Immune System & Body's Defense

Developmental Aspects of Body Defenses:

1. Embryo/ Fetus 2. Newborn 3. Psychoneuroimmunology 4. Old Age

Fever:

1. abnormally high body 2. hypothalamus heat regulation can be reset by pathogens (secreted by WBC) 3. high temperatures inhibit the release of iron and zinc from liver and spleen needed by bacteria 4. fever also increases the speed of tissue repair

Active Humoral Immunity

1. active humoral immunity -B cells encounter antigens & produce antibodies against them -naturally acquired during infections -artificially acquired from vaccines

Passive Humoral Immunity

1. antibodies are donated, not produced by bodys B cells >immediate protection >short-lived >no immunological memory 2. naturally conferred from mother to fetus or infant 3. artificially conferred from gamma globulin

Antibody Targets & Functions

1. antibodies form antigen- antibody or immune complex 2. antibodies can not destroy antigens, they inactivate & tag them for destruction 3. antibodies inactive antigens in a number of ways -neutralization -agglutination -precipitation -complement fixation & activation

Antibody Classes:

1. antibodies of each class have slightly different roles 2. five major immunoglobulin classes -IgM-can fix complement -IgA-ound mainly in mucus -IgD-important in activation of B cells -IgG-can cross the placental barrier -IgE-involved in allergies

Monoclonal Antibodies:

1. antibodies prepared for clinical testing or diagnostic services -diagnosis of pregnancy, STD's, some cancers hepatitis, & rabies -treatment for leukemia, lymphomas, and some autoimmune disease 2. produce from clone descendents of a single cell line 3. tumor cells & B lymphocytes are fused into hybridomas which produce the antibodies

Clonal Selection & Differentiation of B cells:

1. antigen challenge- naïve B lymphocyte is exposed to antigen in lymphoid tissue & activated 2. helps trigger clonal selection 3. most clones become plasma cells, antibody- secreting effector cells 4. some clones become long- lived memory cells

Clonal Selection & Differentiation of T cells:

1. antigens must be presented by macrophages to an immunocompetent T cell (antigen presentation) 2. T cells must recognize nonself and self -class I MHC proteins signal to T cells that infectious microorganisms are hiding in body cells -endogenous antigens=foreign proteins synthesized in a body cell -class II MHC proteins present exogenous antigens (foreign antigens) 3. T cell antigen receptors (TCRs) bind to an antigen- MHC complex on the surface of an APC, step 1 of stimulation 4. co- stimulation -step 2: T cell must recognize one or more costimulatory signals -T cell must bind to other surface receptors on APC -after co- stimulation, cytokine chemicals are released -if no co-stimulation, cytokine chemicals are released -if no co-stimulatory signal received, T cell goes into a state of unresponsiveness called anergy 5. cytokines

Organ Transplants & Prevention of Rejection

1. autographs 2. isografts 3. allografts 4. xenografts 5.preventing rejection

Preventing Rejection

1. blood type is matching first 2. less chance of rejection with closer MHC protein matches 3. immunosuppressive therapy may be used 4. donor bone marrow or fetal stem cells can be given to create a chimeric immune system

Nonspecific Body Defenses: General

1. body surface covering -intact skin -mucous membranes 2. specialized human cells 3. chemicals produced by the body

First Line of Defense: Natural Killer Cells

1. can lyse and kill cancer cells 2. can destroy virus- infected cells

Cytokines:

1. cause the activated T cell to proliferate & differentiate (interleuk in 1 & 2) 2. all activated T cells secrete one or more cytokines 3. types of cytokines -interferons (IFNs) -interleukins (ILs) -migration inhibitory factor (MIF) -suppressor factors -transforming growth factor beta -tumor necrosis factors (TNF)

Humoral (Antibody- Mediated) Immune Response:

1. clonal selection & differentiation of B cells 2. immunological memory 3. active & passive humoral immunity

Cellular (Cell- Mediated) Immune Response:

1. clonal selection & differentiation of T cells 2. specific T cells roles

Antimicrobial Chemicals:

1. complement -a group of at least 20 plasma proteins -activated when they encounter and attach to cells (complement fixation) -damage foreign cell surfaces - has vasodilators, chemotaxis, & opsonization 2.interferon -secreted proteins of virus infected cells -bind to healthy cell surfaces to inhibit viruses binding

Precipitation

1. cross linkage of soluble antigens 2. large complexes settle out of solution 3. easier for phagocytes

Specific T Cells Roles:

1. cytotoxic T cells 2. helper T cells 3. regulatory or suppressor T cells 4. a few members of each clone are memory cells

Antibody Structure:

1. four amino acid chains linked by disulfide bonds 2. two identical amino acid chains are heavy chains 3. the other two identical chains are light chains 4. four chains combine to form a molecule called an antibody monomer 5. variable regions of all four chains form an antigen binding site 6. larger constant region at other end determine antibody class

Mechanism of Antibody Diversity

1. genes for heavy & light chains are on different chromosomes & the chains are manufactured separately 2. coding DNA (exons) are separated by non coding DNA (introns) so antigen binding sites can be varied by somatic recombination 3. hypervariable region result in even more mutations for antibody variations 4. a single plasma cell can produce different classes of antibodies with the same antigen binding site

Embryo/ Fetus:

1. immune system stem cells originate in the liver spleen during weeks 1-9 of development 2. later bone marrow becomes the source of stem cells 3. in late fetal development lymphocytes develop self- tolerance & immunocompelence

Specific Defense Mechanism (immune system): Third Line of Defense

1. lymphocytes 2. antibodies 3. macrophages

Complement Fixation & Activation

1. main method used against cellular antigens 2. antibodies bind to cells & change shapes to expose complement- binding sites 3. triggers complement fixation & cell lysis 4. complement activation causes a positive feedback cycle by amplifying the inflammatory response & promoting phagocytosis via opsonization

Nonspecific Defense System:

1. mechanisms protect against a variety of invaders 2. responds immediately to protect body from foreign materials

Agglutination

1. multiple antigen- binding sites per antibody 2. bind to more than one cell bound antigen 3. cross linkage causes clumping 4. IgM is especially potent (10sites)

Psychoneuroimmunology:

1. nervous system plays a role in the immune response 2. immune response impaired with depression & severe stress

Newborn

1. no functioning lymphocytes 2. only passive immunity from mother's antibodies 3. immune response gets stronger by exposure to microbes

Body Defenses:

1. nonspecific defense mechanisms 2. specific defense mechanisms (immune system)

Two Defense Systems for Foreign Materials:

1. nonspecific defense system 2. specific defense system

Nonspecific Defense Mechanism: Second Line of Defense

1. phagocytic cells 2. antimicrobial proteins 3. the inflammatory response

First Line of Defense: The Skin

1. physical barrier to foreign materials 2. pH of the skin is acidic to inhibit bacterial growth, sebum is toxic to bacteria 3. vaginal secretions are very acidic

Immunological Memory

1. primary immune response -occurs on first exposure to a specific antigen -cellular proliferation & differentiation -has a lag time 2. secondary immune response -occurs with reexposure to an antigen -faster, longer, & more effective -memory cells provide immunological memory

Old Age

1. production of naïve T & B cells decline with age 2. ability to fight infections decline 3. more auto immune diseases 4. great incidence of cancer

Immunodeficiencies

1. production or function of immune cells is abnormal 2. may be congenital or acquires 3. acquired immune deficiency (AIDs) -caused by human immunodeficiency virus (HIV) -destroys helper T cells 4. severe combines immunodeficiency syndromes (SCID) -most devastating genetic defect caused disorders -children have little or no immunity defenses -can sometimes be cured by bone marrow or stem cell transplants

Helper T Cells

1. recruit other cells to fight the invaders 2. interact directly B cells

Regulatory or Suppressor T cells

1. release chemicals to suppress the activity of T & B cells 2. stops the immune response to prevent uncontrolled activity

Allergies (hypersensitivity)

