الرحمن اللة الرحمن بسم اللة بسمالرحيمالرحيم

Cells of Immune SystemCells of Immune System

Cells of Immune SystemCells of Immune SystemStem cells of bon marrowStem cells of bon marrow

differentiate intodifferentiate into cytokines (IL-&, IL-3) cytokines (IL-&, IL-3) colony stimulating factorcolony stimulating factor

Lymphoid series Myeloid seriesLymphoid series Myeloid series

B-lymphocytes T-lymphocytes NKB-lymphocytes T-lymphocytes NK

monocytee-macrophages dendritic cells eosinophils mast cellsmonocytee-macrophages dendritic cells eosinophils mast cells

The Life Of The B CellThe Life Of The B Cell B lymphocytes are formed within the bone B lymphocytes are formed within the bone

marrow and undergo their development theremarrow and undergo their development there

They have the following functions:They have the following functions: To interact with antigenic epitopes, using their To interact with antigenic epitopes, using their

immunoglobulin receptors immunoglobulin receptors To subsequently develop into plasma cells, To subsequently develop into plasma cells,

secreting large amounts of specific antibody, or secreting large amounts of specific antibody, or To circulate as memory cells To circulate as memory cells To present antigenic peptides to T cells, To present antigenic peptides to T cells,

consequent upon interiorization and processing of consequent upon interiorization and processing of the original antigenthe original antigen

* B cells become * B cells become plasma cells, which plasma cells, which produce antibodies produce antibodies

when a foreign when a foreign antigen triggers the antigen triggers the

immune responseimmune response

B-lymphocytesB-lymphocytesin bon marrowin bon marrow

* The lymphoid stem cells differentiate into B cells* The lymphoid stem cells differentiate into B cells

* B-cells precursors mature, differentiate into * B-cells precursors mature, differentiate into immunocomptent B-cells with a single antigen immunocomptent B-cells with a single antigen specificityspecificity

* Immature B-cells that express high affinity receptors * Immature B-cells that express high affinity receptors for self antigens, die or fail to mature for self antigens, die or fail to mature

i.e negative selection or clonal deletioni.e negative selection or clonal deletion

* This process induces central self tolerance and * This process induces central self tolerance and reduces autoimmune diseasesreduces autoimmune diseases

B-lympocytesB-lympocytes* Immature B cells express IgM receptors on the surface * Immature B cells express IgM receptors on the surface

* Mature B cells express IgM, IgD molecules on surfaces* Mature B cells express IgM, IgD molecules on surfaces

* IgM and IgD molecules serve as receptors for antigens* IgM and IgD molecules serve as receptors for antigens

* Memory B-cells express IgG or IgA or IgE on the surface* Memory B-cells express IgG or IgA or IgE on the surface

* B-cells bear receptors for Fc portion of IgG and a receptor * B-cells bear receptors for Fc portion of IgG and a receptor for C3 component of the complementfor C3 component of the complement

* They express an array of molecules on their surfaces that * They express an array of molecules on their surfaces that are important in B-cells interactions with other cells such are important in B-cells interactions with other cells such as MHC II, B7 and CD40as MHC II, B7 and CD40

Mechanism of Humoral immunityMechanism of Humoral immunity* Antibodies induce resistance through:* Antibodies induce resistance through:

1) Antitoxin neutralize bacterial toxins (diphtheria,tetanus)1) Antitoxin neutralize bacterial toxins (diphtheria,tetanus) Antitoxin are developed actively as a result of: Antitoxin are developed actively as a result of: a- Previous infectiona- Previous infection b- Artificial immunizationb- Artificial immunization c- Transferred passively as antiserumc- Transferred passively as antiserum * Neutralization of toxin with antitoxin prevents a * Neutralization of toxin with antitoxin prevents a

combination with tissue cells combination with tissue cells

Mechanism of Humoral immunityMechanism of Humoral immunity2) Antibodies attach to the surface of bacteria and2) Antibodies attach to the surface of bacteria and a- act as opsonins and enhance phagocytosisda- act as opsonins and enhance phagocytosisd b- prevent the adherence of microorganisms to b- prevent the adherence of microorganisms to their target cells, e.g. IgA in the guttheir target cells, e.g. IgA in the gut c- Activate the complement and lead to bacterial lysisc- Activate the complement and lead to bacterial lysis d- Clump bacteria (agglutination) leading to d- Clump bacteria (agglutination) leading to phagocytosisphagocytosis

Activation of B cells to make antibodyActivation of B cells to make antibody

T-LmphocytesT-Lmphocytes T-lmphocytes migrate from bon marrow to enter thymusT-lmphocytes migrate from bon marrow to enter thymus

