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Immununology Block 3
T cell & Infection
50
Medical
Professional
10/13/2009

Additional Medical Flashcards

 


 

Cards

Term

Characteristics of the Adaptive Response

 

There are 4 characteristics of the Adaptive Response. Name them.

Definition

The 4 characteristics of the Adaptive response are:

  1. Specificity
  2. Inducibility
  3. Diversity
  4. Memory
Term

Characteristics of the Adaptive Response

 

What provides specificity?

Definition

Specificity is provided by the TCR
[signal 1 (clonal selection)]

Term

Characteristics of the Adaptive Response

 

______ is when a _____ naive T lymphocyte matures (terminal differentiation) after exposure to an ______.

Definition

Inducibility is when a preformed naive T lymphocyte matures (terminal differentiation) after exposure to an Ag/Immunogen

Term

Characteristics of the Adaptive Response

  • Diversity- an immune response is generated that best protects the host.
  • this response is directed by the secretion of specific _____ in response to the type of ______ or trauma
  • type of ___signals allows the ___ response to respond to the type of infection/disease
Definition
  • this response is directed by the secretion of specific cytokines in response to the type of infectious agent or trauma
  • type of induction signals allows the adaptive response to respond to the type of infection/disease
Term

Characteristics of the Adaptive Response - Diversity

  • ___ is primarily Cell mediated against _____ pathogens, transformed cells
  • ___ is primarily ____ against ___ pathogens

 

 

Definition

SM impt

  • Th1 is primarily Cell mediated against intracellular pathogens, transformed cells
  • Th2 is primarily Humoral against extracellular pathogens
  • Note: all the Th considered CD4+
Term

Characteristics of the Adaptive Response

  • ____ is increased number of Ag specific cells primed to response upon ___ exposure to the ____ Ag
  • To what does this contribute?
  • About what cells are we talking?

 

 

Definition
  • Memory is increased number of Ag specific cells primed to response upon 2nd exposure to the specific Ag
  • This contributes to: Faster response on second exposure
  • Memory cells are G0 & will expand when stimulated
Term

T cell activation

Step 1

  • ____ cells, a type of APC, take up bacterial Ags in the skin & then move to enter a draining lymphatic vessel
Definition
  • Dendritic cells, a type of APC, take up bacterial Ags in the skin & then move to enter a draining lymphatic vessel
Term

T cell activation

Step 2

  • Dendritic cells bearing Ag enter the draining lymph node, where they settle in the ___ areas (Bonus: name the specific area)
Definition
  • Dendritic cells bearing Ag enter the draining lymph node, where they settle in the T-cell areas (Bonus: name the specific area - paracortex)
Term

T cell activation

Step 3

  • Naive T cells can enter lymph nodes in the ___ lymph as well as from the ____
  • ___ enter a lymph node across ____ in the cortex.
Definition
  • Naive T cells can enter lymph nodes in the afferent lymph as well as from the blood
  • T cells enter a lymph node across high endothelial venules in the cortex.
Term

T cell activation

Step 4

  • T cells monitor Ag presented by ____ & ____
  • Binding of ___ (on the T cell) to GlyCAM-1 & ___ (on ECM) allows rolling interaction
Definition
  • T cells monitor Ag presented by macrophages & dendritic cells
  • Binding of L-selectin (on the T cell) to GlyCAM-1 & CD34 (on ECM) allows rolling interaction
  • Note: T cells check out APCs by adhesion mlcs, i.e., causes "rollover" of each, "loose binding"
Term

T cell activation

Step 5

  • T cells that do not encounter specific Ag leave the node in the ____ lymph
Definition
  • T cells that do not encounter specific Ag leave the node in the efferent lymph
  • Note: T cells already have a recirculation pattern of coming to lymph nodes whether it's going to see Ag or not
Term

