lymphatic & immune systems

Lymphatic & Immune Systems

p 809

Lymphatic SystemReabsorbs about 15% of

fluid filtered by blood capillaries & returns it to blood

Provides immunity & protection from foreign cells & matter in the body

Absorbs dietary lipids in small intestine & transports them to blood

p 810

Lymph = fluid in lymphatic vessels• Usually clear, colorless fluid• Originates in lymphatic capillaries

p 811

Lymphatic Vessels

Histology similar to veins•Thinner walls•More valves

Flow of Lymph

Like venous; low pressure & speed

Primary driving force is rhythmic contractions of vessels

Assisted by Milking & “Thoracic pump”

p 817

Lymph Nodes

In-line filters that cleanse the lymph as it passes through

Reticular fibers act as a filter and delay microbes & debris

Macrophages & reticular cells remove about 99% of impurities from lymph

Lymphatic CellsNatural killer (NK) = lymphocytes that attack

& destroy bacteria, transplanted cells, & host cells that are cancerous or viral-infected

Provide immune surveillance

T lymphocytes = mature in thymus & provide cell-mediated immunity

B lymphocytes = mature in bone marrow & provide antibody-mediated immunity

Lymphatic CellsMacrophages = develop from monocytes into large highly phagocytic cells that destroy foreign matter and dead tissues & cells

Act as antigen-presenting cells (APCs) by breaking down foreign matter & displaying parts of it on their cell membrane

Lymphatic CellsDendritic cells = APCs that engulf foreign

matter by endocytosis

Located in epidermis (Langerhans cells), mucous membranes, & lymphatic organs

Reticular cells = act as APCs in thymus

Form blood-thymus barrier that isolates lymphocytes from blood-borne antigens

Produce hormones that promote development & actions of T cells

Lymphatic TissuesLymphatic Nodules = dense masses of

lymphocytes & macrophages

Some appear temporarily to fight infections

Permanent nodules are found in;

• Lymph nodes

• Tonsils

• Appendix

• Ileum of Sm. Intestine (Peyer’s Patches)

p 814

Red Bone Marrow

Source of all blood cells which enter the blood through sinusoids

Site where

B lymphocytes mature

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Thymus•Site where T lymphocytes mature•Shrinks to small size in adults•Secretes hormones that stimulate development and activities of T lymphocytes

p 819

Tonsils.Patches of lymphatic tissue that guard entrances to the pharynxSurface has deep pits called crypts that help trap foreign materials

p 819

Spleen:

Largest lymphatic organ

Acts as in-line filter for blood, with reticular fibers as filter and macrophages to ingest microbes & foreign material

“Erythrocyte graveyard” where worn out RBCs are phagocytized by macrophages

Nonspecific Defenses

Protection against a wide range of pathogens

Pathogens = anything capable of causing disease

• Bacteria

• Viruses

• Toxic chemicals

• Radiation

Nonspecific Defenses

• External Barriers

• Leukocytes & Macrophages

• Immunological Surveillance

• Interferons

• Complement System

• Inflammatory Response

• Fever

External Barriers

Skin

Mucous Membranes

Secretions;

Tears, saliva, urine, vaginal secretions, perspiration

Lysozymes = antibacterial enzymes that breakdown cell walls

Stomach acid

Leukocytes & MacrophagesNeutrophils

Phagocytosis, plus

Lysozymes release enzymes that trigger the respiratory burst, which produces;

Superoxide (O2-)

Hydrogen peroxide (H2O2)

Hypochlorite (HClO)

All highly toxic, so form a killing zone, that kills many bacteria & neutrophils

Eosinophils

Phagocytosis

Release toxic chemicals

Particularly effective against allergens & parasites

Basophils

Secrete histamine (vasodilator)

Secrete heparin (anticoagulant)

Stimulated by Eosinophils

Monocytes

Leave blood and become macrophages

• Wandering (Free) macrophages

• Fixed macrophages

Includes;

• Dendritic cells

• Microglia

• Alveolar macrophages

• Hepatic macrophages (Kuppfer’s cells)

Interferons

Small proteins

Released from viral-infected cells & bind to receptors on surface of nearby cells causing them to make antiviral proteins that prevent viral replication, thereby protecting those cells

Act as cell to cell signals to stimulate activities of macrophages and NK cells

p 823

Complement System

Group of 30 or more proteins

Important role in both Specific and Nonspecific defenses

p 824

Membrane Attack Complex

p 824

Immune Surveillance

Natural Killer (NK) Cells patrol body looking to find & destroy bacteria, transplanted cells,

viral-infected cells, & cancer cells.

