Chapter 17
Adaptive (Specific) Defenses
Adaptive (Specific) Defenses
• Recognizes specific foreign substances and immobilizes, neutralizes or destroys them
• 3 characteristics of specific immunity1. Antigen-specific – recognizes particular antigens
2. Systemic – not restricted to infection site
3. Has memory
• Dual nature – two types of immune response • 2 divisions of specific immunity
1. Humoral (antibody mediated) immunity– Involves antibodies found in body fluids ( humors)
2. Cellular (cell mediated ) immunity – Protection comes from living cells (Lymphocytes)
• Immunity may be innate (genetic) or acquired– Acquired naturally or artificially
Active or Passive Immunity
• Active immunity – when B cells encounter antigens and produce antibodies against them
1. Naturally acquired – antibodies produced due to infection
2. Artificially acquired – antibodies produced due to vaccine
• Passive immunity1. Naturally acquired – antibodies cross placenta and
breast milk from mother to fetus – baby is protected from all antigens the mother has been exposed to
2. Artificially acquired – serum containing antibodies is infused – provide immediate protection, but effect is short lived (2-3 weeks) - used to treat snake bits, rabies, tetanus ect...
• Antigens – Surface molecules involved in identification
– Large, complex molecules found on the surface of viruses and cells
– Mobilize immune system; provoke immune response– Most antigens have several epitopes
• antibody binding site
• Haptens – small molecules that can bind to a larger protein and act as epitopes for the protein
– Neither protein nor hapten can act as an antigen alone
• Antibodies – protein produced in response to an antigen that is capable of binding to that antigen
• Titer - the quantity of a substance required to illicit a response– Antibody titer is the amount of an antibody required to bind to and
neutralize a particular quantity of antigen
• Antibodies recognize and react with antigenic determinants or epitopes
• MHC Proteins (Self-Antigens) – proteins that cover the external surface of our cells
– not foreign or antigenic to us but very antigenic to others
• Blood groups
– Specific group of glycoproteins that mark cells as self
– No 2 people (except identical twins) have the same MHC proteins
– 2 Groups of MHC proteins1. Class 1 MHC proteins – found on all body cells
2. Class II MHC proteins – found only on specific cells involved in immune response
Cells and Tissues of Immune System
• 3 critical types of cells1. Antigen presenting cells (APCs)
– Do not respond to specific antigens– Play an auxiliary role
2. B Lymphocytes (B cells)– Plasma cells - Secrete antibodies – Other B cells become memory cells
3. T Lymphocytes (T cells)– Do not produce antibodies– Seek out and destroy pathogens
• Lymphocytes are white blood cells– made in red bone marrow
• It becomes a T cell or B cell based on where it becomes immunocompetent (able to recognize specific antigens)– T cells – thymus
• Also develop self-tolerance; T cells that bind to strongly with self antigens (MHC proteins) are destroyed
– B cells – bone marrow– Bone marrow and thymus are primary lymphoid
organs• all others are secondary lymphoid organs (spleen, nodes)
– Immunocompetent B and T cells display unique receptors on their surface that bind with specific antigens
• bind with only 1 antigen type• Genetics determine which antigens the immune system will
recognize
• Antigen-Presenting Cells (APCs)– Major role is to engulf foreign particles and
present fragments on their own surface• Signal flags to be recognized by T cells• Dendritic cells, Langerhan’s cells,
macrophages and activated B cells• Dendrites and macrophages also secrete
soluble proteins that activate T cells
Humoral Immune Response
• Antigen challenge – 1st encounter between lymphocyte and antigen– If it is a B cell, humoral immune response is initiated
and antibodies are produced against the antigen– The naïve but immunocompetent B cell is activated
when the antigen binds to its surface receptors – antigen specific
– This activity triggers clonal selection • B cells multiply rapidly to form identical clones
– Most clones become plasma cell which produce antibodies (2000 per sec) for 4 – 5 days then die
