Anatomy Final Immune System

Phagocyte Mobilization:

1) Leukocytes: Injured cells release chemicals called leukocytosis-inducing factors. In response, neutrophils enter blood from bone marrow and within a few hours, the # of neutrophils in blood increases 4 to fivefold. This leukocytosis, increase of WBC's, is a characteristic of inflammation 2) Margination: Inflamed endothelial cells sprout cell adhesion molecules (CAM's) that signal "this is the place." As neutrophils encounter these CAM's, the slow and roll along the surface, eventually achieving an initial foothold. When activated by inflammatory chemicals, CAM's on neutrophils bind tightly to endothelial cells. Margination refers to this phenomenon of phagocytes clinging to the inner walls (margins) of capillaries and post capillary venules. 3) Diapedesis: Continued chemical signaling prompts the neutrophils to flatten and squeeze between the endothelial cells of capillary walls 4) Chemotaxis: Inflammatory chemicals act as homing devices, or more precisely, chemotactic agents. Neutrophils and other WBC's migrate up the gradient of chemotactic agents to the site of injury (positive chemotaxis). Within 1 hr after the inflammatory response has begun, neutrophils have collected at the site and are devouring any foreign material present. Neutrophils ->Monocytes -> Macrophages

Phagocytosis:

1) Phagocyte adheres to pathogens 2) Phagocyte forms pseudopods tht eventually engulf the particles, forming a phagosome 3) Lysosome fuses with the phagocytic vesicle, forming a phagolysosome 4) Lysosomal enzymes digest the particles, leaving a residual body 5) Exocytosis of the vesicle removes indigestible and residual material

Neutrophils & Macrophages:

***Generally neutrophils & macrophages kill ingested prey by acidifying the phagolysosome and digesting its contents with lysosomal enzymes. However some pathogens are resistant to lysosomal enzymes. So helper T cells come in and release chemicals that stimulate the macrophage, activating additional enzymes that produce a lethal respiratory burst. This respiratory burst promotes killing of pathogens

Natural Killer Cells:

-"Police" the body in blood and lymph, are a unique group of defensive cells that can lyse and kill cancer cells and virus-infected body cells before the adaptive immune system is activated. -Part of a small group of large granular lymphocyte -Not phagocytic. Kill by directly contacting target cell, inducing to undergo apoptosis. Also secrete potent chemicals

Cells of Adaptive Immune System

-3 crucial types of cells: 2 distinct populations of lymphocytes, plus antigen-presenting cells (APC's) -B Lymphocytes (B cells): oversee humoral immunity -T Lymphocytes (T cells): non-antibody-producing lymphocytes that constitute the cellular arm of adaptive immunity -APC's do not respond to specific antigens as lymphocytes do. Instead, they play essential auxillary roles

Complement Activation

-3 pathways converge at C3 -C3 cleaves into C3a & C3b -This event initiates a common terminal pathway that enhances inflammation, promotes phagocytosis, and can cause cell lysis

Basic Structure of AB

-4 looping polypeptide chains linked together by disulfide bonds -4 chains combined to form a molecule—antibody monomer with 2 identical halves -T or Y Shaped -Heavy chains: 2 identical chains (loops are created by S-S bonds), flexible hinge region at approximate "middles" -Light chains- identical but half as long as H chains Variable region- Each chain forming an antibody has this region at 1 end and a Constant region at the other end **Antibodies responding to different antigens have very different V regions but their C regions are the same in all antibodies of a given class **In each arm of the monomer, the V regions of the heavy and light chains combine to form an antigen-binding site shaped to "fit" a specific antigenic determinant

Immune Response:

-A functional response who components attack foreign substances or prevent their entry into the body 1) It is specific: Recognizes and targets particular pathogens or foreign substances that initiate the immune response 2) It is systemic: Immunity is not restricted to the initial infection site 3) It has "memory": After an initial response, it recognizes and mounts even stronger attacks on previously encountered pathogens

Antigenic Determinants:

-Ability of a molecule to act as an antigen depends on both its size and complexity -Only certain parts of the antigen called antigenic determinants are immunogenic -Free bodies or lymphocytes bind to these antigenic determinants

Fever:

-Abnormally high body temp, systemic response to invading microorganisms -When leukocytes and macrophages are exposed to foreign substances in the body, they release chemicals called pyrogens (pyro=fire) -Pyrogens act on the body's thermostat—a cluster of ions in the hypothalamus---raising the body's temp above normal

Humoral Immunity:

-Antibodies specific for that antigen are made. B cells are responsible for humoral immunity B Cell Activation: Activated when matching antigens bind to its surface receptors and cross-like adjacent receptors together -Interactions with T cells are usually required to help B cells achieve full activation