T cell activation

Step 6

  • T cells that encounter specific Ag proliferate & ____ to ____ cells
  • ___ (on T cell) is activated by chemokines bound to ECM 
  • Activated LFA-1 binds tightly to ___
  • ____ lymphocyte leaves blood & enters lymph node
Definition
  • T cells that encounter specific Ag proliferate & differentiate to effector cells
  • LFA-1 (on T cell) is activated by chemokines bound to ECM
  • Activated LFA-1 binds tightly to ICAM-1
  • Diapedesis lymphocyte leaves blood & enters lymph node
  • Note: DC →combo of MHC & peptide see if the T cell will stick to the DC for a long period of time "tight binding" event.
Term

Co-stimulatory & accessory mlcs

  1. CD28 on T cell binds __ , __ on APCs (constitutive)
  2. ___ (pan T cell) binds LFA-3 (APC)
  3. LFA-1 binds ___
  4. ___ - signal transduction
  5. ___ induced on T cell binds CD86, CD80 (downregulatory)
  6. CD40L induced on T cells binds ___ on __ cells, macrophages
  7. ICAM-3 on T cell binds to ___ (APC)

 

Definition
  1. CD28 on T cell binds CD86, CD80  on APCs (constitutive) [Note: 2nd signal in activation , necessary for IL-2 production]
  2. CD2 (pan T cell) binds LFA-3 (APC) [Note: cell-cell adhesion, activation]
  3. LFA-1 binds ICAM-1 (Note: cell-cell adhesion; also binds ICAM-2, pic shows it on T cell, inside-out binding)
  4. CD45 (T-cell) - signal transduction  binds CD22 (APC) (Note: Phosphatase in cytoplasmic domain)
  5. CTLA-4 induced on T cell binds (co-stimulatory mlcs) CD86, CD80 (downregulatory)
  6. CD40L induced on T cells binds CD40 on B cells, macrophages (Note: CD40L also helps CD8+ bud doesn't require binding event)
  7. ICAM-3 on T cell binds to DC-SIGN (APC) [from pic]
Term

T cell surveillance

  1. T cells bind ___ adhesion mlcs
  2. If they do not bind/recognize specific ___, they detach & move to next ___
  3. Upon ___ engagement, LFA-1 is induced to bind w/ higher ___
Definition
  1. T cells bind APC adhesion mlcs
  2. If they do not bind/recognize specific Ag/MHC, they detach & move to next APC [SM impt]
  3. Upon TCR engagement, LFA-1 is induced to bind w/ higher affinity
Term

Conversion of LFA-1 to high affinity

  1. T cell initially binds DC via ____ LFA-1 : ICAM-1 interactions
  2. Subsequent binding of TCRs sends signal to ___
  3. Conformational Δ in LFA-1 ↑ affinity & prolongs _____
Definition
  1. T cell initially binds DC via low-affinity LFA-1 : ICAM-1 interactions (Note: adhesion mlcs stick out further (others are shorter), "loose binding"; low Ab affinity is 105, T cell is 104)
  2. Subsequent binding of TCRs sends signal to LFA-1 (Note: signal recognition event caused this "tight binding" requires hours of contact)
  3. Conformational Δ in LFA-1 ↑ affinity & prolongs cell-cell contact
  • Note: CD4,TCR & LFA-1 on T-cell; ICAM-1 & MHC class II w/Ag on DC (could be CD8 & class I)
Term
  • Professional APCs have MHC ___ & ____
  • What does the MHC expression look like on the APCs?
  • What does the co-stimulator delivery look like?
Definition
  • Professional APCs have MHC class I & II & CD80/CD86
  • MHC expression:
  • DC - low on tissue DCs, high on DCs in lymphoid tissues
  • Macs - inducible by bacteria & cytokines - to +++
  • B cells - constitutive ↑ on activation +++ to ++++
  • Co-stimulator delivery:
  • DCs - constitutive by mature, nonphagolytic lymphoid DCs ++++
  • Macs & B cells - inducible - to +++

 

