Immunology Final Exam (Part 1: Lecture 25, 26)

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Stress Molecules

Can be recognized by gamma delta T cells and that fill critical gaps in host defense; respond by proliferating and differentiating into gamma delta Th and gamma delta CTL effectors

What makes a T cell double negative?

Carries homodimeric CD8alpha alpha co receptors or no co receptor

What is the primary function of NK cells?

Non-specifically kill tumor or virally-infected cells secrete cytokines

Explain recognition of target cells by NK cells

Not MHC restricted some cases show similar NK-cell activity with syngeneic and allogeneic tumors

Gamma delta TCRs interact with ligands similar to ligand recognition by

Pattern Recognition Receptors (PRRs)

NK cell tolerance

Self tolerant

What happens to a patient when they have complete absence of NK cells

Serious varicella virus (chickenpox) & cytomegalovirus infection

Explain Stress molecules sizes

Small pyrophosphate-like molecules Peptides or whole proteins (heat shock proteins (HSPs))

gamma delta T cells Ag Recognition

Specific to stress molecules such as injury infection or cancerous transformation may be regulated more like that of NK cells

Natural killer group 2 (NKG2) & Killer Ig-like receptor (KIR) class include

both activating & inhibitory members

NKT cells immediately __________

commence cytokine secretion (rapid response & first line of defense)

NK cells are involved in

early response to infection with certain viruses & intracellular bacteria and are the first line of defense against virus infection

When gamma delta T cells are activated by Ag they generate ______

effectors in a manner similar to alpah beta T cells even thoguh the signaling pathways linking TCR stimulation to new transcriptions are slightly different

What is the first wave of T cells produced in humans or mice?

gamma delta T cells (provide immune defense in fetus and neonates before adaptive immunity)

Natural killer (NK) cells are what kind of cells?

non-phagocytic lymphoid cells that possess cytoplasmic granules

Activated NK cells DO NOT

proliferate & differentiate (responds within hours of infection)

gamma delta are a major population in what species

ruminants (cows and sheep) & pigs

Gamma delta T cells are interspersed among ____ leading to them being the first defenders

the epithelial cells (SALT) and mucosae (MALT)

NK cell receptors are generally _______ proteins

transmembrane

Define Natural cytotoxicity

"Missing self"; contain perforin & granzymes that induce apoptosis in target cells; have preformed granules

In humans what are the majority of T cells?

CD4+ CD8+ and alpha beta T cells

NKT cell receptors

- 'semi-variant' TCR alpha beta (TCRalpha chain is essentially invariant) - Invariant or iNKT cells - CD3 complex - CD4+CD8-, CD4-CD8+ or CD4-CD8-

What do the TCRs of NKT cells recognize?

- Glycolipid - Glycosphingolipid - Lipids presented on non-polymorphic CD1d molecules

NKT cell antigens

- Glycolipids - Microbes that contain CD1d-restricted glycolipid Ags - Microbes that do not contain such glycolipid Ags can still activate NKT cells (via indirect routes)

Cytokines produced by gamma delta Th effectors

- activate NK cells and macrophages - support differentiation of activated alpha beta Th0 cells - influence isotype switching in B cells - influence leukocyte trafficking and wound healing

Define NK activating receptors in natural cytotoxicity

-Triggered by ligands either constitutively expressed on healthy cells or may be induced or up regulated in response to viral infection, malignant transformation (tumor) or other stresses -Non-classical NHC molecules

What is a bridge for innate adaptive immunity?

Natural Killer cells, gamma delta T cells and NKT cells

What are two factors that contribute to the intensity of NK cell response in natural cytotoxicity?

1. How many inhibitory versus activatory receptors are engaged 2. Affinity of those receptors for their ligands

What are two surface receptors that help trigger NK-mediated natural cytotoxicity

1. NK activating receptors 2. NK inhibitory receptors

What are two examples that non-peptide Ags are also presented by

1. non-classical Class Ib molecules 2. non-polymorphic CD1

What percentage of NK cells are in the peripheral blood cells?

10-15%

What is the lifespan of a NK cell?

7-10 days

In sites of inflammation ____ may help to activate gamma delta T cells

APCs

Natural cytotoxicity receptor (NCR) class contains only _______

Activating receptors

What immune system is NKT cells a member of?

Adaptive immune system and exhibit some characteristics of cells in the innate immune system

Natural killer (NK) gamma delta T cells and NKT cells are part of what immunity reaction?

Adaptive immunity

Gamma delta T cells serve as what to alpha bata T cells

Antigen presenting cells (APCs)

What can Cytolysis be induced by?

Natural cytotoxicity, ADCC or cytotoxic cytokines

Define NK inhibitory receptors in natural cytotoxicity

Bind only to classical MHC class I molecules

Where do NK cell originate from?

Bone marrow-derived hematopoietic precursors

gamma delta T cells can be activated with phosphorylated metabolites without

CD28 or CD40 mediated costimulation

NK cells that survive infection show

Characteristics of memory lymphocytes

gamma delta T cells in peripheral tissues

Conventional CD28-mediated costimulation

Gamma delta T cells in epidermal & intestinal

Costimulated when other surface receptors are engaged by stress ligands

What is promoted when NK cell and DCs interact?

DC maturation & efficient induction of Th & CTL responses

Define "induced self"

Elevated amounts of ALs which results in abnormal host cell to be killed

Explain the importance of the balance between activating & inhibitory signals in natural cytotoxicity

NK cells are able to distinguish healthy cells from infected cancerous or abnormal cells (opposing-signals model)

Where are NK cells found?

