Ph 162A Lec 9: Immunizations Immunopathology

Front 1

what is immunization?

Back 1

is the enhancement of the immune response usually by artificial means.

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In order to develop an active immunity, in order for it to work at its best, the immune system has to be ____

Back 2

pre-sensitized

notes: you need both the acquired and innate immunities working at the same time

Front 3

There are two types of immunization:

Back 3

passive and active

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Passive immunization

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the enhancement of the immune response by providing the host w/ performed antibodies to the antigen of interest

Front 5

there are 2 types of passive immunity/passive immunizations:

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1. maternal antibodies (IgG) crossing the placenta to the fetus
2. Anti-serum, immune globulin

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1. maternal antibodies (IgG) crossing the placenta to the fetus:

What kind of protection does this passive immunity do?

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this provides protection to the newborn during the first 6 weeks of life when hes/her immune system is not yet fully developed

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maternal antibodies especially IgA, found in colostrum and milk:

this provides_____...

Back 7

this provides protection against intestinal infections during the period when the baby is nursing

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2. Anti-serum, immune globulin:

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these antibodies are derived from other humans and animals, who have high level of antibody to the specific microorganism or chemical

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An immunoglobulin is

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a collection of antibodies from other individuals

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when or where anti-serum, immune globulin is used?

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1. rapid immune protection is needed
2. no vaccine is available
3. the host is immunodeficient or immunosuppressed

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what is a gamma globulin shot?

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is a whole bunch of antibodies

that are just in a mixed pool.

**can give this to somebody to get a broad protection

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Another type of anti-serum is called an antitoxin. What is it?

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these are derived from animal that have hyper-immune serums

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What is the disadvantage w/ passive immunization?

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**possible to get a severe allergic reaction when you get the shot
**sometimes you have to deliver this intramuscularly (IM)--- sometimes causing a negative feedback on the immune system (this can delay your response.

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2. Active immunization: what is it?

Back 14

is the act of sensitizing or inducing the immune system into action (where you need vaccine to do this)

Front 15

what is a vaccine?

Back 15

is an infectious unit or agent, or a part of an infectious agent that is given for purpose of establishing resistance to an infectious disease

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Vaccines that are introduced IM (intramascular) injection will typically stimulate ____ and ____ antibody stimulation

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IgM and IgG

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Oral vaccines will stimulate ____

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IgM, IgG, and IgA

**b/c its on mucosal membranes

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Many vaccines are administered in a sequence of 1-3 infections over a period of months w/ ____ over periods of many years.

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boosters

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What is the purpose of this (boosters)?

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To stimulate secondary immune responses w/ increases the strength (memory) of the immune response to those particular antigens

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What are the qualities of good vaccines?

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1. Effective
**stimulates long term immunity that is strong enough to prevent disease
2. Safe-- few side effects
3. Stable-- can withstand long term storage, transportation, and changes in temperature

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There are different types of vaccines that activate the immune system. They are:

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1. toxoid
2. killed whole organism vaccine
3. subunit vaccine
4. live attenuated vaccine
5. DNA vaccine
6. Herd immunity

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toxoid

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an inactivated toxin that has been chemically altered so that it is no longer harmful but still immunogenic.

**toxoids stimulate the host to stimulate an immune response

note: antitoxins are antibodies different from toxoid

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Toxoids are usually complexed w/ an _____ to enhance immunogenicity.

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adjuvant

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Toxoids are used to protect againts ____...

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disease whose pathogenicity is due to a potent toxin e.g diphtheria, tetanus, botulism

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Toxoids stimulated the _____ immunity

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humoral
**B cells going to plasma cell

note: no cell-mediated response

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Is toxoid safe?

Back 26

yes, and have very little side effect.

Front 27

2. killed whole organism vaccines: what is it?

Back 27

made from preparation of the microorganism that you have inactivated chemically or by heat to eliminate infectivity-- but still retain immunogenicity

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For the killed whole organism vaccine, the ____ immunity is activated

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humoral

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what is the disadvantage to the killed whole organism vaccine?

Back 29

**there are many impurities and irrelevant substances present which may cause side effects
and takes lots of energy to produce antibodies

Front 30

3. geneticaly engineer subunit vaccine or recombinant vaccine:

what is the procedure for getting this type of vaccine?

Back 30

1.You have to know what the epitope in advance. Once you find it you have to know what gene in the organism makes that epitope.
2. Once you find it you introduced to a yeast or bacterium--- to make the strain
3. You purify and harvest the strain and administer the epitope as a vaccine

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The subunit vaccine is used mainly to protect against

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bacteria and viruses

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The ____ immunity is stimulated.

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humoral

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what is the major advantage of using the subunit vaccine?

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You don't have all this extraneous material, thus you have less chance for side effects

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4. live attenuated vaccine: what is it?

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these vaccines are manufactured by mass cultivation of attenuated (less virulent) forms of viruses that are too weak to cause disease in normal host, but still retain immungenicity.

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This vaccines stimulate

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both humoral and CMI (cell mediated immunity)

notes: advantage--> infect host cell and are presented on the cell surface in conjunction w/ MHC I molecules.

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What is the disadvantage of the live attenuated vaccine?

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cannot be given to immunocompromised host or fetus--> can cause disease b/c their immune are too weak

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5. DNA vaccine: what is it?

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naked cDNA is injected into muscle where it enters the muscle cells and serves as a template for transcription of mRNA and translation of the desired antigenic protein.