– Other clones become long-lived memory cells
Immunological Memory
• Primary immune response– Occurs on the 1st exposure to an antigen– Typically has a lag time of 6-7 days– Antibody production peaks in about 10 days then
begins to decline
• Secondary immune response – Occurs when re-exposed to same antigen– Faster, more prolonged, more effective– Memory cells provide immunological memory– Antibody production peaks in 2-3 days and can
persist for weeks or months
Antibodies• Immunoglobulins (Igs) - gamma globulin part of
blood proteins– Soluble proteins secreted by B cells in response to
antigens• Capable of binding with that specific antigen
– Each antibody has the same basic structure • 4 looping polypeptide chains
– 2 heavy chains and 2 light chains– Combine to for a Y shaped molecule (antibody monomer) – Each chain has a variable and constant region– Constant region determines class of antibody – Variable regions form antigen-binding site – Each monomer has 2 antibody-binding sites– Monomers combine to form different antibodies
Antibody Classes
• Five major classes – IgM, IgA, IgD, IgG, IgE (MADGE)– IgM – fixes complement – IgA – found primarily in mucus and other body
secretions– IgD – bound to B cell surface; acts as a receptor site – IgG – most abundant; crosses the placenta; fixes
complement– IgE – rarely found in blood; active in allergies
• Pentamer• 5-10% of serum
antibodies• Found primarily on B
cell membranes • Fix complement• Agglutinates
microbes• First Ab produced in
response to infection• ABO blood group Ab
IgM antibodies
• Dimer• 10-15% of serum
antibodies• Found primarily in
mucus and other body secretions– Abundant in colostrum
• Fix complement
IgA antibodies
• Monomer• 0.2% of serum antibodies• Bound to B cell surface
– acts as a receptor site– Beyond that function is
unknown
IgD antibodies
• Monomer• 80% of serum antibodies• Fix complement• Cross placenta• Present in milk• Enhance phagocytosis;
neutralize toxins & viruses– protects fetus & newborn
IgG antibodies
• Monomer• 0.002% of serum
antibodies• Found on mast cells
and basophils• Allergic reactions• Lysis of parasitic
worms
IgE antibodies
Antigen-Antibody Reactions
• Antibodies themselves can’t destroy invaders
– they inactivate them and tag them for destruction by forming an antigen-antibody complex
• 4 defensive mechanisms they use1. neutralization
2. Agglutination
3. Precipitation
4. Complement fixation (only IgG and IgM and IgA)– PLAN of action – precipitation, lysis (by
complement), agglutination and neutralization
• Complement fixation and activation– Antibodies bind to cells changing their shape to
expose complement binding sites on their constant regions
– Triggers complement fixation onto antigenic cell’s surface resulting in cell lysis
– Molecules released during complement fixation also amplify inflammation and induce phagocytosis
• Neutralization– Antibodies block specific sites on viruses or
bacterial toxins– Loses its toxic effect – can’t bind to receptors on
tissue cells to cause damage
• Agglutination– Antigen-antibody complexes can be cross-linked
into large lattices– Causes clumping of antigenic cells
• Precipitation– Soluble molecules (instead of cells) are cross-
linked into large complexes that settle out of solution
– These immobilized antigen molecules are easier to capture and engulf by phagocytes
Cell Mediated Response
• T cells mediate cellular immunity– More complex then B cells– 2 major classes of T cells
1. Helper T cells (TH)
2. Cytotoxic (killer) T cells (TC)
– There are also delayed hypersensitivity T cells (TDH), suppressor T cells (TS) and memory T cells (TM)
– T cells are unable to see free antigens• Recognize and respond to processed fragments of
proteins displayed on body cell surfaces (APCs)
– T cells are activated when a recognized antigen binds to their surface receptor
– T cells have a double recognition process• Recognize non-self antigens and self (MHC proteins)
Specific T Cell Roles• Helper T Cells – regulatory cells
– Chemically or directly stimulate proliferation of other T cells and B cells
– Do not bind to antigen themselves– Produce cytokines that provide signal to attract other
immune cells
• Cytotoxic T Cells – killer T cells– Directly attack and kill other cells, primarily virus