Immunological Memory:

-Cellular proliferation and differentiation constitute the primary immune response, which occurs on the first exposure to a particular antigen

Antibodies (Immunoglobulins)

-Constitute gamma globulin part of blood proteins Definition: Antibodies are proteins secreted in response to an antigen by effector B cells called plasma cells, and the antibodies bind specifically with that antigen The proteins secreted by plasma cells

Vaccines:

-Contain pathogens that are dead/ attenuated (living but extremely weakened) or their components 2 Benefits: - Spare us most of the symptoms and discomfort of the disease that would otherwise occur during the primary response -Their weakened antigens provide functional antigenic determinants that are both immunogenic and reactive

What is the function of APC?

-Engulf antigens and then present fragments of them, like signal flags, of their surfaces where T cells can recognize them ***Naive T cells can only be activated by antigens that are presented to them on MHC proteins by APC's

Antimicrobial Proteins:

-Enhance our innate defenses by attacking microorganisms directly or by hindering their ability to reproduce -Most important AP's are interferons and complement proteins

Hapten (incomplete antigen)

-If small molecules link up with the body's own proteins, the adaptive immune system may recognize the combination as foreign and attack it which is harmful rather than protective -Unless attached to protein carriers, haptens have reactivity but not immunogenicity -Hapten examples) Poison ivy, detergents, cosmetics

Antibody Targets and Functions

-Inactivate antigens and tag them for destruction

Naturally:

-Naturally: Antibodies passed from mother to fetus via placenta; or to infant in her milk

Self-Antigens: MHC Proteins:

-Not foreign or antigenic to you but are strongly antigenic to other individuals (this is the basis of transfusion reactions and graft rejection) MHC Proteins: (Major Histocompatibility Complex) -Genes that code for MHC proteins ***T Lymphocytes can only bind antigens that are presented to them on MHC proteins

Passive Humoral Immunity:

-Not made by plasma cells, antibodies are introduced into your body -B cells are not challenged by antigens, immunological memory, does not occur, and the protection provided by the "burrowed" antibodies ends when they naturally degrade in the body

Cytotoxic T Cells:

-Only T cells that can directly attack and kill other cells. They roam the body -Main targets are virus-infected cells

Antibody Actions

-Partial Immunity -Prey: Extracellular pathogens (intact bacteria, free viruses, and soluble foreign molecules) -Antibodies can act intracellularly by attaching to a virus before entering cell and "dangling on." There they can activate intracellular mechanisms that can destroy the virus -But antibodies are still not that tough though against antigens

Beneficial Effects of Inflammatory:

-Prevents spread of damaging agents to nearby tissues -Disposes of cell debris and pathogens -Alerts the adaptive immune system -Sets the stage for repair

Humoral Immunity: (anti-body mediated immunity)

-Provided by antibodies present in the body's "humors" or fluids (Blood, lymph, etc.) Antibodies are produced by lymphocytes -Extracellular targets: Bacteria, bacterial toxins, and free viruses Antibodies bind to extracellular targets and inactivate them temporarily, marking them for destruction by phagocytes or complement. (flag them! Batman's helper)

Inflammatory Chemical Release:

-Released by injured/stressed cells, and immune cells -Can also be formed from proteins circulating in blood Ex) Mast cells- a key component of inflammatory response, release the potent inflammatory chemical, histamine -Macrophages (epithelial cells lining the GI tract and respiratory tract) have special membrane receptors that allow them to recognize foreign invaders and sound a chemical alarm.

Respiratory T Cells:

-T cells dampen the immune response. They act either by direct contact or by releasing inhibitory cytokines -They prevent autoimmune reactions because they surpress self-reactive lymphocytes in the periphery---outside lymphoid

Antigens:

-Trigger the activity of the remarkable cells involved in adaptive immunity -Antigens are substances that can mobilize the adaptive defensins and provoke an immune response. Ultimate targets of all adaptive immune responses -They are intruders, or NONSELF (bad guys)

Cellular Immunity: (cell-mediated immunity)

-When lymphocytes themselves rather than antibodies defend the body (living cells provide protection) -Cellular targets: Virus-infected or parasite-infected tissue cells, cancer cells...) -Lymphocytes act against such targets either directly, by killed the infected cells, or indirectly, by releasing chemicals that enhance inflammatory response or activate other lymphocytes or macrophages

Classes of Antibodies

IgM-Huge in plasma, constructed from 5 y-shaped units (monomers) linked together to form a pentamer IgA-Occurs in both monomer and dimer (2-linked monomers) forms IgD-Monomers- same basic y shaped structure IgE- Monomers- same basic y shaped structure IgG- Monomers- same basic y shaped structure (MADGE)

Antigen Encounter and Activation:

In lymph node and spleen Activation: When a lymphocyte's antigen receptors bind its antigen, that lymphocyte can be activated Proliferation and Differentiation: Activated lymphocytes proliferate and then differentiate into effector cells and memory cells which then circulate in blood and lymph (antigen challenge. Batman vs Joker!)

