PRINCIPLES OF IMMUNE SYSTEMPRINCIPLES OF IMMUNE SYSTEM

PRESENTER

Shakira Ghazanfar

PhD ScholarShakira_sulehri@yahoo.com

24-1-2013ISLAMABAD,PAKISTAN

الرحمن اللة الرحمن بسم اللة بسمالرحيمالرحيم

Immunity : Defence capacity of the body to combat diseases counter infection.

The cells and molecules responsible for immunity constitute the immune system.

Their collective and coordinative response to introduction of foreign substance represent the immune response.

Components of immune system :

1. Innate / natural immunity - defense mechanisms present prior to exposure to infectious microbes or foreign molecules. - exist since fetal development period and persist permanently throughout life. - create nonspecific response nonspecific immunity - represent the first line of defense mechanisms against foreign invasion into the body.

2. Acquired / adaptive immunity - defense mechanisms acquired in a certain period of life. - create specific response specific immunity. - develop due to induction / stimulation of foreign substance that successfully invade the body. - foreign substances capable of inducing immune response are called antigen.

Specific/acquired immunity

Acquired as a result of induction & exposure to foreign substances (antigen).

Fundamental characteristics of specific immunity :- create immune memory provide more effective response in further secondary infection basic principle of vaccination.- create focus response to certain/fixed antigen that invades body & eliminate/destroy it increase protective capacity of innate immunity.

Specific Immunity involves 2 types of immunity :

1. Humoral immunity : is mediated by molecules (serum proteins) which recognize and eliminate free antigens (do not attach the cell or are not cell component) called antibody bind and react specifically to antigen.

2. Cellular immunity (cell mediated immunity) : is mediated by cells T lymphocytes recognize and bind antigen on the cell surface or nonself antigen produce immune mediator or lyse/destroy such cell expressing antigen.

Antibodies and specific T lymphocytes are potentially transferred to naive individuals passive immunisation.

Humoral and cellular response to antigen stimulation indicate fundamental characteristics :

1. SpecificityThe immune response is specific to a particular antigen.The antibody or lymphocyte are able to recognize part of protein complex or any other macromolecules. Part of molecules recognized by specific antibody or lymphocyte is called determinant or epitope.

2. DiversityThe total number of antigenic specificities of the lymphocytes in an individual lymphocyte repertoire estimated the capacity to discriminate 109 determinants.

When a lymphocyte is stimulated by antigen the lymphocyte is going to proliferate yielding a specific clone “clonal selection theory”.

3. MemoryThe effectiveness of immune response to a particular antigen is increasing in secondary exposure to this antigen and so on called “immunological memory” & mediated by “memory cells”.

4. Self limitationNormal immune response is declining & disappearingafter a period of destimulation (stimulation is sunpended)

5. Discrimination of self from nonselfAble to discriminate foreign antigen from self components. Lymphocytes react to foreign antigen stimulation otherwise give no response to self molecules or self components immune tolerance.

Failure of immune tolerance to self components autoimmune diseases create pathological consequences for the sufferer.

Organs involved in immune system

Organs of immune system are classified into two groups based on their function in immune system :- primary (central) lymphoid organs.- secondary (peripheral) lymphoid organs.

Immature lymphocytes are undergoing maturation to become mature lymphocytes in primary lymphoid organs

becoming immunocompetent cells.

The primary lymphoid organs in mammals are :- bone marrow B lymphocyte maturation- thymus T lymphocyte maturation

Secondary lymphoid organs collect antigens from tissues or circulation & provide sites for immuno- competent cells to interact effectively with antigens.

Lymph nodes collect antigens from intracellular fluid of various tissues.

Lien (spleen) filtered antigen from blood/circulation create response to systemic infection.

Mucous associated lymphoid tissue (MALT) in gut, respiratory tract, genitourinary tract (Peyer’s patch, tonsils, adenoids) trapped antigens which enter via mucous membrane.

Cells involved in specific immune system

The entire cells of specific immune system derive from pluripotent “stem cells” in bone marrow & develop through hematopoeisis process.They differentiate into 2 lineages :1. myeloid lineage produce phagocytes and other blood cells.2. lymphoid lineage produce lymphocytes.

Phagocytes are differentiated into two groups :- monocytes able to pass away from vascular system & transform to tissue phagocytes macrophages.- Polymorphonuclear cells neutrophyls, basophyls, eosinophyls.

Lymphocytes are produced in bone marrow, circulate in blood and lymphoid system & occupy lymphoid organs.

Lymphocyte recognize & interact with antigen through itsreceptor on the cell surface.

2 types of lymphocytes discriminated based on their membrane protein marker :B lymphocytes CD 11 marker on their surface.T lymphocytes CD 3 marker on their surface.

