BY

Mr. RAGHUVEER RODDA M.Pharm. (Ph.D)

NBA- coordinatorAssociate professor

Dept. of PharmacologyMIPER, KURNOOL

Email: rodda.raghuveer@gmail.com

HOST PARASITE RELATIONSHIP

Introduction-

➢ The relationship between two organism can be verycomplex.

➢ The normal flora present in its normal site in human bodyprovides some benefits to the host they live in the perfectsymbiosis in their natural habitate.

➢ The host parasite relationship is two types –

1) Beneficial

2) harmful

Simbiosis

Simbiosis is define as “life together”. i.e. that two organisms live in an association with one

another.

Types of Simbiosis

•Commensalism- parasite

Driving nourishment to the host

without causing any harm or benefit to the host.

• Parasitism- the relationship

may be in which one organismdamage the other.

• Mutalism- Both members of

association benefit.

SOME IMPORTANT TERMS

Host- Host are the large animal and plant organism

on or in which a parasite can live.

Parasite- lives on or within a host organism. They

cause disease in the host.

Pathogen-Pathogen is a microorganism is able to

produce disease.

Pathogenicity-It is the ability of a microorganism

to cause disease in another organism.

Reservoir-Any person, plant, soil and substance in which an infectious agent normally lives andmultiplies.Virulence-Degree of pathogenicity of microorganism agent to cause disease.It involves adherence, invasion andtoxigenicity.Adherence- The process by which bacteria stick to the surface of host cell.Ffimbriae / pili (hair like structure) of bacteria.Capsule (sticky polysaccharide material) of bacteria.Capsid spikes of viruses.Invasion- process by which bacteria, parasite enter into the host cell and spread in the body. There are many barriers present on host by the breaking of these barriers the parasite enters into the host cell. Eg.- skin / mucous membrane.Toxigenicity- The ability of microorganism to produce toxins.

Normal flora

• The body of a healthy individual is inhabited by many different microorganism.

• Normal flora is acquired after birth from food and environment.

• They occupy site.

• i.e. Skin, Mouth, Respiratory tract, Intestinal tract and genitourinary tract.

ENTRY OF MICROORGANISM INTO HOST

• There are several sites for the entry of Microorganism.

1) Skin / Mucous membrane

2) Nose

3) Eyes

4) Mouth cavity

5) Respiratory tract

6) Intestinal tract

7) Genitourinary tract

SKIN / MUCOUS MEMBRANE

• Skin – It consist of two parts.

1) Epidermis –• It is acidic.

• Microorganism attached with this layer removed by washing.

2) Dermis –• It contains hair follicle, sweat glands, sebaceous

glands secrete sebum.

• It maintain pH(3-5) it restrict the entry of microorganism.

• The microflora consist Staphylococcus epidermidis,Propionibacterium acne .

• Under certain condition, S. epidermidis can penetrate skin, sometimes it leads to life threatening bloodstream infection.

Mucous Membrane

Mucous membrane of respiratory tract, intestinal tract and genitourinary tract are barrier to microbial

invasion.

There are two strategy for that i.e.

a) Direct uptake

b) Antigen sampling exploitation process

DIRECT UPTAKE

- Microorganism attached with cell receptor.-Secrete invasin enzyme, degrade cell membrane and enter into the cell.

- After entry the vesicle of microorganism attached with lysosome.- Lysosome degrade the microorganism and release the debris by the process

of exocytosis.- If it is not degraded they may cause disease.

Antigen sampling exploitationprocess

- Bacteria enter into the cell by the M cell of the epithelial cell.- these bacteria carrying into the lymph node, present just below the

endothelial cell of intestine.- in lymph node many macrophage and immune cells are present which

engulfe that foreign material.

The eyes are moistend continously with tears, which contain an enzyme lysozyme which helps in the limiting bacteria.

