Immunity

1. CHAPTER 10: IMMUNITY EDWARD JENNER The Influenza Epidemic of 1918 1919 killed 22 million people in 18 months

10.1 IMMUNE RESPONSE

Describe Definition: Immunity

Describe Antibodies: Structure and Classes

Explain and Compare Humoral and Cell Mediated immunity

Describe Lymphoid Organs Roles in Immunity

Describe Antigen-antibody Reactions

An animal must defend itself against unwelcome intruders the many potentially dangerous viruses, bacteria and other pathogens it encounters in the air, in food and in water

It must also deal with abnormal body cells, in some cases , may develop into cancer

Three cooperative lines of defense have evolved to counter this threats

Two of these are non-specific that is they do not distinguish one infectious agent from another

Intact skin is a barrier that cannot normally be penetrated by bacteria or viruses although even minute abrasions may allow their passage

Likewise, the mucous membranes that line the digestive, respiratory, and genitourinary tracts bar the entry of potentially harmful microbes

In humans, secretions from sebaceous and sweat glands give the skin a pH ranging from 3 to 5, which is acidic enough to prevent colonization by many microbes

Microbial colonization is also inhibited by the washing action of saliva, tears and mucous secretion

All these secretions contain antimicrobial proteins

One of these, the enzyme lysozyme, digests the cell walls of many bacteria, destroying them

Microbes that penetrate the first line defense face the second line defense, which depends mainly onphagocytosis , the ingestion of invading organisms by certain types of white cells.

Phagocyte function is intimately associated with an effective inflammatory response and also with certain antimicrobial proteins.

Constitute about 60 - 70% of all leukocytes

Cells damaged by invading microbes release chemical signals that attract neutrophils from the blood

The neutrophils enter the infected tissue, engulfing them and destroying microbes there

Neutrophils tend to self-destruct as they destroy foreign invaders, and their average life span is only a few days

About 5% of leukocytes

Provide an even more effective phagoytic defense

After a few hours in the blood, they migrate into tissues and develop into macrophages : large, long-lived phagocytes

About 1.5% of all leukocytes

Contribute to defense against large parasitic invaders, such as the blood fluke,Schistosoma mansoni

Eosinophils position themselves against the external wall of a parasite and discharge destructive enzymes from the cytoplasmic granules

The blood fluke Schistosomainfects 200 million people, leading to body pains, anemia, and dysentery.

Damage to tissue by a physical injury or by the entry of a microorganisms triggers a localized inflammatory response

One of the chemical signals is histamine

Histamine is released by circulating leukocytes called basophils and by mast cells in connective tissues

Cells of a tissue injured by physical damage or bacteria release chemical signals such as histamine and prostaglandin

In response to the signals, nearby capillaries dilate and became more permeable. Fluid and clotting elements move from the blood to the site and clotting begins.

Chemokines and other chemotactic factors released by various kinds of cells attract phagocytic cells from the blood

When the phagocytic cells arrive at the site of injury, they consume pathogens and cell debris, and the tissue heals

While microorganisms are under assault by phagocytic cells, the inflammatory response and antimicrobial proteins, they inevitably encounter lymphocytes, the key cells of the immune system

Lymphocytes generate efficient and selective immune responses that work throughout the body to eliminate particular invaders

The vertebrate body is populated by two main types of lymphocytes :

B lymphocytes (B cells)

T lymphocytes (T cells)

~Both types of lymphocytes circulate throughout the blood and lymph and are concentrated in the spleen, lymph nodes and other lymphatic tissue.

Lymphocytes, like all blood cells, originate from pluripotent stem cells in the bone marrow or liver of a developing fetus.

Early lymphocytes are all alike, but they later develop into T cells or B cells, depending on where they continue their maturation.

Lymphocytes that migratefrom the bone marrow tothymus develop into T cells.

Lymphocytes that remainin the bone marrow andcontinue their maturationthere become B cells.

