A substance the body recognizes as FOREIGN and to which it mounts IMMUNE response -Non-self -Immunogenic: Stimulates an immune response(immunogen) -Reactive: reacts w/ immune response -Large complex molecules
Composed of many antigenic determinants(epitopes)
-The part of the Ag that actually stimulates & reacts with the immune response
Antigens based on?
Diversity of structure How long is stays in the body -Some molecules are too small to be antigens
A molecule that by itself is too small to be immunogenic -Is immunogenic when attached to a larger molcule
Key cells are?
-Arise in bone marrow -Primarily involved in antibody-mediated immunity
-Arise in the thymus gland -Primarily involved in cell-mediated immunity
Do B-cells and T-cells have different receptors?
yes, each have an antibody molecule that recognizes and binds to a specific Ag
General Properties of Immune responses(Recognition of self vs non-self)
-Self=host tissue -non-self=all foreign substances Tolerance=The host doesn't mount an immune response to "self" Ags, under normal circumstances(tolerant)
General properties of Immune responses(specificity)
-Each immune reaction if directed toward a specific Ag -The response to 1 Ag doesn't affect the response to another -Yet, cross-reactions can occur if 2 Ags are similar(share Epitopes)
General properties of Immune responses(Diversity)
-The immune system can respond to many different Ags( >1billion)
General properties of immune responses(Memory)
-The immune system can recognize Ags it has previously encountered -It responds more quickly the second/subsequent time it encounters that Ag
-Proteins that circulate in the bloodstream -Immunoglobins-Immune, globins(antibody factories) -Synthesized and secreted by plasma cells -B lymphocytes that circulate in the bloodstream and synthesize & secrete Ab -Each Ab is specific for 1 particular antigenic determinant -React w/ Ag that is outside host cell; Ex: toxins, viruses
Development of Ab response(Ags enter Lymphatic tissue and encounter B cells)
-B cells have specific Ab on surface -Ag & Ab interact, activating the B cell
Development of Ab response(Activated B cells interact with T helper cells)
-Helper T cells secrete cytokines, which further activate B cells -B cells differentiate into -Plasma cells-Ab-producing cells in the blood stream -B memory cells- remain in tissues, responsible for immunologic memory.
Cell communication molecule; released by one cell to signal another.
Structure of Ab molecule
-4 Polypeptide chains-2 heavy, 2 light -Ag-binding site: Each Ab molecule can bind 2 Ag molecules(Ag-Ab complexes) -Complement-activating(binding) site -Binding to macrophage-Ab are opsonic -Cell-binding site; Each Ab molecules has a cell binding site -Binding to B cells, as a surface receptor
-A pentamer - First to appear. especially in primary Ab responses -In bloodstream: on surface of B cells
A monomer -The major circulating Ab, Appears later than IgM, especially in secondary Ab responses Crosses placenta
A monomer or dimer -occurs in Serum(monomer) and in Secretions(dimer); secreted onto mucosal surfaces, in tears, saliva, & colostrum.
A monomer -on surface of mast cells and plays a role in Allergic reactions
A monomer -Surface receptor on B lymphocytes
Primary Ab response
-Occurs first time an Ag is encountered -Ab begins to appear in ~5days -First Ab is IgM, then it wanes -Next Ab is IgG, appears in greater amount
Secondary Ab response
-Occurs at second/subsequent Ag exposure -Results from B memory cells -Occurs more quickly than primary response -Produces more Ab then primary response -Last longer then primary response
What will happen at the 3rd Ag response?
Same as 2nd Ag response
What is a booster shot?
A trigger to get a secondary response
Why are some vaccines given as a series of shots?
To ensure a secondary Ab response results
Why do we have a secondary response
Because there is more Ab -Last longer than primary response
If you find a specific Ab to a pathogen in serum, what does that mean?
Either present infection, or previous exposure
How could you use Ab to diagnose infections?
Look for IgM-for current infection -Compare Titer in acute & convalescent sera (titer=amount of Ab)
Can an antibody kill a microbe all by itself?