Term

Steps in Adaptive T cell Mediated Immune Response

Recognition Phase

  • ____ binding of APC by an Ag specific T cell, primarily in peripheral lymph organs
  • Signal 1 - APCs present peptide-MHC (Ag/MHC) to ___ on ____ (Th cells)
  • TCR-__
  • T cell - CD8 or CD_
  • APC - Ag/MHC _ or Ag/MHC II
  • Signal 2 - APCs present co-stimulatory mlcs to ___ on T cell leading to ___ production & IL-2R expression
  • T cell - CD28
  • APC - ___, ___ (CD80/86) [look for IL-1, IL-α
Definition
  • Clonal selection binding of APC by an Ag specific T cell, primarily in peripheral lymph organs
  • Signal 1 - APCs present peptide-MHC (Ag/MHC) to TCR on CD4+ T cells (Th cells) (G0 → G1 (SM)) [Note: specificity should trump everything, selective about activation = tight binding]
  • TCR-CD3
  • CD8 or CD4
  • Ag/MHC I or Ag/MHC II
  • (note: give us time to look for co-stimulatory mlcs)
  • Signal 2 - APCs present co-stimulatory mlcs to CD28 on T cell leading to IL-2 production & IL-2R expression (G1 → S (SM))
  • T cell - CD28
  • APC - B7-1, B7-2 (CD80/86) [look for IL-1, IL-α]
Term

Steps in Adaptive T cell Mediated Immune Response

Activation Phase

  • _____ - T cells are now receptive to autocrine (CD4+ T) & paracrine (CD8+ T) growth factors (IL-2, IL-4) leading to proliferation
Definition
  • Clonal expansion - T cells are now receptive to autocrine (CD4+ T) & paracrine (CD8+ T) growth factors (IL-2, IL-4) leading to proliferation 
Term

Steps in Adaptive T cell Mediated Immune Response

Activation Phase cont'd

  • ____ T cells respond to cytokines (ILs) to become effector and/or ____ T cells
Definition
  • Differentiation - T cells respond to cytokines (ILs) to become effector and/or memory T cells
Term

Steps in Adaptive T cell Mediated Immune Response

Effector Phase

  • Macrophage ____ (CD4)
  • B cell activation ___ production (CD4)
  • Inflammation
  • ___ T cell (CD4 or CD8)
  • T cell mediated ___
Definition
  • Macrophage activation (CD4)
  • B cell activation, Ab production (CD4)
  • Inflammation
  • memory T cell (CD4 or CD8)
  • T cell mediated cytolysis

Note: T cells want to act on cells not just hand out cytokines

Term

Outcomes of Signal 1 + 2, 1 alone, 2 alone

  1. Which one causes the T cell to become anergic?
  2. Which one activates the T cell?
  3. Which one has no effect on the T cell?
Definition
  1. Anergy - Specific signal (1) alone [Note: even if cell @ 2nd time had co-stimulatory mlcs]
  2. Activates - Specific & co-stimulatory signal (1 + 2)
  3. No effect - Co-stimulatory signal alone
Term

2 signal model of T cell activation

  1. Phagocytosis & breakdown of bacteria by ____ induces expression of MHC class II & __
  2. Macrophage delivers a ____ signal to T cells recognizing bacterial ____ ____
  3. Proliferation & differentiation of ___ specific for bacterial protein
Definition
  1. Phagocytosis & breakdown of bacteria by macrophage induces expression of MHC class II & B7
  2. Macrophage delivers a co-stimulatory signal to T cells recognizing bacterial peptide antigen
  3. Proliferation & differentiation of T-cells specific for bacterial protein
Term

