Chapter 12

The complement system

-Another non-specific defense mechanism. -Involves complement proteins. -The complement system punches holes in microorganisms and destroys them. -Two ways by which complement system is activated: alternate complement pathway (non-specific) and classic complement pathway (specific).

Specific clonal selection

-B cell clone specific to the antigen is activated. -Expands in number by proliferation. -Differentiates into plasma and memory cells. -Plasma membrane produces antibodies, memory cells set aside for future encounter, primary and secondary responses (vaccination)

Origins of B and T cells

-B cells are matured in Bone marrow. -T cells are matured in Thymus. -Cytokines can stimulate B and T cell production.

Cells involved in adaptive immune response

-B cells: humoral immunity, produce antibodies. -T cells: cell mediated immunity. -each B and T cells are specific for one particular foreign material. -the chosen lymphocytes multiply and expand to launch a highly targeted attack against the invaders. -memory cells are created for future defense.

Formation of membrane attack complex (MAC)

-C5 through C9 assemble into a large, donut shaped protein complex. -embeds itself in the surface membrane of nearby microorganisms, creating a large channel through the membrane.

Clonal selection theory accounts for the specificity of antibody production

-Diverse B lymphocytes are produced during fetal development. -Each B cell contains unique receptor for recognizing specific antigens. -Clone: family of identical cells producing same antibodies.

Immune complex diseases

-Freely circulating antigen-antibody complex can be trapped in kidneys, joints, brain, small vessel of skins. -cause widespread inflammation and tissue damage.

Events taking place during inflammation

-Localized vasodilation: induced by histamine. -increased capillary permeability. -localized edema. -walling off the inflamed area. -emigration of leukocytes.

Physical hindrance of antigens

-Neutralization: antibodies combine w bacterial toxins and prevent harmful chemicals from interacting with susceptible cells. -Agglutination: multiple antibody molecules cross-link numerous antigen molecules into chains or lattices of antigen-antibody complexes.

Cytotoxic T cells secrete chemicals that destroy target cells.

-Perforin: poke hole in cell. -Granzymes: enter cell and induce apoptosis. -cytotoxic T cells are microscopic "hit men" -most frequent target are host cells infected with viruses.

Helper T Cells: 1, 2, TH17, and TFH

-Promote different patterns of immune response

Hybrid natural killer cells

-Subset of cytotoxic T cells, recently discovered. -have properties of both NK cells and cytotoxic T cells. -function not clear but found to be important for suppression of autoimmunity and in tumor rejection.

Amplification of innate immune responses

-activate complement system. -IgG acts as opsonin and enhances phagocytosis by innate immune cells. -Stimulate natural killer cells.

Antiviral effect of interferon

-acts as a whistle-blower. -warn of viral infection in healthy cells. -interferon stimulates synthesis of enzymes that degrade viral messenger RNA

Cytotoxic T-cells fatally attack only the specific types of virus-infected cells.

-attack previously exposed virus-infected cells and cancer cells. -need maturation period before launching attack, so is slower than NK cells but are specific.

T cells bind directly with their targets

-cell mediated immunity. -TCR recognize foreign antigen only when presented with self antigen. -need antigen presenting cells to present self antigens known as Major Histocompatibility Complex (MHC). -like B cells, T cells are also specific and form memory cells. -has primary and secondary response

Function of cytokines

-endogenous pyrogen. -decreases plasma IRON concentration: reduce iron available to support bacteria multiplication. -stimulate release of C-reactive protein, non specific opsonin. -TNF stimulates histamine release from mast cells: histamine promotes local vasodilation and increased permeability. -IL-1 promotes proliferation of B and T cells. -Cytokines orchestrate the inflammatory response.

Functions of lymphoid tissue: Lymph nodes, tonsils, adenoids, appendix, gut-associated lymphoid tissue

-exchange lymphocytes with lymph. -resident lymphocytes produce antibodies and activated T cells, which are released into the lymph. -resident macrophages remove microbes and other particular debris from the lymph.

Functions of lymphoid tissue: Spleen

-exchanges lymphocytes with the blood. -resident lymphocytes produce antibodies and activated T cells, which are released into the blood. -resident macrophages remove microbes and other particular debris, most notably worn-out red blood cells from the blood. -stores a small percentage of red blood cells, which can be added to the blood by splenic contraction as needed.

Anticancer effects of interferons

-markedly enhances actions of cell-killing cells. -natural killer cells and cytotoxic T cells (attack and destroy both virus-infected cells and cancer cells).

Cytokines

-messenger molecules released by immune cells. -chemical means by which immune effector cells can communicate (IL-1, IL-6, TNF). -cytokines are involved in aggravating inflammatory response.

Natural killer cells destroy virus-infected cells and cancer cells.

-naturally occurring, lymphocyte-like cells. -non-specifically destroy virus infected cells. -release chemicals that lyes the membrane of infected cells. -provide an immediate, non-specific defense.