MOUTH CAVITY

EYES

RESPIRATORY TRACT

• A mucociliary blanket cover much of the respiratory tract and trap foreign pathogen agent.• Blanket contain lysozyme and cilia which trap and expels out the microorganism with the help of ciliarymovement.

• Infection occurs – Disturbance and removal of the mucociliary blanket by prior condition cause bronchitis and viral influenza.

•Microflora of nose consist of gram positive cocci found on skin. It is an important site of Stephylococcusaureus residence.

NOSE

INTESTINAL TRACT▪ Infected by contaminated food and water.

▪ In human adults gastric juice is highly acidic (pH1-2).

▪ Mucin layer cover and protect the lining of stomach from acidic pH.

▪ In stomach Helicobacter pylori present in human adults.

▪ Infection occurs – If pathogen can resist host defence.

Genitourinary tract-Kidney and bladder is sterile, may became contaminated with the microbes present in the lower urethra.-The primary component of microflora is human vagina is Lactobacillus sp. which maintain the low pH of vaginal secretion in adults and thus has a protective role.

- When antibiotics are used, the number of Lactobecilli is reduced resulting in growing of disease

causing microorganism such as Candida albicanes.- Infection occurs – Most prevalent in the female because of the shortness of the urethra and proximity of the urethra to the anus where gram negative bacterial sp. are abundent etc.

Characteristics DISEASE INFECTION

DEFINITION

Condition of the body,caused by the effects of excessive or unusual stimuli. Derivation from the normal life of the organism, accompanied by structural and functional changes.

Contagion of the body tissues with pathogenic microorganisms, their multiplication in the cells and the specific immune response of the body to these microrganisms and the toxins they produce.

CAUSES

Injury, infections, hereditary factors, lifestyle, environmental factors,etc.

Viruses, bacteria, macroparasites and fungi.

SYMPTOMS

Nausea, vomiting, swelling pain, breathing problems, diarrhoea, bleeding symptoms, etc.

Painful swollen wound, appearance of pus,fever,runny nose, cough, muscle and joint pain, fast hearbeat, dizziness,etc.

TRANSMISSIBILITY Contagious or Non-contagious Contagious

TREATMENTMedicines, lifestyle changes, healthy diet,surgery,etc.

Antibodies, anti-inflammatory drugs, wounds cleaning, etc.

EXAMPLES

High blood pressure, heart diseases, autoimmune diseases,etc.

Tuberculosis, Pneumonia, Chicken pox, Gonorrhoea, Syphillis, etc.

DISEASE Vs INFECTION

KOCH & RIVER’S POSTULATES

CHAIN OF INFECTION

DEFENSE MECHANISMS

1. External Defense2. Internal Defense3. Immune Defense

• Skin acts as barrier to microbes and viruses- sweat has a low pH

• Mucus traps foreign particles• Tears

- Lysozyme has antimicrobial action• Gastric stomach acid

1st Line of Defense

Body Coverings: TheSkin

sweatgland

epidermis

sebaceous glands

BODY COVERINGS: MUCOUSMEMBRANES

mucus

cilia

• Phagocytic cells (WBCs)- Natural Killer (NK) Cells: attack virus

infected cells••

Inflammatory Response Antimicrobial proteins- Lysozyme- Interferon- Antibodies

2nd Line of Defense

MECHANISM OF PHAGOCYTOSIS

INFLAMMATORY RESPONSE

Histamine &

prostaglandins

released

Capillaries dilate

Clotting begins

Chemotactic factors

attract phagocytic

cells

Phagocytes

consume

pathogens & cell

debris

Lymphatic System3rd Line of Defense

IMMUNITY:

• The state of being immune from or insusceptible to a particular

disease.

• The condition that permits either natural or acquired

resistance to disease.

• The ability of the cell to react immunologically in the presence

of antigen.

