Applied Physiology

1.B lymphocytes: oversee humoral immunity – antibody producing

2.T lymphocytes: non anti-body producing lymphocytes, “cellular arm” of adaptive immunity

3.Antigen presenting cells (APCs): unresponsive to antigens, auxiliary role

•Origin: bone marrow from hematopoietic stem cells

•Maturation: lymphocytes become T cells or B cells, “educated”, twofold process:

1.Immunocompetence: display unique receptor, enables lymphocyte to recognize & bind to specific antigen, non-self cell recognition

2.Self-tolerant:  thymus/T cells or bone marrow/B cells, each lymphocyte relatively unresponsive to self-antigens, won’t attack “self” cells, self cell recognition

•Engulf antigens & “present” fragments of these antigens on their surfaces,  recognized by T cells

•Dendritic cells: body surfaces that have contact with external environment

•Phagocytose antigens & migrate to lymphoid organs to present antigens to T cells

•Macrophages: throughout lymphoid organs & connective tissues

•Present antigens to T cells in order to be activated by T cells into aggressive phagocytes

•B lymphocytes: antibody mediators

•Present antigens to helper T cells to become more fully activated B cells

•Primary immune response occurs on first exposure to particular antigen, lag time ≈3–6 days

•Secondary immune response occurs on re-exposure to same antigen

•Immune system has been “primed”, memory cells on alert

•Faster, more prolonged, & more effective response

•Immunological memory utilized

•Within few hours of encountering “old enemy”, army of plasma cells rises to peak concentration after 2–3 days

•These antibodies have higher binding affinity for antigen, & blood levels may persist for weeks or months

•Active immunity: body mounts immune in response to antigen

•Naturally acquired active immunity: person suffers through symptoms of infection

•Artificially acquired active immunity: person given a vaccine

•Passive immunity: person given preformed antibodies

•Naturally acquired passive immunity: mother’s antibodies enter fetal circulation

•Artificially acquired passive immunity: person given preformed antibodies harvested from another person

•Vaccine: product that produces disease immunity

•administered via injection, oral, or aerosol

•Vaccination: injection of inactivated or live attenuated organism, produces immunity against that organism

•Immunization: process by which individual becomes protected from a disease

•Caused by: vaccines & disease exposure after recovery from disease

•All vaccines:

•Must go through “clinical trials” for safety & efficacy before approval by FDA

•Approved only if FDA determines safety & efficacy for its intended use

•Must be licensed by FDA for use in United States

•Vaccines prevent outbreaks of disease & save lives

•Critical portion of community immunized against contagious disease

•Most members of community protected against that disease, reduces spread of disease, “outbreak”

•Those not vaccinated, i.e. infants, pregnant women, immunocompromised, get some protection as spread of contagious disease is contained

•In U.S., seasonal influenza kills >36,000 & hospitalizes 200,000 more

•NIAID scientists worldwide working together to find better ways to prevent, diagnose, & treat seasonal & pandemic influenza

•proteins secreted by plasma cells in response to antigen, bind to that antigen

•Structure: 4 looping polypeptide chains linked together by disulfide bonds

•5 classes based on their structure: IgM, IgG, IgA, IgD, and IgE

•Targets antigens, basically engulf & destroy antigen

•Monoclonal antibodies: commercially prepared, specific to single antigenic determinant

1.IgM – synthesized by naïve B cells, insert into own plasma membranes; predominant class, produced after initial contact with antigen, numerous binding sites, fixes & activates complement

2.IgG – 75% of blood antibodies; predominant antibody of secondary antibody response, fixes & activates complement

3.IgA – major class in mucous membranes, saliva & tears, also plasma; prevents pathogens from attaching to epithelial cell surface

4.IgE – trace amounts in plasma; antigen binding triggers release of histamine & other chemicals, mediates allergic rxn, but can also produce allergic reaction

5. IgD – small amount in blood, functions as B cell antigen receptor

•T cells best suited for cell to cell interaction, antigen presented to T cell, provoke cellular immune response

•Diverse & more complex than B cells

•2 major populations of T cells, based on Cell Differentiation

•CD4 cells

•Usually become helper T cells, help activate B cells, T cells, & macrophages

•Some become regulatory T cells that moderate immune response

•CD8 cells

•Become cytotoxic T cells that destroy cells or other foreign substances

•https://www.youtube.com/watch?v=jgJKaP0Sj5U

•Both CD4 & CD8 become memory T cells

•Helper (CD4): secrete chemical signals, direct immune activity; assist in activating cytotoxic T cells; work closely with B cells

•Cytotoxic (CD8):  “killer” T cells, destroy virally infected cells & tumor cells, also implicated in transplant rejection

•Regulatory: “suppressor” T cells, crucial for maintenance of “immunological tolerance” release cytokines, suppress activity of B & other T cells