No, it needs help
How do antibodies work?(neutralize viruses)
Prevent them from entering/infecting cells
How do antibodies work?(neutralizing viruses)
Prevent them from binding to receptor to affect host
How do antibodies work?(Block adhesion)
Bind adhesion, prevent from attaching and colonizing host
How do antibodies work?(Opsonize)
enhance phagocytosis -Ab is an opsonin, a handle for phagocytosis
How do antibodies work?(agglutinate)
Clump particles together, making them easier to phagocytose
How do antibodies work?(precipitate)
Clump soluble molecules together, making them easier to phagocyose
How do antibodies work?(Activate complement)
Forms MAC(memory attack complex) resulting in Lysis, killing of pathogens
Antibody mediated immunity -Depends primarily on? -More active against?
-B cells & Ab -Extracellular, microbes and molecules
Cell mediated immunity -Depends primarily on? -More active against?
-T cells & their direct action against microbes -Infected cells, Cancer cells, Transplanted cells
Main cell types in Cell-mediated immunity(Antigen-presenting cells)
-Usually macrophages -Function; Find, process & present Ag to T-cells
Main cells type in Cell-mediated immunity(Cytotoxic T cells)
-CD8 corecptor on surface -Function: kill & lyse target cells that display their particular Ag
Main cell type in cell-mediated immunity(Helper T-cells)
CD4 coreceptors on surface -Function: help in development of Ab or a cell-mediated immune response
Main cell types in cell-mediated immunity(memory T cells)
-Function: provide memory response; respond quickly with subsequent exposure
Development of cell-mediated Immune response
1. Ag is recognized and phagocytosed by macrophages-Antigen-presenting cells 2.Macrophages finds corresponding helper T cell: presents Ag(binds) 3.Helper T cell becomes activated -Cytokines-cell communication molecules; released by one cell to sign or stimulate another cell (ex: interluekin) 4.Helper T cell starts dividing, expanding into a clone of help T cells 5.Ag-presenting cells also activate cytotxic T cells to divide 6.Cytotoxic T cells binds & destroys target cell. PEFORINS-Released from cytotoxic T cells: forms pores in target cell memebranes
Why does HIV infection result in immunodeficiency
-Infects Helper T cells; Its receptor is CD4 -Helper T cells are destroyed, host can't develop Immune response
Why is it so difficult to make a vaccine for HIV/Aids?
-The virus destroys a hosts ability to make an immune response
Types of acquired immunity(passive vs active)
Passive-Immune response provided to the host Active-Immune response develops within the host
Types of acquired immunity(natural vs artificial)
Natural-Immune response develops naturally -Artificial-Immune response develops after an intentional or purposeful action
What is natural,active immunity?
-exposure to infectious agent, or occurrence of infection -Clinical or subclinical disease can trigger immune response
What is Artificial,active immunity
Ex: immunization, vaccine
What is natural, passive immunity
-Maternal Ab provided to fetus/newborn -Ab crosses the placenta( protects for 3-6 months) -Ab in colostrum & breast milk, protects G.I. tract
What is Artificial, passive Immunity
-Administration of preforms Ab to a host -Antiserum, hyperimmune serum, immune globulin, or gamma-globulin This is done:Botulism antitoxin,Antivenon,Tetanus immune globulin, Rabies immune globulin.
Active, passive immunity How quick is the host immune? How long does it last? Caution?
Instant ~month -Ab might be seen as foreign-can cause Serum Sickness(an allergic reaction)
-Whole bacterium or virus is killed and administered as an Ag Ex: Influenza vaccine, inactivated polio virus Advantage? No danger of getting disease from vaccine Concern? Side affects, due to extraneous microbial components
Live vaccine with reduced pathogenicity, is administered, causing a small subclinical infection Advantage? Longer-lasting immunity than inactivated vaccine Concerns?Reverse to virulence Immuno-surpressed patient
Only 1 subunit or part of an organism is the Ag, not the whole organism Advantage?Clean, fewer side effects
Inactive toxin is given as Ag: has lost its toxic activity but retained its immunogenicity ex: tetanus, botulism vaccines
A subunit is linked or conjugated to another molecule to increase its immunogenicity
a conjugate vaccine, capsular polysaccharide conjugated to diptheria toxoid.