How immunitydevelops

• During the body’s first encounter with a pathogen there will be few lymphocytes with specific receptors

• It takes time to divide to form clones, B lymphocytes to secrete antibodies, T lymphocyte production

• If the same pathogen invades again persisting memorycells can give a faster, more effective response

CHARACTERISTICS OFIMMUNITY

• Recognition of self versus non-self

• Response is specific

• Retains a “memory” allowing an accelerated second

response

• Can respond to many different materials

• Involves lymphocytes and antibodies

TYPES OFIMMUNITY

• Active Immunity

- Naturally-Acquired Active Immunity

- Artificially-Acquired Active Immunity

• Passive Immunity

- Naturally-Acquired Passive Immunity

- Artificially-Acquired Passive Immunity

TYPES OF IMMUNITY

• An infection is an example of acquiring naturalimmunity. It is called ACTIVE as your body needs towork to produce the necessary antibodies

• When a mother breast feeds her baby she passesantibodies to it. This is a way of acquiring PASSIVEimmunity as it is a way of gaining antibodieswithout the immune system having to producethem.

• The thick, yellowish milk (colostrum) that isproduced for the first few days after birth isparticularly rich in antibodies.

NATURAL IMMUNITY: ACTIVE ANDPASSIVE

ARTIFICIAL IMMUNITY: ACTIVE ANDPASSIVE

• An alternative to natural immunitydeveloping is to give vaccinations(artificial immunity)

• Antigen is injected into the body.

• This may be in the form of aninactivated bacterial toxin orattenuated (not harmful) viruswhich would promote ACTIVEimmunity;

• or the injection of antibodies orantitoxins which would promotePASSIVE immunity (eg Clostridiumtetani)

• The production of antibodies against a specific disease bythe immune system.

• Naturally acquired through disease

• Artificially acquired through vaccination• Vaccines include inactivated toxins, killed microbes, parts of

microbes, and viable but weakened microbes.

• Memory cells are only produced in active immunity.

• Protection for active immunity is permanent whereas in passive immunity it is only temporary.

• Antigens are only encountered in active immunity.

• Active immunity takes several weeks to become activebut passive is immediate

ACTIVE IMMUNITY

• A vaccinated person has a secondary response based onmemory cells when encountering the specific pathogen.

• Routine immunization against infectious diseases such asmeasles and whooping cough, and has led to theeradication of smallpox, a viral disease.

• Unfortunately, not all infectious agents are easilymanaged by vaccination.

• HIV vaccine in the works

• Passive Immunity- Protection against disease throughantibodies produced by another human being or animal.

• Ex. Maternal antibodies , Colostrum

• Passive immunity doesn’t last as long as active immunity(only weeks or months):

• No lymphocytes are stimulated to clone themselves

• No memory cells have been made

• Effective, but temporary as this type of immunity can onlylast as long as the antibodies/toxins last in the blood

PASSIVE IMMUNITY

• Passive immunity can be transferred artificially by injecting antibodies from an animal that is already immune to a disease into another animal.

• Rabies treatment: injection with antibodies against rabies virus that are both passive immunizations (the immediate fight) and active immunizations (longer term defense).

IMMUNE SYSTEM RESPONSE TOANTIGENS

A. Humoral Immunity• Involves antibodies (secreted from B cells) dissolved in the

blood plasma.• Demonstrated as a immune response using only the blood

serum.• Defense against bacteria, bacterial toxins, & viruses.

B. Cell-Mediated Immunity• Involves the activities of specific white blood cells (T cells).• Defense against cancer cells, virus-infected cells, fungi,

animal parasites, & foreign cells from transplants.

LYMPHOCYTE FORMATION

B Cells

• Mature in bone marrow• Involved in humoral immunity• Once activated by antigen,

proliferate into two types ofclones

• Plasma cellsthat secrete antibodies and• memory cellsthat may be converted into

plasma cells at a later time

B Cellsantibodies

Activation of B Cells byAntigenantigen

Clonal Selection

Clonal Selection

plasma cells memory cells

antibodies

T Cells

• Mature in thymus• Involved in cell-mediated immunity• Activated when another cell presents

antigen to them• Several types of T cells:

• cytoxic T cells,• helper T cells,• suppressor T cells,• memory T cells

• There are two main types of T cells, andeach responds to one class of MHCmolecule.