•Natural killer T cells: bridge adaptive with innate immune system – don’t confuse with NK cells

•Two basic mechanisms:

1.Hypersensitivity - inappropriate or excessive immune system response; overreact to antigens, 3 major types:

i.Allergy

ii.Autoimmunity

iii.Isoimmunity

2.Deficiency - failure of immune system mechanisms to defend against pathogens; fail to react to antigens, 2 broad categories:

i.Congenital

ii.Acquired

•Both can cause disease

I.Allergy: hypersensitivity to relatively harmless environmental antigens

•Allergens: antigens, trigger allergic response

•Antigen-antibody rxn of immunoglobulin IgE

•1 in 6 Americans genetically predisposed to some type of allergy

•Repeated exposure to allergen → “sensitized” → antigen-antibody rxn, → release histamine, kinins, etc, → runny nose, conjunctivitis, hives

•Serious reactions: airway restriction, vasodilation, arrhythmia can progress to anaphylactic shock

•Mast cells in tissue often involved in allergic or hypersensitivity reactions

•Reactions triggered when mast cells encounter allergen, release chemical mediators, i.e. histamine

•Medicines used to block histamine’s action: Benadryl (Diphenhydramine) & Allegra (Fexofenadine)

II.inappropriate & excessive response to self-antigens, “autoimmune” diseases

•Systemic Lupus Erythematosus (SLE): chronic inflammatory disease, affects joints, blood vessels, kidney, nervous system, skin

•Systemic nature results from production of IgG antibodies against individual’s own DNA

•Other autoimmune diseases:

•IDDM(Type I)

•Myasthenia gravis

•Rheumatoid arthritis (RA)

•Multiple sclerosis

•Grave’s disease

III.normal but undesirable reaction to antigens from different individual, e.g. pregnancy & tissue transplants

•Erythroblastosis fetalis: mother Rh-, baby Rh+

•Tissue/Organ Transplants: rejection from skin grafts, donated blood, bone marrow

–Human leukocyte antigen (HLA) system: genes encode for MHC, major cause of organ transplant rejections

»Host vs. graft rejection: recipient’s immune system recognizes foreign HLAs, attacks them, destroying donated tissue

»Graft vs. host rejection: donated tissue attacks recipient’s HLA’s, destroying tissue throughout recipient’s body, may lead to death

–Tissue typing & immunosuppressive drugs reduce rejections

•immune deficiency, failure of immune system mechanisms to defend against pathogens

•May result from failure of B & T cell function

•Chief characteristics:  development of unusual or recurring severe infections or cancer

•Immunodeficiency is not cause of death, infections & cancer are

1.Congenital: improper lymphocyte development before birth

•Disease depends on stage of stem, B or T cells defect occurrence

•Ex: SCID/Severe Combined Immune Deficiency, stem cells missing or improperly developed

2.Acquired: develops after birth, not genetic

•Contributing factors: nutritional deficiencies, immunosuppressive drugs, trauma, stress, viral infection

•Best known is AIDS, caused by HIV

•HIV: retrovirus, RNA produces own DNA inside infected cell, viral DNA becomes part of cell’s DNA

•Change in CD4 (subset of T cells) lymphocyte number, principle clinical method for monitoring AIDS

1.Creates barrier, prevents microbes from entering

2.Detects & eliminates microbes before they reproduce

3.If microbes reproduce, eliminates them

•Self:  cell surface molecules, unique to individual, immune system identifies as non-threat

•Non-self:  abnormal cell surface molecules, immune system identifies as foreign

•Self tolerance: immune systems ability to attack abnormal cells, spares  “normal” cells

•Foot soldiers, attacks within minutes anything foreign “non-self”

•2 lines of defense/barricades:

1.External body membranes, e.g. skin & mucous membranes, technically not part of the immune system, but vital barrier against invaders

2.Antimicrobial proteins, phagocytes, inhibit spread of foreign invaders – hallmark of this response “inflammation”

•3rd line of defense, requires time to initiate response

•Elite force, high tech weapons, attacks particular foreign “non-self” invaders

•Primary cells: T-cells & B-cells

•Both release & recognize same defensive molecules

•Innate not as non-specific, do have specific pathways for targeting invaders

•Innate system “alerts” adaptive system to foreign invaders

•Homeostatic immune system effectively protects body from most foreign invaders, e.g. infectious microorganisms, cancer cells, tissue transplants

•Innate: what we’re born with

•Skin: mechanical & chemical barrier to most microorganisms

•Mucous membranes: mechanical & chemical barriers for GI, respiratory, urinary, reproductive tracts

•Protective chemicals:

•Acids (stomach)

•Enzymes (saliva)

•Mucins (respiratory)

