The Immune System

Others are transformed into plasma cells:

-Produce 2000 antibody proteins/sec. when exposed to antigen. -

What are the 3 major groups of phagocytic cells?

1. Neutrophils- 1st to arrive at infection 2. Mononuclear phagocytic system- Macrophages and monocytes 3. Organ specific phagocytes- Microglia and Kupffer cells.

Antibody structure

100 million trillion antibody molecules that contain 4 polypeptide chains. 2 long H chains and 2 shorter L chains. -Fab regions are variable. Provide specificity for a bonding to an antigen -Fc region of different antibodies are constant

What percentage of lymphocytes in blood?

65-85%

Allergy

Abnormal Immune responses to allergies: Immediate hypersensitivity: -Dendritic cells stimulate Th2 cells to secrete interleukin 4 and interleukin 13: Stimulate B cells and plasma cells to secrete IgE antibodies. (do not circulate in the blood)

What are interfeurons (cytokines)?

Act as short acting messangers that protect other cells in the vicinity from viral infection.

Theta interferon

Activates macrophages and induces MHC II antigens

What does leukocytes interact with within endothelial cell?

Adhesion molecules. Chemotaxis occurs, attracting leukocytes. -Diapedesis occurs. -First to arrive are neutrophils, then monocytes, and T lymphocytes

What does the immune system deal with?

All structures and processes that provide a defense against pathogens.

Classic pathway:

Antibodies of IgG and IgM attach to antigens on invading cell membranes . -Binding to C1 activates the process Activated C1 hydrolyzes C4 into C4a and C4b C4b binds to the cell membrane and becomes and active enzyme C4b splits C2 into C2a and C2b. C2a attaches to C4b and cleaves C3 into C3a and C3b Alternate pathway converges with classic pathway -Fragment C3b becomes attached to the complex in the cell membrane C3b converts C5 ti C5a and C5b

What cells have antibodies that serve as receptors for antigens?

B cells

What flags the cell for phagocytic attack?

Bacterial carbohydrates

Primary lymphoid organs

Bone marrow and Thymus: Produce the T and B lymphocytes. -Both T and B cells function in specific immunity.

When do the proteins C1-C9 become activated?

By the attachment of antibodies to antigens

What are the complement proteins

C1-C9

Chemotaxis in the Complement system

C5a acts as a cytokine to attract neurtorphils and monocytes to the site. -Attract phagocyes

What are the effects of aging and stress?

Cancer risks increases -Aging lymphocytes accumulate genetic errors that decrease effectiveness -Thymus functions decline Stress: Tumors grow faster -Increased production of corticosteriods

T Cells (Lymphocytes)

Cell mediated immunity Lymphocytes that seed the thymus become T cells. -Have surface characteristics and immunological function that differ from other lymphocytes. -Do not secrete antibodies -Must come in close contact to destroy them

How are neutrophils and monocytes recruited to the site of infection?

Chemotaxis

Monoclonal Antibodies

Commercially prepared Exhibit specificity for one antigenic determinant only Results in more sophisticated clinical laboratory tests. -May aid in the diagnosis of cancer May result in production of drugs combined with monoclonal antibodies against specific tumor antigens.

What tissue has the resident population of all leukocyte types?

Connective tissue

What happens if lysosomes are released into the infected area before vacuole is completely fused?

Contributes to the inflammation

Killer T cells interact with antigens

Coreceptor CD8 permits each type of T cell to interact only with a class 1 MHC molecule

Autoimmunity

Diseases produced by failure in the immune system to recognized and tolerate self antigens -Activates autoreactive T cells and stimulates production of autoantibodies by b cells. -Antibodies may be produced that are directed against other antibodies(rheumatoid arthritis) -Antibodies produced against foreign antigens may cross-react with self antigens (rheumatic fever) -Self antigens may be presented to the helper T cells together with class MHC II molecules. (type 1 diabetes)

Phagocytosis

Distinguish between the kinds of carbohydrates that are produced by mammalian cells and those produced by bacteria.

What does immunological competence occur?

During the 1st month postnatally -ability to produce antibodies against non-self antigens while tolerating self antigens -requires continuous exposure to these antigens

What resets thermostat?

Endogenous pyrogens-cell wall of gram-bacteria contains endotoxin

Autoantibodies

Exposure to self antigens results in antibody production

In active immunity what happens in the primary response? IgM

First exposure to pathogen, immune response insufficient to combat disease Latent period of 5-10 days before measurable amts of specific antibodies appear in blood

IgM

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

What is used to treat particular forms of cancer?

Gamma interferon -Lymphomas, renal carcinoma, melanoma, kaposis sarcoma

What do T cells secrete other than Perforins?

Granzymes: Enter the victim cell activating caspases: -Enzymes involved in apoptosis -Destruction of victims cell's DNA

Thymus

Grows during childhood, gradually regresses after puberty. Lymphocytes from the fetal liver and spleen; and bone marrow postnatally, seed the thymus. -Become transformed into T cells In adulthood, repopulation is accomplished by production in secondary lymphoid organs.

