leukocytes stimulate vascular changes

Histamine, kinins, prostaglandins, leukotrienes

Vasodilate, increase permeability, stimulate emigration and chemotaxis

Cause heat, redness and swelling

Nonspecific Resistance to Disease Step 2. Phagocyte

migration leukocytosis-inducing

factors chemotaxis Emigration

neutrophils - rapid monocytes - slower

Nonspecific Resistance to Disease Step 3. Tissue

repair Tissue regrowth and

repair of damage Pus

dead phagocytes, damaged tissue

if too numerous for easy removal may form abscess

Nonspecific Resistance to Disease 4) Fever

increase effects of antimicrobial substances inhibits some microbes increase rate of body repair

Nonspecific Resistance to Disease Surface Barrier – Skin and mucosa Internal Defenses

1) Antimicrobial proteins2) Natural killer cells and Phagocytosis3) Inflammation4) Fever

Immunity

Immunity ability of body to defend itself against specific

invaders specificity and memory differentiate this from

non-specific system two types

Humoral (antibody mediated) immunity Cellular (cell mediated) immunity

Antigens Antigen - substances

that provoke immune response

Epitope antigen part that triggers

immune response most antigens have

many epitopes

Antigens (cont.) Chemical nature of

antigens large, complex

molecules - mostly proteins, nucleo-, lipo-, glyco-

smaller substances may be incomplete antigens - hapten

react with antibodies but not cause immune response

poison ivy toxin usually foreign

substances

Antigens (cont.) Antigen receptor diversity

>1 billion different epitopes recognized by body

diversity - genetic recombination, shuffle, reorganize different genes

Major Histocompatibility Complex antigens (MHC)

unique to each individuals cells, help in identifying foreign bodies

2 classes of MHC antigens class I MHC - all body cells but

RBC's class II MHC - only on antigen

presenting cells (APC’s), thymus cells, activated T cells

Pathways of Antigen Processing For immune response to occur, B and T

cells must recognize foreign antigen B cells can recognize, bind to antigens in

ECF, blood, lymph T cells only recognize antigen protein

fragments presented w/ MHC self-antigens - good/bad proteins

Pathways of Antigen Processing During protein digestion and production in cell,

small peptides used to stabilize MHC proteins if peptides from normal body cells, no response if peptides from antigens

T cells recognize them immune response!

preparation of foreign antigen for cell surface known as processing and presenting of antigen

Antigen Presenting Cell's (APC’s) macrophages, activated B cells, dendritic cells process exogenous antigens present them w/ MHC

class II molecules to T cells

Pathways of Antigen Processing Processing of exogenous antigen – produced outside cell

1) phagocytosis/endocytosis 2) digestion3) vesicles fuse, peptide fragments bind to MHC-II’s 4) exocytosis to membrane5) move to lymphatic tissue, present antigen to T-cells

Pathways of Antigen Processing Processing of endogenous antigen –

produced within body cells viral proteins from viral infection of cell produced, incorporated into MHC-I

molecules during normal cell growth put on surface of cell identifies cell as infected, signals that cell

needs help

T and B cell formation

Both B and T cells produced from stem cells in bone marrow

Development of immunocompetence occurs in different sites B cells complete

maturation in Bone marrow

Pre-T cells move to Thymus - complete maturation in thymus

Immunity - General Before mature

cells leave home:

both types acquire surface proteins - antigen receptors

T cells exit as CD4+ or CD8+ cells w/ different functions

CD4+ cells become helper T cells

Immunity - General 2 Types of

immune responses

Cell-mediated immunity

Antibody-mediated immunity

General Initial activation of

Helper T cells Helper T cells aid

both types of immune responses

Pathogens often activate both types of responses

Immunity - General1) Cell-mediated

immune (CMI) responses

CD8+ cells change into killer T cells with aid from Helper T cells

directly attack infecting antigen

Effective against: intracellular

pathogens some cancer cells foreign tissue

transplants

Immunity - General2) Antibody-

mediated immune (AMI) responses

B cells transform into plasma cells with aid of Helper T cells synthesize,

secrete specific proteins (antibodies or immunoglobulins)

antibodies bind and inactivate antigens

Effective against: antigens in body

fluids EC pathogens

(bacteria)

Cell -Mediated Immunity

Basic steps1. Recognition of APC antigen by T cell

receptors (TCR’s) – first signal2. Costimulation for activation3. Proliferation and differentiation 4. Clone effector cells capable of recognizing

initial activator (antigen)5. Elimination of intruder

Cell-Mediated Immunity (cont.) T cell recognition,

proliferation, differentiation

APC presents antigen TC’s recognize, bind

foreign antigen - millions of T cells each specific for 1 antigen

Need co-stimulator 20 known, cytokines,

interleukins, needed for full immune response

prevent false activation?

