Immune system

Complement System (nonspecific response)

-A nonspecific or specific immune response -Major mechanism -Triggered by non-specific mechanism or triggered by antibodies -Formation of MAC (membrane-attack complex): inactive plasma proteins produced by the liver are already circulating in the blood. When the mechanism is triggered, the inactive proteins are converted into active proteins via a cascade of activation. This leads to the formation of a complex of several proteins: MAC. -The MAC punch holes in victim cells, causing them to lyse. This is a way to destroy bacteria without phagocytosis

Natural Killer Cells (nonspecific response)

-Another type of nonspecific immune response -Natural killer cells are naturally occurring, lymphocyte-like cells that nonspecifically destroy virus-infected cells and cancer cells by releasing chemicals that directly lyse (rupture) -They are similar to cytotoxic T cells which are specific for certain cells (cytotoxic T cells can only attack specific types of virus-infected cells and cancer cells to which they have been previously exposed).

Functions of Antibodies

-Antibodies cannot directly destroy foreign organisms/unwanted materials on binding with antigens on their surfaces. However, they can do other things to exert a protective function: (1) Physically hinder antigens: neutralization, agglutination, precipitation --> destroyed by phagocytosis. In agglutination, multiple antibody molecules cross link numerous antigen molecules into chains or lattices of antigen-antibody complexes. Then, foreign cells, such as bacteria or mismatched transfused RBCs, bind together in a clump. When linked antigen-antibody complexes involve soluble antigens, the lattice can become so large that it precipitates out of the solution. -Most important function of antibodies = enhance the nonspecific immune responses: ---Antibodies mark foreign material as targets for destruction by nonspecific mechanisms (complement, phagocytes, killer cells). ---Antigen-antibody complex activates the complement system-->membrane attack complex which attacks the antigen (most important effect of antibodies protection).

B-lymphocytes: anti-body mediated immunity

-B lymphocytes produce antibodies: one B lymphocyte forms a clone of B cells. -B lymphocytes reside in lymphoid tissue throughout the body -Each B cell is programmed to respond to only 1 of 100 million + antigens. Have at least one B cell for every possible antigen that we might ever encounter. -When they enter lymph tissue, a single B lymphocyte can form a clone of B lymphocytes (cells): Diverse B lymphocytes are produced during fetal development, each capable of synthesizing an antibody against a particular antigen before ever being exposed to it. All offspring of a particular ancestral B lymphocyte form a family of identical cells, or a clone, that is committed to producing the same specific antibody. -B cells remain dormant, not actually secreting their particular antibody product nor undergoing rapid division until they come in contact with appropriate antigen. When an antigen gains entry to the body, the particular clone of B cells that bear receptors (B-cell receptors: BCRs) on their surface uniquely specific for that antigen is activated or "selected" by the antigen binding with the BCRs. -When BCRs bind w/ an antigen (specific receptors for specific antigens), binding causes the activated B-cell clone to multiply and differentiate into two cell types: most B cells differentiate into active plasma cells while other become dormant memory cells. -Plasma cell: produces antibodies that can combine with the specific type of antigen that stimulated activation of the plasma cell: contain binding sites for the antigen. This is the primary response; takes 5-10 days, then plasma cell dies. Has highly productive but short life span. -Memory cells: some of the new B lymphocytes produced by the activated clone differentiate into memory cells, which do not participate in the current immune attack against the antigen but instead remain dormant and expand this specific clone. If a person is ever reexposed to the same antigen, these memory cells are primed/ready for even more immediate action. -Antibodies (proteins) are released into the blood or lymph-->gamma globulins (immunoglobulins) -Antibodies (immunoglobulins) are grouped into 5 subclasses based on differences in their biological activity. --IgG antibodies produce the most specific immune responses against bacterial invaders and a few types of viruses; IgG = most abundant in body --IgE = the antibody mediator for common allergic responses such as hay fever, asthma, and hives.