•Defensins (antimicrobial peptides)

•Sebum & dermicidin (sweat, toxic to bacteria)

•Structural modifications counteract invaders

•Tiny mucus-coated hairs inside nose trap inhaled particles

•Warm, moist environment of URT ideal for bacterial growth

•Cilia on mucosa of URT “sweep” dust & bacteria-laden mucus for expulsion

•Everyday activities put us at risk for infections, e.g. brushing teeth, shaving, paper cuts, splinters

• Non-specific cellular & chemical defenses
  • Phagocytes
  • Natural killer cells
  • Antimicrobial proteins
  • Fever/Inflammation: macrophages, mast cells, leukocytes, pathogen killers, tissue repairers
• Identify harmful substances, bind to surface of invader, i.e. bacteria, viruses, fungi, and destroy them

•Neutrophils: “bacteria slayers”, most numerous

•Active phagocytes, chemical attraction to inflammation

•Eosinophils:

•Attack parasitic worms

•Complex role in asthma & allergies

•Important immune modulator

•Basophils: least numerous

•Contain histamine, promotes inflammation & vasodilation, draws other WBCs to inflamed site

•Lymphocytes: 2nd most numerous

•In “lymphoid” tissue, crucial role in immunity

•T-lymphocytes: virus-infected & tumor cells

•B-lymphocytes produce antibodies/immunoglobulins

•Monocytes: largest WBC

•Active phagocytic macrophages

•Crucial for viral defense, some bacterial parasites, chronic infections

•Activate T-lymphocytes for immune response

•aka “pit bulls” of defense system, police the body in blood & lymph

•Defensive cells, lyse cancer & virus-infected body cells before adaptive activated

•Work with lymphocytes, but not as picky, detect general abnormalities

•Triggered when body tissue injured, e.g. trauma, heat, chemical, infection (bacteria, virus, fungi)

•Benefits of response: prevents spread, digests pathogens, alerts adaptive system, sets stage for repair

•Macrophages, “big eaters”, special membrane receptors recognize invaders, sound a chemical alarm

•Inflammatory chemicals released, dilate arterioles, weaken capillaries, attract leukocytes

•Inflammatory chemicals: histamine, cytokines, kinins, prostaglandins

•cardinal sign of inflammation

•Clotting factors & antibodies seep from blood into tissues

•Causes localized edema, presses on nerves, gives sensation of pain

•Pain also from bacterial toxins & sensitizing effects of prostaglandins & kinins

•Benefit of edema: contains proteins, assist with healing

•Analgesics: pain reducers, e.g. aspirin, NSAIDS, inhibit prostaglandin synthesis

•Severe infections

•Pus:  mixture of dead or dying neutrophils & broken down tissue in wound

•Abscess: inflammatory mechanism failure – may require surgical draining

•Tuberculosis bacilli - TB

•Resist macrophage digestion, antibiotic resistance within macrophage host

•Infectious granulomas: “tumorlike” growths of infected macrophage

•Asymptomatic individual: can harbor granulomas for years, becomes immunocompromised, bacteria activated, break free, clinical disease develops - TB

•enhance our innate defenses, directly attack or hinder ability of microorganisms to reproduce

•Two most important:

1.Interferons (IFNs): proteins released from virus-infected (and other) cells that protect uninfected cells from viral takeover – also inhibit some cancers

2.Complement proteins:  blood borne proteins, when activated enhance inflammatory & immune responses

•abnormally high body temperature, systemic response to invading microorganisms

•Adaptive response, most often beneficial

•Leukocytes & macrophages exposed to foreign invaders, release “pyrogens”

•Pyrogens act on body’s thermostat (in hypothalamus) – raise body temperature above normal 98.6°F

•Fever causes:

•Liver & spleen to sequester iron & zinc, inhibits bacterial growth

•Increases metabolic rate of tissues, speeds up repair process

•Stalks & eliminates with near precision almost all pathogens

•If fails or disabled, diseases such as cancer and AIDs can result

•Amplifies inflammatory response, responsible for complement activation

•Exposure to antigen “primes” the adaptive system, creates antibodies

•3 key points:

1.Specific: recognizes & targets particular pathogens

2.Systemic: not restricted to initial infection site

3.Memory:  after initial exposure, recognizes & mounts stronger repeat attacks

1.Antibody-mediated, “humoral” immunity, B lymphocytes

•Antibodies/immunoglobulins present in “humors” (blood & lymph)

•Circulate freely, bind to antigens (extracellular targets, i.e. bacteria, viruses, etc.), inactivate & mark them for destruction

2.Cellular/cell-mediated immunity, T lymphocytes

•Lymphocytes defend body

•Cellular targets, i.e. virus or parasite infected tissue cells, cancer cells or tissue transplant