Syntheitc vaccine/ recombinant vaccine
a Subunit or part of an organism is produced using genetic engineering ex:Hep b virus-hep B surface Ag is produced in yeast cells
Advantage of Synthetic vaccine
Ease of production No danger of whole virus contamination lower side effects
Does everyone in a population need to be vaccinated to be protected from disease?
yes, at an individual level no, at a population level
90-90% of population vaccinated difficult for a disease to spread in the population in a sufficient number of individuals immunized.
What happens if % of people vaccinated in population drops below herd numbers?
Herd immunity breaks down, disease re-enters.
Adverse reactions to vaccines
Soreness at injections(non-specific defenses) Hypersensitivity or allergy to vaccine components Reaction to preservative-thimersol(mercury)
Measles, Mumps, Rubella,-a very effect vaccine
Highly communicable disease Enveloped, ssRNA(- strand) with spikes Red, macupapular rash that fades after ~1 week Measles vaccine-1963
Is spread my respiratory droplets Systemic virus infection with painful swelling of the parotid(salivary) glands possible complication with young adult males-orchitis(testes inflmmation) mumps vaccine 1967
as an acute but mildly infectious disease red maculopapular rash begining on face and spreading to the body and extremities risk of spreading to fetus Rubella vaccine 1969
Hepatitis B vaccine-the first recombination vaccine
HepB can be acute or chronic an enveloped, icosahedral, dsDNA virus in the depadnaviridae Hepatitis B surface Ag is a viral envelope protein -produced in excess and circulates in the blood stream
Hepatitis B effects
transmitted by contact with blood or body fluids of infected person. Virus infects liver, cytotoxic T cells destroy virus-infected liver cells->liver damage->liver failure a few develop hepatic cancer
Acute&chronic infection of Hep B
Acute-Asymptomatic to fever, fatigue,abdominal pain, jaundice Chronic-Host is a carrier of the virus Treatment Acute-Symptomatic Chronic-Antivirals(including interferon) and monitor liver
Hep B vaccine
a recombination vaccine -HepB surface Ag produced in yeast cells -95% effective in preventing hepatitis B -Recommended for health care workers -Became available in 1986
Administered by scraping/poking attenuated virus into skin of the upper arm, stopped in 1972. Was purposefully spread in years was less variolation
Smallpox bio terrorism
Vaccinations have stopped worlwide; many people have immunity, immunity is waning in vaccines -aerosal dispersal of virus could infect lerge number highly transmissible
An increased,exaggerated, or inappropriate immune response that negatively affects the host. too much of a good thing. A host is senstized, if they are hypersensitive to a particular Ag. Sensitizing dose-1st exposure, proactive dose-2nd or later
4 types of hypersensitivity
type 1(immediate-type hypersensitivity) type 2(Cytotoxic hypersensitivity) type 3(Immune complex hypersensitivity) type 4(Cell-mediated hypersensitivity)
Type 1(immediate type)
IgE that binds to surface involved mast cells, and basophils degranulation-histamine -Wheal and flare-skin reaction characterized by a swollen white center surrounded by redness, itching happens in secs-mins Treatment:anti-histamines
asthma-occurs in the lower respiratory tract systemic anaphylaxis-Ag in the bloodstream -Can be rapidly fatal(~15 mins) ex: bee stings, drugs Treatment: Epi-pen(epinephrine)-inhibits degranulation, constricts blood vessels, relaxes smooth muscles.