– Cytotoxic T cells (TC) have antigen receptorsthat bind to protein fragments displayed bythe body’s class I MHC molecules.

– Helper T cells (TH) have receptors thatbind to peptides displayed by the body’sclass II MHC molecules.

T Cells

Cytotoxic TCell

perforin

pores in target cell

Helper TCells

interleukin 1macrophage

helper T cell

bacterium

bacterial antigens

T cell receptor

Humoral Immune Response

time (days)

anti

bo

dy

con

cen

trat

ion

first exposure to antigen A

Humoral Immune Response

time (days)

anti

bo

dy

con

cen

trat

ion

first exposure

to antigen A

primary response: concentration of anti-A antibody

second exposure to

antigen A

Humoral Immune Response

time (days)

anti

bo

dy

con

cen

trat

ion

secondary response:

concentration of anti-A

antibody

second exposure to

antigen A

first exposure

to antigen B

Humoral Immune Response

time (days)

anti

bo

dy

con

cen

trat

ion

primary response: concentration of anti-B antibody

first exposure to antigen B

Antibody Molecule

• Antibodies constitute a group of globular serum proteins called immunoglobins (Igs).• A typical antibody molecule has two identical antigen-binding sites

specific for the epitope that provokes its production.

antigen binding sites

antigen

light chains heavy chains

Mechanisms on AntibodyAction

• Precipitation of soluble antigens• Agglutination of foreign cells• Neutralization• Enhanced phagocytosis• Complement activation leading to cell lysis• Stimulates inflammation

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

The classical complimentary pathway, resulting in lysisof a target cell

OVERVIEW OF IMMUNE SYSTEM RESPONSES

VACCINATION

• Vaccination is a method of giving antigen to stimulate theimmune response through active immunization.

• A vaccine is an immuno-biological substance designed toproduce specific protection against a given disease.

• A vaccine is “antigenic” but not “pathogenic”.

One of the most effective «weapons» in medicine

1798 Edward Jenner immunizes first time against smallpox

1885 Louis Pasteur prepares the 1st vaccine against Rabbies

1927 BCG (bacillus Galmette-Guerin)

1955 Salk vaccine against poliomyelitis

1960 MMR (Measles, Mumps and Rubella)……..

TYPES OFVACCINES

Live

vaccines

Live

Attenuated

vaccines

Killed

Inactivated

vaccines

Toxoids Cellular

fraction

vaccines

Recombinan

t vaccines

•Small

pox

variola

vaccine

•BCG

•Typhoid

oral

•Plague

•Typhoid

•Cholera

•Pertussis

•Plague

•Rabies

•Salk polio

•Intra-

muscular

influenza

•Japanise

encephalitis

•Diphtheria

•Tetanus

•Meningococcal

polysaccharide

vaccine

•Pneumococcal

polysaccharide

vaccine

•Hepatitis B

polypeptide

vaccine

•Hepatitis B

vaccine

•Oral polio

•Yellow

fever

•Measles

•Mumps

•Rubella

•Intranasal

Influenza

•Typhus

Abnormal immune function can lead

to disease

• 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.

Abnormal Immune Function

• Autoimmune Disease• Allergy• Immunodeficiency

Autoimmunity

• Autoimmunity literally means “protection against self”;

• In practice it leads to “injury to self.”

Auto or Self antigens

– Antigens present in ones own cells.

– Altered by the action of bacteria, viruses, chemicals or drugs as a non-self.

Auto antibody

– Altered cell (Auto Ag) - elicits the productions of Antibody.

Auto Immunity

▪ Immune response of auto Ab againstself Ag.