Immunological Synapse

  • T cell interacts w/ the APC to create a tight jxn (pep-MHC migrates from outside to inside)
  • At the jxn you have a "bulls-eye" like area with the c-SMAC (enriched by TCRs) in the middle & p-SMAC (a ring of adhesion mlcs) surrounding it
  • What mlcs are found in the c-SMAC?
  • What mlcs are found in the p-SMAC?
Definition

c-SMAC

  • TCR
  • CD2
  • CD4
  • CD8
  • CD28 - signal 2
  • PKC-θ - will become activated

p-SMAC

  • LFA-1
  • ICAM-1
  • talin
Term

ITAM phosphorylation

  1. In the resting T cell ___ are not phosphorylated
  2. Binding of MHC ligand to the ___ leads to phosphorylation of the ITAMs by _____
  3. When the co-receptor binds to the MHC ligand ___ binds to phosphorylated ___ ITAMs & is phosphorylated & activated by ___
Definition

On APC: MHC class II

On T cell: TCR, CD4, Lck, Fyn, ZAP-70, ITAMs

  1. In the resting T cell ITAMs are not phosphorylated
  2. Binding of MHC ligand to the TCR leads to phosphorylation of the ITAMs (CD3) by receptor associated kinases (Src family kinases, eg. Lck & Fyn)
  3. When the co-receptor binds to the MHC ligand ZAP-70 (kinase not Src, need to get from cytoplasm to cell membrane) binds to phosphorylated ζ-chain ITAMs & is phosphorylated & activated by Lck (CD4 or CD8)

Note: mutation in ZAP-70 (genotype), person is CD8 deficient (phenotype)

Term

Big picture: Naive T cell recognition of specific Ag presented by a DC initiates pathways of signal transduction that lead to clonal expansion & differentiation

Definition
  1. Naive T cell interacts w/ DC presenting its specific Ag
  2. Activation of the kinase ZAP-70 initiates a series of rxns leading to the activation of PLC-γ
  3. PLC-γ cleaves PIP2 to DAG & IP3
  4. DAG → PKC-θ → tranx factor NF-κβ
  5. DAG also → RasGRP → MAPK → Fos (component of AP-1 tranx factor)
  6. IP3 → ↑ Ca2+ → calcineurin → tranx factor NFAT (also true for B cells)
  7. NF-κβ, NFAT & AP-1 Δ the pattern of gene expression
  8. Cell division, proliferation & differentiation  to effector T cells

 

Term

Signal 2

  1. Naive T cells express the low-affinity IL-2R (β,γ chains) bind IL-2 w/ moderate affinity
  2. Activated T cells express the high affinity IL-2R (α,β,γ) & secrete IL-2
  3. Binding of IL-2 to the IL-2Rα sends a signal to the T cell
  4. The signal sent from the IL-2Rα induces T cell proliferation
Definition

Key points:

  1. Signal 2 induces expression of IL-2 & IL-2Rα (IL-2Rα = CD25)
  2. IL-2R composed of γ, β
  3. w/o signal 2 = anergy
  4. CD8 would put IL-2Rα but not IL-2; would get IL-2 from CD4 (paracrine)
  5. CD4 cell would get high affinity receptor & IL-2 (autocrine)
  6. CD25 - need FoxP3 as addt'l marker to distinguish Tregs from everday activated CD4

 

Term

Mechanisms of T cell activation

 

Normal


Foreign Ag

  • recognition results in activation of ≈ 1/100,000  T cells

 

Definition

Exceptional

 

Allogenic MHC

  • foreign MHC recognition → activation of ≈ 1% of T cells [note: a lot of T cells will recognize foreign MHC @ the start]


Term

Exception

 

Superantigens

  •  bacterial exotoxins - mimic specific Ag & cause T cells to divide & differentiate into effector T cells
  • circumvent specificity of TCR
  • bind simultaneously to MHC class II & TCR (in absence of specific peptide Ag - form a bridge)
  • Bind & cross-link MHC class II
  • bind to CRR1 & CDR2 loops of Vβ domain of TCR
  • superAg stimulation → of up to 20% of CD4 T cells (bind to sites shared by many TCRs → massive polyclonal response)

note: bringing together MHC w/ TCR, thinks it got activated, not processed & presented, only on surface

