Name: Chanaka LakshanStudent ID: BS/15/10/15 Facilitator: Dr.AriffSubject: PharmacologyStream: Biomedical Science

Contents1) Phagocytosis2) Antibody & Antigen3) Immunity4) Cytokines Activity5) Complement System

Immune SystemThe immune system is a system of many biological

structures and processes within an organism that protects against disease.

To function properly, an immune system must detect a wide variety of agents, known as pathogens, from viruses to parasitic worms, and distinguish them from the organism's own healthy tissue.

Defence Mechanisms

Phagocytosis1) It is a process by which living cells

(phagocytes) ingest or engulf other cells or particles.

2) It may be a free-living one-celled organism or one of the body cells. In some forms of animal life, such as amoebas, phagocytosis is a means of feeding.

3) In higher animals, its a defensive reaction against infection and invasion of the body by foreign substances (antigens).

4) It was first noted by Canadian physician William Osler.

The steps of phagocytosis1) Detection of the foreign particle and movement

of the phagocyte to the area.2) Attachment of the foreign particle to the

phagocyte.3) Engulfment or ingestion of the foreign particle

into a vesicle called a phagosome.4) Fusion with lysosome and formation of

the phagolysosome.5) Intracellular killing and digestion.6) In the case of

macrophages, egestion and antigen presentation.

Anti-body Formation1) Macrophage eats bacteria.2) Proteins (antigens) from the bacteria are broken down into

short peptide chains and those peptides are then "displayed" on the macrophage surface attached to special molecules called MHC II .

3) Bacterial peptides are similarly processed and displayed on MHC II molecules on the surface of B lymphocytes.

4) When a T lymphocyte "sees" the same peptide on the macrophage and on the B cell, the T cell stimulates the B cell to turn on antibody production.

5) The helper t cell stimulates b cells through the release of cytokines.

6) The stimulated B cell undergoes repeated cell divisions, enlargement and differentiation to form a clone of antibody secreting plasma cells.

7) That antibody then binds to the bacteria making them easier to ingest by white cells.

8) Antibody combined with a plasma component called "complement" may also kill the bacteria directly.

AntibodyIt is a large, Y-shaped

protein produced mainly by plasma cells  found in our body.

It is also known as Immunoglobins (Ig).

They are usually found in blood.

It is produced in response to antigens.

It is used by the immune system to identify and neutralize pathogens such as bacteria and viruses.

Antibody Structure It has 4 polypeptide chains. The 2

polypeptide chains are long and identical whereas the other 2 are identical and short.

The long chains are known as Heavy chains (H chains) and the short chains are known as Light chains (L-chains).

Both are held together by disulphide bonds like magnets.

Both chains have a distinct region and a variable region.

Variable region acts like in the lock and key mechanism, and is used to combine with antigens in a death wrap. This action site is also known as paratopes.

AntigenAny foreign substance which

can stimulate the immune system of our body is an antigen.

It is any substance that causes an immune system to produce antibodies against it.

They are substances produced by foreign bodies.

They may be proteins, carbohydrates, nucleic acids or lipids.

They trigger the formation of antibodies.

Types Of Antibodies1) IgA – Protects the body

against gastro-intestinal & respiratory problems. It is found in milk and saliva

2) IgD– Activates the B-Cell after interacting with any antigen similar to an informant

3) IgE – Controls allergic reactions4) IgG– Stimulate phagocytes 5) IgM – Activation of B-Cells

Functions of Antibodies

Antigen-Antibody ReactionThe epitopes of antigen reacts with paratopes of antibody forming

antigen-antibody complex. It follows these steps:Agglutination:  Antibodies clump the antigens together which are later

destroyed by phagocytes. Therefore, phagocytes can detect them more easily.

Precipitation: Soluble antigens are precipitated and destroyed by the phagocytes.

Opsonization: Antibodies are coated on microbial surface after which antigen locks in. This makes it more susceptible to phagocytosis.

Neutralization: Antibodies blocks or neutralizes the harmful chemicals produced by antigens. These are later destroyed again by phagocytosis.