1) In the outer cortex of thymus:1) In the outer cortex of thymus: - T-lymphocytes acquire specific receptors (TCRs)- T-lymphocytes acquire specific receptors (TCRs) - This receptor commit lymphocyte to a single antigen - This receptor commit lymphocyte to a single antigen specifictyspecificty - Responding by proliferation and production of a - Responding by proliferation and production of a clone of cells (clonal selection)clone of cells (clonal selection) - They differentiate to express CD3, both CD4 and - They differentiate to express CD3, both CD4 and CD8 coreceptors (double positive cells)CD8 coreceptors (double positive cells)

* T lymphocytes become * T lymphocytes become CD4+ (helper T cells) CD4+ (helper T cells) or or* CD8+ cells (which in turn * CD8+ cells (which in turn can become killer T cells) can become killer T cells) also called cytotoxic T cells also called cytotoxic T cells

T-LmphocytesT-Lmphocytes2) In the medulla of thymus:2) In the medulla of thymus: - TCRs recognize MHC molecules, loaded with normal - TCRs recognize MHC molecules, loaded with normal self-peptides (p-MHC)self-peptides (p-MHC) - TCRs capable of binding with low affinity to p-MHC - TCRs capable of binding with low affinity to p-MHC will receive positive selection signals to divide and will receive positive selection signals to divide and establish clonesestablish clones - TCRs that bind too strongly to p-MHC undergo - TCRs that bind too strongly to p-MHC undergo (negative selection)(negative selection) - This selection process will eliminate the potentially - This selection process will eliminate the potentially most harmful self reactive T-cells (central self most harmful self reactive T-cells (central self tolerance)tolerance)

T-LmphocytesT-Lmphocytes3)Immature T-cells express both CD4 and CD8 (DP) 3)Immature T-cells express both CD4 and CD8 (DP)

As they mature As they mature * T-cell with TCRs that have affinity to bind to MHC * T-cell with TCRs that have affinity to bind to MHC class II will become helper T-cells with CD4 class II will become helper T-cells with CD4 molecule onlymolecule only

* T-cell with TCRs that have affinity to bind with MHC * T-cell with TCRs that have affinity to bind with MHC class I will become cytotoxic T-cells with CD8 class I will become cytotoxic T-cells with CD8 molecule onlymolecule only

T-LmphocytesT-Lmphocytes4) Mature positively selected T-cells are MHC restricted4) Mature positively selected T-cells are MHC restricted

* CD4 T-cells are MHC II restricted and only recognize * CD4 T-cells are MHC II restricted and only recognize specific foreign peptide only when they are presented specific foreign peptide only when they are presented in association with specific MHC II moleculesin association with specific MHC II molecules

* CD8 T-cells are MHC I restricted and recognize * CD8 T-cells are MHC I restricted and recognize specific foreign peptidees only when they are specific foreign peptidees only when they are presented in association with specific MHC I presented in association with specific MHC I moleculesmolecules

T-cell surface markersT-cell surface markersThese are molecules that by witch we can identify These are molecules that by witch we can identify

T-cells and divide them to T-cells and divide them to subsets subsets

They are required to for interactions between T-cells They are required to for interactions between T-cells and APC and for antigen recognitionand APC and for antigen recognition

These are TCRs, CD3, CD4, CD8, CD2, CD28,and CD40 These are TCRs, CD3, CD4, CD8, CD2, CD28,and CD40 on activated T-cellson activated T-cells

T-cell subpopulationT-cell subpopulation

1) CD4 T helper lymphocytes (TH)1) CD4 T helper lymphocytes (TH) - TH lymphocytes recognize antigen on the surface of - TH lymphocytes recognize antigen on the surface of

APC in association with class II MHC moleculesAPC in association with class II MHC molecules - They are activated and secrete several cytokines- They are activated and secrete several cytokines

- There are two main subsets of TH cells (THI and TH2) - There are two main subsets of TH cells (THI and TH2)

- The two subsets are differentiated on basis of the - The two subsets are differentiated on basis of the cytokine they produce cytokine they produce

1) CD4 T helper lymphocytes Subsets1) CD4 T helper lymphocytes Subsets

Th1 produce mainly :Th1 produce mainly : - Cytokines of CMI and inflammation- Cytokines of CMI and inflammation e.g. IFN-e.g. IFN-γγ, TNF- , TNF- ββ, IL-3 and IL-2 , IL-3 and IL-2

TH2 produce mainly:TH2 produce mainly: - Cytokines that stimulate B-cells - Cytokines that stimulate B-cells - Suppressor cytokines- Suppressor cytokines e.g. Il-4, IL-5, IL-6 and IL-10e.g. Il-4, IL-5, IL-6 and IL-10

2) CD8 Cytotoxic T-lymphocytes 2) CD8 Cytotoxic T-lymphocytes (CTLs)(CTLs)

