Immunology: Basic Principles of Adaptive Immunity and

Immunizations2007

Adaptive Immunity

Recognize non selfRespond to a foreign invaderDistinguish between

invaders( potential pathogen)

Antigen

Is a substance( molecule) that the body identifies as foreign and it mounts an immune response.

It is also known as an immunogenMost antigens are proteinsSome are glycoproteins,

nucleoproteins, or polysaccharides

Proteins as antigens

Proteins are generally more immunogenic

Their structure is more complex

Large proteins may have several epitopes or antigenic determinants

Hepatitis antigens

Hepatitis surface antigen is a molecule attached to the exterior or the virus

Evokes an immune response

First antigen detectable

Haptens

Haptens are smaller molecules that can be antigenic if they bind to a larger molecule

The antigen is the result of the combination. Neither is antigenic by itself

Antibody

Antibodies are molecules that are produced as a response to foreign invaders

It is specific for an antigen

It has the capacity to bind to the antigen

Titer

Titers are the quantitiy of an antigen required to evoke an immune response

It is quantifiable Measured in clinical

situations to determine immunity,the presence of disease,the course of an infection

Antibody titer( definition and importance)

Quantity to bind to and neutralize a particular quantity of an antigen

Rubella is a virus that produces teratogenic effects in a fetus

Rubella titers are diagnostically significant in young women planning on pregnancy

Effector Response

Recognition of a non self presence causes a series of response reactions

Divided intoa. Humoral response – Based upon

the presence to antibodiesb.Cellular response – based upon the

activity of special cells such as T lymphocytes

Development of the immune system( Immune cells) Differentiation of stem

cells into lymphocytes is influenced by other tissues

B cells are differentiated in the bone marrow

Found in the lymph nodes, spleen, gut associated lymphoid tissues( GALT)

B CELLS

T cells are are differentiated in the thymus

They are located in lymph nodes

They are the majority of circulating lymphocytes

T CELLS

T lymphocytes and cellular immunityAttack and destroy Produce cytokines that enhance

specific immunity and non specific mechanisms of defense

T lymphocytes

T lymphocytes

Cytotoxic T cells – destroy virally infected cells and tumor cells

Helper T cells – they divide rapidly and secrete cytokines

Memory T cells – They are antigen specific cells

Regulatory T cells( suppressor T cells) – Cell mediated immunity

Natural Killer Cells – Connects the innate and the adaptive immune system

Other subsets of cells

Natural Killer Cells( Doc Kaiser Microbiology)

Apoptosis( Doc Kaiser Microbology)

MHC - 1

Endogenous antigens, such as viral proteins, pass through proteasomes where they are degraded into a series of peptides.2. The peptides are transported into the rough endoplasmic reticulum (ER) by a transporter protein called TAP.3. The peptides then bind to the grooves of newly synthesized MHC-I molecules.4. The endoplasmic reticulum transports the MHC-I molecules with bound peptides to the Golgi complex.5. The Golgi complex, in turn, transports the MHC-I/peptide complexes by way of an exocytic vesicle to the cytoplasmic membrane where they become anchored. Here, the peptide and MHC-I/peptide complexes can be recognized by CTLs by way of TCRs and CD8 molecules having a complementary shape.

MHC I and viruses

Humoral immunity

The result of circulating immunities

When stimulated by an antigenm the B lymphocytes initate a process that leads to the release of antibodies

Most effective at defending the body against viruses and bacteria

Works on the basis of

a. Specificityb. Diversityc. Memoryd. Self vs. Non self

Humoral immunity

Dependent upon the ability of white blood cells to recognize specific antigens

Antigens are generally exposed on the outer surface of a pathogen or are toxins

Antibody Response

Each B cell carries an antibody on its outer membrane

It has the ability to bind to a specific antigen

The binding of an antigen sensitizes or activates the B cells

This causes the cells to divide may times

The B cell divides to produce

a. Plasma cells that actively produce antibodies at a rapid rate

b. They also produce a memory cell that retains the information necessary to produce the antibody

B cells

After the binding of the antigen to the antibody, the B cells processes the antigen, by breaking it into tiny fragments

The fragments bind to molecules on the surface of the B cell MHCII

APC( Antigen Presenting Cell)

Antigen Presentation and MHC II The antigen is

presented on the surface of the B cell by MHC II

The T cells are activated to produce interleukin 2

The activation further stimulates the production of more B cells - memory cells

MHC I and II

There are five classes of Immunoglobulins - The basic form of antibodiesIgGIgAIgMIgDIgE

Basic structure

Basic unit is a Y shaped structure

They are composed of four polypeptide chains

The chains are held together by disulfide bonds

They possess both variable and constant regions

IgG

IgG-The main class of antibodies

Produced as a secondary response

Attach to antigens on microorganisms and their receptors attach to phagocytic cells

They work effectively with phagocytic cells

The tails section also activates complement

Crosses the placenta

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IgM

Pentameric structure( secreted by Plasma cells)

Monmeric on the surface of B cells

It is the first antibody made in response to an infection

It has ten antigen binding regions

Activates complement and causes clumping of microbes

IgA

Occurs in bodily secretions

Found in breast milk Attaches to the lining

of the digestive, respiratory, and gastrointestinal tract

Transported through epithelial cells

Attaches to microbes before they invade tissues

Activates complement Exists as a dimer

IgD

Found primarily on the membranes of B cells

It may help in immune responses

It also may be active in allergic responses

IgE Has specially affinity for

receptors on the basophils

In the blood or mast cells in the tissues

When IgE binds to antigens, the associated B cells secrete specific molecules that are related to allergic responses

Histamine is one of these molecules

IgE is found primarily in tissues and bodily fluids

Immune Disorders- SCIDS

SCIDS Most cases of SCID are

due to mutations in the gene encoding the common gamma chain (γc),

A protein that is shared by the receptors for InterleukinsIL-2, IL-4, IL-7, IL-9 and IL-15.

