Microbiology Lecture exam 3

First-Line Defenses

-Physical Barriers: body's borders -Skin -Mucous Membranes -Antimicrobial Substances -Normal Microbiota (Flora)

destructive immune response called

anaphylaxis

Basophils

Involved in allergic reactions, inflammation -Mast cells similar; found in tissues

Innate immunity is

routine protection. Although considered non-specific, involves pattern recognition of specific molecules

Passive Immunity:

*Antibodies from another -Natural: during pregnancy, mother's IgG antibodies cross placenta; breast milk contains secretory IgA --No memory; protection is lost once antibodies degrade -Artificial: injection of antiserum (contains antibodies) --Can prevent disease before or after likely exposure --Limit duration of certain diseases --Block action of microbial toxins ---Antitoxin is antiserum that protects against a toxin --Hyperimmune globulin (antibodies to specific disease) --Immune globulin (IgG fraction from many donors; variety)

Autoimmune Disease

*Developing lymphocytes that respond to self (autoantigens) normally eliminated -Autoimmune disease results from failure to remove -Causes not entirely clear, likely numerous --Deficiency in action or control of regulatory T cells --Genetic components, possibly MHC molecules --Environmental factors including infections --Pathogen's ability to evade immune system via mimicry --Injury where self antigens released from privileged sites

Type IV Hypersensitivities: Delayed-Type Cell-Mediated

*Due to antigen-specific T-cell responses -Can occur almost anywhere in body --Peak 2 to 3 days following antigen exposure -Delayed-Type Hypersensitivity in Infectious Diseases --Cell-mediated immunity plays central role in combating intracellular microbial infections ---Effector cytotoxic T cells destroy infected host cells ---Prevents spread of infection, but also damages tissue; chronic infections yield extensive damage ---E.g., damaged sensory nerves of leprosy -Contact Hypersensitivities (contact dermatitis) --Caused by effector T cells responding to small molecules that penetrate intact skin ---Results in irritating rash, sometimes blisters *Nickel jewelry, leather, cosmetics, latex, poison ivy and poison oak common causes

Type III Hypersensitivities: Immune Complex-Mediated

*Formation of immune complexes -IgG or IgM antibodies bound to soluble antigen -Usually removed by phagocytes binding to Fc regions --If antigen in slight excess, smaller complexes form, remain in circulation or at sites of formation in tissue --Can trigger blood-clotting cascade and activate complement system, which recruits phagocytes ---Phagocytes release pro-inflammatory cytokines, may also release enzymes, toxic molecules -May occur during variety of bacterial, viral, protozoan infections; also from inhaled dust, bacteria; injected medications (e.g., penicillin)

Primary Immunodeficiencies

*Generally rare -May affect B cells, T cells, natural killer (NK) cells, phagocytes, or complement components -Many gene defects are known -Antibody deficiencies --Selective IgA deficiency --Agammaglobulinemia --Severe combined immunodeficiency (SCID) --DiGeorge syndrome --Defects in phagocytic cells -Chronic granulomatous disease (CGD) -Defects in complement system components

Immunization

*Immunization is process of inducing immunity -Has probably had greatest impact on human health of any medical procedures -Example of how knowledge is power with respect to fighting disease -Useful applications of immunological reactions in diagnostic tests

Vaccine

*Is preparation of pathogen or its products -Used to induce active immunity -Protect individual; prevent spread in population --Herd immunity develops when critical portion of population is immune to disease; infectious agent unable to spread due to insufficient susceptible hosts --Responsible for dramatic declines in childhood diseases ---Diseases sometimes reappear and spread as result of failure to vaccinate children --Effective vaccines should be safe, have few side effects ---Give long lasting protection ---Ideally low in cost, stable, easy to administer

Inactivated whole agent vaccines:

*Multiple different types: -Toxoids: toxins treated to destroy toxic part, retain antigenic epitopes --Includes diphtheria, tetanus -Subunit vaccines: consist of key protein antigens or antigenic fragments from pathogen --Avoids cell parts that may cause side effects --E.g., acellular pertussis (aP) vaccine -Recombinant vaccines: subunit vaccines produced by genetically engineered microorganisms --E.g., hepatitis B virus; yeast cells produce part of viral protein coat