 

Definition

Exceptional

mitogens

 

Polyclonal (in vitro stimulation = diagnostic test for T cell fxnality)

  • PHA (CD2), ConA (plant-lectin mitogens; T cell only) [note: LPS is for B cells only]
  • lectins are 4 subunits used for cross-linking; recognize Mannose -OH
  • Anti-CD3 + anti-CD28 mAbs (T cells think they are activated)

note: no receptor stimulus req'd i.e. do NOT act via TCR or Ig

Pts w/ T cells want to know if they are fxnal need to get proliferation - anergized T cells do not proliferate

Term

Allogeneic MHC

  • convential recognition of Ag/MHC w/ TCR is full contact (both Ag & MHC)
  • Proposed extremes of allorecognition 1. MHC only (very high affinity binding, enough to activate) 2. Ag only (due to polymorphism of MHC mlc dif peptide will be bound (same protein)
  • accidental recognition of allogeneic has to do w/ fact that MHC types look alike, existence of allogeneic is unknown to T cell as it's being educated
Definition
  • if self MHC I → see foreign MHC I, CD8
  • if self MHC II see foreign MHC II, CD4
  • see the same HLA specific as well
  • TCR carefully selected to recognize a self MHC (& peptide); same TCR will see a foreign MHC
  • cross-reactive recognition: meant from self-MHC used to recognize foreign. Not processed & presented only on surface (intact MHC)
Term

Mitogens

  • Anti-CD3 & anti-CD28 activation of T cells
  • Immobilized Abs or presence of APCs
  • mimic signal 1 & signal 2
  • polyclonal activation - all T cells would have CD3 & CD28
Definition

PMA & Calcium ionophore - mimics

  • artifically activate T cells - mimic intracellular 2nd messengers
  • PMA (DAG) (PKC activation, [Ca2+]i ↑) [1st phosphorylation event]
  • ionomycin (ionophore insert into membrane, cause Ca2+ channel to form, allow for EC Ca2+ to enter cell, [2nd event ↑ in IC free Ca2+]
Term

Mechanisms of unresponsiveness to self Ags

  • Central tolerance - ____ self-reactive ___ that recognize self ___ in the thymus undergo ___ (deletion)
  • Peripheral tolerance - ___ self-reactive T lymphocytes that escape ____ & recognize self Ags in peripheral tissues can be inactivated (___), killed (deletion) or _____ (suppressed)
  • "Clonal ignorance" - ____ self-reactive lymphocytes do not respond to ____ in non-inflamed settings
Definition
  • Central tolerance - Immature self-reactive T lymphocytes that recognize self Ags in the thymus undergo negative selection (deletion) [Tregs are here]
  • Peripheral tolerance - Mature self-reactive T lymphocytes that escape central tolerance & recognize self Ags in peripheral tissues can be inactivated (anergy), killed (deletion) or regulated (suppressed) [Tregs can be generated from naive, mature T cells & come into periphery]
  • "Clonal ignorance" - Mature self-reactive lymphocytes do not respond to self Ag in non-inflamed settings
Term

Downregulatory APC & T cell interactions

  • APC & CD4+ T cell
  • Signal 1 - MHC __ w/ TCR
  • Signal 2 - B7 (CD80/86) w/ ___
  • downregulatory signal B7 (CD80/86) w/ ___ [inducible]
Definition
  • APC & CD4+ T cell
  • Signal 1 - MHC TCR w/ TCR
  • Signal 2 - B7 (CD80/86) w/ CD28
  • downregulatory signal B7 (CD80/86) w/ CTLA-4 [inducible]
Term

Response against intracellular microbes

  • Delayed type hypersensitivity (DTH) Th1
  • Cytotoxic T cell response (CTL) CD8
  • Antibody Dependent Cell-mediated Cytotoxicity (ADCC) NK
Definition

