Lymphocytes : Structure & immunological Function

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CD4 T-HELPER CELL EFFECTOR FUNCTIONS CD8 CYTOLYTIC T LYMPHOCYTES (CTL)

Transcript of Lymphocytes : Structure & immunological Function

Page 1: Lymphocytes : Structure & immunological Function

CD4 T-HELPER CELL

EFFECTOR FUNCTIONS

CD8 CYTOLYTIC T

LYMPHOCYTES (CTL)

Page 2: Lymphocytes : Structure & immunological Function

antigen recognition does not occur at site of entry, but usually in lymph nodes/spleen

activated T cells then migrate to target

tissues

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IL2R – complex of αβγ that associate non-covalently, essential for immune function, as its chains are involved in MANY ILR’s

IL2 is not absolutely

necessary b/c other

cytokines can replace function

ag:MHC complex binding to TCR triggers IL2R assembly/synthesis

ensures that IL2 only activates

clonal expansion of ag-specific

cells

ag:MHC complex binding to TCR can also stimulate IL2 SYNTHESIS

some cells can make IL2 autocrine/endogenous

can be used

can’t make IL2 paracrine/exogenous IL2

necessary

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TH1 – synthesize IL2/3, TNFα, γ-INTERFERON

activates macrophages and enhances their

ability to kill ingested microbes (bacteria,

fungi, protozoa)

TH2 – synthesize and release IL4//5/6/10

activate B-cell growth/differentiation

CD4

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TH1

1) γ-inteferon is released in response to macrophage MHC II antigen presentation

• these combined enhance macrophage lysosome-phagosomefusion

• DTH – delayed type hypersensitivity can be used to determine immune status (Tb skin test- PPD)

2) CD40 (macrophage) binds CD40L(T cell) and/or TNF (T cell)

interacts with TNF-R (macrophage)

• - occurs in response to antigen-activation of TH1 cells that are already sensitized to the specific antigen

• - positive test indicates presence of sensitized T cells indicates past infection

- inflammation results from local accumulation

of macrophages

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TH2

synthesize and release IL4//5/6/10 activate B-cell growth/differentiation

B cell antigen receptors (Ig) can take up antigen very efficiently

presents antigen on MHCII in high quantities

TH2 cells recognize this on B cells CD40/CD40L interaction

IL4/5/6 is produced and released to activate B cell class switching

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CD4 T cells do not differentiate into TH1 or TH2 until antigen is encountered

NK cells secrete IL12 induces T-BET TH1 pathway

IL12 is secreted as

part of response to

infection

IL10 is secreted by TH2 cells

INHIBITS TH1 differentiation

IL4 induces GATA-3 TH2

IL4 is secreted by a small subset of NK cells early in infection

also secreted by other TH2 cellsinhibited by interferon-γ made by

TH1 cells

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CD8 CYTOLYTIC T LYMPHOCYTES (CTL):

Function

virally infected cells

(MAJOR)

bacterial infected cells

tumor cells

graft rejection

important that their activity is confined only to target cells

some CD4 and some NK cells also have cytolytic activity

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PROTECTION AGAINST VIRAL INFECTION

antigenic viral proteins can be cytosolic or nuclear-localized

viral escape mechanisms –

latent infection

privileged site

replication (cells

lacking MHC I)

inhibit class I MHC

expression

inhibit TAP1/2 activity

(peptides cannot enter

ER)

mutation in antigenic peptide

sequence

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PROTECTION AGAINST BACTERIAL

INFECTION

• while this might elicit MHCII/CD4 response in some cells, certain cell types

several types of bacteria can reside

and replicate WITHIN host cells

Salmonella, Listeria, Myobacteria

LACK these proteins and the MHCI/CD8

route is the only alternative

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ACTIVATION OF CTL

• initial stages are CD4 independent, but CD4 is required eventually

• mechanism is unclear but maybe…

• CD40/CD40L binding

• CD4 effect on APC’

• “Cross Priming” – if APC’s are not directly infected

• due to protein fragments that are released from cytolysed infected non-APC’s

• fragments are taken up and presented by APC’s on MHCI to CD8+ cells

after activation, clonal

expansion and expression of cytokines also expression of

cytolyticproteins (perforin,

granzymes)

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MECHANISM OF CYTOLYSIS

initial contact is antigen-independent (ICAM on target, LFA1 on T cell)if TCR encounters antigen:MHCI, then CD8 will bind MHCI also signal cascade is initiated

effect – ICAM/LFA interaction strengthens unidirectional cytolysis

perforin – self-polymerizes and makes a

pore for granzymes

granzymes – serine proteases that activate

CAPSASES

granulysin – saposin like protein; highly cytolytic

Specificity

directional release of cytotoxins from T cell towards target cell

perforins cannot diffuse through extracellular fluid

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OTHER MECHANISMS OF CYTOLYSIS

expression of FAS-L on some activated CD8+ cells (and CD4+)activates apoptotic pathway

accounts for some cytolysis in perforin-deficient mice

activated T-cells express Fas may help reduce T-cell response by affecting T cell death

in some cases, one of the pathways will kill bacteria and the other will SPREAD it