Nature of the Immune System

I. Non-Specific Immunity

Terry Kotrla, MS, MT(ASCP)BB

Immunity – Very Complex System

Cellular versus Humoral Immunity Cellular - Researchers observed that foreign

substances were removed by specialized cells in a process known as phagocytosis.

Humoral - Other researchers postulated that substances in the blood provided protection from microorganisms, humoral immunity.

Natural versus Acquired Immunity Natural immunity – born with the ability to

resist infections by normal bodily functions. Acquired immunity – requires exposure to a

pathogen or microbial agent, upon recovery lifelong immunity is acquired.

Natural (Nonspecific , Innate) Immunity

Non-specific immunity First line of defense against infection Two mechanisms – external and internal

External Composed of structural barriers to keep

infectious agents out of the body. Intact skin Cilia Physiological factors.

Physical barriers – Intact Skin

Intact Skin Difficult for a pathogen to penetrate,

Sweat creates high salt conditions. Oil layer, fatty acids and acid pH present makes

an inhospitable environment for microorganisms. Normal flora prevent other microorganisms

from establishing an infection – “competitive exclusion”.

Natural Immunity - Cilia

Natural Immunity Stomach acid (HCl) kills pathogens and sterilizes food. Mucus lining of lungs traps pathogens and cilia move

particles out to throat and it is swallowed. Coughing and sneezing. Tears wash away pathogens and have bacteriocidal enzymes. Flushing action of urine Circulating cells and tissue cells Wax in ears http://tinyurl.com/27lk4og Normal flora prevents growth of opportunistic pathogens in

mouth, large intestine and reproductive system

Factors Modify Defense Mechanisms Age Hormones Drugs and chemicals Malnutrition Fatigue and stress Genetic determinants

Nonspecific Immunity: Second line of defense Inflammatory response - four classic signs are

redness, swelling, heat and pain. Dilation of capillaries (hyperemia) to increase blood

flow to area Chemotaxis - chemicals released which cause phagocytic

white cells to migrate to the area. Increased capillary permeability allowing white cells to

go to injured area, a process known as “diapedesis” Formation of exudate - same composition as plasma and

it contains antibacterial substances, phagocytic cells, and drugs and antibiotics, if present.

Inflammatory Response

Inflammatory Response

Phagocytosis The following 3 diagrams illustrate the

process of phagocytosis. Be intimately familiar with the process.

Inflammatory Response

Second Line of Defense If bacteria are not successfully killed locally, may further

invade the host by way of the lymphatics to the regional lymph nodes. within lymph nodes the bacteria meet other phagocytic cells bacteria may overcome these and gain access to the

bloodstream where they meet circulating phagocytes (neutrophils and monocytes).

may pass through the bloodstream and reach organs such as the liver and spleen where they come into contact with tissue macrophages.

although a powerful defense system, this final phagocytic barrier may be overcome, with seeding of the microorganism to organs such as bone, brain, and kidney, terminating in fatal septicemia.

Phagocytosis -MEMORIZE1. Initiation is caused by damage to the tissues, either by trauma or as a

result of microbial multiplication.2. Chemotaxis, attraction of leukocytes or other cells by chemicals.3. Opsonization - Opsonization coating a pathogen by substances so as to

enhance phagocytosis.4. Adherence - firm contact between phagocyte and microorganism.5. Engulfment into cytoplasm and enclosed in a vacuole.6. Digestion enzymatic contents in vacuole destroy the microorganism.

Number of killing mechanisms operating in the vacuoles of phagocytic cells. One of the major mechanisms involves hydrogen peroxide which, acting

along with an intracellular enzyme, is rapidly lethal to many bacteria.

Phagocytosis

Phagocytosis http://www.cellsalive.com/ouch.htm http://health.howstuffworks.com/adam-200096.htm

http://tinyurl.com/6oa779

Cells of the Non-Specific Immune System

Cells involved in non specific immunity. Phagocytic cells

Mononuclear phagocytes Polymorphonuclear phagocytes Eosinophils

Mediator cells Basophils and mast cells Platelets

Cells involved in specific immunity

Lymphocytes Plasma cells

Origin of immune cells Origin of all these cell types are from pluripotential stem

cells found in the bone marrow. These self replicating cells differentiate into two types of

"committed" stem cells. One group differentiates further and matures to become platelets,

erythrocytes (red blood cells), monocytes or granulocytes. Second group produces cells of the lymphoid line only.

The lymphoid line will develop into 2 different types, T and B cells, depending upon where they complete their maturation, thymus or bone marrow.

Will be discussed in detail later

Phagocytic Cells Mononuclear phagocytes - include both circulating blood

monocytes and tissue macrophages found in various tissues of the body. Arise from bone marrow stem cells Not end cells, they may divide. Ingest and destroy material such as bacteria, damaged host cells or

tumor cells (non-specific immunity). Stay in peripheral blood 70 hours - migrate to tissues, double in size,

then called tissue macrophages. Tissue macrophages named according to tissue location-

liver=Kupffer cells, brain-microglial cells, etc. Phagocytosis takes place to a greater degree in tissues.