Polymorphonuclear granulocytes

-Class of leukocytes; meaning "many-shaped nucleus" and "granule-containing cells." -Cytoplasm contains abundance of granules (can see under microscope) -types of polymorphonuclear granulocytes: neutrophils, eosinophils, basophils

Agranulocytes

-Class of leukocytes; name means "cells lacking granules" -Types of agranulocytes: monocytes (phagocytes) and lymphocytes

Cytotoxic T cells (killer T cells)

-Destroy host cells bearing foreign antigen (such as body cells invaded by viruses, cancer cells that have mutated proteins, and transplanted cells). -Virus-infected cells: --Antigenic properties of the virus are incorporated into the host cell's membrane (for recognition). --Specific cytotoxic T cells (for the virus) bind to the viral antigens and self-antigens on the surface of the infected cell -> destroys the cell and the virus (by releasing chemicals). -Other nonspecific defense mechanisms also come into play to combat viral infections: NK cells, interferon, macrophages, and complement system. -Virus-infected neurons are not destroyed: antibodies destroy viruses in the ECF and may also attack viruses inside neurons. It is good that virus-infected neurons are not destroyed, b/c we cannot generate new neurons. -Persistant virus: herpes virus persists in neurons for years -> occasional flare ups. -After cell-mediated immune attack is over and infection is cleared, T cells, except memory cells, die by apoptosis (suicide)

Helper T cells

-Don't directly participate in immune destruction of invading pathogens. Instead, they modulate activities of other immune cells. -They secrete cytokines which enhance the immune response (amplify activity of other immune cells): --Cytokines (also called interleukins): chemicals produced by leukocytes -> stimulate the immune system (chemotaxins lure neutrophils and macrophages to site of inflammation). --B-cell growth factor: stimulates antibody formation by activated (antigen-bound) B cells (activates B cells to produce antibodies) --T-cell growth factor: interleukin-2 --> inc activity of cytotoxic cells. -Helper T cells = immune system's master switch: turns on full power of all other activated lymphocytes and macrophages ---The AIDS (HIV) virus selectively invades helper T cells and destroys and incapacitates them.

infectious mononucleosis

-Epstein-Barr virus and other viruses -Elevation of circulating lymphocytes, test for antibodies to the virus; also diagnosed based on symtpoms: fatigue, sore throat, low grade fever, swollen lymph nodes in neck/armpits, swollen tonsils, headache, skin rash, soft swollen speech.

Inflammation (nonspecific response)