These interleukins and their receptors are involved in the development and differentiation of T and B

Another well-known form of SCID is caused by a defective enzyme, adenosine deaminase (ADA),

Necessary for the breakdown of purines. Lack of ADA causes accumulation of dATP.

This metabolite will inhibit the activity of ribonucleotide diphosphate reductase, the enzyme that reduces ribonucleotides to generate deoxyribonucleotides

Genetic Diseases of the Immune System Severe combined

immunodeficiency Multiple types X linked and

autosomal Affect both

cellular and humoral aspects of the immune system

T cell-negative (T-), B cell-negative (B-), natural killer cell-positive (NK+)

Gene map locus 11p13, 11p13

SCIDS

Immune Disorders

Immune disorders #301000, WISKOTT-

ALDRICH SYNDROME; WAS

The manifestations of Wiskott-Aldrich syndrome are eczema, thrombocytopenia, proneness to infection, and bloody diarrhea.

Death usually occurs before age 10 years.

Bone Marrow transplants are a treatment possibility

Genetics of Immunoglobulins

Generation of Immunoglobulins

Genetics of Immunoglobulins Genes for the constant

region Genes for the variable

region Light and heavy

chained molecules are synthesized separately

The diversity of antibody-binding sites comes from the random combinations of variable gene segments that join with constant gene segments

Naturally Acquired Active immunityThe immune system responds to

an invader by producing antibodies and activated lymphocytes

This can produce a life long immunity

Naturally Acquired Passive ImmunityAntibodies transferred across the

placenta to the fetusTransfer of antibodies through the

colostrum in the breast milkBoth of these provide temporary

immunity to an infant

Artificially Acquired Passive Immunity When antibodies made by other hosts

are introduced into a new host An example of this is rattlesnake

antivenin injection Antivenins are antibodies produced by

other animals such as horses or cows The host does not make new antibodies

- the antibodies supplied circulate for as long as a month and are eventually destroyed in the host

Venom

Rattlesnake venom is a mixture of enzymes that possess the ability to destroy cells

Can be a neurotoxin as well

Injected like a hypodermic

Antivenin

Antivenin is a polyvalent preparation of globulins prepared by the fractionation of horse’s serum

It is a mixture of globulins from different types of rattlesnakes

One of antigens in rattlesnake venom

Artificially Acquired Active Immunity When an individual is exposed to

a vaccine a. The vaccine might include

attenuated( weakened) organism, portions of

the organism, toxins, subunits of antigenic portions of the organism

Chicken Pox – Varicella Zoster Chickenpox begins

as a cold Sneezing,

coughing, and a runny nose

Two days later a rash begins

Usually begins on the chest and face

It may spread all over the body

Chicken Pox

Infection spread by aerosolized droplets

It is contagious 1-2 days prior to the onset of symptoms

It takes 20 days to develop symptoms

It takes 5-10 days for the immune system to defeat the virus

All children between 12 and 18 months of age should have one dose of chickenpox vaccine.

Children who have had chickenpox do not need the vaccine.

No tests need to be administered to determine immune status - a parent's recollection of the disease is considered a reliable measure of previous infection and therefore immunity. ･

Children between 19 months and their 13th birthday who have not had chickenpox should be vaccinated with a single dose. ･ People 13 and older who have not had chickenpox should get two doses of the vaccine 4 to 8 weeks apart.

Primary Immune Response

In humoral immunity the primary response occurs when the antigen is first recognized by host B cells

B cells divide to form plasma cells

Antibodies begin to appear - IgM

Cytokines trigger the proliferation of B cells

IgG synthesis accelerates

Memory cells are formed

Secondary Response

The secondary response occurs when the immune system sees an antigen for the second time

Memory cells divide more rapidly than B cells

IgM is still produced first, but in smaller quantities than the secondary response

IgG is produced second, but in greater amounts

Response of B cells

T independent antigens - This response only produces IgM and no B memory cells are formed

T- dependent antigens - B cell becomes the antigen presenting cell, makes contact with the T helper cell and the T helper then produces lymphokines that stimulate thethe B cell to differentiate

Primary and Secondary

Inactivation of the antigen( microbe)

Neutralization - IgG is the main neutralizer of these infections

Prevents the toxin from doing further damage

Antibiotics are required to kill the microbe causing the infection

Viruses can be inactivated by neutralization

Viruses with envelopes can be removed by complement

Neutralization Reaction http://people.eku.edu/ritchisong/neutralization2.gif

Neutralization of a toxin

Agglutination reactions

Bacteria are large particles

When they react with bacteria they can clump

IgM causes strong agglutination reactions

IgG also causes agglutination

Ingestion by macrophages

Both agglutination and neutralization effectively inactivate the microbe by binding to the antigenic site

Macrophages can then ingest the pathogen

COMPLEMENT

Pathway for the elimination of microbes

Cascade Lysis of cells Augmentation of

immune response Disposal of waste

by products

Complement action

Perforin is a cytolytic protein found in the granules of CD8 T cells and NK. Upon degranulation, perforin inserts itself into the target cell's plasma membrane forming a pore

This finally results in the lysis of a cell

Classical Complement Pathway