* They constitute 35% 0o peripheral T-cells* They constitute 35% 0o peripheral T-cells

* CTLs recognize antigen on suurface of target cells * CTLs recognize antigen on suurface of target cells (infected APC or other infected nucleotid cell) in (infected APC or other infected nucleotid cell) in association with MHC-I association with MHC-I

* They are activated and kill the virus infected cell or * They are activated and kill the virus infected cell or tumour celltumour cell

Professional APCsProfessional APCsDendritic cells, macrophages, and B-lymphocytesDendritic cells, macrophages, and B-lymphocytes

Dendritic cells:Dendritic cells:- They are the most efficient APCs- They are the most efficient APCs- They are the main inducers of primary immune response- They are the main inducers of primary immune response- Presenting antigen to and activating native T-cells in the - Presenting antigen to and activating native T-cells in the

recognition phaserecognition phase- They express class I and class II MHC molecules- They express class I and class II MHC molecules- Dendritic cells are primarly located under skin and - Dendritic cells are primarly located under skin and

mucosa of most organsmucosa of most organs- They capture foreign antigens and transport them to local - They capture foreign antigens and transport them to local

lymph nodslymph nods- They present antigen to native helper T-cells- They present antigen to native helper T-cells

MacrophagesMacrophages* Derived from myeloid stem cells in bon marrow* Derived from myeloid stem cells in bon marrow

* They exist as free cells in blood e.g. monocytes and * They exist as free cells in blood e.g. monocytes and fixed cells in tissues e.g. Kupffer cells of liverfixed cells in tissues e.g. Kupffer cells of liver

* They are important link between innate and aquired * They are important link between innate and aquired immune responsesimmune responses

* They are activated and attracted to the site of foreign * They are activated and attracted to the site of foreign material by action of different cytokinesmaterial by action of different cytokines

e.g IFN-e.g IFN-γγ , C5a , C5a

Functions of MacrophagesFunctions of Macrophages1) Pagocytosis1) Pagocytosis

2) Opsonization2) Opsonization

3) APCs: they ingest foreign material, process it, and 3) APCs: they ingest foreign material, process it, and fragments of antigen are presented on its surface fragments of antigen are presented on its surface

(in association with MHC molecules) for interaction (in association with MHC molecules) for interaction with T-cellswith T-cells

4) Macrophages may kill antibody coated infected cells or 4) Macrophages may kill antibody coated infected cells or tumour cells through release of lytic enzymestumour cells through release of lytic enzymes

5) They produce IL-1, IL-6, IL-12, IL-15, TNF-alpha5) They produce IL-1, IL-6, IL-12, IL-15, TNF-alpha

6) They secret prostaglandins and synthesize 6) They secret prostaglandins and synthesize complement componontscomplement compononts

Natural killer (NK) CellsNatural killer (NK) Cells* Large granular lymphocytes which lack most surface * Large granular lymphocytes which lack most surface

markers of B and T-cells markers of B and T-cells

* They comprise 5-10% of the peripheral lymphocytes* They comprise 5-10% of the peripheral lymphocytes

* They function mainly in innate immunity* They function mainly in innate immunity

* They have spontaneous non-specific cytotoxic activity * They have spontaneous non-specific cytotoxic activity on virus infected cells, tumour cells and graft cellson virus infected cells, tumour cells and graft cells

* They are not MHC restricted and MHC I inhibits their * They are not MHC restricted and MHC I inhibits their killing functionskilling functions

* The mechanism of NK mediated cytolysis is as that of * The mechanism of NK mediated cytolysis is as that of CTLsCTLs

NK cells differ from CTLs inNK cells differ from CTLs in1)They are non-specific1)They are non-specific

2)They act spontaneously without prior recognition or 2)They act spontaneously without prior recognition or activationactivation

3)They do not require antigen presentation by MHC3)They do not require antigen presentation by MHC

4)They destroy cells coated with antibodies, 4)They destroy cells coated with antibodies, a mechanism called antibody dependant cellular a mechanism called antibody dependant cellular

cytotoxicity (ADDCC)cytotoxicity (ADDCC)

Antibodies produced by B-cells of the immune systemAntibodies produced by B-cells of the immune systemrecognize foreign antigens and mark them for destructionrecognize foreign antigens and mark them for destruction

Activation of helper T cellsActivation of helper T cells

Activation of cytotoxic T cellsActivation of cytotoxic T cells

Primary And Secondary ResponsePrimary And Secondary Response

Primary Response:Primary Response: Slow in Onset Slow in Onset Low in Magnitude Low in Magnitude Short Lived Short Lived IgM IgM

Secondary Response:Secondary Response: Rapid in Onset Rapid in Onset High in Magnitude High in Magnitude Long Lived Long Lived IgG (Or IgA, or IgEIgG (Or IgA, or IgE

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