Rejection of Transplanted Tissues

*Special case of delayed-type cell-mediated hypersensitivity -Most human transplants are allografts: tissues of donor and recipient are not genetically identical --Antigenic differences, especially MHC molecules, lead to rejection of graft --Autografts (from elsewhere in body) and isografts (from identical sibling) avoid these problems --Xenografts (from animals) evoke vigorous response -Effector cytotoxic T cells, natural killer cells reject --Minimized by matching donor and recipient, also indefinite use of immunosuppressive drugs ---But increases susceptibility to infections and cancer

Inactivated Vaccines

*Unable to replicate -Advantage: cannot cause infections or revert to pathogenic forms -Disadvantage: no replication, so no amplification in vivo; immune response is limited --Several booster doses usually needed --Often contain adjuvant to enhance immune response -Multiple different types: --Inactivated whole agent vaccines: contain killed microorganisms or inactivated viruses ---Treated with formalin or other chemical that does not significantly change surface epitopes ---Includes influenza, rabies, Salk polio vaccine

Attenuated Vaccines:

*Weakened form of pathogen -Replicates in recipient; disease undetectable or mild --Grown under conditions resulting in mutations, or genetically manipulated to replace genes -Advantages: single dose usually induces long-lasting immunity due to microbe multiplying in body --Can also inadvertently immunize others by spreading -Disadvantages: can sometimes cause disease in immunosuppressed individuals --Can occasionally revert or mutate, become pathogenic --Generally not recommended for pregnant women --Usually require refrigeration to keep active -Measles, mumps, rubella, chickenpox, yellow fever, Sabin vaccine against polio are examples

IgM

- 5-13% of circulating antibodies -First class produced during primary response -Principal class produced in response to some T-independent antigens -Pentamer --Five monomeric subunits give 10 antigen-binding sites --Aggregates very effectively -Large size prevents crossing from bloodstream to tissues --Primary role therefore in bloodstream infections -Most efficient class in triggering classical pathway of complement system -IgM production begins at birth; infected fetus can make

IgG

- 80-85% of total serum immunoglobulin --Also exits vessels to enter tissues -Provides longest-term protection: half-life is 21 days -Generally first and most abundant circulating class produced during secondary response -Protect via neutralization, aggregation, opsonization, complement activation, and antibody-dependent cellular cytotoxicity -Transported across placenta to fetus's bloodstream --Women cautioned to avoid pathogens to which they lack immunity (e.g., Toxoplasma gondii in raw meat, cat feces) -Maternal IgG protects fetus and newborn --Degrade gradually over 6 month period --Infant begins producing -IgG found in colostrum (first breast milk); absorbed by newborn's intestinal tract

Adaptive immune system

-"Remembers" mechanism that proved effective against that specific antigen --If encountered again, a stronger secondary response results

Grave's disease: organ-specific

-Antibodies attack receptors on thyroid gland for thyroid-stimulating hormone --Activates, leads to increased hormone production and gland enlargement; may show as goiter

Type II Hypersensitivities: Cytotoxic

-Antibodies react with molecules on cell surface -Transfusion Reactions -Hemolytic Disease of the Newborn

Cell Death and Inflammatory Process

-Apoptosis: programmed cell death; does not trigger inflammatory response -Pyroptosis: if pattern recognition receptors are triggered, cell may undergo cell death with inflammatory response

Variable region

-At ends of Fab regions; accounts for specificity --Antigen-binding site attaches to specific epitope --Fit precise but reversible: numerous non-covalent bonds

Comparison of Attenuated and Inactivated Vaccines

-Attenuated: elicits stronger immune response, but can sometimes cause disease -Inactivated: elicits weaker immune response, but cannot cause infections

