OverviewOverview of the immune systemof the immune system

Immune System

Innate(Nonspecific)

Adaptive(Specific)

CellularComponents

HumoralComponents

CellMediated

Humoral(Ab)

Differences between:Differences between: Non specific (innate or natural immunity)

Response is antigen-independent.

There is immediate maximal response.

Not antigen-specific.

Exposure results in no immunologic memory

Specific Immunity (acquired or adaptive)

Response is antigen-dependent.

There is a lag time between exposure and maximal response.

Antigen-specific.

Exposure results in immunologic memory

Host DefensesHost Defenses

Mechanical Factors:Mechanical Factors:

Physical barriers to pathogens

Skin

Epidermis consists of tightly packed cells with keratin which is a protective protein.

Mucous membranes

First line of DefenseFirst line of Defense

Lacrimal apparatus: Washes eye

Saliva: Washes microbes off

Urine: Flows out, flushing.

Vaginal secretions: Flow out

Fungistatic fatty acid in sebum.

Low pH (3-5) of skin.

Lysozyme in perspiration, tears, saliva, and tissue fluids except CSF.

Low pH (1.2-3.0) of gastric juice and vaginal acidity.

Transferrins in blood reduce iron so inhibit microbial growth.

Chemical FactorsChemical Factors

Microbial antagonism/competitive exclusion:

Normal microbiota antagonize pathogen:

1-By competing with pathogens for nutrients, for colonization site by producing substances harmful to the pathogen.

2- By altering conditions that affect the survival of the pathogen. e.g. normal microbiota in vagina alters pH to prevent overpopulation of C.albicans which is a pathogenic yeast caused vaginitis.

Normal MicrobiotaNormal Microbiota

Second line of DefenseSecond line of Defense

1.Phagocytosis

2.Inflammation

3.Fever

4.Antimicrobial substances

Nonspecific DefensesNonspecific Defenses Nonspecific defenses deny pathogens access to the body or destroy them

without distinguishing among specific types.

Nonspecific DefensesNonspecific Defenses Nonspecific defenses deny pathogens access to the body or destroy them

without distinguishing among specific types.

Formed Elements In Blood (note functions)RBC’s

WBC’sAgranulocytes

1 .Monocytes and

2 .Lymphocytes Granulocytes

1 .Neutrophils (PMNs)

2 .Basophils and 3 .Eosinophils

Immune System

Myeloid Cells Lymphoid Cells

Granulocytic Monocytic T cells B cells

NeutrophilsBasophils

Eosinophils

MacrophagesKupffer cells

Dendritic cells

Helper cellsSuppressor cellsCytotoxic cells

Plasma cells

NK cells

Cells of the Immune System

Organs of the immune systemOrgans of the immune system

During embryonic life, haemopoeitic stem cells develop in fatal liver and other organs, these stem cells reside in the bone marrow in postnatal life.

There is primary lymphoidprimary lymphoid system which is responsible for the evolution and maturation of immune cells (Bone marrow and thymus).

and secondary lymphoidsecondary lymphoid system (tonsils, peyer patches, spleen and other lymph nodes all over the body), responsible for trapping of foreign antigen, residence of immune cells.

Phagocytosis

.

RednessPainHeatSwelling (oedema)In acute-phase proteins are activated (complement, cytokine, kinins) - chemical messengersVasodilation (histamine, kinins, prostaglandins, leukotrienes) - bring in more helpMargination and immigration of WBCsTissue repair

InflammationInflammation

Chemicals Released by Damaged CellsChemicals Released by Damaged Cells

•Histamine Vasodilation, increased permeability of blood vessels

•Kinins Vasodilation, increased permeability of blood vessels

•Prostaglandins Intensity histamine and kinin effect

•Leukotrienes Increased permeability of blood vessels, phagocytic attachment

In serum 30 proteins produced by the liver, activated in a cascade as previous catalyzes the next step.

Outcomes of Complement system1. Opsonization2. Chemotaxic3. Cell lysis

The Complement SystemThe Complement System

Effects of Complement ActivationEffects of Complement Activation

Opsonization or immune adherence: enhanced phagocytosis

Membrane attack complex: cytolysis

Attract phagocytes

Classical PathwayClassical Pathway

Alternative PathwayAlternative Pathway

Antiviral proteins

Alpha IFN & Beta IFN: Cause cells to produce antiviral proteins that inhibit viral replication

Gamma IFN: Causes neutrophils and macrophages to phagocytize bacteria

Interferons (IFNs)Interferons (IFNs)

Interferons (IFNs)Interferons (IFNs)

1

2

3

4

5

Viral RNA from an infecting virus enters the cell.