Other chemicals:

In the skin, some lipids in sebum and dermcidin in eccrine sweat are toxic to bacteria.

Artificially:

Injection of exogenous antibodies (from outside body) as gamma globulin. -Exogenous antibodies: Prevent hepatitis A and treat snake bites

Inflammatory chemicals:

Kinins, Prostaglandins, & Complement -Dilate local arterioles and make local capillaries leakier -Many attract leukocytes to injured area and have individual roles

Fixed Macrophages:

Like stellate macrophages in the liver, are permanent residents of particular organs. All are similar structurally and functionally ex. In the brain

Enzymes:

Lysozome---found in saliva, respiratory mucus, and lacrimal fluid of eye---destroys bacteria. Protein-digesting enzymes in stomach kill many different microorganisms

Free Macrophages:

Macrophages-Wander through tissue spaces in search of cellular debris/foreign invaders

Neutrophils:

Most abundant type of WBC become phagocytic

Macrophages:

Most voracious phagocytes (big eaters) and derive from WBC's called Monocytes that leave the bloodstream, enter tissues, and develop into macrophages

Defensins:

Mucous membranes and skin secrete small amounts of broad-spectrum antimicrobial peptides called defensins. Defensin output increases dramatically in reponse to inflammation when surface barriers are breached. Defensins help to control bacterial and fungal colonization in exposed areas.

Defensive Mechanisms

Neutralization: Simplest. Occurs when antibodies block specific sites on viruses or bacterial exotoxins (chemicals secreted by bacteria)

IFN gamma:

Or immune interferon, is secreted by lymphocytes and has widespread immune mobilizing effects, such as activating macrophages

Lymphocyte, Development, Maturation, and Activation of B & T cells

Origin: Lymphocytes originate in red bone marrow from hematopoietic stem cells Maturation: Immunocompetence- Each lymphocyte must become able to recognize its one specific antigen by binding to it -T cells mature in thymus and B cells in red bone marrow. ***Primary lymphoid organs are the thymus and bone marrow.

Phagocytes:

Pathogens (virus, bad guy) are confronted by these

Helper T Cells:

Play a central role in mobilizing both its humoral and cellular arms -Once activated by APC presentation of antigen, TH cells help activate B and T cells, and induce B and T cells to proliferate. Without the help of "director" T cells, there is no adaptive immune response

4 Cardinal Signs:

Redness, Heat, Swelling, and Pain...impaired function too

Complement:

Refers to a group of at least 20 proteins that normally circulate in blood in an inactive state Ex) C1 thru C9, factors B, D, & P, plus several regulatory proteins -Activated compliment also lyses and kills certain bacteria and other cell types

Body's first line of defense is the

Skin & Mucous Membranes

Precipitation:

Soluble molecules (instead of cells) are cross-linked into large complexes that settle out of solution. ***Precipitated antigen molecules are much easier for phagocytes to capture and engulf than are freely moving antigens

TLR's:

Toll-like receptors/surface membrane receptors that play a central role in triggering immune responses -11 types -Once activated, a TLR triggers the release of inflammatory chemicals called cytokines

Inflammatory Reaction:

Triggered whenever body tissues are injured by physical trauma

Vasodilation and Increased Vascular Permeability:

Vasodilation: Accounts for 2 of cardinal signals of inflammation -Redness and heat of an inflamed region are both due to local hyperemia (congestion with blood) that occurs when local arterioles dilate Permeability: Increased of local capillaries Exudate- Fluid containing clotting factors and antibodies-seeps from the blood into the tissue spaces -Causes local swelling (edema) and presses on nerve endings causing a sensation of pain

Agglutination:

When cell-bound antigens are cross-linked the process causes clumping of foreign cells

Naturally:

When you get a bacterial/viral infection, during which time you develop symptoms of the disease and suffer a little

Artificially:

When you receive vaccines

Active Humoral Immunity:

When your B cells encounter antigens and produce antibodies against them. Establishes immunological memory -Acquired in 2 ways: Naturally and Artifically

Antibody titer:

Within 2 to 3 days the antibody concentration in the plasma rises steeply to reach much higher levels than in the primary response -Check if you are immune to something

C3a:

and other cleavage products formed amplify the inflammatory reponse by stimulating mast cells and basophils to release histamine and by attracting neutrophils and other inflammatory cells to the area

C regions in stem:

determine antibody class and serve common functions in all antibodies. They are the effector regions of the antibody that dictate: 1) Cells and chemicals of the body that the antibody can bind to 2) How the antibody class functions to eliminate antigens

Primary Immune Response

has a lag period of 3-6 days after antigen encounter -This lag period mirrors the time required for the few B cells specific for that antigen to proliferate and for their offspring to differentiate into Plasma cells -If or when someone is re-exposed to the same antigen the 2nd immune response occurs.