Cell-Mediated Immunity (cont.) T cell enlarges,

makes clones capable of recognizing antigen

Cell-Mediated Immunity (cont.) Clones

Helper T (TH) cells - CD4+

after co-stimulation helpers secrete co-stimulators

co-stimulates helper T cells, cytotoxic T cells, B cells

Cytotoxic T (TC) cells - CD8+ recognize antigen fragments associated w/ MHC-I molecules,

some tumor cells and tissue transplant cells become cytolytic need stimulators from helper T cells

Cell-Mediated Immunity (cont.) Tc elimination of

invaders1. Migrate from lymph to

infection site2. Recognize, attach to

target antigen/cell3. Kill invaders 4. Detach, seek out

another invader w/ proper antigen

Cell-Mediated Immunity (cont.) More Clones

Suppressor T (TS) cells

produced with other clones

downregulate immune system by producing other cytokines

Memory T (TM) cells recognize original invading antigen second response rapid due to large numbers of TM cells present

Antibody-Mediated Immunity Body contains millions

of B cells located in lymphoid

tissue each responds to

specific antigen Become activated

in presence of foreign antigen unprocessed antigen

weak response need to process

antigen for stronger response

Antibody-Mediated Immunity Unprocessed

antigen taken into cell incorporated into

MHC-II self-antigen activates helper T

cells Costimulation -

production of cytokines

Antibody-Mediated Immunity Some B cells change into

plasma cells secrete specific antibodies, at high

rate for 4-5 days antibodies circulate in lymph and

blood to site of invasion Circulating antibodies combine

w/ antigens neutralizes antigen immobilizes bacteria agglutinating (clumping) antigens activates complement system enhances chance antigen will be

phagocytized

Antibody-Mediated Immunity

Activated B cells some turn into

memory B cells respond more rapidly,

forcefully if antigen appears again

Antibodies Antibodies (Abs)

Globulins (proteins) specific for antigenic determinant of antigen that triggered its production

5 different classes - IgG, IgA, IgM, IgD, IgE

Immunological Memory Long lived

antibodies and lymphocytes arise during activation of antigen-stimulated B, T cells

Immunization possible because memory B cells and memory T cells remain after 1º response w/ secondary exposure system responds more

quickly, forcefully secondary response - antibodies produced during

second exposure have a higher attraction for antigen

Acquired Immunity

Self-recognition and Self-tolerance

The Immune System - Pathologies Immunology and cancer

With development of cancer cell surface proteins (tumor antigens) appear that rarely appear

If body recognizes surface proteins as non-self will destroy them

most effective in eliminating viral tumor cells Hypersensitivities - allergies

first exposure sensitizes to allergen - IgE production next exposure anaphylaxis - massive histamine

release local - surface exposure systemic - body

The Immune System - Pathologies Autoimmune diseases

multiple sclerosis - white matter destruction myasthenia gravis - effects nerve/muscle

communication Graves disease - excessive thyroid hormone

production Type I diabetes - destruction of pancreatic

islet cells glomerulonephritis - impaired renal function rheumatoid arthritis - destruction of the joints

Acquired Immunodeficiency Syndrome Human Immunodeficiency Virus

Enters cells through receptor mediated endocytosis

infects mainly helper T cells uses the CD4 protein on cell surface

A retrovirus carries genetic material as RNA inserts genetic material into host DNA w/

enzyme reverse transcriptase cell makes copies of the virus, releases

them for further infection May be carried unknowingly in cells

for years, being passed on during cloning

Activation will destroy Helper T’s Poor immune response to simple

things

Applied Immunity and HIV Enter the body?

Spread?

Effect of infection?

Cause of death?