InflammationInflammation is a local defensive response to

injury, like trauma or infection

Purposes;

1. Limit spread of pathogens & eventually destroy them

2. Remove debris of damaged tissue

3. Start tissue repair

Words ending in itis denote inflammation of that tissue (arthritis, dermatitis, etc)

Signs = heat, redness, swelling, pain

InflammationVasodilation triggered by histamine & other

chemicals released from basophils, mast cells & damaged cells (flow=heat, redness)

These chemicals also cause Increased Blood Vessel Permeability as intercellular clefts widen & allow increased filtration of;

• Fluids (swelling)• Leukocytes• Proteins (complement, antibodies, clotting

factors)

p 826

Neutrophil Behavior

Margination = loose adhesion to vessel wall

Diapedesis = crawl thru gaps between cells

Chemotaxis = move toward chemical signals from damaged cells

Phagocytosis = engulf and digest foreign cells & molecules

Neutrophils release signaling molecules to attract more phagocytes (neutrophils & macrophages) through chemotaxis

Macrophages engulf & destroy pathogens, and casualties, like tissue cells & neutrophils

Macrophages secrete colony-stimulating factors, that trigger increased production of more leukocytes (reinforcements)

What remains is Pus which is the dead cells, tissue debris & fluid that are eventually absorbed

Pain receptors are stimulated by;

1. Direct injury

2. Pressure from edema

3. Chemicals released by damaged cells (like prostaglandins & bradykinin) and bacterial toxins

p 827

Fever

Fever is an abnormal increase in body temp due to hypothalamus raising the set point for body temp.

Pyrogen (fever-causing agent) = interleukin-1, that triggers hypothalamus release of prostaglandin E (PGE) which raises set point for temp

Specific Immunity

Specific immunity is directed at

one and only one specific pathogen

An initial exposure to a pathogen will create a memory

When exposed again to the same pathogen the body reacts so quickly

that there is no noticeable illness.

Specific Immunity

Cellular (cell-mediated) immunity = lymphocytes directly attack & destroy foreign cells or diseased host cells where

Pathogen is inside human cells

Intracellular Viruses, Bacteria,

Protozoans, & Yeast

Cells of Transplanted Tissue & Cancer Cells

Specific ImmunityHumoral (antibody-mediated) immunity =

antibodies tag or mark the pathogen for destruction by other mechanisms

Indirect attack by antibodies,

instead of immune cells directly

Extracellular Viruses, Bacteria,

Protozoans, & Yeast

Molecular (noncellular) pathogens

like, toxins, venoms and allergens

AntigensAntigen = any molecule that triggers an

immune response, normally proteins, polysaccharides, glycoproteins, & glycolipids

Antigenic Determinant Sites (epitopes)

= portions of the exposed surface of the antigen that actually make it an antigen, (trigger an immune response)

= sites where antibodies bind

Immune system must distinguish between;

Self vs. Nonself molecules

Haptens• Too small to be an antigen

• Bind host macromolecule = then antigenic

• Second exposure may not require binding

• Include many allergens;

• Cosmetics

• Detergents

• Industrial chemicals

• Poison ivy

• Animal dander

T Lymphocytes (T Cells)“Born” in bone marrow, then to thymus where

they become immunocompetent, meaning they get receptors on their surface for one antigen

Must pass a test to be sure they can recognize foreign antigens, but not attack self-antigens (only 2% pass)

Graduation = multiple & form clones of identical T cells that recognize that one specific antigen, then leave thymus as naive T lymphocytes

B Lymphocytes (B Cells)Born and become immunocompetent in

bone marrow (develop receptors on surface for specific antigen)

Must pass same test to be sure they will tolerate “self” cells and recognize foreign or “nonself” cells

Then multiple & form clones of identical B cells that recognize that one specific antigen and leave marrow as naive B lymphcytes

Major Histocompatiblity Complex (MHC) Proteins

Complex = genes are on chromosome #6

Glycoproteins on surface of cells (except RBC), about 200,000 per cell

Unique to each person

Shaped like hotdog bun, they pick up antigens from inside the cell, migrate to the surface & hold them in their central groove

Class I on all cells (except RBC)

. Acting like an information relay, the MHC Class I (MHC-I) molecules retrieve bits and pieces of the proteins from inside the cell and display them on the cell surface.