B Lymphocytes (B cells)

Humoral Immunity -Most of the lymphocytes that are not T cells are B lymphocytes (B cells). -Processed in the bone marrow -Function in specific immunity. -B Cells combat bacterial and some viral infections. -Secrete antibodies into the blood and lymph. -Provide humoral immunity as blood and lymph are body fluids (humors). -Stimulate production of memory cells: -Important in active immunity.

What regulates body temperature?

Hypothalamus (thermoregulation center)

What are Helper T cells?

Identified by CD4 coreceptor, Indirectly participate by regulating the response of both T killer and B cells. B cells must be activated by helper T cells before they produce antibodies.

Immediate hypersenstivity

IgE antibodies attach to mast cells and basophils. -When exposed again to same allergen, the allergen binds to antibodies attached to mast cells and basophls. Stimulate secretion of histamine, leukotrienes, and prostaglandin D. (produce symptoms)

Passive Immunity

Immune protection produced by the transfer of antibodies to a recipient from a donor. -The donor has been actively immunized -Person who receives these ready made antibodies is passsively immunized -Occurs naturally in mother to fetus during pregnancy and mother to infant during nursing.

What does C3a and C5a do with the stimulation of mast cells to secrete histamine?

Increase blood flow and capillary permeability. -Bring in more phagocytes

What does the release of cytokines do?

Increased activity of neutrophils Increased activity of interferon

Fever

Increased body temperature.

Suppressor T cells

Indirectly participates in the specific immune response Inhibit T cell and B cell activities Affect the amount of antibodies secreted Moderate immune response

What occurs when bacterial breaks in skin(enters the body)?

Inflammatory reaction initiated by nonspecific mechanisms of phagocytosis and complement activation. -Complement activation brings new phagocytes to the area. -After some time, B lymphocytes are stimulated to produce antibodies against specific antigens.

Beta interferon

Inhibits viral replication, increases NK cells and induces MHC I antigens

Alpha Interferon

Inhibits viral replication, increases NK cells and induces MHC-I antigens

What type of defenses?

Innate (nonspecific) Acquired (specific)

Neutrophils

Ist to arrive at infection

What are diseases caused by the Immune System?

It can be deranged in its ability to tolerate self antigens while it identifies and attack foreign antigens. Diseases caused by the immune system can be grouped into 3 categories: 1. Autoimmune disease 2. Immune complex disease' 3. Allergy or hypersensitivity

What does Interleukin 2 activate?

Killer T and B lymphocytes

Autoreactive T cells

Killer T cells attack self-antigens

Secondary Lymphoid Organs

Lymph nodes, spleen, tonsils, and Peyer's patches -Located in areas where antigens could gain entry to the blood of lymph. Lymphocytes migrate from the primary lymphoid organs to the secondary lymphoid organs. -Spleen filters blood -Secondary lymph nodes in tonsils and Peyer's patches filter lymph.

Mononuclear phagocytic system

Macrophages and monocytes

IgA

Main antibody type of external secretions, such as saliva and mother's milk

IgG

Main form of antibodies in circulation; production increased after immunization; secreted during secondary response. (passage of IgG antibodies from a pregnant mother to her fetus)

All cells except what cells are genetically marked with histocompatability antigens on the membrane surface?

Mature RBC -Also called human leukocyte antigens (HLAs)

Clonal Selection Theory

Mechanism by which secondary responses are produced -B lymphocytes inherit the ability to produce a particular antibody -T lymphocytes inherit the ability to respond to a particular antigen. A given B cell can produce only 1 type of antibody with specificity for 1 antigen Exposure stimulates specific lymphocytes to divide many times until large population of genetically identical cells(clone) is produced. Some cells become plasma cells that secrete primary response Others become memory cells that secrete antibodies during the secondary response Antigens select lymphocytes that area already able to make antibodies

Organ specific phagocytes

Microglia and Kupffer cells

Antigens

Molecules that stimulate the production of specific antibodies -Combine specifically with antibodies produced. -Foreign to blood and other body fluids Immune system can distinguish "self" molecules from nonself antigens. Large, complex molecules can have different antigenic determinant sites

What does Endotoxn stimulate?

Monocytes and macrophages to release cytokines. -Interleukin 1 -Interleukin 2 -TNF

Diapedesis

Neutrophils and monocytes are able to squeeze through tiny gaps between adjacent endothial cells

The complement system

Nonspecific defense system -Combination of antibodies with antigens does not cause destruction of the antigens or pathogen, Antibodies serve to identify the targets for immunological attack. -Stimulate opsinization. Antibody induced activation of the complement.

What are innate defenses?

Nonspecific; inherited as part of the structure of each oragnism.