Innate immune responses

-nonselectively defend against foreign material. -first line of defense. -immediate response. -do not have memory.

Functions of lymphoid tissue: bone marrow

-origin of all blood cells. -site of maturational processing for B lymphocytes.

Innate immune response: Toll-like receptors

-recognize exogenous pathogen-associated molecular patterns (PAMPs). -toll-like receptors (TLRs) activate immune response genes. -TLRs are the eyes of the immune system.

function of helper T cells

-secrete chemicals that amplify the activity of other immune cells. -B-cell growth factor (IL-4, IL-5, IL-6). -T dependent B cells cannot produce antibodies without help from Th cells. -T-cell growth factor (IL-2). -Produce chemotaxins to recruit neutrophil and macrophages to invaded area. -Localization of macrophages by inhibiting their outward migration. -Eosinophils activation (IL-5). -IL-4 promotes development of IgE to defend against parasitic worms. -T helper 1, T helper 2, TH17, and TFH.

Adaptive responses

-selectively target particular invaders. -highly specific. -ultimate weapon. -late response. -has memory

Functions of lymphoid tissue: Thymus

-site of maturational processing for T lymphocytes. -Secretes the hormone thymosin

Modes of passive immunity

-transfer of IgG across placenta during intrauterine fetal development. -colostrum (first milk) contains IgA. -passive immunity sometimes used clinically to circumvent extremely viral infection such as rabies virus, tetanus virus, snake venom, etc. -anti-serum can elicit allergic reactions in some individual called serum sickness

Defense in the nervous system

-usual method of virus immunity does not work for nervous system. -neurons cannot be replaced by cell division, so destroying infected cells is not ideal. -antibodies target viruses for destruction in the ECF, and also can eliminate viruses inside neurons.

Innate immune response: Intracellular pattern recognition receptors

-viral DNA and RNA. -bacterial cell wall. -damage associated molecular patterns.

Immune system functions

1. Defend against invading pathogens (disease producing microorganisms). 2. Remove worn-out cells and tissues damaged by trauma or disease, paving the way for wound healing and repair. 3. Providing immune surveillance: identifying and destroying abnormal cancer cells that have originated in the body.

Types of Innate Immunity

1. Inflammation: a nonspecific response to tissue injury in which phagocytic specialists play a major role. 2. Interferon: a family of proteins that nonspecifically defend against viral infection. 3. Natural killer cells: special clad of lymphocytelike cells that spontaneously and no specifically rupture. 4. Complement system: a group of inactive plasma proteins that bring about destruction of foreign cells by attacking plasma membranes.

The goal of inflammation is to bring to the invaded or injured area phagocytes and plasma proteins that can

1. Isolate, destroy, or inactivate invaders. 2. Remove debris. 3. Prepare for subsequent healing and repair.

Inflammation

A nonspecific response to a foreign invasion or tissue damage. -defense by resident tissue macrophages.

Alternate complement pathway

Activated by carbohydrate chain present on surface of microorganisms. Innate immune response.

Classical complement pathway

Activated by response to specific antibodies produced against a specific foreign invader. Adaptive immune response

Augmenting inflammation

Activated proteins in the complement cascade act on their own to augment the inflammatory process. -serving as chemotaxins. -acting as opsonins. -promoting vasodilation and increased vascular permeability. -stimulating release of histamine. -activating kinins- pro-inflammatory.

Adaptive immunity

An antigen induces an immune response against itself. -large, unique molecule that triggers a specific immune response against itself when it gains entry into the body. -in general, the more complex a molecule is, the greater its antigenicity.

Adaptive immune responses include

Antibody-mediated immunity (humoral immunity, B cells) and Cell-mediated immunity (T cells).

Viruses in the ECF

Are destroyed by phagocytic cells, neutralizing antibodies, and the complement system.

T-dependent antigens

Are typically protein antigens, do not directly stimulate production of antibody without the help of a helper T cell.

IgE

Attach to mast cells and basophils, releases histamine that induces allergic reaction

Major targets of the immune system

Bacteria and viruses

IgG

Binds to phagocytic cell and serves as opsonin

Passive immunity

Borrowed immunity conferred in receipt of preformed antibodies.

Emigration of leukocytes: Chemotaxis

Chemoattraction of leukocytes guide their movement to the site of infection. -chemokines: cytokines that act as chemotaxins

Chronic illness: inflammation

Chronic inflammation occurs when the triggering agent persists long term. -either not or entirely eliminated. -or because it is constantly present or continually renewed.

Leukocytes are the effector cells of the immune system.

Consists of neutrophils, eosinophils, basophils, monocytes/macrophages, and lymphocytes.

Inflammasomes

Cytosolic, multi protein complex triggered in response to activated NLRs that bring about inflammatory response.

The three types of T cells are cytotoxic, helper, and regulatory.