Response again extracellular microbes or soluble foreign Ags [toxic proteins made by bacteria]

  • T help for humoral immune response (Th1, Th2)
  • ADCC, [picked up by Eosinophils - NK cells won't pick up EC pathogens, has to recognize a cell]

 

Term

T cell differentiation

Type of effector of response depends on:

  • Type of Ag (EC vs. IC)
  • Type of APC presenting the Ag determines which cytokines will be produced
  • These interactions occur during the induction phase of Ag-depend T cell activation & differentiation
Definition
  • Don't confuse IC & EC pathogens w/ endo/exogenous pathways
  • EC - pathogens like to replicate outside cells
  • IC - pathogens come from outside but like to grow inside eg. TB bacteria, viruses (inert have to be in our cells to activate), will be processed & presented by APCs
  • CD4+/MHC II exogenous pathway, worse situation is not have CD4+ T cells
Term

Signal 3 - cytokine microenvironment

  • Signal 1 is Specificity (TCR:MHC/Ag)
  • Signal 2 is Activation (CD28:B7)
  • Signal 3 is Differentiation
  • For full division (mitosis) get signal 1 & 2
  • LPS binds to TLR4 (binds to B cells)
Definition

Signal 3 - Differentiation

  • IL-1, IL-6 or IL-12 (cytokines)
  • Bind to the IL-12R on CD4+ T cell
  • T cell daughters will bind cytokines & gain differentiation effector fxn
Term

Effector T cell subsets

T cells fxn by making contact w/ other cells & inducing them to Δ

  1. CD8 T cell contacts a virus-infected cell, outcome?
  2. CD4 T cell + macrophage, outcome?
  3. CD4 T cell + B cell, outcome?
Definition
  1. CD8 T cell + virus-infected cell = dead virus-infected cell
  2. CD4 T cell + macrophage = activated macrophage (cytokines present)
  3. CD4 T cell + B cell = plasma cell + Abs
Term

Naive CD4 T cell → Proliferating T cell → Immature effector T cell -Th0 →Th1, Th2, Th17, Treg differentiation is determined by cytokine microenvironment

Th0 → Th1 [note: Th0 is undifferentiated CD4+]

  • APC producing IFN-γ IL-12
  • macrophage & B-cell activation
  • production of opsonizing Abs such as IgG1 (growth factor req'd for Ig switch)
  • Intracellular microbes
  • Under ctrl of tranx factor Tbet

Note: APCs have PAMPs - recognize mlc structure that generally we don't have

 

Definition

Th0 → Th2

  • Extracellular microbes
  • IL-4 production (probably by mast cells) [Th2 respond to IL-4 to make IL-4; + feedback]
  • IL-5
  • general activation of B cells to make Abs (respond to cytokines)
  • Under ctrl tranx factor GATA-3
Term

Differentiation pathways of CD4 T-cells

Need to know the sequence & key cytokines

FoxP3, RORγt, T-bet & GATA-3 are tranx factors impt in deciding which protein will be made

Definition
  1. Treg cells: TGF-β → FoxP3 → TGF-β, IL-10  
  2. Th1 cells: IL-12, IFN-γ →T-bet → IL-2, IFN-γ 
  3. Th2 cells: IL-4 → GATA-3 → IL-4, IL-5
  4. IL-17 producing Th cell: IL-23 → IL-23R → RORγt → IL-17 & IL-17F

    Note: TGF-β is anti-inflammatory cytokine, this plus IL-10 are down regulatory of inflammatory response