-Inflammation = a nonspecific response to tissue injury in which the phagocytic specialists-neutrophils and macrophages-play a major role, along with supportive input from other immune cell types. -Initiated by foreign invasion (bacteria, viruses, or fungi), tissue damage, or both. -Goal of inflammation = bring to the invaded or injured area phagocytes and plasma proteins that can (1) isolate, destroy, or inactivate the invaders; (2) remove debris; and (3) prepare for subsequent healing and repair. 1) Vascular events: mediated by chemical mediators (histamine, prostaglandins, cytokines, etc.) A) Localized vasodilation: almost immediately after invasion, arterioles dilate, increasing blood flow to site of injury. This vasodilation is induced by histamine. The area becomes hot and red. Increased local delivery of blood brings more phagocytic leukocytes/plasma proteins to site, which are crucial for defense response. B) Increased capillary permeability: Released histamine also increases capillaries' permeability by enlarging capillary pores: plasma proteins and fluids leak into injured area, causing localized edema. C) Stimulation of nerve endings (edema presses on pain nerve endings/histamine stimulates them) --> Pain D) Characteristic symptoms of inflammation: redness, heat, swelling (edema), and pain--all occur quickly 2) Cellular Events (hours): phagocyte mobilization and increased activity A) Macrophages in tissues and neutrophils from bone marrow ---Bone marrow releases more neutrophils, which enter the blood and travel to inflamed area. Inflamed area is creating signals-chemotactic factors (chemotaxins)-which attract neutrophils and monocytes to injury. B) Phagocyte (neutrophils and macrohages) activity: ---Phagocytes "recognize" targets (cell debris and bacteria) for destruction: different surface characteristics of targets; targets are marked-coated with antibodies. ---Phagocytosis: phagocytic cells engulf target to destroy, encase it in a vesicle, import it into phagocytic cell->lysosomes fuse with vesicle and break down material inside (intracellular lysosomal enzyme degradation). This clears the inflamed area of infections agents and debris. After neutrophils and macrophages consume max amount of bacteria, they die. C) Phagocytes release chemicals: ---Mediators of inflammation -> vascular effects ---Chemotactic factors cause phagocyte (leukocytes) migration to area ---Enhance proliferation of B and T lymphocytes -> antibodies and cell-mediated immunity (e.g. macrophages produce interleukin 1 which stimulates T and B lymphocytes). 3) Tissue repair: A) goal of inflammation = eradicate infectious organisms and clear area for repair B) Repair: --Cell division of healthy cells to replace lost ones (skin, bone, liver) ---In non-regenerative tissues such as nerve and muscle, lost cells are replaced by scar tissue. Fibroblasts, a type of connective tissue cell, start to divide rapidly and secrete large amounts of the protein collagen, which fills in the region vacated by the lost cells and results in the formation of scar tissue. (fibroblasts -> protein collagen -> scar tissue -> fills the area (for non-generative tissues such as nerve and muscle)). 4) Drugs which suppress inflammation: aspirin and related drugs and glucocorticoids.

Lymphocytes

-Type of agranulocyte -Formed in bone marrow, then are released from bone marrow and settle in lymphoid tissue-lymphocyte-containing tissues that produce, store, or process lymphocytes (lymph nodes and tonsils). -lymphocytes provide immune defense against targets for which they are specifically programmed -Two types of lymphocytes: B lymphocytes and T lymphocytes. -B lymphocytes produce antibodies, which bind with and mark specific foreign matter for destruction. -T lymphocytes produce T cells and directly destroy their specific target cells by releasing chemicals--a process called cell-mediated immunity. ---T lymphocytes destroy cells invaded by viruses/cancer cells; and have a longer life span than other WBCs.

Neutrophils

-Type of polymorphic granulocyte -Phagocytic specialists: they engulf and destroy bacteria intracellularly. -Increase in blood during a bacterial invasion -The first defenders on the scene of a bacterial invasion (differential white blood cell count (pneumonia or meningitis) bacterial or viral origin. -They also clean up debris--phagocytize all debris so area can recover.

Eosinophils

-Type of polymorphic granulocyte -These increase during allergic conditions (asthma, hay fever) and parasitic infestations (worms) -Attach to worms and secrete substances that kill it -Released in high numbers

Leukemia

-cancerous condition that involves uncontrolled proliferation of WBCs -Most WBCs produced are immature or abnormal--they have inadequate defense capabilities and cannot perform normal defense functions-->infections. -(high conc of WBCs, but they are nonfunctional) -Other consequence of leukemia: cells displace other cell lines in bone marrow-->crowd out other cells that are produced by bone marrow (reduction of RBCs and platelets). This results in anemia and deficit of platelets (internal bleeding).

Nonspecific Defense Responses (innate or inherent)

-come into play immediately on exposure to threatening agent -Non-selectively defend against foreign or abnormal material of any type--try to attack pathogen regardless of what it is -This system is initiated even with no prior exposure to the offending agent. -Try to contain infection/prevent spreading -Types of innate defenses: 1) inflammation 2) interferon 3) natural killer cells 4) complement system

Monocytes (phagocytes)

-type of agranulocyte -monocytes emerge from bone marrow while still immature and settle down in various connective tissues throughout the body, where they mature and grow into macrophages (macrophages = tissue phagocytes) -Macrophages = first responders ("eaters"-phagocytic activity) -Life span varies from months to years unless it is destroyed sooner while performing phagocytic activity. can ingest only a limit amount of foreign material before dying. Once they die, new monocytes travel to that tissue and develop into macrophages (replacement)

Allergy and hypersensitivity

Abnormal immune response to a particular antigen.