There are four main types of T cells:

Cytotoxic T cells (T C )(killer cells) ~ destroy the antigen directly by attaching to them and releasing the chemical perforin to kill them

Helper T cells (T H )~ attract and stimulate macrophages and promote the activity of other T- and B- cells to increase antibody production

Memory T-cells~ have no action but multiply very fast if a second invasion of the antigen occurs, producing an even bigger clone of T-lymphocytes and resulting in rapid destruction of antigen

Suppressor T-cells~ slow down the vigorous response of the T Cand T Hcells, so slowing down and the stopping the immune response

There are three different types of B cells :

Plasma B cells~ secrete antibodies into the circulation

Memory B cells~ livefor a long time in the blood. They do not produce antibodies but are programmed to remember a specific antigen and respond very rapidly to any subsequent infection

Dividing B cells~ produce more B lymphocyte cells

Because lymphocytes recognize and respond to particular microbes and foreign molecules, they are said to displayspecificity

B cells and T cells specialize in different types of antigens, and they carry out different, but complementary, defensive actions

Definition :

Any substances capable of stimulating an immune response, usually a protein or a large carbohydrate that is foreign to the body

Foreign to host ~ chemical groupings (markers) must be different from those on host cells (receptors) called antigenic determinants or epitopes

Possesses two or more antigenic determinants ~ epitopes (2 bivalent, many multivalents)

May be soluble, particular, cellular

4. Examples :

a. Soluble toxins, enzymes, venoms, plant extracts, medications, foreign serums (proteins)

b. Particulate ~ cell structures (cell walls, flagella, capsules, pili), viruses, mold spores, pollens, house dusts

c. Cellular ~ microorganism, viral infected host cells, foreign tissue cells, neoplastic cells, altered host cells

One way that an antigen elicits an immune response is by activating B cells to secrete proteins called antibodies

Each antigen has a particular molecular shape and stimulates certain B cells to secrete antibodies that interact specifically for it.

Antibodies are glycoproteins which belong to a special group of blood proteins known as immunoglobulin

The basic structure of an antibody consists of two pairs of polypeptide chains

Two of the chains are long and are referred to asheavy (H) chains

The other two shorter chains are referred to aslight (L) chains

The chains are held together by disulphide (S-S) bridges to form the Y-shaped molecule

Each antibody molecule has two identicalantigen binding sites

These are different for each kind of antibody, which allows the antibody to recognize and attach specifically to a particular antigen

The antigen attachment site is known asvariableregion and specific to each antigen

The rest of each polypeptide chain is termed theconstantregion.

10.1.3

CLASSES OF ANTIBODIES

B cells responds to antigens by producing antibodies

Antibodies are secreted into the blood and other body fluids and thus providehumoral immunity

(Humor = body fluid)

T cells do not secrete antibodies but instead directly attack the cells that carry the specific antigens

These cells are described as producingcell-mediated immunity

A central location for the collection and distribution of the cells of the immune system

Consists of a network of lymphatic capillaries, ducts, nodes and lymphatic organs

The fixed macrophages in the spleen, lymph nodes and other lymphatic tissues are particularly well located to contact infectious agent

Interstitial fluid, perhaps containing pathogen, is taken up by lymphatic capillaries, and flows as lymph, eventually returning to the blood circulatory system

Along the way, lymph must pass through numerous lymph nodes, where any pathogens present must encounter macrophages and lymphocytes

Microorganisms, microbial fragments and foreign molecules that enter the blood encounter macrophages when they become trapped in the netlike architecture of the spleen

The antibody becomes attached to the antigen at the antigen binding site like a key in a lock

This causes the antibody to change from a T shape to a Y shape

This exposes part of the antibody to substances in the plasma that are together known as complement

It is the combined effect of antibody and complement that determines the action of antibody

The binding of antibodies to antigens to form antigen-antibody complexes is the basis of several antigen disposal mechanisms

Neutralization

Agglutination

Precipitation

Complement-fixation

The antibody binds to and blocks the activity of the antigen

E.g.: Antibodiesneutralizea virus by attaching to molecules that the virus uses to infect its host cell.