    IL-1, IL-6, TNF-α are inflammatory cytokines

    1-3 have + feedback loops

    Treg also has CD4+, CD25+

    Term

    Th1  or Th2 differentiation or polarization

    • Th1: IFN-γ bind to IFN-γR → STAT1 → Tbet → [↑IFNγ, ↑IL-12R, ↓IL-4 (feedback to Tbet)] → [IL-12, IL-12R, STAT 4 →] & Th1 [IFN-γ stabilized; IL-4 silenced]
    • Th2: IL-4 bind to IL-4R → STAT6 → GATA-3 → [↑IL-4, ↓IFN-γ ↓IL-12R (feedback to GATA-3)] → Th2 [IL-4 stabilized; IFN-γ silenced]
    • IL-17 producing Th cell: IL-23 → IL-23R → RORγt → IL-17 & IL-17F
    Definition
    •  It takes about a week for this path to occur i.e. from Th0 → Th1 or Th2
    • Fate of daughter cells from originally selected Th0 could choose either pathway
    • Once subset made, it remains a stable subset
    • T cell response comes up faster w/ memory cells, i.e. it won't take a week to make Th1 or Th2
    • All 3 start w/ naive CD4+ T cell w/ IL-12Rβ1 and signals through CD28 and/or ICOS
    Term

    Activation of T lymphocytes

    1. Ag recognition - APC w/naive CD4+ or CD8+
    2. Activation - IL-2R on T cell w/IL-2 cytokines
    3. Clonal expansion
    4. Differentiation into effector & memory CD4+ & CD8+ T cells
    5. Effector fxns: CD4 - activation of macrophages, B cells, other cells
    6. Effector fxns: CD8 (CTL) - Killing of infected "target cells"; macrophage activation

    Note: 1-4 happen in the lymphoid organs & 5-6 happen in peripheral tissues

    Definition
    • IFN-γ, IL-2: need the IL-2 to get the ytolytic mechanism already present in NK cells
    • Recognized by MHC I whereas NK match by KIR for MHC I
    Term
    • Inititation: Ag/MHC, SuperAg, Co-stimulation → naive T cell encounters Ag
    • Clonal expansion: IL-2/IL-2R → most activated T cells become effector cells; some activated and/or effector cells become long-lived memory cells
    • Contraction: FasL ≈ TNFα; Fas ≈ TNFR (cell that's destined to die) → many effector cells are short-lived & die by apoptosis; cytokines may be req'd for survival; IL-7, IL-15 (long-lived memory)
    Definition
    • Suicide & fratricide
    • how effector cells disappear
    • anti-apoptotic - stay alive, maintenance factor vs. growth factor
    • actually divide
    Term
    • CD8 T cells [CTLs - cytotoxins, FASL] bind to virus infected cell [FAS] →T cell secretes effector mlcs onto surface of target cell
    • cytotoxins: perforin, granzymes, granulysin
    • cytokines: IFN-γ, LT
    Definition
    • CD4 T cells: Th1 cells [cytokines, CD40L] bind to macrophage containing bacteria [CD40, intra-vesicular bacteria]
    • cytokines: IFN-γ (impt for IL-2 growth factor), GM-CSF, TNF-α, LT, IL-3
    • Th2 cells: cytokines & CD40L bind to B cell presenting specific Ag [CD40, bacterial toxin]
    • cytokines: IL-4 (+ feedback), IL-5 (eosinophil recruitment), IL-10 (anti-inflammatory), IL-13, TGF-β (mast cells & allergies)
    Term
    • all T cells
    • integrin: LFA-1 (αL & β2)
    • APC
    • adhesion mlc: ICAM-1
    Definition
    • activated effector T cells
    • integrin: VLA-4 (α4, β1)
    • activated endothelium
    • adhesion mlc: VCAM-1