How do we control Type 1 hypersensitivities
Avoid contact with allergen Prophylactic antihistamine
How to fix/cure Type 1
Desensitization repeated injections of small amounts of denatured Ag May prevent B cells from maturing into IgE-secreting plasma cells May induce tolerance to the Ag
Blocking Ab in type 1
Immunizing with the denatured allergen to produce serum IgG Serum IgG "blocks" allergen from reaching Ig
What is allergen testing
poking with allergens, looking for reactions
What are allergy shots
Once a week, then eventually once a month, 50% rate works Build up desensitization
Why are allergy and asthma rates increasing
States that lack of early childhood exposure to Ags & infectious agents leads to a weakened immune system and predisposes to allergies/asthma
Type 2 cytotoxic hypersensitivity
Ab-usually IgG or IgM Ag- on the surface of cells -Complement -Timing: adverse effects appear within min-hours
Transfusion reaction( Type 2)
ABO bllod groups-A,B,AB,O Polysaccharide Ag on rbc surface Ab in serum to the Ags you don't have Your Ab will destroy incompatible rbc Anemia, with clogged circulation & kidneys
Persons with what blood type are at greatest risk for transfusion reaction?
O-antibodies to both types
Persons with what blood type are at least risk for transfusion reaction?
AB- no antibodies
What happens when Rh-neg woman marries Rh-pos man and has a child?
First prego-nothing-woman builds Rh antigen ab
Subsequent prego-Anti-Rh antibodies enter fetal circulation, fetal rbc's destroyed
Treatment of Hemolytic disease of the newborn
Rhogam: rh AB-artificial passive administered at birth of first Rh+ child Binds up Rh Ag, preventing it from stimulating mothers immune system So that anti-Rh Ab is not produced
Type 3 immune complex hypersensitivity
Ags-usually soluble; usually large amount entering the host Abs-IgM or IgG Complement PMNS(neutrophils) Timing: adverse effects appear within hours-days
Serum sickness(type 3)-sensitized
Ab develops to Ags in an antiserum preparation Next administration: Ag-Ab complexes form and damage kidneys
Arthus reaction(type 3)
Immune complex formation where large amounts of Ag is entering the body. Ex: farmers lung-Ag's in moldy hay
Type 4 cell-mediated hypersensitivity
Ags-usually displayed on cells or have become attached to cell surfaces Sensitized T cells -Generated upon first exposure to Ag -React on second exposure to Ag Often observed as a skin reaction Timing: Delayed; starts after more than 12 hours up to week
Contact dermatitis(type 4)
CMI response develops to Ag deposited on the skin Poison ivy Other contact allergens
Tuberculin sensitivity-Tb test
CMI response develops from infection tuberculin skin test provides second exposure to Ag Positive test occurs-raised skin Positive test-means exposure, not that you have it
Macrophages have phagocytosed pathogens but can't kill them Sensitized T cells respond to form a granuloma Tubercle Leproma grumma(syphilis)
Hosts mounts immune response against its OWN ag's, cells, or tissues -Host should be TOLERANT to self -a good thing turned bad reaction typically results in the destruction of host cells or tissues
The self Ag to which the host is responding. Immune response may involve AutoAB, or may involved cellular response
How does Immunity to self develop?
Antigenic mimicry->cross-reactions between a foreign and self antigen Tolerance failed to develop-cells that respond to "self" Ags were not destroyed in development of the immune system -immune response to lens of the eye -genetic factor
Myasthenia gravis( autoimmune disorder)
-affects skeletal muscles; unable to contract properly -AutoAb against neurotransmitter receptor at nerve-muscle junction
AutoAg unclear (possibly nuclear Ags) Immune complexes from in the joints
Systemic lupus erythromatosus
Ab to nuclear components of host's cells Immune complexes form in the skin, organs
Immune system responds inadequately to an Ag, due to a genetic or acquired defect defect in the immune system Too little of a good thing
Genetic or developmental defect in immunity
Results from damage to immune cells after they have developed normally Ex: HIV,cancer,leukemia
what will be the effect or appearance of immunodeficiency
Sick all the time
What would you expect if B lymphocytes failed to develop in bone marrow
Antibodies,plasma cells, b cells would be missing, it would show after 6-12 months due to breastfeeding
how to treat failed development of B lymphocytes
Bone marrow transplant, no vaccines
Sever combined immunodeficiency Occures when stem cells in bone marrow don't develop into B,T cells (whole immune system missing) Treatment: Bone marrow transplant, Possible gene therapy.