Similarly, antibodies may bind to the surface of a pathogenic bacterium

These microbes, now coated by antibodies, are readily eliminated by phagocytosis

In a process calledopsonization (coating) , the bound antibodies enhance macrophage to, and thus phagocytosis of, the microbes

Antibody-mediated agglutination (clumping) of bacteria or viruses effectively neutralizes and opsonizes the microbes

Agglutination is possible because each antibody has at least two antigen-binding sites (IgG)

IgM can link together five or more viruses or bacteria

These large complexes are readily phagocytosed by macrophages

In precipitation, the cross-linking of soluble antigen molecules molecules dissolved in body fluids forms immobile precipitates that are disposed of by phagocytosis

During complement fixation, the antigen-antibody system activates the complement system, a complex of 20 different serum proteins

In an infection, the first in a series of complement proteins is activated, triggering a cascade of activation steps, each component activating the next in series

Completion results in the lysis of many types of viruses and pathogenic cells

Lysis can be achieved in two ways:

The classical pathway

The alternative pathway

Is triggered by antibodies bound to antigen and is therefore important to immune response

Begins when IgM or IgG antibodies bind to a pathogen

The first complement component links two bound antibodies and is activated, initiating a cascade

Ultimately, complement proteins generate a membrane attack complex (MAC), which forms a pore in the bacterial membrane, resulting in cell lysis.

Antibody molecules attach to antigens on pathogens plasma membrane

Complement proteins link two antibody molecules

Activated complement proteins attach to pathogens membrane in step-by step sequence, forming a membrane attack complex (MAC)

MAC pores in the membrane causes cell lysis.

Is triggered by substances that are naturally present on many bacteria, yeast, viruses and protozoan parasites

It does not involved antibodies and thus is an important non specific defense.

In both the classical and alternative pathways, many activated complement proteins contribute to inflammation.

Some triggers the release of histamine by binding the basophils and mast cells

Several active complement proteins also attract phagocytes to the site.

One activated complement protein coats bacterial surfaces and stimulates phagocytosis, like antibody

During immune adherence, microbes coated with antibodies and complement adhere to blood vessels walls, making the pathogens easier prey for phagocytic cells circulating in the blood

Describe and explain primary and secondary immune responses to antigen.

Explain the concept of self and non-self recognition and its application in organ transplant, grafting and blood transfusion.

Antigens interact with specific lymphocytes, inducing immune responses and immunological memory

Although it encounters a large repertoire of B and T cells, a microorganism interacts only with lymphocytes bearing receptors specific for its various antigenicmolecules

The selection of a lymphocytes by one of the microbes antigens activate the lymphocyte, stimulating it to divide and differentiate and eventually, producing two clones of cells

One clone consists of a large number ofeffector cells , short-lived cells that combat the same antigen

Effector cellsare populations of cells resulting from divisions of lymphocytes that were activated by the binding of antigens to their antigen receptors

The other clone consists ofmemory cellsbearing the receptors for the same antigen

The selective proliferation and differentiation of lymphocytes that occur the first time the body is exposed to an antigen is theprimary immune response

About 10 17 days lag period between initial exposure and production of effector cells

During this period, selected B cells and T cells generate antibody-producing effector B cells, called plasma cells, and effector T cells respectively

While this response is developing, a stricken individual may become ill, but symptoms of the illness diminish and disappear as antibodies and effector T cells clear the antigen from the body

A second exposure to the same antigen at some later time elicits the secondary immune response

This response is faster (only 2 to 7 days), of greater magnitude and more prolonged

The antibodies produced in the secondary response tend to have greater affinity for the antigen than those secreted in the primary response

The immune systems capacity to generate secondary immune response is calledimmunological memory , based not only on effector cells, but also clones of long-lived T and B memory cells

Memory cells are not active during primary response and survive in the system for long periods.

When the same antigen that caused a primary immune response again enters the body, the memory cells are activated and rapidly proliferate to form a new clone of effector cells and memory cells

These new clones of effector and memory cells are the secondary immune response

1. Immunity to smallpox in Jenners patients occurred because their inoculation with cowpox stimulated the development of lymphocyte clones with receptors that could bind not only to cowpox but also to smallpox antigens.