IFN alpha and IFN Beta:

have the anti-viral effects and also activate NK cells

Interferons:

indirect role in fighting cancer -Infected cells secrete small proteins called Interferons (IFN's) to help protect cells that have not yet been infected -IFN's diffuse to nearby cells, which they stimulate to synthesize proteins that "interfere" with viral replication in still-healthy cells by blocking protein cynthesis and degrading viral RNA -IFN's are a family of immune modulating proteins produced by a variety of body cells, each having a different effect

C3b:

molecules that coat the microorganisms, provide "handles" that receptors on macrophages and neutrophils can adhere to, allowing them to engulf the bacteria more rapidly (opsonization)

Acid:

Acidity of skin, vaginal, and stomach secretions---acid mantle---inhibits bacterial growth

Plasma Cells:

Antibody-secreting effector cells of the humoral response -Most cells of the clone differentiate into plasma cells -Clone cells that do not become plasma cells become long-lived memory cells

Cell Lysis:

Begins when C3b binds to the target's cell surface and triggers the insertion of a group of complement proteins called MAC (membrane attack complex) into the cell's membrane. MAC forms and stabilizes a hole in the membrane that allows a massive influx of water, lysing the target cell

Duration of Ab in blood:

Blood levels of secondary response antibodies remain high for weeks to months

Memory cells:

Can mount and almost immediate humoral response if they encounter the same antigen again in the future

3 Pathways of Complement Activation

Classical Pathway: Involves anti-bodies, water-soluble protein molecules that the adaptive immune system produces to fight off foreign invaders -Complement fixation: Double-binding of antibodies Lectin Pathway: Involves lectins, water soluble protein molecules that the innate immune system produces to recognize foreign invaders. When lectins bind specific sugars on the surface of microorganisms, they can bind and activate complement Alternative Pathway: Triggered when spontaneously activated C3 and other complement factors interact on the surface of microorganisms. These microorganisms lack the complement activation inhibitors our own cells have

Opsonins:

Complement proteins that provide "handles" to which phagocyte receptors can bind ***Any pathogen can be coated with opsonins (opsonization) "to make tasty," which greatly accelerates phagocytosis of that pathogen

Complete Antigens:

Complete Antigens: 2 Important functions -Immunogenicity- the ability to stimulate specific lymphocytes to proliferate(multiply) -Reactivity- the ability to react with the activated lymphocytes and the antibodies released by immunogenic reactions ***Foreign proteins, polysaccharides, and lipids & nucleic acids can act as complete antigens ***Proteins are the strongest Antigens -Bacteria, fungi, and virus particles: Immunogenic -Peptides and nucleotides: Not immunogenic

Example of a Cytokine

Cytokine: General term for mediators that influence cell development, differentiation, and responses in the immune system Cytokines are chemical messengers involved in cellular immunity belong to these group of molecule Ex) Interferons and interleukins Some cytokines promote T cell proliferation

Major types of cells acting as APC's are...

Dendritic: found on skin. Antigen catchers Macrophages: Widely distributed throughout lymphoid organs and connective tissues B Lymphocytes: Do not activate T cells like dendritic and macrophages. They present antigens to a certain kind of T cell ***These APC's present antigens to T cells on MHC proteins

Mucin:

Dissolved in water forms thick, sticky mucus that lines the digestive and respiratory passageways. This mucus traps many microorganisms. Much in watery saliva traps microorganisms and washes them out of the mouth into the stomach where they are digested.

Secondary Immune Response:

Faster, more prolonged, and more effective because the immune system has already been primed to the antigen and sensitized memory cells are already on "alert" -Memory cells provide Immunological Memory: Adaptive (or acquired) immunity creates immunological memory after an initial response to a specific pathogen, leading to an enhanced response to succeeding encounters with that same pathogen or 22nd time, a secondary

Cell/ Roles in Cell-Mediated Immunity

Helpter T, Respiratory T, Cytotoxic T Cells

2 Adaptive Arms of Adaptive Immunity

Humoral and Cellular Immunity