Immune System & Humoral Immunity

8/4/2019 Immune System & Humoral Immunity

1/55

Dr.P.S.N.RajuP.G in PhysiologyAndhra Medical CollegeVisakhapatnam

A.P , India


2/55

THE IMMUNE SYSTEM

The Latin term IMMUNIS means EXEMPT, referring to

protection against foreign agents. Immunity is the ability of the bodyto specifically counteract foreign organisms or substances, called antigens.


3/55

S pecific Defenses of the Host:The Immune Response

Acquired immunity Developed during anindividual's lifetime


4/55

A NATOMY OF THE IMMUNE SYSTEM


5/55

DEFENCECOUNTRY

ATTACKED

TWO WAYS

TO FIGHTHIRE A TRAINED FORCE - QUICK

PREPARE OWN FORCE TAKES TIME

WHICH IS BEST?


6/55

ATTACK INFECTION

INFECTIONINFECTION

INFECTION


7/55

DEFENCE

HIRE(PASS IVE)MAKE OWN(ACTIVE)

PHYSICAL(SKIN)


8/55

Cells of Immune System


9/55

Lymphocytes

Large nucleiCapable of proliferationExtensive Rough ER

Synthesize antibodies Phagocytosis

Direct killing of targetcells Modulation of the

immune response


10/55

Naturally Acquired immunity.

B-cells : humoral immunity (blood-specificimmunity )

Secrete antibodies into blood stream

Ingest, digest and display parts of antigens

T-cells : cell mediated immunity T cells secretelymphokines - activate / repress immune

response. (e.g. interleukin-2) Direct cell-cell contact Bind to infected cells, deliver toxins, Induce apoptosis


11/55

Distinct Cells in Immune System

Lymphocytes ( B cells, T cells ) Determining specificity of immunity

Monocyte/macrophage, dendritic cells, natualkiller cells and other members of myeloid cells

Antigen presentation Mediation of immunologic functions

Specialized epithelial and stromal cells Providing anatomic environment


12/55

Acquired immunity.

Characteristics:

Immunological recognition .

Discrimination between self & non-self.Depending on displaying of specific markersCapacity to make Immune response to foreign A g is developed in latefoetal stage or after birth. Immunilogical Silence.

Immunological specificity .Immunological memory .


13/55

Acquired immunity.

Immune system mounts immune response .

Immune response must:

R ecognise micro-organism / parasite as foreign.

R espond by production specific antibodies &lymphocytes.

Mediate elimination of organisms.


14/55

The discovery of B cell immunity

1954 - Bruce Glick, Ohio S tate University

S tudies on the function of the bursa of Fabricius, a lymphoid organ in thecloacal region of the chicken

Bursectomized chickenswere later used in

experiments to raise

antibodies to Salmonellaantigens

None of thebursectomized

chickens made anti-Salmonellaantibodies

Bursa was later found to be the organ in which antibody producing cells developed antibody producing cells were thereafter called B cells

Mammals do not have a bursa of Fabricius


15/55

1 . Cellular immunity - B

lymphocytes.Found in lymph nodes, liver & spleen.

Bone marrow-derived.

Mature in Peyers Patches of Intestine.

During maturation, antigen-specified Abdisplayed on cell surface.

If the cell activated by antigen, B cells secreteantibody.


16/55


17/55

R

Markers of Self

Muscle cell

Nervecell

Epithelialcell

Leukocyte

Class I MHC self-marker protein


18/55

R

Ma r r f - lf

- lf l t

A tib d

itlass I MHC r t i

it

A tib d

A tig

A tig

Bac t ri a

Non -se lf ne r e ce ll

AR ir s


19/55

Major Histocompatibility Complex (MHC)

The major histocompatibility complex (MHC) is a largegenomic region or gene family found in the short arm of chromosome 6.HLA antigen system-Group of genes present in MHC mol.The proteins encoded by the MHC are expressed on thesurface of cellsClass MHC I found in every cell , presents Ag to Cytotoxic TcellsClass MHC II on B cells , otherAPC , Presents A g to TH cells


20/55

Humoral Immunity

A ntibody ( A b) Proteins made in response to exposureto bacteria and other pathogens,

toxins, plant polen and red blood cellsthat the body recognized as alien, ornonself

A ntigen ( A g) A substances that causes thebody to produce specific

antibodies or sensitized T cells


21/55

An antigen (or immunogen) is a chemical substance thatcauses the body to produce specific antibodies(anti body g e n eration)As a rule, antigens are proteins or large

polysaccharides .Antibodies are formed against specific regions onantigens called epitopes , or antigenic determinants.

The Nature of Antigens


22/55

Haptens

A hapten is a low-molecular-weight substance that cannot cause theformation of antibodies unless combined with a carrier molecule;

once the antibody against hapten has been formed haptens willreact with their antibodies independent of the carrier molecule.

Figure 17 .4


23/55

The Nature of Antibodies

An antibody, or immunoglobulin (Ig), is a protein producedby B cells in response to an antigen and is capable of combining specifically with that antigen .Antibodies recognize and react with antigenic determinantsor epitopes .

Figure 17 .3


24/55

Antibody S tructure

Figure 17 .5 a-c


25/55

Generation of immune response.

~ 4 -7 days to generate immune response.

> 7 days get primary immune response .1 st IgM produced then IgG.After ~3 weeks primary immune response turnedoff.Ab producing cells & memory B cells formed.

Memory B cells secrete ab when same agentencountered again.This is secondary immune response .Memory lasts weeks / years.