2. As a result of clonal selection, a second exposure, this time to smallpox, stimulates the immune system to produce large amounts of the antibody more rapidly than before.

Lymphocytes do not react to most self antigens, but T cells do have a crucial interaction with one important group of native molecules

These are a collection of cell surface glycoproteins encoded by a family of genes called themajor histocompatibility complex (MHC) or specifically in humans, human leukocyte antigens (HLA)

Two main classes of MHC molecules mark body cells as self

Class I MHC molecules are found on almost all nucleated cells that is on almost every cells

~ the interaction between the antigen-presenting infected cell is greatly enhanced by a T cell surface protein called CD8

ii.Class II MHCmolecules are restricted to few specialized cell types, including macrophages, B cells, activated T cells and those inside the thymus

~ The interaction between antigen-presenting cell and a T Hcell is greatly enhanced by CD4

It is unlikely that any two people, except identical twins, will have the same set of MHC molecules

The MHC provides a biochemical fingerprint virtually unique to each individual

MHC molecules vary from person to person because of their central role in the immune system

There are two main types of T cells, and responds to one class of MHC molecules

Cytotoxic T cells (T C ) have antigen receptors that bind to protein fragments displayed by the bodys class I MHC molecules

~ Tc responds by killing the infected cells

A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and transported to the cell surface.

The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection.

ii. Helper T cells (T H ) have receptors that bind to peptides displayed by the bodys class II MHC molecules

~ Macrophages and B cells (antigen - presenting cells, APCs), ingest bacteria and viruses and then destroy them

A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and transported to the cell surface.

The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection.

Humoral immunity: involves B cell activation and results from the production of antibodies that circulate in the blood plasma and lymph

Circulating antibodies defend mainly against free bacteria, toxins and viruses in the body fluid

Cell-mediated immunity: T lymphocytes attack viruses and bacteria within infected cells and defend against fungi, protozoa and parasitic worms

They also attack non-self cancer and transplant cells

The humoral and cell-mediated immune responses are linked by signalling interactions, especially via the T cells

1. Helper T lymphocytes function in both humoral and cell-mediated immunity

Both types of immune responses are initiated by interactions between antigen-presenting cells (APCs) and T Hcells

The APCs, including macrophages and some B cells, tell the immune system, via T Hcells, that a foreign antigen is in the body

At the heart of the interactions between APCs and T Hcells are class II MHC molecules produced by the APCs, which bind to foreign antigens

An APC engulfs a bacterium and transport a fragment of it to the cell surface via a class II MHC molecule

A specific T Hcell is activated by binding to the MHC-antigen complex. The CD4 protein of the T Hcells enhances the activation, as does interleukin-1 (IL-1) secreted by the APC

The activated T Hcell proliferates, giving rise to a clone of identical clones (not shown), all with receptors keyed to the same MHC-antigen combination. These cells secrete cytokines (e.g. : Interleukin-2)

The cytokines further stimulate the T Hcells and also help activates B cells and T Ccells

Activated TH cells that bind to a class II MHC-antigen complex on an APC are induced to differentiate into either of two clones of cells :

i.Activated T Hcells~ secrete cytokines, factors that stimulate other lymphocytes (e.g. : IL-2 stimulates differentiation of B cells into antibody-secreting plasma cells and induces T Ccells to become active killers)

ii.Memory T Hcells~ IL-1 secreted from APCs, promotes activation of the T Hcells and the subsequent secretion of IL-2 from the activated T Hcell.

~ T Hcells themselves are regulated by cytokines

2. In the cell-mediated response, cytotoxic T cells defend against intracellular pathogens

Antigen-activated T Ccells, kill cancers cells and cells infected by viruses and other intracellular pathogens

This is mediated through class 1 MHC molecules

All nucleated cells continuously produce class 1 MHC molecules, which capture a small fragment of one of the other proteins synthesized by that cell and carries it to the surface

An infected cell (or cancer cell) displays as an antigen fragment on its surface using a class I MHC molecule. A specific T Ccell is activated by binding to the MHC-antigen complex. The CD8 protein of the T Ccell enhances the activation, along with IL-2 from T Hcells (not shown)

The activated T Ccell discharges perforin molecules, which create pores in the membrane of the infected cell.