The infecting virus replicates into new viruses.

The infecting virus also induces the host cell to produce interferon on RNA (IFN-mRNA), which is translated into alpha and beta interferons.

Interferons released by the virus-infected host cell bind to plasma membrane or nuclear membrane receptors on uninfected neighboring host cells, inducing them to synthesize antiviral proteins (AVPs). These include oligoadenylate synthetase, and protein kinase.

New viruses released by the virus-infected host cell infect neighboring host cells.

AVPs degrade viral m-RNA and inhibit protein synthesis and thus interfere with viral replication.

6

Specific Defenses of the Host: The Immune Response

*Antigen (Ag) : A substances that causes the body to produce specific antibodies or sensitized T ells, also called immunogen.*Antibody (Ab): A proteins produced by the body in response to an antigen, and capable of combining specifically with that antigen.

Serology: Study of reactions between antibodies and antigens.

Antiserum: Generic term for serum because it contains Ab.Globulins: Serum proteinsGamma () globulin: Serum fraction containing Ab.

Serum ProteinsSerum Proteins

The Immune Response The Immune Response Two armsTwo arms

Acquired immunity:The ability obtained and developed during an individual's lifetime, to produce specific antibodies or T-cell.

The factors involved in this immunity known as:1. Humoral immunity: from humors, because they

were found in the body fluid, it Involves Ab produced by B cells (B lymphocytes).

2. Cell-mediated immunity: Involves specialized lymphocytes T cells or T lymphocytes

Acquired ImmunityAcquired ImmunityNatural Acquired:( Active and passive).Artificially Acquired:( Active and passive).

*Naturally acquired active immunityResulting from Antigen enter the body naturally (infection).

*Naturally acquired passive immunityAntibodies via transplacental or via colostrum

*Artificially acquired active immunityInjection of Antigen (vaccination)

*Artificially acquired passive immunityInjection of performed Antibody.

Antigenic DeterminantsAntigenic DeterminantsA specific region on the surface of an antigen to which antibodies recognize and react with, it is called epitopes.

HaptensHaptensit is a molecule too small to stimulate the antibody formation by itself but only when combine with a

carrier molecule. e. g. penicillin antibiotic.

Factors Influencing ImmunogenicityFactors Influencing ImmunogenicityA. The ImmunogenThe Immunogen

1- Foreignness The immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic.

2- Size: the larger the molecule the more immunogenic it is likely to be.( generally substances with mol.wt.> 100,000 dalton are potent immunogenic).

3- Chemical Composition: The more chemical complexity of the substance is the more immunogenic it will be.

4- Physical form - In general particulate antigens are more immunogenic than soluble ones and denatured antigens more immunogenic than the native form.

5. Degradability - Antigens that are easily phagocytosed are generally more immunogenic. This is because for most antigens (T-dependant antigens) the development of an immune response requires that the antigen be phagocytosed, processed and presented to helper T cells by an antigen presenting cell (APC).

CHEMICAL NATURE OF IMMUNOGENS:A. Proteins -The vast majority of immunogens are

proteins. These may be pure proteins or they may be glycoproteins or lipoproteins. In general, proteins are usually very good immunogens.

B. Polysaccharides - Pure polysaccharides and lipopolysaccharides are good immunogens.

C. Nucleic Acids - Nucleic acids are usually poorly immunogenic. However, they may become immunogenic when single stranded or when complexed with proteins

.D. Lipids - In general lipids are non-immunogenic, although they may be haptens.   In an antigen, the same antigenic determinant repeated many times .

TYPES OF ANTIGENS

T-independent Antigens - T-independent antigens are antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help .

In general, polysaccharides are T-independent antigens.

T-dependent Antigens - T-dependent antigens are those that do not directly stimulate the production of antibody without the help of T cells. Proteins are T-dependent antigens.

LYMPHOCYTESLYMPHOCYTESBoth B B cells and TT cells originate from stem

cells in adult red bone marrow or in the fetal liver. (RBCs, macrophages, neutrophiles, and other WBCs also originate from these same stem cell).

Some cells pass through the THYMUS THYMUS and

emerge as mature T-cells.T-cells.

Other cells probably remain in the Bone Bone marrow marrow and become B-cells.B-cells.

Both types of cells then migrate to lymphoid tissues, such as lymph nodes or spleen.

Once in these organs, B cells recognize antigens by means of antigen receptors antigen receptors which are antibody molecules on their surface (IgD).(IgD).

After antigen exposure, B-cells changed to memory cellsmemory cells and antibody-secreting plasma plasma cells.cells.