High frequency in spleen, liver, uterus & peripheral blood and more moderate numbers in bone marrow, lymph nodes and peritoneum

Phagocytes & innate leukocytes produce what cytokines upon activation

IFN alpha/beta, IL-12, IL-15, TNF (Prime NK cells and induce them to synthesize IFN-gamma)

NK activity is stimulated by what cytokines

IFN-alpha, IFN-beta, IL-12

What cytokines are required to activate resting NK cells?

IFN-alpha, IFN-beta, IL-12 or IL-15 present in a site of infection and induce up regulation of many activating & inhibitory receptors and adhesion molecules (no effector differentiation)

What chemokines, growth factors, and cytokines are present in the activation of primed NK cells by FCgamaRIIA?

IFN-gamma, TNF (can mediate cytotoxicity), IL-1, IL-3, & IL-6 (these play an important role in both innate & adaptive immunity

NKT cells may not be activated unless what receptors are engaged?

IL-12/IL-18 or IFNalpha/beta

What drives immature NKT cells to maturation?

IL-15

Explain in general Ag recognition

Respond to a wide variety of bacterial protozoan & viral molecules & products (Some specific to certain type of determinants that can counter whole group of pathogens)

Activatory receptors signal through associated

ITAMs

Inhibitory receptors signal through associated

ITIMs

Explain of NKT cells are developed

In the Thymus from NK/T precursors and follow the alpha beta T cell developmental pathway diverge from them during the DP stage

Explain 'Experienced NK cells'

Increase their longevity & second time infection can proliferate & exhibit enhanced cytolytic & cytokine secretion capabilities

Explain placenta and NK cell receptors

Induce maternal uterine NK cells to secrete cytokines to help ensure a successful pregnancy

IFN-gamma

Influence the innate immunity by activation of macrophages and enhance TH1 cell development

What makes NK cells different from NKT, B & T cells

Lack of TCRs or BCRs expression and have TCR or BCR genes in germline configuration

Infected & cancerous cells frequently downregulate their _____

MHC class I

Gamma delta T cells DO NOT require involvement of

MHC or processing & presentation of peptide Ags by APCs (respond to a broad range of pathogens or abnormal cells)

What is not a feature of gamma delta T cells?

Memory

Explain missing self

Missing normal levels of MHC class I on healthy cells therefore kill the target cells

What are two surface expressions NK cells show?

NCAM; CD56 FC gamma RIIIA (CD16)

What are NKT cells effector functions?

Prominent in induced innate immunity and immediately carry out their effector functions by activating cytokine and chemokine secretion

What are examples of TCR gamma delta ligands?

Proteins or peptides, non-protein Ags, and lipids & phosphorylated nucleotides (Soluble or bound to cell surface)

Define induced innate response

Rapid & involve broad recognition of Ag independent of classical pMHC

NK cells can be __________ when an infection & inflammation is present in almost any tissue in the body.

Rapidly recruited

Explain the development of gamma delta T cells

Rearrangement of TCRgamma delta genes is detected in thymocytes by 8 weeks in human fetus; and under the influence of fetal thymic stromal cells distinct waves of gamma delta T cells populate specific organs

What do NK cells cytokines directly regulate?

T & B cells functions & differentiation

Explain NKT cells

T lineage cells that have characteristics common to CTL & NK cells and found virtually everywhere T and NK cells are found

What are gamma delta T cells composed of?

TCR gamma, TCR delta, and CD3 complex

Cytokines produced by NKT cells have powerful effects on ________

alpha beta T cells differentiation and function (adaptive defense)

Explain what the engagement of FCgammaRIIIA (CD16) and NK cells causes

The release of cytotoxic granules

Killing by natural cytotoxicity also results when

There is normal level off self MHC class I but abnormally high levels of activating ligands (ALs)

Explain why TCRs lack the fine antigenic specificity

They bind directly to non-peptide antigens without the need for presentation by another molecule

What is a secondary source of NK cells?

Thymus (generate a subset of thymic NK cells)

Where do gamma delta cells develop?

Thymus from NK/T precursor (positive & negative thymic selections & peripheral tolerance occurs)

Explain NK-mediated ADCC

Triggered by binding to IgG molecules and have engaged epitopes on tumor cells or virus infected cells

In the secondary lymphoid tissues and thymus there are _______ numbers of gamma delta T cells

Very low

NK cells control

Viral replication during the time required for activation, proliferation & differentiation of CTL-p cells into effector CTLs

When is the Antimicrobial compound nitric oxide (NO) produced?

When activated gamma delta T cells induce neighboring epithelial cells

How are NK/T precursors generated?

When common lymphoid progenitors (CLPs) that remain in the bone marrow

When is keratinocyte growth factor (KGF) secreted and what is its function?

When gamma delta T cells in the skin are activated and stimulates growth and differentiation of skin epithelial cells

Gamma delta T cells express

a dominant or 'canonical' TCR containing specific V gene segments (Human intestines: Vgamma1 Vdelta2 TCRs) (Human Skin and peripheral blood: Vgamma9 Vdelta 2 TCRs)

Single Stress Af in response to

a variety of infections/injuries and monitor a variety of assaults

Natural killer (NK) gamma delta T cells and NKT cells have an influence on what two cells?

alpha beta T cell and B cells


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