Water and ions flow into the infected cell, and the cell lyses.

Destruction of the host cell not only removes the site where pathogens can reproduce, but also exposes the pathogens to circulating antibodies from humoral response.

T Ccontinue to live after destroying the infected cell and may kill many others displaying the same antigen-class I MHC marker

T Calso function to destroy cancer cells

Cancer cells possess distinctive markers not found on normal cells, known astumor antigen

T cells recognize these markers as non-self and attach and lyse the cancer cells

Certain types of cancers and viruses have diminish the amounts of class I MHC proteins on affected cells, thereby reducing the ability of T Cto recognize and destroy them

3. In the humoral response, B cells make antibodies against extracellular pathogens

The humoral response occurs when an antigen binds to B cell receptors that are specific for the antigen epitopes

The B cells differentiate into a clone of plasma cells which begin to secrete antibodies that are most effective against pathogens circulating in the blood and lymph

Memory cells are also produced and form the basis for secondary immune responses

A macrophage ingests a pathogen

Class II MHC proteins within the cell bind to fragments of the pathogen and transport them to the cell surface

A T Hcell with a receptor specific for the presented antigen contacts the macrophage and is induced to proliferate and secrete cytokines

The activated T Hcell binds with a B cell that has previously taken up antigen. As an APC, the B cells class II MHC molecules present fragments of the antigen. Cytokines help activate the B cell.

The B cell proliferates and differentiates into memory cells and plasma cells that secrete antibody molecules specific for the bacterium.

When activated a B cell gives rise to a clone of plasma cells.

Each of these effector cells secretes up to 2000 antibodies per second into body fluids for its 4 5 day lifespan

The specific antibodies help eliminate the foreign invader from the body

In addition to attacking pathogens, the immune system will also attack cells from other individuals.

For example, a skin graft from one person to a nonidentical individual will look healthy for a day or two, but it will then be destroyed by immune responses.

Interestingly, a pregnant woman does not reject the fetus as a foreign body, as apparently, the structure of the placenta is the key to this acceptance.

One source of potential problems with blood transfusions is an immune reaction from individuals with incompatible blood types.

In theABO blood groups , an individual with type A blood has A antigens on the surface of red blood cells.

This is not recognized as an antigen by the owner, but it can be identified as foreign if placed in the body of another individual.

B antigens are found on type B red blood cells.

Both A and B antigens are found on type AB red blood cells.

Neither antigen is found on type O red blood cells.

A person with type A blood already has antibodies to the B antigen, even if the person has never been exposed to type B blood.

These antibodies arise in response to bacteria (normal flora) that have epitopes very similar to blood group antigens.

Thus, an individual with type A blood does make antibodies to A-like bacterial epitopes - these are considered self - but that person does make antibodies to B-like bacterial epitopes.

If a person with type A blood receives a transfusion of type B blood, the preexisting anti-B antibodies will induce an immediate and devastating transfusion reaction.

However, another blood group antigen, theRh factor , can cause mother-fetus problems because antibodies produced to it are IgG.

This situation arises when a mother that is Rh-negative (lacks the Rh factor) has a fetus that is Rh-positive, having inherited the factor from the father.

If small amounts of fetal blood cross the placenta as may happen late in pregnancy or during delivery, the mother mounts a T-dependent humoral response against the Rh factor.

The danger occurs in subsequent Rh-positive pregnancies, when the mothers Rh-specific memory B cells produce IgG antibodies that can cross the placenta and destroy the red blood cells of the fetus.

To prevent this, the mother is injected with anti-Rh antibodies after delivering her first Rh positive baby.

She is, in effect, passively immunized (artificially) to eliminate the Rh antigen before her own immune system responds and generates immunological memory against the Rh factor, endangering her future Rh-positive babies.

Briefly explain SLE, AIDS

Explain the mechanism of action of HIV Infection and Symptoms of AIDS.

List the possible causes and prevention of HIV Infection.

Malfunctions of the immune system can produce effects ranging from the minor inconvenience of some allergies to the serious and often fatal consequences of certain autoimmune and immunodeficiency diseases.