    VLA = very late Ag

    Term

    Regulatory T cells

    • Most are CD4+, CD25+, Foxp3+ (CD3) Tregs
    • → most clinically relevant Tregs, oral immuntity - stuff we ingest we're going to be tolerant to
    • Regulation is mediated by cytokines
    • Tregs downregulate inflammatory response
    Definition
    • Normal response: Ag recognition & T cell response
    • APC bind to naive T cell → effector T cells (T cell proliferation & differentiation) w/IFN-γ → activated macrophage
    • Suppresion: APC bind to naive T cell → Suppressor (regulatory) T cells → immunosuppressive cytokines →
    • IL-10 inhibits fxns of APCs (IL-12 secretion, B7 expression)
    • TGF-β inhibits T cell proliferation
    • IL-10, TGF-β inhibit macrophage activation
    Term
    • Suppression of autoreactive T cells by regulatory T cells (Treg) requires them to interact w/ the same Ag-presenting cell
    • Treg binding same APC as CD4 T cell causes APC not to be a good APC - suppression of self-reactive T cells
    Definition
    • cell-cell interaction event involved w/Tregs
    • Tregs to insulin should block T cell recognition of insulin (as foreign) not something else like influenza
    • It isn't just 1 peptide for every protein processed & presented; could be identical or different - block humoral & cell-mediated b/c CD4+ @ crux of both
    • MHC mlcs will have peptides but all dif; self-MHCs some have multiple peptides
    • CD8 seeing self in absence of CD4 seeing self is going to go nowhere, don't have IL-2 (growth factor)
    Term

    CD4+ T cells that differentiate into Th1 cells secrete

    • IFN-γ: acts on macrophages to ↑ phagocytosis & killing of microbes in phagolysosomes & on B lymphocytes to stimulate production of IgG Abs that opsonize microbes for phagocytosis
    • IL-2 predominant autocrine growth factor made by this subset of T cells & [along w/ IFN-γ can contribute to the differentiation of CD8+ T cells to CTLs (SM impt)]
    • Lymphotoxin (LT) activates neutrophils
    Definition

    Activated Th1 cell

    • IFN-γ & CD40L → activates macrophages to destroy engulfed bacteria (upregulate IC killing)
    • FasL or LT → kills chronically infeced macrophages, releasing bacteria to be destroyed by healthy macrophages
    • IL-2 → induces T-cell proliferation, ↑ing the # of effector T cells
    • IL-3 + GM-CSF → Induces macrophage differentiation in the bone marrow
    • TNF-α + LT → activates endothelium to induce macrophage adhesion & exit from blood vessel (diapedesis) @ site of infection (if too abundant cause a problem)
    • CXCL2 → causes macrophages to accumulate @ site of infection (chemotaxis)
    Term

    Activation of macrophages by CD4+ Th1 cells

    • Th1 cell & infected macrophage come together → T cell [CD40L & IFN-γ] binds to, & activates, macrophage [CD40 & IFN-γR] → killing of intravesicular bacteria

     

    Definition
    • Partial activation of macrophage → granuloma formation (mycobacteria, multi-nucleated giant cell, epitheloid cell, T cells)
    • macrophage has IC bacterium upregulated killing mechanisms but bacteria survive
    • indication of macrophages trying to get rid of IC pathogen, encircle it & wall off granuloma
    • Immunosuppressed, T cells not variant; things coming out of granuloma e.g. TB reactivation coming from granulomas
    Term

    Effector fxns of CD4+ Th2 cells

    • IL-4 (& IL-13 - SM) → B-cell → (1) neutralizing IgG Abs (EC bacteria, viruses, toxins) & (2) IgE → mast cell degranulation (helminths, allergies)

    Note: IgE bound by tissue mast cells encounters Ag binding event, triggers mast cell degranulation

    Definition
    • IL-5 → eosinophil → eosinophil activation (helminths)
    • IL-10, IL-4 → activated macrophage → suppression of macrophage activation

    Note: bind to bacteria, block toxin = block disease; deal w/parasites

    recruiting eosinophils - elaborate toxic substances on surface of worms?

    Term

    T cell help for B cells

    • Ag recognition induces expression of ___ & cytokines by the Th2 cell, which activates the __
    • B-cell proliferation & differentiation to ____
    Definition
    • Ag recognition induces expression of CD40L & cytokines (IL-4, 5, 6) by the Th2 cell, which activates the B cell
    • B-cell proliferation & differentiation to Ab-secreting plasma cells
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