▪ Humoral or cell mediated immuneresponse against the constitutes of thebody’s own tissues.

▪ There are more than 80 different kindsof diseases caused by autoimmunity.

AUTOIMMUNE DISEASES• Normally, the immune system does not attack

the self.

• However, there is a large group of autoimmunediseases in which the immune system attackself-cells.

• Autoimmune diseases is a group of disorders inwhich tissue injury is caused by humoral (auto-antibodies) or cell mediated immune response(auto-reactive T cells) to self antigens.

• The attack can be directed either against a veryspecific tissue or to a large No. of tissues.

• Once started, it is hard to stop.

CAUSES OF AUTOIMMUNE DISEASES1. Sequestered or Hidden antigens

• Ag in the secluded places - are not accessible to the immune system.

• E.g. Lens Ag, Sperm Ag & Thyroglubulin.

2. Neo antigens

Altered or Modified Antigens – by physical (irradiation), chemical (drugs) or microbial agents ( intracellular viruses).

3. Cessation of Tolerance

It may result when tolerance to the self-Ag is abrogated.

4. Cross reacting Antigens

• A foreign Ag which resembles self Ag.

• Many species share organ specific Ags.

• E.g. Ag of Human brain & Ag of sheep brain,Streptococcal M protein & Heart muscles,Nephritogenic strains of Streptococci Ags &Renal glomeruli shares similar epitopes.

5. Loss of Immunoregulation

• Loss of Self tolerance - caused by overactivity or lowered activity of T and B- cells.

CLASSIFICATION OF AUTOIMMUNE DISEASES

• It is classified into 3 groups:

1. Haemolytic autoimmune diseases.

2. Localised autoimmune diseases.

3. Systemic autoimmune diseases.

Haemolytic autoimmune diseases

- Clinical disorder due to destructions of blood components.

- Auto Ab are formed against one’s own RBCs, Platelets or Leucocytes.

- E.g. Haemolytic anaemia, Leucopenia, Thrombocytopenia.

Localised autoimmune diseases or

Organ specific autoimmune diseases

- A particular organ is affected due to auto Abs.

- For example:

– Thyroiditis (attacks the thyroid).

– Multiple sclerosis (attacks myelin coating of nerve axons).

– Myasthenia gravis (attacks nerve-muscle junction).

– Juvenile diabetes or Type I DM (attacks insulin-producing cells).

Systemic autoimmune diseases or

Non-organ specific autoimmune diseases

• Immune complexes accumulate in many tissues and cause inflammation and damage.

• Affects many organs or the whole body.

- For example:

– Systemic Lupus Erythematosus (anti-nuclear Ab.): Harms kidneys, heart, brain, lungs, skin…

– Rheumatoid Arthritis (anti-IgG antibodies): Joints, hearts, lungs, nervous system.

– Rheumatic fever: cross-reaction between antibodies to streptococcus and auto-antibodies.

AUTOIMMUNE DISEASES

AUTOIMMUNE HEMOLYTIC ANEMIA

• Lysis of RBC is due to the production ofautoantibodies against the RBC-antigens.

• RBC half life= 21 days, Ha. Anaemia <7days

• Caused by infections or Drug therapy [Penicillin,Anti-hypertensive agent results in destruction ofRBCs].

• Antibody mediated autoimmune diseases.

• 2 classes of autoantibodies involved are:

• IgM.

• IgG.

THROMBOCYTOPENIA

• Characterized by low platelet count due to theproduction of antiplatelet Ab. (IgG).

▪ Mechanism

• An interaction of Ab with bound drug or newAg. causes intravascular agglutination ofplatelets & can be eliminated by phagocyticcells.

• Antibody mediated autoimmune diseases.

THYROTOXICOSIS OR GRAVE’S DISEASE

• The Ab (IgG) is directed against the receptor forthyroid stimulatory hormone (TSH).