B lymphocytes

Produced and develop in bone marrow. Equipped with Ab molecules as antigen receptor; the ab receptor is fixed in cell membrane through its Ch terminal. When naive B cell get in contact with specific antigen it will proliferate & differentiate to be B memory cells capable of secreting specific antibody plasma cells.

T lymphocytes

Develop from stem cells in bone marrow. They migrate to the thymus & differentiate to become mature T lymphocytes.

Mature T cells express “antigen binding protein” on their surface, represent as T cell receptor (TCR) compose of 2 protein subunits or , connected to each otherby disulphide bonds.

TCR recognize antigen on the cell surface in association with (presented by) MHC (HLA) molecules.

When naive T cell contact to antigen T cell proliferate & differentiate to become memory and effector T cells.

Subpopulation of T cells :Helper T cells (TH) & Cytotoxic T cells (TC) discriminated based on their protein marker on the cell surface CD4 marker for TH

CD8 marker for TC

After contact with antigen TH cells develop into effectorcapable of cytokine (lymphokine) secretion activateB cells, TC cells, phagocytic cells etc.

TC develop into effector which mediate cytotoxic reactions killing/ lysis cells expressing antigen :- virus infected cells- cells infected by intracellular microbes- tumor cells- allograft cells

Major Histocompatibility Complex (MHC)

Membrane proteins, expressed by gene cluster & inherited in tight linkage modes.

MHC products play important roles in antigen (Ag) recognition by immunocompetent cells & discrimination between self and nonself define tissue compatibilityamong individuals of the same species called transplantation antigens.

MHC is also critical for the creation of humoral and cell mediated immunity TH & TC recognize Ag in association with MHC molecules establish antigen repertoire which give response to TH & TC implicatein the susceptibility to disease & autoimmunity.

HLA code for 3 kind of molecules : HLA class I, class II & class III.

HLA class I is coded by regio A, B and CHLA class II is coded by regio DP, DQ and DR

each regio constitute alleles which are multiple create huge variation of individuals, despite of brothers or sisters.

HLA class I molecules present Ag recognized by TC carried by almost all nuclear cells.HLA class II molecules present Ag recognized by TH carried by antigen presenting cells (APC) macrophages, dendritic cells, B lymphocytes, etc.

Humoral immunity

Mediated by antibodies, proteins that are presence in serum & body liquid of mammals belong to protein serum fraction, globulin immunoglobulin (Ig).

Produced and secreted by B lymphocytes that has been stimulated by specific antigen becoming committed cells (sensitized B lymphocytes) and develop to plasma cells.

Function as effector that mediate binding to free antigen(no attachment or not part of cell components), neutralize and eliminate such antigen away from the body.

Immunoglobulin molecule variations

1. Isotype variation defined by determinant present in

Ch and Cl which discriminate Ig of the same species.

2. Allotype variation defined by the variation of amino acids in either H or L chain, coded by different alleles expressed by individuals of the same species.

3. Idiotype variation defined by variation of Vh and Vl constructing Ag binding site define the specificity of Ig to Ag.

5 Ig classes available in all species, defined by Ig H chain.

IgG – the predominant Ig in normal serum, constitute 70 – 75% of total Ig. Distribute intra and extra vascular; represent dominant antibodies accumulate during secondary immune response, especially function as anti-toxin.

IgM – include 10% of total Ig. Present as pentamer molecules, distribute intravascular. Represent the predominant Ab in early response to microbial infection.

IgA – include 15 – 20% of total Ig. Present in dimeric conformation, equipped with “secretory component”, recognized as sIgA. Predominant in mucous secret i.e. saliva, tracheobronchial secret genitourinary mucous, etc.

IgD – less than 1% of total Ig, fixed in cell membrane of B lymphocytes. Function as antigen receptor & necessary for B cell stimulation to become plasma cells.

IgE – available in small proportion, attach to basophyl and mast cell membrane. Involved in developing immunity to parasites (helminthes) and hypersensitivity disease i.e. asthma.

Phases of immune response :

1. Cognitive phase – antigen recognition through antigen

binding to specific receptor on lymphocyte surface. B lymphocyte – bind Ag to surface Ig. T lymphocyte – bind Ag fragment – MHC (HLA) to TCR.

2. Activation phase - lymphocyte proliferation – clonal expansion of specific lymphocyte to certain antigen. - lymphocyte differentiation B lymphocyte secreting cells (plasma cells) Ab bind to free Ag (soluble Ag).

T lymphocyte mediated killing activate macrophages to kill

intracellular microbes. lysis of cells expressing foreign Ag or viral Ag.

3. Effector phase – elimination and neutralisation of Ag. Require participation of nonlymphoid cells collectively recognized as effector cells. Ag-Ab complex are phagocyted by polymorpho nuclear & mononuclear cells (in circulation). Ag-Ab complex activate complement system to mediate lysis & phagocytosis of microorganisms. Sensitized T lymphocytes secrete cytokine activate cytolysis & phagocytosis.

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