Monocyte and Tissue Macrophage

Neutrophils Characterized by a large nucleus, 3 - 5 lobes,

and specific granules in the cytoplasm. Arise from bone marrow stem cells. They are end cells. Primary function is ingestion (phagocytosis). Clear body of debris such as dead cells and

thrombi. Able to move into tissues by diapedesis.

Neutrophils with Ingested Material

Neutrophil Involved in Phagocytosis

Eosinophils Easily distinguished by the presence of large granules in their

cytoplasm which appear red when stained by routine hematology stains.

Much less phagocytic than macrophages or neutrophils Function is far from clear, however the numbers increase

greatly in certain parasitic diseases and allergic diseases. Both neutrophils and eosinophils contain specific granules,

the granules contain various enzymes which are released under certain circumstances.

Eosinophil

Mediator Cells Influence the immune response by releasing various

chemical substances into the circulation. Have a variety of biological functions

Increase vascular permeability Contract smooth muscle Enhance the inflammatory response

Two types basophils/mast cells Platelets

Basophils

Basophils easily identified due to large numbers of bluish-black granules in the cytoplasm.

The granules are a source of mediators such as histamine (vasoactive amine that contracts smooth muscle) and heparin.

Basophils and platelets are found in the circulation, mast cells are situated in the tissues of skin, lung and GI tract.

Bind IgE, a type of antibody formed during allergic reactions. Circulating basophils greatly resemble tissue mast cells and it

is likely that they are closely related in function. Basophils exist on a few hours in bloodstream. Both of these cells play a role in hypersensitivity (allergic)

reactions

Basophil

Mast cells Resemble basophils. Fixed in the tissues they are connective tissue

cells. Widely distributed through out the body. Long life span, 9-18 months. Plays a role in hypersensitivity reactions by

binding IgE.

Platelets Small non-nucleated cells derived from

megakaryocytes of the bone marrow. Important in blood clotting. Contribute to the immunological tissue injury

occurring in certain types of hypersensitivity reactions by releasing histamine and related substances which are contained within specialized granules in their cytoplasm.

Megakaryocyte & Platelets

Dendritic Cells Primary function is phagocytosis. Process antigen material and present it on the

surface to other cells of the immune system, function as antigen-presenting cells.

Act as messengers between the innate and adaptive immunity.

Classified according to tissue location. Found on skin and all major organs.

Soluble Factors Many soluble tissue and serum substances help to suppress

the grow of or kill microorganisms. Interferons - family of proteins which are important non-

specific defense mechanisms against viral infections. Transferrin - Bacteria do not thrive well in serum that

contains low levels of iron but high levels of transferrin. Complement - a group of proteins that are essential for

bacterial destruction and plays an important role in both non-specific and specific immune mechanisms.

Acute Phase Reactants (Proteins) Defined-normal serum constituents that increase rapidly

because of infection, injury, or trauma to tissues. Acute-phase proteins are a class of proteins whose plasma

concentrations increase or decrease in response to inflammation.

This response is called the acute-phase reaction . In response to injury local inflammatory cells (neutrophils,

granulocytes and macrophages) secrete a number of cytokines into the bloodstream, most notable of which are the interleukins.

The liver responds by producing a large number of acute-phase reactants.

C-Reactive Protein Increases rapidly within 4-6 hours of infection

or injury. Returns to normal rapidly once condition

subsides. Used to monitor healing and has also

increased in usefulness in diagnosing Myocardial Infarction.

Serum Amyloid A Major protein secreted during the acute phase

of inflammation. Has several roles, including

Removes cholesterol from cholesterol-filled macrophages at site of injury – clean up.

recruitment of immune cells to inflammatory sites, and

Thought to play a role in cholesterol metabolism

Complement A series of serum proteins involved in

mediation of inflammation but also involved in opsonization, chemotaxis, and cell lysis.

Alpha-1 Antitrypsin Increases during acute inflammation. Protects tissues from enzymes of inflammatory cells,

especially elastase. When the lungs do not have enough alpha-1

antitrypsin, elastase is free to destroy lung tissue. As a result, the lungs lose some of their ability to

expand and contract (elasticity). This leads to emphysema and sometimes makes breathing difficult.

Haptoglobin Binds irreversibly to free hemoglobin to

protect kidneys from damage and prevent loss of iron by urinary excretion.

Haptoglobin - hemoglobin complex removed by RES, mainly spleen.

Used to monitor hemolysis

Fibrinogen A coagulation factor integral to clot formation

which serves as a barrier to prevent spread of microorganisms further in the body.

Levels increase with tissue inflammation or tissue destruction.

Thought to play a key role in the inflammatory response and development of rheumatoid arthritis.

Ceruloplasmin Principal copper transporting protein in plasma, plays a role

in iron metabolism and histamine regulation. Stimulates the immune system to fight infections, repair

injured tissues and promote healing. Depletion found in Wilson’s disease, causes the body to

absorb and retain excessive amounts of copper. Copper deposits in the liver, brain, kidneys, and the eyes. The deposits of copper cause tissue damage, necrosis (death of the

tissues), and scarring, which causes decreased functioning of the organs affected.

Liver failure and damage to the central nervous system (brain, spinal cord) are the most predominant, and the most dangerous, effects of the disorder.

References http://www.horton.ednet.ns.ca/staff/Selig/isu/Immunity/Innate.htm

http://www.metacafe.com/tags/neutrophil/most_popular/