infected cells, but also attack bacteria infected tissues– Binds to target cell; inserts perforin into the plasma
membrane; then detaches from target cell – lethal hit resulting in cell lysis
– Perforin molecules polymerize causing cell lysis – Some release other chemicals like lymphotoxin which
targets DNA or tumor necrosis factor
• Other T cells– Suppressor T cells
• Regulatory cells; release cytokines that suppress T cell and B cell activity
• Vital in stopping immune response after an antigen has been successfully inactivated or destroyed
– Delayed-Hypersensitivity T Cells• Instrumental in promoting allergic responses
– Each type of T cell has a role in the immune response
Chapter 18
Immunological Disorders
• Factors that modify immune response– Compromised host– Immunization
• Vaccine or toxoid
• Immunological Disorders – inappropriate or inadequate immune response – Hypersensitivity
• Immune system reacts in an exaggerated or inappropriate way to a foreign substance
– Immunodeficiency • Inadequate response due to defects in B cells or T cells
– Auto Immune Disorders• Become hypersensitive to specific self antigens
– Transplantation• Immune system attacks transplanted cells or tissues
• Hypersensitivities – An allergen is an antigen that evokes a
hypersensitivity response • Pollen, foods, insect stings, pet dander
1. Type I – immediate allergic response– Anaphylaxis – from prior exposure to antigen
2. Type II – cytotoxic effects• Typically transfusion reaction or childbirth
3. Type III – immune complex– Antigens in vaccines
4. Type IV – cell-mediated or delayed – Exposure to foreign substances, pathogens,
transplanted tissues
Type I – immediate allergic response
• Sensitization– B cells are activated
• Production of IgE antibodies– Bind to mast cells and basophils
• Allergen-IgE reactions– As allergins bind to IgE antibodies mast cells and
basophils release histamine, prostagladins and leukotrienes
• Local and Systemic effects – Capillary dilation and increased permeability, airway
constriction, mucus secretion, pain and itching
• Normal human red blood cells have surface antigens that are genetically determined that form the basis for the 4 blood types
• A transfusion reaction will occur when a patient is given blood cells displaying the wrong antigen
• A person has no antibodies against their normally present antigen – If you have the A antigen then you have type A blood
and DO NOT have antiA antibodies – You would however have antiB antibodies – If you received cells with B antigens they would be
clumped and destroyed (agglutination)
Type II – Cytotoxic
• Erythroblastosis fetalis or hemolytic disease of the newborn is another example of a cytotoxic reaction
• Red blood cells also have rh antigens– If you have the antigen you are rh+ if you do not have
it you are rh-
• When an rh – mom carries an rh+ baby she is exposed to a foreign antigen and she begins to make anti-rh antibodies – The 1st baby will be uneffected, but if she get
pregnant a 2nd time and the baby is rh+ her body will attack the baby’s red blood cells
– If the 2nd baby is rh- there is no problem
• Immunodeficiences – both congenital and acquired conditions where
production or function of immune cells, phagocytes or complement is abnormal
– Severe combined immunodeficiency syndrome (SCID)
• boy in the bubble • congenital
– Acquired immune deficency syndrome (AIDS)• Caused by a virus (HIV- human
immunodeficiency virus)
• Autoimmune Diseases – immune system loses the ability to tell self from
non-self– Turns on itself– Multiple sclerosis – destroys white matter of brain
and spinal cord– Systemic lupus – systemic disease affects most
body systems– Rheumatoid arthritis – destroys joints
Organ Transplants and Rejection
• Four major varieties 1. Autografts – tissues transplanted from one
body site to another in the same person
2. Isografts – grafts donated by a genetically identical person – only identical twins
3. Allografts – transplanted from individuals who are genetically similar – same species
4. Xenografts – grafts taken from another animal species – baboon heart
– Immune rejection presents a major problem
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