1. result when the immune system cause tissue damage as it fights off a perceived but not actual threat 2. immediate hypersensitivity (actual or type 1) -triggered by release of histamine from IgE binding to mast cells -reaction begins within seconds of contact with allergen -anaphylactic shock- life threatening systemic hypersensitivity response 3. subacute hypersensitivities -cytotoxic (type II) reactions >occur when IgG or IgM bind to antigens on specific body cells >stimulates phagocytes & complement-mediated lysis >seen in transfusion reactions -immune- complex type (III) hypersensitivity >occur when IgG or IgM from insoluble antigen- antibody complexes that cannot be cleared >intense inflammatory reaction occurs >involved in autoimmune disorders 4. delayed hypersensitivity (type IV) reactions -triggered by the release of lymphokines from activated helper T cells (cell- mediated immunity) -symptoms usually appear 1-3days of after contact with antigen -allergic contact dermatitis with haptens

First Line of Defense: Stomach Mucosa

1. secretes hydrochloric acid 2. has protein- digesting enzymes

Neutralization

1. simplest 2. antibodies block specific sites on viruses or bacterial exotoxins 3. blocked sites can not bind to tissue cells 4. eventually destroyed by phagocytes

Antibodies (Immunoglobulins)(lgs):

1. soluble proteins secreted by B cells (plasma cells) 2. carried in blood plasma as gamma globulin 3. capable of binding specifically to an antigen

Cytotoxic T cells

1. specialize in killing infected cells 2. insert a toxic chemical (perform)

Specific Defense System:

1. specific defense is required for each type of invader 2. also known as the adaptive immune system

Nonspecific Body Defenses:

1. surface membrane barriers- first line of defense 2. inflammatory response 3. antimicrobial chemicals 4.fever

Autoimmune Diseases

1. the immune system does not distinguish between self and nonself 2. the body produces antibodies & sensitized T lymphocytes that attack its own tissues 3. most common autoimmune disease -multiple sclerosis-destroys the white matter of the brain & spinal cord -myasthenia gravis- impairs communication between nerves & skeletal muscle -graves disease- prompts thyroid gland to produce excessive amounts of thyroxine -type 1 diabetes mellitus (insulin dependent)- destroys pancreatic beta cells -systemic lupus erythematosus (SLE)- anti- DNA antibodies attack their entire body -glomerulonephritis- severe impairment of renal function -rheumatoid arthritis- destroys bone joints 4. self tolerance breakdown or autoimmunity causes -inefficient lymphocyte programming -appearance of self-proteins in the circulation that have not been previously exposed to the immune system -cross-reaction of antibodies produced against foreign antigens with self-antigens

Nonspecific Body Defenses: Surface Membrane Barriers- First Line of Defense

1. the skin 2. stomach mucosa 3. saliva & lacrimal fluid 4. mucus trap microorganisms 5. phagocytes 6. natural killing cells

Isografts

1. tissue grafts from a genetically identical person (identical twin or clone) 2. are ideal donors

Xenografts

1. tissue taken from a different animal species 2. never successful

Allografts

1. tissue taken from an unrelated person 2. are more successful with a closer tissue match

Autografts

1. tissue transplanted from one site to another on the same person 2. are ideal donors

Inflammatory Response: Second Line of Defense

1. triggered when body tissues are injured 2. produces 4 cardinal signs -redness -heat -swelling -pain 3. results in a chain of events leading to protection and healing 4. functions of the inflammatory response -prevents spread of damaging agents -disposes of cell debris -sets the stage for repair 5. steps in the inflammatory response

Disorders of Immunity:

1.immunodeficiencies 2. autoimmune diseases 3. allergies

Nonspecific Defense Mechanism: First Line of Defense

1.skin 2. mucous membrane 3. secretions of skin and mucous membranes

Body is Constantly in Contact with....

bacteria, viruses, & fungi

First Line of Defense: Phagocytes

defense cells (neutrophils and macrophages) 1. engulfs foreign material into a vacuole 2. enzymes from lysosomes digest the materials 3. events of phagocytosis

First Line of Defense: Mucus Trap Microorganisms

in digestive & respiratory pathways

Adaptive Defenses:

the third line of defense