Overview of Humoral Immunity

-B lymphocytes or B cells are responsible -Develop in organ in birds called the bursa, hence name -In humans, develop in bone marrow -Triggered to proliferate, differentiate into plasma cells in response to extracellular antigens --Produce Y-shaped proteins called antibodies Bind to antigens with high degree of specificity --Many different antibodies needed for wide array of antigens --Some B cells form long-lived memory B cells ---Respond quickly if antigen encountered again

IgE

-Barely detectable in normal blood --Tightly bound via Fc region to basophils and mast cells ---Allows these cells to detect, respond to antigens ---E.g., antigen binds to two adjacent IgE molecules carried by mast cell, cell releases histamine and other inflammatory mediators ---Basophils and mast cells also release chemicals when IgE binds to normally harmless foods, dusts, pollens, yielding allergic reactions of coughing, sneezing, swelling ---Some allergic (hypersensitivity) reactions can be life-threatening

Antibodies protect

-Both directly and indirectly -Directly by binding to antigen, preventing attachment to cell -Indirectly by tagging antigen for elimination

The Spectrum of Autoimmune Disease

-Can be organ-specific or systemic; damage results from antibodies and/or cell-mediated immune response -Type 1 diabetes mellitus: organ-specific -Grave's disease: organ-specific -Systemic lupus erythematosus (SLE) -Myasthenia gravis -Rheumatoid arthritis

Lymphatic vessels (lymphatics)

-Carry lymph --Fluid from body's circulatory system filters out, not all returns to capillaries; enters lymphatics instead ---Contains white blood cells and antigens from tissues ---Returns to lymph nodes; proteins, cells, other materials are removed ---Lymph then empties back into circulatory system ---Inflammatory response causes more fluid to enter tissues; increases antigen-containing fluids entering lymphatic system

Defects in phagocytic cells

-Chronic granulomatous disease (CGD) is failure to produce hydrogen peroxide and other oxygen species; phagocytes unable to kill some organisms -Chediak-Higashi disease: lysosomes lack certain enzymes, unable to destroy phagocytized bacteria -Leukocyte adhesion deficiency: white blood cells fail to leave circulation to concentrate at sites of infection

Lymphatic system is

-Collection of tissues and organs --Brings population of B cells and T cells into contact with antigens --Important since lymphocytes specific to only one or a few antigens --Lymphocyte must encounter appropriate antigen

Normal Microbiota (Flora)

-Competitive exclusion of pathogens --Cover binding sites, consume available nutrients -Production of toxic compounds --Propionibacterium degrade lipids, produce fatty acids --E. coli may synthesize colicins in intestinal tract --Lactobacillus in vagina produce low pH -Disruption of normal microbiota (e.g., antibiotic use) can predispose person to infections --Clostridium difficile in intestine --Candida albicans in vagina

Mononuclear Phagocytes

-Comprise mononuclear phagocyte system (MPS) -Includes monocytes (circulate in blood) and cell types that develop as they leave blood stream -Macrophages, dendritic cells differentiate from monocytes -Often named after location where found in body

What are cytokines?

-Cytokines are "voices" of cell --Produced by cell, diffuse to others, bind to appropriate cytokine receptors to induce changes such as growth, differentiation, movement, cell death --Act at low concentration; effects local, regional, systemic --Chemokines: chemotaxis of immune cells --Colony-stimulating factors (CSFs): multiplication and differentiation of leukocytes -Interferons (IFNs): control of viral infections, regulation of inflammatory response -Interleukins (ILs): produced by leukocytes; important in innate and adaptive immunity -Tumor necrosis factor (TNF): inflammation, apoptosis

Type 1 diabetes mellitus: organ-specific

-Cytotoxic T cells destroy β-cells of pancreas --Cells of body no longer properly take up glucose

Adaptive Immunity Develops Throughout Life

-Develops most effective means to eliminate invader --Takes a week or more to build following first exposure --Innate immunity must protect during this time ---In some cases, person may not survive long enough --Adaptive immunity has memory ---Stronger response to re-exposure --Vaccination relies upon this ability --Response has molecular specificity --Must distinguish between "healthy self" and "dangerous" ---Pathogens, cancerous cells

Adaptive immunity

-Develops throughout life: antigens cause response, system produces antibodies to bind. -Can also destroy host cells.