Front 38

What is the advantage of DNA vaccines?

Back 38

**stimulation of CMI w/o the risk of getting the disease
**Easier storage, longer shelf life

Front 39

The other type of immunity (aside from passive and active) is called

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herd immunity

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herd immunity is

Back 40

is where you protect the susceptible indv. in the community by vaccinating everybody else.

**disease will not be contagious
**prevents outbreaks of diseases

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herd immunity is also know as

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ring immunization

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[detrimental aspect of the immune system that can occur]

Hypersensitivity is when

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you are getting too strong of an immune response

Front 43

there are 4 types of hypersensitivity:

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types I, II, II, IV

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type 1 Hypersensitivity

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**allergy-type response follow by sensitization (sensitive to antigens)
e.g hay fever, asthma, anaphylaxis

**allergen (a type of antigen, but not parasitic) in the blood stimulates T helper 2 cells that stimulate B cells to form plasma cells--> which code for IgE. The IgE Fc tail will attach to a basophil or a mast cell stimulating them to dump their cytokines on the spot and destroy the allergen

**there are lots of cytokines being produce such as histamine which can cause anaphylactic shock (blood vessel dilation through your body leading to blood pressure drop= fatal), also constriction in the airway, and allergy response

note:
--IgE is the antibody that mediate this response and can occur w/in 15 minutes of exposure
--mast cell is the key producers of chemicals

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Type 1 hypersensitivity is treated by anti-histamine

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**anti-histamine
**or try to stimulate the B cell to make an IgG response using the T helper cell that is involved (this will intercept the allergen)

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Type II hypersensitivity

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**antibodies bind to antigens on the patient's own cell surfaces. The antigens recognized in this way may either be intrinsic ("self" antigen, innately part of the patient's cells) or extrinsic (absorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen). These cells are recognized by macrophages or dendritic cells which act as antigen presenting cells, this causes a B cell response where antibodies are produced against the foreign antigen.

**B cell proliferation will take place and antibodies to the drug are produced. IgG and IgM antibodies bind to these antigens to form complexes that activate the classical pathway of complement activation to eliminate cells presenting foreign antigens (which are usually, but not in this case, pathogens). That is, mediators of acute inflammation are generated at the site and membrane attack complexes cause cell lysis and death (tissue damage)

**this system is rapid, usually w/in 8 hrs

**main application is Rh incompatibility

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Type III Hypersensitivity:

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**also Arthrus reaction or immune complex

**When these antigens bind antibodies, immune complexes of different sizes form[2]. Large complexes can be cleared by macrophages but they have difficulty binding to small immune complexes for clearance. These immune complexes insert themselves into small blood vessels, joints, and glomeruli, causing symptoms.
--these antigens can attracts other cells (basophils, neutrophils, mast cell) that are dumping enzymes e.g histamine---> leading to vasodilation and destruction of host tissue

symptoms: fever, joint pain, and a bad rash.

**response takes up to 8 hrs.

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Type IV hypersensitivity:

Back 48

**the immunogen can be either an infectious agent or a non-infection agent (toxins can cause this type of rxn).
**Type IV requires pre-sensitized
**response is cell-mediated immunity
**T helper cells produce a compound called migration inhibition factors (MIF)= purpose is to keep the microphages on the scene. Overtime the T helper cells not only recruiting macrophages in the area, but also prevent them form moving away---> so you get a large of macrophages in one area and it begins to feed on itself---> it continues and forms a mass called granuloma

**types IV is trigger by poison oaks, poison sumac, or poison ivy.

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[Autoimmune Disease]

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These are disease that acquired immunity has reactivity (susceptibility to chemical change) to self antigens. ---> this can lead directly to host tissue damage

**about 3.5% of the general population has some type of autoimmune disease

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What kind of mechanism stimulates this type of immune response?

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**molecular mimicry--- when the host becomes infected by a microorganism that has an epitope similar to a host tissue. e.g rheumatic fever, people w/ this have a weak heart b/ the body is attacking the heart muscle

**exposure later in life to antigens hidden during fetal development and therefore not programmed as self.

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Examples of the most common autoimmune disease

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1. Grave's disease/ hyperthyroidism-- excessive thyroid activity
2. Type I diabetes-- destruction of insulin-- producing cells of the pancreas
3. rheumatoid arthritis-- destruction of synovial membrane of joints
4. multiple sclerosis-- destruction of myelin sheath or nerves
5. systemic lupus erythematosus-- reaction against DNA of all cells

Front 52

what are some non-immune factors contributing to autoimmune disease?

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1. genetics-- there is a high genetic predisposition to autoimmune disease. Each autoimmune disease is found more frequent in person w/ a certain genetic of MHC (e.g lack of proper MHC class II proteins that distinguish the self in the maturing thymus can be a problem)

2. Gender-- incidence in female>male (8:1)

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there are also classes of disease called immunodeficiency disease. what is that?

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this is when the immune system fails to develop. Lack of B cells or T cells or both and has to depend on their innate immunity. Or if C3 is deficient, you can not carry out opsonization---with this you can not phagocytose microorganism.

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[Secondary (acquired) immunodeficiency]

what is this?

Back 54

this is when your immune system is suppress due to

1. infectious agent e.g HIV
2. immunosupressive drugs
3. radiation treatment
4. malnutrition
5. aging