MHC complexes essentially give

a read out of what's inside the cell

p 831

Antigen-Presenting Cells (APCs)

1. Phagocytosis of antigen

2. Break down into molecular fragments

3. Display (present) the epitopes on its MHC proteins

Class II MHC proteins on APCs only

macrophages, B cells, reticular & dendritic cells

Cellular ImmunityCytotoxic T (TC) cells = carry out direct attack

on enemy cells

Also known as T8, CD8, or CD8+ cells because they have a surface glycoprotein for binding to other cells called CD8

Helper T (TH) cells = promote actions of TC cells and play a key role in humoral immunity & nonspecific defenses

Also known as T4, CD4, or CD4+ cells due to CD4 glycoprotein

Cellular ImmunityMemory T (TM) cells = descended from

cytotoxic T cells and provide memory of initial exposure to an antigen, providing for a very rapid response if exposed again

Immunity as a Three Act Play

Act One = Recognition

Act Two = Attack

Act Three = Memory

OR

“the three Rs of immunity”

Recognize

React

Remember

p 833

Recognition

Naive T cells inspect cells MHC proteins & antigens

Self antigens = okay

Viral proteins, abnormal antigens made by cancer cells = Respond

Like a sign that says,

“I’m infected” or

“I’m a cancer cell”

TC cells only MHC-I

TH cells only MHC-II

p 833

T Cell Activation

Receptor on T cell surface must match foreign antigen on MHC

= binds MHC

Second binding called costimulation required for activation

Triggers clonal selection, repeated mitosis which produces a clone of T cells with receptors for same epitope

p 833

T Cell Attack

Helper T cells secrete interleukins that;

1. Attract neutrophils & natural killer cells

2. Atrract macrophages & stimulate phagocytosis

3. Stimulate T and B cell mitosis & maturation

p 833

T Cell Attack

Cytotoxic T cells attack & destroy cell with a release of chemicals

For example, Perforin creates pores in cell membrane that kill it

Recall the Membrane Attack Complex

Memory

Some TC and TH cells become memory cells

Memory T cells are long-lived & much more numerous than naive T cells

They require fewer steps, so respond to antigens much more rapidly

If the body is exposed to that antigen again, the attack, called the T cell recall response is so quick that there are no symptoms

Humoral Immunity

Instead of directly attacking enemy cells, the B lymphocytes produce antibodies that bind to antigens and tag them for destruction by other means.

Like cellular immunity, it also has 3 parts;

1. Recognition

2. Attack

3. Memory

p 835

Recognition

Immunocompetent B lymphocytes act as APCs

1. Receptor must bind to its specific antigen

2. Endocytosis

3. Digestion of antigen

4. Presentation of epitope in MHC-II on cell surface

Now called sensitized B lymphocyte

p 835

Recognition (cont’)

Sensitized B lymphocytes then must bind with a helper T cell, which secretes interleukins that complete activation

Activation triggers clonal selection – B cell mitosis giving rise to a battalion of identical B cells with receptors for the same antigen.

p 835

Recognition (cont’)

Most B cells become plasma cells that develop mainly in the germinal centers of the lymphatic nodules of the lymph nodes.

Plasma cells produce antibodies at a rate of 2,000 per second over 4 to 5 days until they die.

p 837

Note the;

Variable region with a specific antigen-binding site

Constant region is the same for each class

5 classes include; IgA, IgD, IgE, IgG, and IgM

Antibodies, also called immunoglobulins (Ig) have a monomer made of four polypeptides

An individual probably makes about

2 million different antibodies.

The human immune system may be capable

of making at least 10 billion antibodies

and possibly 1 trillion antibodies.

p 838

How Antibodies Render Antigens Harmless

1) Neutralization Only the part of an antigen that binds human cells is pathogenic, so antibodies bind these active regions & neutralize them.

p 837


2) Complement Fixation

Antibodies IgM and IgG bind to foreign cells, particularly bacteria and mismatched RBCs, which allows complement to bind & trigger cytolysis.

p 838


3) Agglutination An antibody may have up to 10 binding sites; thus, it can bind to antigens on more than one cell at a time. This immobilizes microbes and prevents them from spreading.

Effective in mismatched

RBCs and more

importantly against

bacteria.

p 838


4) Precipitation Antibodies link antigen molecules (not whole cells) together.


This creates large Ag-Ab complexes that come out of solution so they are available for complement to bind them to RBCs or be phagocytized by eosinophils .

As RBCs pass through the liver & spleen, the macrophages remove and destroy the Ag-Ab complexes.

This is the principle means of clearing foreign antigens from the blood.

p 838

Memory

During clonal selection memory B cells are also created in the germinal centers in lymph nodes. They form plasma cells within hours and mount a very quick secondary response, that prevents any symptoms.

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