Origins of B and T cells

Both B and T lymphocytes, like all blood cells, are derived from a common stem cell in bone marrow. -B cells differentiate and mature in the bone marrow -T cells: during fetal life/early childhood, some immature lymphocytes from the bone marrow migrate through blood to the thymus, where they undergo further processing to become T lymphocytes. (Thymus = lymphoid tissue located in chest cavity). -Once being released into blood from either the bone marrow or thymus, mature B and T cells take up residence and establish lymphocyte colonies in peripheral lymphoid tissues. Here, they produce new generations of B and T cells. -Foreign invasion by antigen (an antigen triggers an immune response against itself). -B cells recognize specific foreign antigen-->antibody-mediated response -T cells recognize bad cells -> cell-mediated immune response

Primary and secondary response

During initial contact w/ an antigen, the antibody response is delayed for days until plasma cells are formed. This is the primary response. Meanwhile, symptoms persist for the person with the infection. -If the same antigen ever reappears, the long-lived memory cells launch a more rapid, more potent, and longer lasting secondary response than occurred during the primary response. This occurs within hours. -The secondary response is often adequate to prevent or minimize overt infection on subsequent exposures to the same microbe, forming the basis of long-term immunity (protection; active immunity) against a specific disease.

Thymus

Function: Maturation process for T lymphocytes; production of thymosin: a hormone that stimulates T cell process--enhances proliferation of new T cells within peripheral lymphoid tissues.

Lymph nodes, tonsils, adenoids, appendix, GI tract lymphoid tissue

Function: Resident lymphocytes (--> antibodies or sensitized T cells) and macrophages

Spleen

Function: resident lymphocytes and macrophages, stores some RBCs

Plasma cells

Most B-cells multiply and differentiate into ACTIVE plasma cells, which are prolific producers of customized antibodies that contain the SAME ANTIGEN-BIDNING sites as the surface receptors. In the blood, the secreted antibodies combine with the invading, free-existing antigen, MARKING it for destruction by the complement system, phagocytic ingestion or NK cells.

Memory cells

Some B-cells multiply and differentiate into memory cells, which are dormant until the second exposure to the antigen--then they are activated-->Secondary response

granulocyte colony-stimulating factor

Stimulates increased replication and release of granulocytes, especially neutrophils, from bone marrow.

Bone marrow

function: origination of all blood cells; maturation of B lymphocytes

Defense systems

-Two categories of immune responses: (1) non-spedific defense responses (innate or inherent); ( 2) Specific defense responses (acquired or adaptive)--ultimate weapon against pathogens. -Responses of these two systems differ in timing and selectivity of defense mechanisms

Interferon (nonspecific response)

-Interferon = family of proteins (nonspecific defense)(antiviral, anticancer) -Interferon is released from virus-infected cells (into ECF), and briefly provides nonspecific resistance to viral infections by transiently interfering with replication of the same or unrelated viruses in other host cells. "interferes with viral replication" -Stimulates healthy cells to synthesize enzymes that inhibit replication of viruses -Effects are rapid and of short duration: produced quickly but destroyed quickly -Anticancer and antiviral: enhances the actions of natural killer cells and T lymphocytes (cytotoxic T cells) ->destroy virus-infected and cancer cells. -Species-specifc: Had to produce human interferon by recombinant-DNA procedures.

Active immunity

-Production of antibodies as a result of exposure to an antigen--already had the disease, so develop immunity to it. Developing memory cells, so can be protected for years and years. -Offers long-term protection--duration of resistance is long (up to years) -Things that cause active immunity: 1) Vaccination: exposes the person to a pathogen that has been stripped of its disease-inducing capability but that can still induce antibody formation against itself 2) having had the disease: you were exposed to a specific virus, and initiated a specific immune response. If exposed to the same virus again--more rapid response, eradicated very quickly (memory cells). ---Don't form memory cells for strep throat--can get it over and over again.

