Unit 2 seminar:Unit 2 seminar:

Adaptive immunityAdaptive immunityT & B lymphocytesT & B lymphocytes

Reminders:-Use references in discussion and be sure to rephrase information in your own words -Evaluate the quality of reference materials before using

T lymphocytes (T cells)T lymphocytes (T cells)Develop in the thymusStem cells from bone marrow migrate to

thymus in fetal lifeEarly thymocytes develop from stem cells

in the thymus cortexLate thymocytes develop from early

thymocytes in the thymus medullaT cells develop from late thymocytes in the

medullaMaturation and release occurs along with

the training to differentiate self from non-self ◦ Positive selection◦ Negative selection (apoptosis)

T cells - TCR complexT cells - TCR complexTCR ( T Cell Receptor complex)T cell receptor- antigen specific -

◦ Has 2 chains - & ◦ Has constant and variable domains◦ Structure like immunoglobulin light chain

CD3 receptor- carries signal from the cell membrane to the cell cytoplasm

CD4 or CD8 receptors- determine the function of T cell

T cell receptorT cell receptorAntigen specific receptor on T cellHeterodimer ( &) chains- Two external domains each- C,

C , V and Va transmembrane segment Cytoplasmic extension

CD receptorsCD receptorsT cell differentiation markers (CD= Cluster

of Differentiation)Mature T cells- 4 important typesCD2, CD3, CD4 and CD8CD2- Present on all peripheral T cells

◦ receptor for attachment to cellsCD3 - Associated with TCR

◦ consists of 5 molecules (,, and two )◦ Transduces signals across the membrane.

CD receptors ( Contd.)CD receptors ( Contd.)CD4 receptors

◦present mainly on T helper cells◦Interact with MHC class II antigens◦target for HIV ( AIDS virus)

CD8 receptors◦present mainly on T-cytotoxic and T suppressor cells

◦recognize MHC class I antigen

Other accessory molecules of T Other accessory molecules of T cellscellsCD 28- Costimulation- signal

transductionCTLA-4:Signal transductionLFA-1: AdhesionVLA-4: Adhesion

T cell accessory molecules (Fig 5-3 B)T cell accessory molecules (Fig 5-3 B)

Antigen doesn’t Antigen doesn’t bind directly to bind directly to TCR.TCR.

T cell receptor T cell receptor and CD receptor and CD receptor work together work together to interact with to interact with peptide (from peptide (from antigen antigen processing) and processing) and MHC moleculesMHC molecules

T cell - subtypesT cell - subtypesT helper/inducer cells ( TH)T suppressor cells ( Ts)T cytotoxic cells (CTL or Killer

cells)T cells involved in Delayed type

of hypersensitivity( T DTH )T memory cells ( Usually a subset

of T helper cells)

T helper/inducer cellT helper/inducer cellCD4 receptorFunction-

◦Recognize antigen epitope in conjunction with MHC class II antigen

◦Reacts with IL1 (interleukin-1) from macrophages

◦Produces IL2 and expresses IL2 receptors◦Is activated by IL2◦Stimulate B cell growth and differentiation

with a variety of lymphokines.

T suppressor cellT suppressor cellHas CD8 receptorsFunction-

◦Interacts with MHC class I receptors on the cells

◦Inhibits and regulates B cell differentiation into plasma cells

◦Activated by products of T helper cells , IL2.

T cytotoxic cells (Tc)T cytotoxic cells (Tc)Killer cellsPossess CD 8 receptorsFunction

◦Cell mediated cytotoxicity◦Develop after IL2 activation◦require MHC class I receptors for

recognition of foreign antigen

TT DTHDTH- - Delayed Type of Delayed Type of HypersensitivityHypersensitivityPossess CD4 receptorsRequire lymphokines for their activation (

IL1, IL2 and interferon)Function

◦ Immunity against Fungi Mycobacterium leprae Chronic infections

◦ Delayed type of hypersensitivity◦ Major component of granulomatous lesions.

B lymphocytesB lymphocytesDevelop from stem cells in Bone marrowUnique S-Ig receptor for antigen ( can be of

any type of Ig)Differentiate into Plasma cells for

production of antibodies.Receptors- Surface Immunoglobulin

◦ 100,000 copies per cell◦ undergoes capping and endocytosis after

combining with antigen

Plasma cellPlasma cellTerminally differentiated B cellsOvoid shape eccentric spoke-wheel

nucleus Intensely basophilic cytoplasmAverage life span less than 4 daysMostly present in lymphoid tissuesProduce only one type of antibody

Normal circulation of Normal circulation of lymphocytes and other immune lymphocytes and other immune cellscellsLymphocytes and macrophages

do circulate through different organs. Lymphocytes are the only cells allowed in the CNS

But they tend to localize back into the sites they originated from, with the help of lymphocytic homing molecules or vessel addressins

Points to discussPoints to discussDefinitionTypes of cytokinesSources of cytokinesChemokines Interferons InterleukinsTumor Necrosis FactorsCytokine receptorsTherapeutic applications of cytokines

Cytokine- Definition & General Cytokine- Definition & General propertiespropertiesCytokines are low molecular weight

proteins which act as intercellular communication molecules.