26/55

Activation of B cells to produce antibodies

F i u re 17 .4 - O v er vie w

T- de e n de n t an ti e n


27/55

Activation of B cells to produce antibodies

T independent antygen -Antigens that stimulate B cells

without help of T cellsRepeating subunits polisaccharides or lipopolisaccharidesCan bind multiple receptors

F ig r e

.6


28/55

Helper T Cells

Figure 17 .1 3


29/55

S tages of Humoral Immune Response


30/55

Two-Signal Model of Humoral Immune R esponse


31/55


32/55

FUNCTIONING OF THE IMMUNE SYSTEM


33/55

Antigen ReceptorsThe humoral andcell-mediated responsesboth rely on antigen

receptorsReceptor versus LigandAn antigen receptor is a receptor whose

ligand is an antigenAntibodies are only one class of antigenreceptors


34/55

BINDINGBINDING NO BINDING NO BINDING

BACTE R IABACTE R IA

R ECEPTO R R ECEPTO R

L IGANDL IGAND

LYM PHOC Y TELYM PHOC Y TE LYM PHOC Y TELYM PHOC Y TE

R ECOGNIZES BACTE R IAR ECOGNIZES BACTE R IA DOES NOT R ECOGNIZE BACTE R IADOES NOT R ECOGNIZE BACTE R IA

Receptor-ligand interactions lock and key


35/55

Monomer80% of serum antibodiesFix complementIn blood, lymph, intestineCross placentaEnhance phagocytosis;neutralize toxins &viruses; protects fetus &newborn

Half-life = 23 days

IgG antibodies


36/55

Pentamer5 -1 0% of serumantibodiesFix complement

In blood, lymph, on BcellsAgglutinates microbes;first Ab produced inresponse to infectionInvolved in response toABO blood group

Half-life = 5 days

IgM antibodies


37/55

Dimer1 0-15 % of serumantibodiesIn secretions, mucus,salvia, tears, and brestmilkMucosal protection

Half-life = 6 days

IgA antibodies


38/55

Monomer0.2% of serumantibodies

In blood, lymph, on BcellsOn the surface of B

cells, initiate immuneresponseHalf-life = 3 days

IgD antibodies


39/55

Monomer0.002% of serumantibodies

On mast cells andbasophils, in bloodAllergic reactions; lysis

of parasitic wormsHalf-life = 2 days

IgE antibodies


40/55

Ag-Ab Binding

Antigen-antibody complex A ffinity Specificity


41/55

The Results of Ag-Ab Binding

Figure 17 .9


42/55


43/55


44/55

General Categories of ImmunityDisorders

1.Hypersensitivity2.Autoimmunity3.Immunodeficiency


45/55

HYPERSENSITIVITY

overactive or hyperactive state of theimmune system.

Four Mechanisms of Hypersensitivity1.Type 1 Hypersensitivity (Anaphylactic)2.Type 2 Hypersensitivity (Cytotoxic)3.Type 3 Hypersensitivity (Immune Complex

Mediated)4.Type 4 Hypersensitivity (Cell Mediated)


46/55

Type 1 Hypersensitivity (Anaphylactic)

mediated by IgE, formed in response to aparticular antigen (allergen) bound to mast

cells and basophils (release vasoactive aminesand cytokines)

2 phases:

Initial (rapid) responseSecond (delayed) phase


47/55

Type 1 Hypersensitivity (Anaphylactic)

2 Types of AnaphylaxisLocal Anaphylaxis

Asthma, rhinitis, angioedema,urticaria

Systemic AnaphylaxisLife threatening

Laryngeal edema, bronchospasm,pulmonary edema, hypotension


48/55

Type 2 Hypersensitivity (Cytotoxic)

mediated by antibodies against intrinsic orextrinsic antigens adsorbed on the cell surface

or on other tissue components.Transfusion reactionsErythroblastosis fetalisCertain drug reactions

Good Pasteure DiseaseMyasthenia GravisGraves Disease


49/55

Type 3 Hypersensitivity (Immune-Complex)

Mediated by antigen-antibody complexes-immune complexes forming either in the

circulation or at extravascular sites of antigendeposition

Rheumatic fever


50/55

Type 4 Hypersensitivity (Cell mediated)

Initiated by specifically sensitized T-lymphocytes

Delayed type of hypersensitivityTuberculosis

T-cell mediated cytotoxicity

Viral infections, graft rejection


51/55


52/55

IMMUNODEFICIENCY

Subdivided into:Primary

hereditary loss of immune systemSecondary

acquired


53/55

IMMUNODEFICIENCY

Subdivided into:Primary

Brutons disease (deficient B cell)DiGeorge Syndrome (deficient T cell)Isolated IgA DeficiencySevere combined ImmunodeficiencyX-linked agammaglobulinemia (XL A )

patients don t have any mature B cell- can't make antibodies


54/55

Autoimmunedisorder Symptoms

Target of Antibodies

Glomerulonephritis L ower back pain Kidney cell antigen that

resembles Streptococcusantigen

Graves disease R estlessness, weight loss, irritability,increased heart rate and blood

pressure

Thyroid gland antigen

M yasthenia gravis M uscle weakness Nerve message receptors onskeletal muscle cells

Pernicious anemia Fatigue and weakness Binding site for vitamin B oncells lining stomach

R heumatoid arthritis Joint pain and deformity Cells lining joints

Systemic lupuserythematosus

R ed rash on face, fever, weaknessand kidney damage

DNA, neurons, blood cells

Type I diabetes Thirst, hunger, weakness, emaciation Pancreatic beta cells

Ulcerative colitis L ower abdominal pain Colon cells


55/55

Immune System & Humoral Immunity

Documents