Allergiesare hypersensitive (exaggerated) responses to certain environmental antigens, called allergens.

One hypothesis to explain the origin of allergies is that they are evolutionary remnants of the immune systems response to parasitic worms.

The humoral mechanism that combats worms is similar to the allergic response that causes such disorders ashay feverandallergic asthma.

The most common allergies involve antibodies of the IgE class.

Hay fever, for example, occurs when plasma cells secrete IgE specific for pollen allergens.

Some IgE antibodies attach by their tails to mast cells present in connective tissue, without binding to the pollen.

Later, when pollen grains enter the body, they attach to the antigen-binding sites of mast cell-associated IgE, cross-linking adjacent antibody molecules.

This event triggers the mast cell todegranulate- that is, to release histamines and other inflammatory agents from vesicles called granules.

High levels of histamines cause dilation and increased permeability of small blood vessels.

These inflammatory events lead to typical allergy symptoms: sneezing, runny nose, tearing eyes, and smooth muscle contractions that can result in breathing difficulty.

Antihistamines diminish allergy symptoms by blocking receptors for histamine.

Sometimes, an acute allergic response can result inanaphylactic shock , a life threatening reaction to injected or ingested allergens.

Anaphylactic shock results when widespread mast cell degranulation triggers abrupt dilation of peripheral blood vessels, causing a sudden drop in blood pressure.

Death may occur within minutes.

Triggers of anaphylactic shock in susceptible individuals include bee venom, penicillin, or foods such as peanuts or fish.

Some hypersensitive individuals carry syringes with epinephrine, which counteracts this allergic response.

The MHC is responsible for stimulating the rejection of tissue grafts and organ transplants.

Because MHC creates a unique protein

fingerprint for each individual, foreign

MHC molecules are antigenic, inducing

immune responses against the donated

tissue or organ.

To minimize rejection, attempts are made to match MHC of tissue donor and recipient as closely as possible.

In the absence of identical twins,

siblings usually provide the closest

tissue-type match.

In addition to MHC matching, various medicines are necessary to suppress the immune response to the transplant.

However, this strategy leaves the

recipient more susceptible to

infection and cancer during the

course of treatment.

More selective drugs, which suppress helper T cell activation without crippling nonspecific defense or T-independent humoral responses, have greatly improved the success of organ transplant.

In bone marrow transplants, it is the graft itself, rather than the host, that is the source of potential immune rejection.

Bone marrow transplants are usedto treat leukemia and othercancers as well as varioushematological diseases.

Prior marrow transplants, therecipient is typically treated with

irradiation to eliminate the

recipients immune system, leaving

little chance of graft rejection.

However, the donated marrow,

containing lymphocytes, may react

against the recipient, producing graft

versus host reaction, unless well

matched.

Autoimmunity arises when the immune system fails to distinguish between self and non-self (foreign) cells, and attacks self, or body tissues.

Causes generally not known, but may involve genetic, viral and environmental factors or after recovery from infection.

Myasthenia gravis

Multiple sclerosis

Rheumatoid arthritis

Systemic lupus erythematosus

Heart damage following rheumatic fever & Type I diabetes.

In this i ll ness the myelin sheath covering the spinal cord is destroyed, leading to difficulty in walking and other movements. The damage in multiple sclerosis is not produced by an auto antibody but by a lymphocyte that reacts directly with the protective sheath.

In SLE (lupus), the immune system generates antibodies against all sorts of self molecules, including histamines

Lupus is characterized by skin rashes, fever, arthritis and kidney dysfunction

In 1981, increased rates of two rare diseases, Kaposis sarcoma, a cancer of the skin and blood vessels, and pneumonia caused by the protozoanPneumocystis carinii , were the first signals to the medical community of a new threat to humans, later known as acquiredimmunodeficiency syndrome , orAIDS .

Both conditions were previously known to occur mainly in severely immunosuppressed individuals.

People with AIDS are susceptible toopportunistic diseases .