Opsinization

Phagocytes have receptors for C3b. -Form bridges between phagocytes and victim cell

MHC Class 1

Produced by all cells but RBCs Picks up cytoplasmic peptides and transport to membrane

Active Immunity

Produced by antibodies that develop in our bodies in response to antigens

Passive Immunity

Produced by transfer of antibodies from another source.

MHC Class 2

Produced only by antigen presenting cells and B cells -Present class 2 MHC together with antigens to helper T cells Activates T cells -helper T cells react with antigens Promotes B cell responses Appear only on cell membrane when cell is processing antigens Coreceptor CD4 interacts with only a specific class of MHC molecule

G-CSF and GM-CSF

Promote leukocyte development

What do Mast cells secrete?

Prostaglandins, leukotrienes, histamine, cytokines, and TNF alpha.

Antibodies

Proteins that are also known as immunoglobulins -Found in the gamma globulin class of plasma proteins. Different antibodies have different structure, as the antibodies have specific actions.

What does the particle become surrounded by?

Psuedopods and then forms a vacuole. Vacoule fuses with lysosomes which digest the particle.

What are some of the characteristics of inflammation?

Redness, Heat(histamine stimulated vasodilation), Swelling, Pus(accumulation of dead leukocytes), Pain, and if infection continues, endogenous pyrogens

Interleukin 2

Released by helper T cells. Activates killer T cells

Interleukin 4

Secreted by T cells Required for proliferation and clone development of B cells

Interleukin 1

Secreted by macrophages and other cells Activates T cells

Interleukin 3

Serves as a growth factor. Activates killer T cells

What is nonspecific immunity?

Skin-protective barrier to resist infection GI tract-Gastric juice acidity Respiratory tract-Mucus and cilia Urinary Tract-urine acidity Reproductive tract-Vaginal acidity

Haptens

Small organic molecules can become antigens if they bind to proteins. Become antigenic determinant sites on the proteins. -By binding haptens to proteins in the laboratory, new antigens are created for research or diagnostic purposes.

What are acquired defenses?

Specific; Prior exposure (B lymphocytes)

Where are lymphocytes derived from?

Stem cells in the bone marrow

In active immunity what happens in the secondary response? IgG

Subsequent exposure to same antigen, Antibody production is much more rapid -Maximum antibody concentration reached in < 2 hrs -Maintained longer period of time.

Delayed hypersensitivty

Symptoms take longer time to develop (hours to days) -Is cell mediated T cell response Symptoms caused by secretion of lymphokines, not histamine -Antihistamines provide little benefit -E.g. contact dermatitis (poison ivy, latex gloves)

What happens when C5b and C5-C9 are inserted into bacterial cell membrane, to form a membrane attach complex (MAC).

The large pores in the membrane cause a osmotic influx of H20 which kill the bacteria/cell.

Chemotaxis

The process whereby neutrophils and other white blood cells are attracted to an inflammatory site. Movement toward chemical (chemokines) attractants.

Lymphocytes seed what?

The thymus, the spleen and lymph node

How are division of tumor cells controlled?

They are not effectively controlled by normal inhibitory mechanisms Tumor cells also dedifferentiate (become similar to less specialized cells of an embryo) -As tumor cells dedifferentiate, they reveal surface antigens that can stimulate the immune destruction of the tumor.

What do T cells do?

They attack host cells that have become infected with viruses, fungi, transplanted human cells and cancerous cells.

What do Mast cells do?

They increase membrane permeability. Vasodilation of blood vessels. Recruit neutrophils.

How doe stem cells produce the specialized blood cells?

They replace themselves by cell division so the stem cell population is not depleted.

What amplifies nonspecific responses?

When attachment of antibodies to antigens occur: -Activates complement. -Antibodies promote phagocytic activity of neutrophils, macrophages, and monocytes (opzinization)

C4, C2, C3

activation

C5-C9

attack (complement fixation)

Killer (Cytotoxic) T Cells

cell mediated destruction. Destroy specific cells with antigens on their surface Secrete perforins: Perforins polymerize in the cell memebrane and form cylindrical channels through the memebrane -Osmotic destruction of the cell.

Artificial passive immunity

conferred by administration of antibodies to combat infection (immunoglobin shot)

Natural passive immunity

conferred by transfer of material antibodies across placenta or in breast milk

Induced active immunity

develops after administration of antigen to prevent disease (vaccination)

Naturally acquired immunity

develops after exposure to antigens in environment (contact with a person who is sick)

MHC

histocompatability antigens are coded for a group of genes called MHC located on chromosome 6. MHC genes produce 2 classes of MHC molecules -Class 1 -Class2

Natural killer cells

lymphocytes related to T cells but are distinct Provide first line of cell-mediated defense. -NK cells destroy tumors in a nonspecific fashion. -NK cells attach to cells that lack class -MHC1 antigens -Release perforins and granzymes Do not require prior exposure for sensitization to the tumor antigens Stimulated by interferon

Patients treated with lymphocytes with Interleukin 2 produce

lymphokine activated killer t cells

C1

recognition