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