Once re-exposure to antigen, memory cells quickly proliferate to produce more plasma cells.

Further differentiation of the activated B-cell into clone occurs, resulting in the formation of large antibody-secreting cells called plasma cells.

Plasma cells are relatively short-lived (less than 1 week) but excrete large amounts of antibody during this period.

Memory cells, in contrast, are very long-lived cells, and on re-exposure to the initial stimulating antigen, they quickly transform into plasma cells and begin secreting antibody.

Antibody Structure

Monomer

80% of serum antibodies

Fix complement

In blood, lymph, intestine

Cross placenta

Enhance phagocytosis; neutralize toxins & viruses; protects fetus & newborn

Half-life = 23 days

IgG antibodiesIgG antibodies

Pentamer

5-10% of serum antibodies

Fix complement

In blood, lymph, on B cells

Agglutinates microbes; first Ab produced in response to infection

Half-life = 5 days

IgM antibodiesIgM antibodies

C4

J Chain

Dimer

10-15% of serum antibodies

In secretions

Mucosal protection

Half-life = 6 days

IgA antibodiesIgA antibodies

J Chain

Secretory Piece

Monomer

0.2% of serum antibodies

In blood, lymph, on B cells

On B cells, initiate immune response

Half-life = 3 days

IgD antibodiesIgD antibodies

Monomer

0.002% of serum antibodies

On mast cells and basophils, in blood

Allergic reactions; lysis of parasitic worms

Half-life = 2 days

IgE antibodiesIgE antibodies

Bone marrow gives rise to B cells.Bone marrow gives rise to B cells.

Mature B cells migrate to lymphoid Mature B cells migrate to lymphoid organs.organs.

A mature B cells recognizes A mature B cells recognizes epitopes.epitopes.

Clonal SelectionClonal Selection

Clonal SelectionClonal Selection

Self-toleranceSelf-tolerance

Body doesn't make Ab against self

Clonal deletion

The process of destroying B and T cells that react to self antigens

The Results of Ag-Ab BindingThe Results of Ag-Ab Binding

Antibody titerAntibody titer

Is the amount of Ab in serum

Monoclonal AntibodiesMonoclonal Antibodies

Hybridomas are produced by fusing a cancer cell with an Ab-secreting plasma cells

Ideally, if an antibody-producing B cell could be grown by standard cell-culture method , it would produce the Highly specific, only only desired antibody in unlimited amounts. desired antibody in unlimited amounts.

Chemical Messengers of immune cells: Chemical Messengers of immune cells: CYTOKINESCYTOKINES

CYTOKINESCytokines are a diverse group of non-antibody proteins released by immune cells that act as intercellular mediators, especially in immune processes.A. Cytokines are clinically important as biological response modifiers. :1. Monokines - produced by mononuclear phagocytes2. Lymphokines - produced by activated T cells, primarily helper T cells3. Interleukins - name given to many cytokines, abbreviated as IL and given a number, serve as

Communicator between leukocytes .

Helper T Cells (THelper T Cells (THH))

TH1 Activate cells related to cell-mediated

immunity

TH2 Activate B cells to produce, IgM, and IgE

Cytotoxic T Cells ( TCytotoxic T Cells ( TCC))

Destroy target cells with perforin

Classification of T Cells according to function

Delayed Hypersensitivity T Cells (TDelayed Hypersensitivity T Cells (TDD))

Associated with allergic reaction, transplant rejection.

Suppressor T cells (TSuppressor T cells (TSS))

Turn off immune response when Ag no longer present.

Classification of T-cells according Classification of T-cells according to cell-surface receptorto cell-surface receptor

(CD)(CD)

CD4 : A molecule found on human helper T cells and delayed hypersensitivity T cells. It is involved in the interaction with MHC Class II molecules. CD4 is the 'receptor' by which the AIDS virus enters T cells.

CD8: A molecule found on most cytotoxic and suppressor T cells. It is involved in interacting with MHC Class I molecules.

Major histocompatibility complex

Tissue cells of each individual possess:

Uniqueness that is a function of certain surface glycoprotein molecules known as MHC or human leukocyte antigens (HLA), since they are also identified on the surface on WBCs.

Histocompatibility genes that are found on the short arm of chromosome No 6 in humans encodes such glycoprootein.

Class I MHC : encoding 2 polypeptide chains found on the surface of all nucleated cell. Tc and Ts (CD8) recognize antigens associated with MHC class I.

Class II MHC: encoding 2 polypeptide chains found on the surface of B cells,

T cells and macrophage (APC) .

The (CD4) recognize antigens in association with MHC class II.

T-independent AntigensT-independent Antigens

B cell