Cytotoxic T cells (CD8+): destroy host cells harboring anything foreign. TCR are associated with CD8 cocoreceptors. Helper T cells (CD4+): modulate activities of other immune cells. TCR associated with CD4 coreceptors. Regulatory T Cells are a small subset of CD4+ cells. Also contain CD25, a receptor component for regulatory cytokine IL-2.

vaccination

Deliberately exposes a person to the pathogen that has been stripped of its disease-inducing capabilities but can still induce the antibody to form against itself.

Virulence

Disease producing power of a pathogen

Primary response

During initial contact with microbial antigen, the antibody response is delayed for several days until plasma cells are formed and does not reach its peak for a couple of weeks. -regulated by IgM antibodies.

IgM

First responder to infection

Neutrophils

Highly mobile phagocytic specialists that engulfment and destroy unwanted materials.

Thymosin

Hormone produced by thymus. -stimulate the production and maintenance

Secondary response

If the same antigen ever reappears, the long-lived memory cells launch a more rapid/potent and longer lasting response.

Innate defenses

Inflammation, interferon, natural killer cells, complement system.

Mechanism of action of interferon in preventing viral replication

Interferon, which is released from virus-infected cells, binds with other uninvited host cells and induced these cells to produce inactive enzymes capable of blocking viral replication. -the inactive enzymes are activated only if a virus subsequently invades one of these prepared cells.

RLRs (RIG-like receptors)

Intracellular receptor that recognize viral DNA or RNA within the cytosol

NLRs (NOD-like receptors)

Intracellular receptors that distinguish Intracellular PAMPs such as bits of bacterial cell wall engulfed by a phagocyte or parasites that have invaded a non immune cell. -trigger formation of inflammasomes

Antibodies

Largely amplify innate immune responses to promote antigen destruction.

Emigration of leukocytes: margination

Monocytes stick to the inner endothelial lining of capillaries.

Cells involved in innate immune response

Neutrophils, eosinophils, basophils, and monocytes/macrophages.

Bacteria

Nonnucleated, single celled organisms self-equipped with all machinery needed for survival and reproduction.

Anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs: most commonly used NSAIDs (aspirin, ibuprofen), decrease histamine release, inhibits production of prostaglandin and decrease fever. Glucocorticoids: suppress immune system, switch off inflammatory genes.

Virus

Not self-sustaining cellular entities. -consist only of nucleus acids enclosed by a protein coat. -lack cellular machinery, cannot carry out metabolism or reproduce. -only way they can do this is by invading a host cell.

Antigens stimulate B cells to convert into

Plasma cells that produce antibodies. -plasma cells produce antibodies: combine with the specific type of antigen that stimulated activation of the plasma cell. -antibody subclasses: IgM, IgG, IgE, IgA, IgD.

IgA

Present in mucus membrane

Active immunity

Production of antibodies as a result of exposure to an antigen.

Antibodies are Y shaped and classified according to

Properties of their tail portion. -functional properties: what the antibody does once it binds with an antigen.

T helper 1 (TH1)

Rally cell-mediated (cytotoxic T cell) response. -in thymus, IL-12 drive TH1 differentiation from naive T cells.

Basophils

Release histamine and heparin and are also involved in allergic reactions

Interferon

Released from virus-infected cells. -interferes with viral infections. -briefly provides nonspecific resistance to viral infections. -interfere with viral replication.

IgD

Role not clear, but some function in allergic reaction. Bound to mast cells and basophils cells.

Eosinophils

Secrete chemicals that destroy parasitic works and are involved in allergic reactions

Emigration of leukocytes: Diapedesis

Stuck leukocytes start leaving the vessel by a process called diapedesis.

Adaptive (specific) immunity

T cell: cell mediated

B Cells and Antibody-Mediated Immunity

The antigens to which B cells respond can be T-independent or T-dependent.

Immune system

The body system that provides immunity

Immunity

The body's ability to protect itself by resisting or eliminating potentially harmful invaders or abnormal cells.

clonal diversity

The huge repertoire of B cell is built by reshuffling a small set of gene fragments. -VDJ recombination. -Antibodies are proteins synthesized in accordance with a nuclear DNA blueprint.

Lymphoid tissues

Tissues that produce, store, or process lymphocytes. -adenoids. -tonsils. -thymus. -lymph nodes. -spleen. -lymphatic vessel. -Peyer's latched: gut associated tissue. -appendix. -bone marrow.

Monocytes

Transformed into macrophages; which are large, tissue bound phagocytic specialists.

Lymphocytes

Two types: B lymphocytes: produce antibodies that indirectly lead to the destruction of foreign material (antibody-mediated immunity). T lymphocytes: directly destroy virus-invaded cells and mutant cells by releasing chemicals that punch lethal holes in the victim cells (cell-mediated immunity)

Characteristics of inflammation

redness, heat, swelling, pain

T-independent antigens

stimulate production of antibody without any assistance from T cells