• This Ab is called as Long acting thyroid (LATS)stimulator or thyroid stimulating Ab (TSab).

• Primary causes: Stimulation of Thyroid gland tosecrete more TH (Hyperthyroidism) resulting inExophthalmus , bulging eyes & Goitre.

Graves’ disease (anti-thyroid stimulating hormone; anti-TSH)

In Graves’ disease, the antibodies do not destroy the thyroid but act as if they are TSH (i.e., they bind and activate the TSH receptor)

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

• It is a skin disease due to the production ofantinuclear factor (ANF) or antinuclear autoAb.

• ANF reacts with the breakdown products ofnuclei in the normal aging of cells & formimmune complexes which cause the tissuedamage.

• In these patients, LE cell (a matureneutrophil) appears in blood & bone marrow.

– Function – Phagocytosis in the presence of ANF.

MALAR RASH (SLE)

CHARACTERISTICS OF SLE

• Appearance of blood red spots over the bridge ofnose & cheeks. The lesions take the shape of abutterfly.

• Connective tissues of the skin, kidney, heart.Spleen & blood vessels are severely damagedresulting in joint pain, fever & anemia.

• Glomerulonephritis due to deposition of immunecomplex in the glomerulus region.

• It is a systemic disease affecting the whole body

RHEUMATOID ARTHRITIS

• It is a chronic systemic disease of the joints.

• Caused by the auto Antibody of IgM type,called as rheumatoid factors.

Characteristics:

• The synovial fluid of these patients containincreased No. of T-cells & macrophages.

• Marked by inflammatory changes in thesynovial membrane & by atrophy of bones.

• In later stage, deformity & ankylosisdevelops.

RHEUMATOID ARTHRITIS

DIAGNOSIS OF AUTO IMMUNE DISEASE

• Clinical symptoms.

• Confirmed by detecting the auto Ab in the serum of the patients.

• Autoantibodies are demonstrated by immunoflurescent Ab test, haemagglutination, Complement fixation, immunodiffusion, Radio immuno assay, etc.

TREATMENT

• Some autoimmune diseases are treated withmedications that alleviate specific symptoms.

• Haemolytic anaemia: Treated with Vit B12 .

• Throtoxicosis: Treated with antithyroid drugs.

• Myasthenia Gravis: Choline estrase inhibitors.

• Rhemotoid Arthritis: Anti-inflammatory drugs.

Organ transplantation

Is the moving of an organ from one body to another for

the purpose of replacing the recipient's damaged or

failing organ with a working one from the donor site.

Organ donors can be living or deceased

Organs that can be transplanted:

the heart, kidneys, liver, lungs, pancreas, eyes and

intestine.

Tissues that can be transplanted:

bones, tendons, cornea, heart valves, veins, and skin

Types of transplants

1.Autograft

• Transplant of tissue to the same person.

e.g. skin, vein, stem cells

2.Allograft:

• Transplant of an organ or tissue between two genetically non-

identical members of the same species

• Most human tissue and organ transplants are allografts

3.Isograft: (Syngeneic)

• A subset of allografts from a donor to a genetically identical

recipient (e.g. identical twin).

• Isografts don't trigger an immune response.

4.Xenograft:

• A transplant of organs or tissue from one species to another

• e.g. porcine heart valve transplants

Immunologic Basis of Allograft Rejection

Grafts rejection

Is a kind of specific immune response to the organ which

causes failure of the transplant

– Specificity

– Immune memory

Transplantation antigens:

I. Major histocompatibility antigens (MHC molecules)

II. Minor histocompatibility antigens

III. Other alloantigens

I. Major histocompatibility antigens (MHC molecules)

• Main antigens of grafts rejection

• Cause fast and strong rejection

• Difference of HLA types is the main cause of human grafts

rejection

II. Minor histocompatibility antigens

• Also cause grafts rejection, but slow and weak

III. Other alloantigens

• ABO blood group antigens

• Some tissue specific antigens:

