Immune Protection produced by transfer of antibodies to a recipient from a donor.

Donor was actively immunized.  Recipient is passively immunized.

Used to treat snakebites, rabies, tetanus, and hepatitis.

Occurs naturally before and after birth.

Some antibodies from mother pass placenta to fetus during pregnancy and provide passive immunity.

During 1st 2-3 days of nursing, mother produces colostrum which is rich in her antibodies and gives her immunity to infant.

Immunological competence does not develop until 1 month after birth.

Commercially prepared for use in research and diagnostic tests.

Thought that tumor cells arise often but are normally recognized and killed by immune system.

When cancer develops, the immunological surveillance system of T and natural killer cells has failed.

Tumor cells dedifferentiate 9become less specialized like cells of an embryo).

As dedifferentiate, produce surface antigens that are normally recognized by immunological surveillance and destroyed.

Because were absent at the time of immunological competence was established.

Body treats these antigens as foreign.

Presence of these antigens provides basis of lab diagnostic tests for some cancers.

Are lymphocytes related to T cells.

Provide first line of cell-mediated defense.

NK cells destroy tumors in a non-specific fashion; backed up by specific response of killer Ts.

NKs are stimulated by interferon from T cells.

NKs attack cells that lack class-1 MHC antigens.

Kill with perforins and granzymes.

Involve boosting or directing patients own immune responses.

Interferons and interleukins have been useful in treatment of some CA.

Interleukin-2 activates both killer T and B cells.

Against pathogens constitute the immune system.

Grouped into 2 Categories:

Innate: inherited as part of structure of each organism.

Adaptive: function of lymphocytes and changes with exposure.

1st line of defense against invading pathogens.

Includes epithelial barriers, high acidity of gastric juice, phagocytosis, and fever.

Triggered in response to pathogen-associated molecular patterns (PAMP) produced only by microorganisms.  Best know are lipopolysaccaride from gram- bacteria and peptidoglycan from gram+ .

Connective tissue and blood contain mobile WBC, attracted to infection (chemotaxis) by chemokines.

WBCs from blood exit capillaries by extravasation (diapedesis) and ingest pathogens.

Neutrophils - 1st to arrive at infections sites.

Mononuclear phagocytes - macrophages and monocytes.

Organ-specific phagocytes in liver, spleen, lymph nodes, lungs, and brain.

Fixed phagocytes line sinusoids of liver, spleen, and lymph nodes and remove pathogens.

From phagocyte, surround pathogen forming a vacuole which fuses with lysosomes which digest pathogens.

Appears to be component of innate immunity.

Occurs when hypothalamic thermostat is reset upwards by IL1-B and other cytokines (endogenous pyrogens)

Pyrogens are released from WBCs in response to endotoxin from gram- bacteria.

Polypeptides produced by cells infected with virus that provide short-acting, non-specific resistance to viral infection in nearby cells.

alpha, beta, and gamma interferon

Is the acquired ability to defend against specific pathogens by prior exposure to those pathogens.

Mediated by production of specific antibodies by lymphocytes.

Molecules that elicit production of antibodies that specificall bind those antigens.

Are usually large molecules that are foreighn to the body.

Immune system can distinguish "self" molecules from non-self antigens, normally makes antibodies only against non-self antigens.

Large, complex molecules can have a number of antigenic determinant sites.

Small, non-antigenic molecules that become antigens when bound to proteins (form an antigenic determinant site).

Useful for creating antibodies for research and diagnosis.

Are tests that use specific antibodies to identify a particular antigen.

The binding of antibody to antigen causes clumping (agglutination) which can be visualized.

Derived from stem cells in bone marrow, which replace selves by cell division so are not depleted.

Lymphocytes produced by this process seed thymus, spleen, and lymph nodes with self-replacing colonies.

Develop from lymphocytes that seed thymus.

Do not secrete antibodies.

Attack infected host cells, cancer cells, and foreigh cells, thus they provide cell-mediated immunity.

Supply 65-85% of lymphocytes for blood and most of lymphocytes in germinal centers of lymph nodes and spleen.

Fight bacterial infections by secreting antibodies into blood and lymph.

Thus provide humoral immunity.

Have antibodies on surface that are receptors for antigens.

When bound to antigen are stimulated to divide and secrete antibodies.

Binding of B cells to antigen also triggers a cascade of reactions that activate complement proteins.  Complete proteins can kill antigen-bearing cells and promote phagocytosis.

Located below the thyroid gland.

Grows during childhood, gradually regresses after puberty.

Contains T cells that supply other tissues.

T cells can be depleted by AIDS or chemo.

These can only be replenished up to late childhood, after that, repopulation is accomplished by production in secondary lymphoid organs.

Consists of lymph nodes, spleen, tonsils, and Peyer's patches, located in areas where antigens could gain entry to blood or lymph.

Lymphocytes migrate constantly through blood and lymph from one lymphoid organ to another.

Enhances chance that antibody will encounter its antigen.

Spleen filters blood; other lymphoid organs filter lymph.

Occurs when bacteria enter a break in the skin.