They mostly act in autocrine and paracrine manner. A few may act in an endocrine manner.

They are produced mainly by immune system cells but can also be produced by many other cells.

Types of cytokinesTypes of cytokinesMost of these are generally called

cytokinesIf they are produced by

lymphocytes predominantly, they are sometimes referred to as Lymphokines

If they are produced by monocytes predominantly, they are sometimes referred to as Monokines

Types of cytokinesTypes of cytokinesChemokines- involved in chemotaxisInterferons- Inhibitory factorsInterleukins- Mostly cell messenger

functionTumor necrosis factors- mainly apoptosis

signals or cell lytic functionColony stimulating factors (CSFs)Sometimes interleukins and CSFs are

included in a broader family of hematopoietins

ChemokinesChemokines

Chemokines- The cytokines which aid in chemotaxis of phagocytes mainly.

Examples◦IL8, TNF-alpha - for neutrophils

◦MIP-beta : for macrophages

InterferonsInterferons

3 typesAlpha IFN & Beta IFN - secreted by

leukocytes , fibroblasts and other cells infected by a virus ◦make the host cells resistant to viral

invasion and inhibits viral multiplicationGamma IFN - secreted by

lymphocytes to activate the macrophages to enhance intracellular killing.

InterleukinsInterleukinsSo far IL 1 to IL 25 have been

significantly characterized. Many more are being investigated.

A few key interleukins are IL1, IL2, IL4 and related interleukins.

Many of these can induce acute phase reactants from liver

Interleukin 1Interleukin 1Secreted mainly by macrophages,

also by endothelium and epithelial cells

Endogenous pyrogen- fever –signals hypothalamus

Lymphocyte proliferation and activation

Expression of selectins by endothelial cells and increased adhesion of leukocytes

Interleukin 2Interleukin 2Secreted by activated lymphocytes (TH1)

autocrine and paracrine action

T helper cell proliferationT cytotoxic cell activation & proliferation

Natural Killer cell activation

Interleukin 4 familyInterleukin 4 family(IL4,5,10,14)(IL4,5,10,14)Secreted by T lymphocytes and mast cells

Predominant in TH 2 responses

Stimulate IgE production (esp. IL 5)

involved in allergic phenomena

Interleukin 6Interleukin 6Secreted by activated T cells,

monocytes, fibroblasts and endothelial cells

Progenitor cell stimulationPlatelet productionImmunoglobulin production in B

cells.

Tumor necrosis factorsTumor necrosis factorsTNF alpha-

◦Secreted by macrophages, lymphocytes and other cells

◦Chemotactic for neutrophils◦Inflammation and fever◦Cytotoxic for some tumor cells

TNF beta-◦T lymphocytes (esp. T cytotoxic cells)

and natural killer cells◦Cytotoxic for target cells

Cytokine receptorsCytokine receptors

Many different typesOne receptor can interact with

many different cytokinesOne cytokine can interact with

different receptorswhen a cytokine attaches to a

receptor it will induce intracellular messenger which in turn can induce gene transcription change.

Examples of Cytokine Examples of Cytokine receptorsreceptorsInterleukin receptors e.g. IL2RTNF receptor familyInterferon receptor familyImmunoglobulin familyChemokine receptor family.

Therapeutic uses of Therapeutic uses of cytokinescytokinesReceptor antagonists- antibodies

or mimic molecules- rheumatoid arthritis e.g Enbrel, Remicade

Interferons- Hepatitis B, C, Kaposi’s sarcoma, Multiple sclerosis, melanoma

Colony stimulating factors- After bone marrow transplants

Development of T Lymphocytes (Fig Development of T Lymphocytes (Fig 4-13)4-13)

T cell receptor (Fig. 4-5)T cell receptor (Fig. 4-5)

Recognition of a peptide epitope Recognition of a peptide epitope nestled in MHC class I molecule by nestled in MHC class I molecule by TCRTCR

Maturation of lymphocytes (Fig Maturation of lymphocytes (Fig 4-8)4-8)