– Skin, kidney, heart, pancreas ,liver

– VEC (vascular endothelial cell) antigens

Mechanism of allograft rejection

1. Cell-mediated Immunity

2. Humoral Immunity

3. Role of NK cells

Cell-mediated Immunity

• T cell-mediated cellular immune response against alloantigens

on grafts

• T cells of the recipient recognize the allogeneic MHC molecules

i.e. uptake and presentation of allogeneic donor MHC molecules

by recipient APCs

• activated CD4+T cells MΦ activation and recruitment

• Activated CD8+T cells Kill the graft cells

Humoral immunity

• Important role in hyperacute rejection

- Complements activation

- ADCC

- Opsonization

Role of NK cells

• mediators secreted by activated Th cells can promote

NK activation

Classification of Allograft Rejection

1. Host versus graft reaction (HVGR)

Conventional organ transplantation

2. Graft versus host reaction (GVHR)

Bone marrow transplantation

Host versus graft reaction (HVGR)

1. Hyperacute rejection

2. Acute rejection

3. Chronic rejection

Hyperacute rejection

❑ Occurs within minutes to hours after host blood

vessels are anastomosed to graft vessels

❑ Pathology:• Thrombotic occlusion of the graft vasculature

• Ischemia, denaturation, necrosis

❑ Mechanisms:• Antibody against ABO blood type antigen

• Antibody against VEC antigen

• Antibody against HLA antigen

• Complement activationEndothelial cell damage

• Platelets activation Thrombosis, vascular occlusion,

ischemic damage

Acute rejection

❑Occurs within days to 2 weeks after transplantation, 80-90% of cases occur within 1 month

❑Pathology

• Acute humoral rejection:

Acute vasculitis manifested mainly by endothelial cell damage

• Acute cellular rejection:

Parenchymal cell necrosis along with infiltration of lymphocytes and MΦ

❑Mechanisms

• Vasculitis: IgG antibodies against alloantigens on endothelial cell

• Parenchymal cell damage

oDelayed hypersensitivity mediated by CD4+Th1

oKilling of graft cells by CD8+Tc

Chronic rejection

❑Develops months or years after acute rejection reactions

have subsided

❑Pathology

• Fibrosis and vascular abnormalities with loss of graft

function

❑Mechanisms

• Not clear

• Extension and results of cell necrosis in acute rejection

• Chronic inflammation mediated by CD4+T cell/MΦ

• Organ degeneration induced by non immune factors

Graft versus host reaction (GVHR)

• Graft versus host reaction (GVHR)

– Allogeneic bone marrow transplantation.

– Rejection to host alloantigens.

– Mediated by immune competent cells in bone marrow.

• Graft versus host disease (GVHD)

– A disease caused by GVHR, which can damage the host.

– Acute GVHD

– Chronic GVHD

• Conditions

- Enough immune competent cells in grafts.

- Immunocompromised host.

- Histocompatability differences between host and graft.

1. Acute GVHD

• Endothelial cell death in the skin, liver, and gastrointestinal

tract

• Rash, jaundice, diarrhea, gastrointestinal hemorrhage

• Mediated by mature T cells in the grafts

2. Chronic GVHD

• Fibrosis and atrophy of one or more of the organs

• Eventually complete dysfunction of the affected organ

Both acute and chronic GVHD are commonly

treated with intense immunosuppresion

Prevention and Therapy of Allograft Rejection

1. Tissue Typing

• ABO and Rh blood typing

• HLA typing (HLA-A and HLA-BHLA-DR)

• Screening of the recipient for anti-HLA antibodies (also called

antibody screening)

• Lymphocyte cross matching (also called compatibility testing)

2. Immunosuppressive Therapy

• Corticosteroids: block the synthesis and secretion of cytokines

• Azathioprine, Cyclophosphamide: block the proliferation of lymphocytes.