Skin

-Difficult for microbes to penetrate -Dermis: tightly woven fibrous connective tissue -Epidermis: many layers of epithelial cells --Outermost are dead, filled with keratin ---Repels water, maintains dry environment ---Continually slough off along with any attached microbes

Mucous Membranes

-Digestive, respiratory, genitourinary tracts -Constantly bathed in secretions (e.g., mucous) -Peristalsis of intestines, mucociliary escalator of respiratory tract remove microbes

Inflammatory process involves cascade of events

-Dilation of small blood vessels --Greater blood flow (heat, redness); slower flow rate --Leakage of fluids (swelling, pain) -Migration of leukocytes from bloodstream to tissues --Endothelial cells "grab" phagocytes, slow them down --Phagocytes squeeze between cells of vessel (diapedesis) -Clotting factors wall off site of infection -Dead neutrophils, tissue debris accumulate as pus -Acute inflammation is short term; macrophages clean up damage by ingesting dead cells and debris -If acute fails, chronic inflammation results; macrophages, giant cells accumulate, and granulomas form

Diversity in MHC genes

-Ensures proper presentation of proteins from evolving pathogen populations as well as different orientations

Transfusion Reactions

-Erythrocytes have antigenic determinants on surface -Major group is ABO, yields A, B, AB, or O blood types --Individuals have antibodies to the antigens they lack ---Mostly class IgM; appear within six months of birth --Bind to transfused cells, resulting in agglutination ---Cells rapidly destroyed by MACs or NK cells; debris can block vessels, initiate clotting; lead to kidney damage, fever, respiratory and digestive problems that may be life threatening

Eosinophils

-Fight parasitic worms -Also involved in allergic reactions

Overview of the Innate Defenses

-First-line defenses are barriers blocking entry -If invaders breach, sensor systems detect --Send out signals -Innate defenses work to destroy invaders

Immunoglobulin (Ig) Classes

-Five major classes: IgM, IgG, IgA, IgD, IgE -Have same basic monomeric structure -Each class has different constant region of heavy chain -Some form multimers of basic monomeric structure -Each class has distinct functions and properties

Active Immunity:

-Follows antigen exposure --Natural (infection) or artificial (immunization)

The Cells of the Immune System

-Formation, development termed hematopoiesis -Move around body, travel through circulatory systems -Always found in normal blood -Numbers increase during infections -Some reside in various tissues

Antibody molecules

-Have two functional regions -Two identical arms and stem of molecule -Arms bind specific antigen; amino acid sequence of end of arms varies among antibodies, yields specificity -Stem functions as "red flag" to tag antigen, enlist other immune system components to eliminate

Overview of Cell-Mediated Immunity (continued...)

-Helper T cells and cytotoxic T cells must be activated before they can multiply --Confirms antigen signifies danger --Dendritic cells are responsible for T-cell activation --Once activated, T cell proliferates, differentiates ---Forms effector helper T cells (TH cells) or effector cytotoxic T cells (TC cells) ---Both types can form memory cells --TC cells respond to intracellular antigens, induce cell to undergo apoptosis (e.g., virally infected cell) --TH cells help orchestrate humoral and cell-mediated immunity: activate B cells, macrophages; produce cytokines to direct and support T cells

Localized Allergic Reactions

-Hives: skin condition characterized by wheal and flare --Seen in positive skin test for allergens --Antihistamines block --Hay fever: itching, teary eyes, sneezing, runny nose following inhalation of airborne antigen --Antihistamines block -Asthma: respiratory allergy --Inflammatory mediators cause spasms of bronchial tubes, mucus production --Antihistamines not effective

Two basic strategies for countering foreign materials

-Humoral immunity works to eliminate extracellular antigens --Bacteria, toxins, viruses in bloodstream, tissue fluids -Cell-mediated immunity (CMI) or cellular immunity deals with antigens residing within a host cell --E.g., invading virus infecting cell -Both are powerful and can damage body's own tissues if misdirected, so system is tightly regulated --Verification usually required