Complement Activation: When the lock and key mechanism perfectly fits into the place, it leads to Cell lysis.

Cell mediated Immunity It is an immune response that does not involve antibodies, but

involves the activation of phagocytes ,antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen.

It involves mostly T cells and responds to any cell that displays aberrant MHC markers, including cells invaded by pathogens, tumor cells, or transplanted cells. It occurs as Follows:

1) Self cells or APCs displaying foreign antigens bind to T cells.

2) Interleukins (secreted by APCs or helper T cells) co-stimulate activation of T cells.

If MHC‐I and endogenous antigens are displayed on the plasma membrane, T cells proliferate, producing cytotoxic T cells. Cytotoxic T cells destroy cells displaying the antigens.

If MHC‐II and exogenous antigens are displayed on the plasma membrane, T cells proliferate, producing helper T cells. Helper T cells release interleukins (and other cytokines), which stimulate B cells to produce antibodies that bind to the antigens and stimulate nonspecific agents (NK and macrophages) to destroy the antigens.

Cytokines ActivityThey are a broad and loose

category of small proteins that are important in cell signaling.

They are released by cells and affect the behavior of other cells.

 It plays a main role in the innate immune response by means of direct mechanisms against the invading agent or by activating mechanisms for cells such as macrophages, which upon activation, produce more cytokines. 

The main cytokines that have a role in the innate response are: IL 1IL 6IL 12IL 16TUMOR NECROSIS FACTOR (TNF alpha)INTERFERON alpha and gamma

CYTOKINE  STRUCTURE  PRODUCING C.  FUNCTION

IL 1 Monomer (18 kD) Macrophages 

Elevation of the temperatureT Lymphocytes and Macrophages Activation 

IL 6 Monomer (26 kD)

LymphocytesMacrophages

T and B Lymphocytes activation

IL 12 Heterodimer (75kD)

Neutrophils Macrophages 

Lymphocytes differentiationNK cells activation

IL 16 Homotrimer (13kD)  T Lymphocytes  Chemotaxis

Complement SystemComplement was discovered by Jules Bordet as a

heat-labile component of normal plasma that causes the opsonisation and killing of bacteria.

It contains Classical, Lectin & Alternative pathways which converge into a final common pathway when C3 convertase (C3 con) cleaves C3 into C3a and C3b.

Ab = antibodyAg = antigen C1-INH = C1 inhibitor MAC = membrane attack complexMASP = MBL-associated serine proteaseMBL = mannose-binding lectin. Overbar indicates activation.

Classical PathwayThis pathway involves complement

components C1, C2 and C4. The pathway is triggered by antibody-antigen

complexes binding to C1, which itself has three subcomponents C1q, C1r and C1s.

The pathway forms a C3 convertase, C4b2a, which splits C3 into 2 fragments; the large fragment, C3b, can covalently attach to the surface of microbial pathogens and opsonise them;

the small fragment, C3a, activates mast cells, causing the release of vasoactive mediators such as histamine.

Alternative PathwayThis pathway involves various factors, B, D,

H & I, which interact with each other, and with C3b, to form a C3 convertase, C3bBb, that can activate more C3, hence the pathway is sometimes called ‘the amplification loop’.

Activation of the loop is promoted in the presence of bacterial and fungal cell walls, but is inhibited by molecules on the surface of normal mammalian cells.

Mannose-binding Lectin PathwayThis pathway is activated by the binding

of mannose-binding lectin (MBL) to mannose residues on the pathogen surface.

This in turn activates the MBL-associated serine proteases, MASP-1 and MASP-2, which activate C4 and C2, to form the C3 convertase, C4b2a.

Lytic PathwayThis pathway is initiated by the splitting of C5,

and attachment of C5b to a target. C6, C7, C8 and C9 unite with C5b, and this membrane-attack complex (MAC), when inserted into the outer membrane of some bacteria, can contribute to their death by lysis.

Red cells which have antibody bound to the cell surface can also activate the classical and lytic pathways, and become susceptible to lysis.