Basophils

-Rarest type of polymorphic granulocyte -Similar structurally and functionally to mast cells -Like mast cells, basophils synthesize and store histamine and heparin--powerful chemical substances that can be released on appropriate stimulation. Histamine is impt during allergic reactions; heparin speeds up removal of fat particles from blood after fatty meal. Heparin also prevents clotting of blood samples and is used as an anticoagulant drug.

Specific immune response (adaptive/acquired)

-Relies on specific immune responses selectively targeted against a particular foreign material to which the body has already been exposed and has had opportunity to prepare for an attack. -Takes considerably more time than non-specific -Selective attack to eliminate or neutralize a particular offending target: requires prior exposure. -> protection (infectious agents and abnormal body cells) -Antigen-specific, systemic, memory -Responses are mediated by B and T lymphocytes. Each B and t cell can recognize and defend against only one particular type of foreign material, such as one kind of bacterium. -Acquires an ability to more efficiently eradicate an invader when re-challenged by the same pathogen in the future by establishing a pool of memory cells-when later exposed to same agent, it can more swiftly defend against the invader. -two classes of adaptive immune responses: antibody-mediated (humoral) immunity, & cell-mediated immunity. ***Antibody-mediated (humoral) immunity involves production of antibodies by plasma cells derived from B lymphocytes (B cells) ***Cell mediated immunity: production of activated T lymphocytes (T cells), which directly attack unwanted cells.

Passive immunity

-This form of immunity is much shorter (~1 month) -Passive immunity is the direct transfer of antibodies -IgG antibodies are passed from mother to fetus -Ex: mother's colostrum (first milk) contains some antibodies; this milk and therefore the antibodies it contains are transferred to baby. -Antibody-synthesizing develops 1 month after birth. -immediate protection: administer serum containing antibodies (antiserum or antitoxin): harvested from other sources (horses or sheep); tetanus toxin, poisonous snake venom; rabies virus).

T-lymphocytes: Cell-mediated immunity

-This type of specific immune response involves T-lymphocytes; they have DIRECT contact with their targets. -T cells do not secrete antibodies like B cells do. Instead, they directly contact their targets, a process known as cell-mediated immunity. -This immune response defends against viral and fungal infections, and cancer cells -Like B cells, T cells are also clonal and antigen-specific. -T-cells produce chemicals -> destroy infected and cancer cells -this mechanism takes a few days -Thymic education: T lymphocytes originate in bone marrow but mature in the thymus. T cells are activated by a foreign antigen only when it is on the surface of a cell that also carries a marker of the individual's own identity--both foreign antigens AND SELF-ANTIGENS must be on a cell's surface before a T cell can bind with it. During thymic education, T cells learn to recognize foreign antigens only in combo with the person's own tissue antigens. -T-cell activation: T cell recognizes foreign antigen on surface of cell with self-antigens -> binds (sensitized) -> chemicals or enzymes to kill cell (cell-mediated response) -Three types of T cells: cytotoxic, helper, and regulatory

Autoimmune Disease

-Tolerance: preventing your immune system from attacking your own tissues. T cells only recognize to destroy if both self and foreign antigens are present--usually tolerates our own cells and does not attack them (b/c they lack the foreign antigen). -in Autoimmune disease, the immune system fails to make a distinction btw self-antigens and foreign antigens ---MS ---Rheumatoid arthritis ---Type I diabetes mellitis

Long term protection (active immunity)

Original antigenic exposure that induces the formation of memory cells can occur through the person either having had the disease or being vaccinated -Vaccination (immunization) deliberately exposes the person to a pathogen that has been stripped of its disease-inducing capability but that can still induce antibody formation against itself