Principles of Immunization

-Immunity acquired naturally or artificially -Active Immunity -Passive Immunity

Primary lymphoid organs

-Include bone, thymus --Hematopoietic stem cells reside in bone marrow; give rise to all blood cells including lymphocytes ---B cells mature in bone marrow ---T cells migrate to thymus and mature there ---Once mature, lymphocytes gather in secondary lymphoid organs and wait to encounter antigen

Constant region

-Includes Fc and part of two Fab regions --Allows immune system components to recognize otherwise diverse antibody molecules

Hypersensitivity

-Is immune response that injures --Allergy (allergic reaction) is sensitivity to allergen ---Normally harmless environmental substance ---Usually involves IgE response --Autoimmune disease targets body tissues --Immunodeficiency is disorder that occurs when immune system is too weak to prevent infection -Can be categorized into one of four major groups according to mechanisms and timing of response

B-cell receptor (BCR)

-Is membrane-bound version of a B-cell's specific antibody; binding antigen triggers response -Usually needs confirmation from helper T cell

Defects in complement system components

-Lack of early components (C1, C2) may lead to immune complex diseases -Lack of late components (C5, C6, C7, C8) allows recurring Neisseria infections from lack of MACs -Lack of C1-inhibitor: uncontrolled activation

Immunodeficiencies

-Lack of sufficient response -Primary (cogenital) results from genetic defect or environmental factors that impair development -Secondary (acquired) occur as result of infection or other stresses on system (e.g., malnutrition)

IgD

-Less than 1% of serum immunoglobulins -Involved with development and maturation of antibody response --Function in blood not clearly defined

Type I Hypersensitivities: Immediate IgE-Mediated

-Localized Allergic Reactions -Systemic Anaphylaxis

Two types of MHC molecules

-MHC class I present endogenous antigens --Produced by all nucleated cells -MHC class II present exogenous antigens --Produced by antigen-presenting cells (dendritic cells, B cells, macrophages) -T cell recognizes peptide: MHC complex

Some viral infections deplete certain immune cells

-Measles replicates in lymphoid cells, destroys -Syphilis, leprosy, malaria impact T-cell population and macrophage function -HIV destroys helper T cells, results in AIDS -Multiple myeloma is malignancy arising from a single plasma cell that proliferates out of control, produces large quantities of immunoglobulin at expense of others needed to fight infection -Other lymphoid disorders are macroglobulinemia (overproduction of IgM) and some forms of leukemia

IgA

-Monomeric form is 10-13% of serum antibodies -Most IgA is a dimer: secretory IgA (sIgA) -IgA is most abundant immunoglobulin class produced -Secreted form important in mucosal immunity --Gastrointestinal, genitourinary, and respiratory tracts --Also in secretions including saliva, tears, breast milk --Protects breast-fed infants against intestinal pathogens --Protection primarily via neutralizing toxins, viruses and interfering with attachment of microbes to host cells

Clonal Selection Theory

-Population of B cells and T cells is generated --Able to recognize functionally limitless variety of antigens --Each cell only recognizes and responds to a single epitope --Diversity of antigen recognition is random --Lymphocytes residing in secondary lymphoid organs wait for "dream antigen"—antigen with correct epitope --Specificity of antigen receptor governs recognition ---Confirmation from another cell type usually needed --B cell will then begin multiplying, generate population of clones capable of making appropriate antibodies ---Some progeny leave secondary lymphoid organs, migrate to tissues; continue responding as long as antigen present, then undergo apoptosis

Damaging Effects of Inflammation

-Process can be likened to fire sprinkler system: prevents spread, but damages building -Enzymes and toxic compounds from phagocytic cells are released, damage tissues -If limited (e.g., cut on finger) then damage minimal -If in delicate system (e.g., membranes surrounding brain, spinal cord) then can be severe, even life-threatening

Antimicrobial Substances

-Protect skin, mucous membranes -Salt accumulates from perspiration -Lysozyme degrades peptidoglycan -Peroxidase enzymes break down hydrogen peroxide -Lactoferrin binds iron -Defensins form pores in microbial membranes