Inflammatory reaction is intitated by nonspecific mechanisms of phagocytosis and complement activation.

Complement activation attracts phagocytes to area.

As inflammation progresses, B cells produce antibodies against bacterial antigens.

Attachment of antibodies to antigens amplifies nonspecific responses because of complement activation and promotes phagocytic activity of neutrophils, macrophages, and monocytes.

Leukocytes attach to surface of enothelial cells.  Move by chemotaxis to inflamed site.  Neutrophils arrive, then monocytes, then T cells.

Undergo extravasation.

Secrete heparin, histamine, prostaglandins, leukotriends, cytokines, and TNF-a

These produce redness, warmth, swelling, pus, and pain.

Recruit more leukocytes.

If infection continues, endogenous pyrogens are released.

Are proteins called immunoglobulins, part of gamma globulin class of plasma proteins.

Antibodies have same basic structure but their differences provide for antibody specificity.

Main antibody type in external secretions such as saliva and mother's milk.

Responsible for allergic symptoms in immediate hypersensitivity reactions.

Function as antigen receptors on lymphocyte surface prior to immunizations; secreted during primary response.

Y shaped, 2 long heavy (H) chains are joined to 2 shorter light (L) chains.

When cleaved, stal of Y becomes crystallizable fragment, constant among different antibodies.

Arms of Y contain antigen-binding fragment, contains a variable region that confers antibody specificity.

Each person has nearly infitine antibody molecues, with a few million different specificities.  Likely there is an antibody specific for any antigen a person might encounter.

2 mechanisms account for diversity if a few hundred genes code for Hs and a few hundred for Ls, different combinations of these could lead to millions of different antibodies.  Mutations could increase diversity, especially with age.

Part of nospecific defense system.

Activity is triggered by binding of antibodies to antigens (classic) and by bacterial coat polysaccarides (alternative).

Binding of antibodies to antigens does not by itself destroy antigens or pathogens.

Antibodies label targets for complement system attack and also stimulate opsonization.

Series of proteins whose activation forms a membrane attack complex which perforates a cell causing it to lyse.

Complement proteins can be subdivided into 3 functional groups:

C1-recognition

C4, C2, C3 - activation

C5-C9 attack (complement fixation) form the membrane attack complex.

Complement System

Classic Pathway

Antibody-antigen binding activates C1.

C1 hydrolyzes C4 into C4a and C4b.

C4b binds to cell membrane and becomes active, splitting C2 into C2a and C2b.

C2a attaches to C4b and cleaves C3 into C3a and C3b, alternate pathway also cleaves C3.

C3b converts C5 to C5a and C5b.

C5b and C6-C9 are inserted into bacterial cell membrane, forming membrane attack complex.  This creates large pore in membrane, causing osmotic influx of H2O, lysis, and cell death.

That are liberated during activation have a number of effects:

Attracting phagocytes (chemotaxis)

Phagocytes have receptors for C3b which can serve as bridge to victim cell.

C3a and C5a stimulate mast cells to secrete histamine, which increases blood flow and capillary permeability, brining in more phagocytes.

Diseases caused by Immune System

Autoimmune

Immune complex

Allergies

All caused by abnormal functioning of immune system.

Produced by failure of immune system to recognize and tolerate self-antigens.

Autoreactive T cells are formed and B cells produce autoantibodies.

Afflicts women twice as often as men.

Autoimmune Diseases

Failure of Self-tolerance

An antigen that does not normally circulate in blood being presented to immune system. (Hashimot's thyroiditis, antibodies are stimulated to attack thyroglobulin)

Combination of a self-antigen, that is otherwise tolerated, with a foreigh hapten (thrombocytopenia, low platelet count)

Antibodies being produced that are directed against other antibodies (rheumatoid arthritis)

Antibodies against foreign antigens cross-reacting with self-antigens (rheumatic fever)

Self-antigens being presented to helper T cells together with class-2 MHC molecules (Type 1 Diabetes)

Involve formation of immune complexes that are free and not attached to a cell.  These activate complement proteins and promote inflammation.  Can result from infections by bacteria, parasits, and viruses.

Can result from formation of complexes between self-antigens and autoantibodies, occurs in rheumatoid arthritis and lupus.

Abnormal immune response to allergens, comes in 2 forms: Immediate and delayed hypersensitivity.

Immediate is due to abnormal B cell response to allergen; causes effects in seconds to minutes by foods, bees, pollen.

Delayed is abnormal T cell response that causes symptoms 24-72 hours after exposure.

Dendritic cells stimulate a class of helper Ts to secrete interleukin-4 and 13 which cause B and plasma cells to secrete IgE antibodies.

Do not circulate in the blood; are attached to mast cells and basophils.

When re-exposed to same allergen, antibodies on mast cells and basophils bind it and stimulate secretion of histamine, leukotrienes, and prostaglandin D producing allergy symptoms.

Symptoms can take longer to develop.  Is a cell mediated T cell response.

Symptoms caused by secretion of lymphokines, not histamine.  Antihistamines provide little benefit.

Examples, include contact dermatitis caused by poison ivy, oak, or sumac.