Opportunistic disease: infection rarely observed in humans with normal immune response

Eg : ThePneumocystisprotozoan is an ubiquitous organism, yet it does not cause pneumonia in a person with a healthy immune system

In people with AIDS, opportunistic diseases, neurologic damage and physiological wasting, lead to death

In 1983, a retrovirus, now calledhuman immunodeficiency virus( HIV ) , had been identified as the causative agent of AIDS.

With the AIDS mortality close to 100%, HIV is the most lethal pathogen ever encountered.

Molecular studies reveal that the virus probably evolved from another HIV-like virus in chimpanzees in central Africa and appeared in humans sometimes between 1915 and 1940.

These first rare cases of infection and AIDS went unrecognized.

There are two major strains of the virus, HIV-1 and HIV-2.

HIV-1 is the more widely distributed and more virulent.

Both strains infect cells that bear CD4 molecules, especially helper T cells and class II MHC-bearing antigen-presenting cells, but also macrophages, some lymphocytes and some brain cells.

CD4 functions as the major receptor for the virus.

The viral particle includes:

an envelope with glycoproteinfor binding to receptor molecule on T Hsurface

a capsidcontaining:

1. two identical RNA strands as its genome

2. two copies of reverse transcriptase.

The entry of the virus requires not only CD4 on the surface of the susceptible cells but also a second protein molecule, acoreceptor .

Two of the coreceptors that have been identified normally function as receptors for chemokines.

Some people who are innately resistant to HIV-1 owe their resistance to defective chemokine receptors which prevents HIV from binding and infecting cells.

Promiscuity (having many transient sexual relationship)

Through injection drug use

Prenatal infection or in infancy

Blood transfusion.

persistent or recurrent fever

severe dry cough

sore throat

night sweat

chronic fatigue

decreased appetite (rapid

weight loss) blood/mucus in

upper-body rash

(madness) due to the damage

on nervous system (esp. brain

and myelin sheath)

inflammation of lungs

(alveoli filled with fluid)

Glycoprotein on the envelope bind to specific receptors on the hosts membrane (T Hcell)

The envelope fuses with the hosts membrane,

transporting the capsid and viral genome inside

Reverse transcriptase synthesizes double

stranded DNA from the viral RNA

The double-stranded DNA is incorporated as

aprovirusinto the host cell's chromosomal

DNA, where it may lie dormant for years.

Theprovirusis transcribed into mRNA and went

out from the hosts nucleus into its cytoplasm

mRNA are translated to viral protein forming :

protein for capsid

viral RNA

reverse transcriptase enzyme

Protein coats form around viral RNA and reverse

transcriptase molecules and move towards hosts

membrane cell.

Viruses bud from the host cell, acquiring envelopes

as they leave.

In spite of these challenges, the immune system engages in a prolonged battle against HIV.

(1) The immune response diminishes the initial viral load, but HIV continues to replicate in lymphatic tissue.

(2) Viral load gradually rises as HIV is released from lymphatic tissue and helper T cell levels decrease.

(3) This results in extensive loss of humoral and cell-mediated immunity.

HIV concentration increases rapidly within a 6-month of infection but is then almost eliminated by the immune response.

However, in 1 to 3 years of infection, some of the viruses survive and slowly increase the number of the viruses.

In 9 to 10 years of infection, the body almost total loss of cellular immunity.

While the T helper cell concentration decreases, AIDS is the last stage of the process.

No cure for HIV infection is known, although research is intense in the areas of vaccine production and chemotherapy

Several drugs have been identified as helpful in delaying symptoms of AIDS and in some cases in prolonging the life of those infected with HIV

The most promising drugs : Azidothymidine (AZT) is an effective inhibitor of HIV replication

A major problem observed with many AIDS drugs is that the compounds are frequently toxic when used on a long term basis

Treat HIV infection as an illness

Counseling and HIV testing for the patient

Education for children and adults

Health care programme providing antiretroviral therapyto extend life and to reduce HIV transmission rate .

Antiretroviral therapy for pregnant women

toreduce prenatal HIV transmission.

Promote sexual barrier precautions

(use ofcondoms)

War on drug abuse.

Immunity

Education

Transcript of Immunity