Systemic Anaphylaxis

-Rare but serious form of IgE-mediated allergy -Antigen enters bloodstream, spreads throughout body --Binds to IgE on basophils, which release mediators --Extensive blood vessel dilation results in fluid loss, severe drop in blood pressure ---Can lead to heart failure, insufficient blood flow to brain and other vital organs: anaphylactic shock ---Bronchial tubes constrict, can cause suffocation -Bee stings, peanuts, penicillin injections account for most cases --Can usually be controlled by injection of epinephrine

Cytotoxic T cells

-Recognize antigen presented on MHC class I molecules --TC cells respond to endogenous antigens

Helper T cells

-Recognize antigen presented on MHC class II molecules -TH cells respond to exogenous antigens

Three general categories of Immune System Cells

-Red blood cells (erythrocytes) carry O2 -Platelets (from megakaryocytes) involved in clotting -White blood cells (leukocytes) important in host defenses

Lymphocytes

-Responsible for adaptive immunity -B cells, T cells highly specific in recognition of antigen --Generally reside in lymph nodes, lymphatic tissues -Natural killer (NK) cells lack specificity

Secondary Immunodeficiencies

-Result from malignancies, advanced age, pregnancy, certain infections (especially viral), immunosuppressive drugs, or malnutrition -Some viral infections deplete certain immune cells

Hemolytic Disease of the Newborn

-Rh (rhesus) antigen on red blood cells --Rh-positive have antigen; Rh-negative do not --If Rh-negative recipient is given Rh-positive blood, antibodies will develop; future transfused cells destroyed --Pregnant Rh-negative women carrying Rh-positive baby can develop antibodies to Rh antigen ---Will not affect first baby; IgM cannot cross placenta ---But if she carries a second Rh-positive baby, anti-Rh IgG antibodies can cross placenta, damage fetal blood cells ---Maternal enzymes usually protect fetus from toxic products of RBC destruction until after birth ---RhoGAM used to prevent hemolytic disease

Blood cells originate from

Hematopoietic stem cells -Found in bone marrow -Induced to develop by colony-stimulating factors (CSFs)

RhoGAM

-RhoGAM used to prevent hemolytic disease -RhoGAM contains anti-Rh antibodies, bind to any Rh+ erythrocytes that may have entered circulation -Prevents stimulation of primary immune response *Mother is Rh- *Fetus is Rh+

Antibody deficiencies

-Selective IgA deficiency: little or none produced -Agammaglobulinemia: few or no antibodies produced

Dendritic Cells

-Sentinel cells, function as "scouts" -Engulf material in tissues, bring it to cells of adaptive immune system for "inspection" -Usually develop from monocytes

Lymphocyte deficiencies

-Severe combined immunodeficiency (SCID) results when hematopoietic stem cells of bone marrow do not produce T and B lymphocytes -DiGeorge syndrome: thymus does not develop in embryo, so T cells do not differentiate, are absent

Secondary Lymphoid Organs

-Sites where lymphocytes gather to contact antigens --Lymph nodes, spleen, tonsils, adenoids, appendix -Situated throughout body -Peyer's patches allow sampling of intestinal contents via specialized M cells --Part of mucosa-associated lymphoid tissue (MALT) --Mucosal immunity prevents microbial invasion via mucous membranes -Lymphoid tissues under skin are skin-associated lymphoid tissue (SALT)

Vaccines and Immunization Procedures

-Some vaccines routinely given -Others only under certain circumstances -Two general categories: --Attenuated --Inactivated

Fever is important host defense mechanism

-Strong indicator of infectious disease, especially bacterial -Temperature-regulation center in brain normally holds at 37°C but raises during infection in response to pyrogens --Cytokines produced by macrophages following detection of microbial products by TLRs are endogenous pyrogens --Exogenous pyrogens produced by microbes -Growth rates of bacteria optimized for 37°C typically drop sharply above optimum, allows more time for defenses -Moderate temperature rise increases rates of enzymes --Enhances inflammatory response, phagocytic killing by leukocytes, multiplication of lymphocytes, release of attractants for neutrophils, production of interferons and antibodies, release of leukocytes from bone marrow

Myasthenia gravis

-Systemic --Antibodies bind to acetylcholine receptors at neuromuscular junctions, block impulses

Systemic lupus erythematosus (SLE)

-Systemic --Antibodies made against molecules found in cell nuclei --Symptoms include joint pain, swelling in joints, rashes

Rheumatoid arthritis

-Systemic --Connective tissue targeted, most often in joints --T cells and antibodies target

Overview of Cell-Mediated Immunity

-T lymphocytes, or T cells, mature in thymus -Two subsets help eliminate antigens --Cytotoxic T cells and helper T cells --Both have multiple surface copies of T-cell receptor (TCR) --Analogous to BCR, but does not recognize free antigen ---Antigen must be presented by body's own cells -A third subset is regulatory T cells --Formerly T suppressor cells --Recently described; current focus of research --Have TCR, but role is to prevent immune system from mounting a response against "self" molecules

Cluster of differentiation (CD) markers

-TC cells usually CD8 -TH cells usually CD4 --CD4 is receptor for HIV, which infects

Characteristics of Primary Response

-Takes 10-14 days for substantial antibody accumulation -Person may be sick, possibly seriously so, although immune system is actively responding --Some activated B cells continue dividing, others differentiate to form antibody-secreting plasma cells -Additional exposure to antigen yields much faster secondary response -Some B cells differentiate to form plasma cells --Plasma cells generate antibodies --Undergo apoptosis after a few days --Activated B cells continue proliferating and differentiating in presence of antigen, so titer steadily increases

The Inflammatory Response

-Tissue damage results in inflammation --Purpose is to contain site of damage, localize response, eliminate invader, and restore tissue function --Results in swelling, redness, heat, pain, sometimes loss of function --Pattern recognition receptors (TLRs, NLRs) trigger ---Detect PAMPs, DAMPs ---Host cells release inflammatory mediators (cytokines, histamine, bradykinin ---Inducers include microbes, tissue damage ----If blood vessels damaged, two enzymatic cascades activated; lead to coagulation and increased permeability

Antibodies react with molecules on cell surface

-Trigger destruction of cells; two methods --Activate classical pathway of complement system, lead to lysis via membrane attack complexes (MACs) --Trigger antibody-dependent cellular cytotoxicity (ADCC), lead natural killer (NK) cells to bind to Fc regions of antibodies and deliver chemicals to destroy cell -Examples include transfusion reactions and hemolytic disease of the newborn, some autoimmune diseases

Immunity acquired naturally or artificially

-Via normal events (e.g., exposure to infectious agent) or by inducing via immunization -Also passive or active

Antibody Structure and properties critical for function

-Y-shaped proteins with two general parts --Two identical arms (Fab regions) bind antigen --Stem (Fc region) --Named from early studies that yielded two types of fragments: antigen-binding (Fab) fragments and those that could be crystallized (Fc) -Antibodies have basic Y-shape: antibody monomer --Two copies of heavy chain and light chain --Amino acids fold into characteristic domains ---Light chains have two; heavy chains usually four ---Fork of Y is flexible hinge region ---Disulfide bonds join heavy, light chains and two halves

What are the four types of leukocytes?

1) Granulocytes (Neutrophils, Basophils, Eosinophils) 2) Mononuclear Phagocytes 3) Dendritic Cells 4) Lymphocytes

Granulocytes contain

Cytoplasmic granules

Neutrophils

Engulf and destroy bacteria, other material

What do macrophages do?

Phagocytize and digest foreign material

First response to antigen is

Primary response

Immune System

Protective, Can Harm if Uncontrolled

Yet, blood, muscles, bones, organs are

generally sterile. Skin, mucous membranes prevent entry.

Antibodies also called

immunoglobulins

Sensor systems detect

invaders, mount response

To microbes, human body is

nutrient-rich