topic 5 Flashcards

1
Q

How are intracellular organisms able to survive?

A

They resist destruction within vesicles

They get out of the vesicles into cytoplasm

They only replicate within the cytoplasm, not within vesicles

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2
Q

Where do positive and negative selection occur in the thymus

A

positive selection in the cortical epithelial cells

Negative selection on the phagocytic cells in the paracorticomedullary junction

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3
Q

What 3 kinds of intracellular microbes exist

A

microbes that don’t enter through phagocytosis

microbes that can survive in phagolysosome

microbes that can escape from phagolysosomes

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4
Q

What are the steps of naive t cell response to an antigen

A

binds apc

IL-2 is released by T-cell and taken up by IL-2R (autocrine). IL-2 is a t cell growth factor

Clonal expansion

Differentiation into effector T cells or memory t cells

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5
Q

What kinds of molecules are involved in T cell activation

A

Recognition cells, signal transduction cells, and adhesion cells

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6
Q

What molecules are in a T cell receptor complex and what molecules are co-receptors and what are their functions?

A

CD4/8 are co-receptors and are involved in recognition (of the MHC) but also in signal transduction

TCR bind to the MHC/peptide complex. It is part of the T cell receptor complex

CD3 and zeta don’t bind to anything on the APC but are part of the T cell receptor complex and thus when TCR binds, they send out a signal

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7
Q

What are super antigens?

A

They are components of microbes that cause a tcr to bind with a non-specific or non-match MHC/peptide complex. Therefore, many T cells are activated which leads to excess cytokine release which contributes to disease.

This allows the microbe to grow while the t cells are distracted with other things

Staphylcoccus aureus and streptococcus pyogenes are examples

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8
Q

What is co-stimulation

A

If an APC doesn’t express a co-stimulator (B7-1/2), then no t-cell response occurs even if the TCR binds correctly.

However, when an APC does express costimulator B7-1, it is recognized by CD28 on the t cell and leads to IL-2 being express and thus proliferation and differentiation.

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9
Q

What is the role of adhesion molecules? What steps take place?

A

T cells need to be in close proximity with APC for a certain amount of time. Adhesion molecules allow this.

Initially, the integrins (LFA-1) on the T-cell are in a low affinity state.

Signals delivered by chemokines and antigen recognition activate integrins to put them in a high affinity state.

Integrins (LFA-1) binds ICAM-1 on the APC, then integrins cluster creating adhesion which leads to a t cell response.

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10
Q

What is an immune synapse and a SMAC?

A

Receptors and ligands cluster around AG recognition site leading to stable adhesion and optimal signal transduction.

This area of adhesion is referred to as the immunological synapse.

The cluster of molecules is referred to as a supramolecular activation complex (SMAC)

On the inside is the cSMAC containing TCR, CD4/8, CD28, CD3.

On the outside is the p-SMAC containing the LFA-1 and ICAM-1.

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11
Q

What are the basic steps in signal transduction

A

receptor

ITAM-Immunoreceptor tyrosine-based activation motif

biochemical intermediates

active enzymes

Transcription factors

Expression of IL-2, IL-2R, other cytokines and growth factors.

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12
Q

What are some general properties of T cell cytokines

A

Produced in response to antigen, only when needed

Acts usually by autocrine means but maybe paracrine with nearby cells

pleiotropism-Each has multiple biological affects

Redudancy-many do the same thing

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13
Q

What are the special activation requirements for CD8 T cells and how does it happen?

A

They require co-stimulation

They require helper T cells.

A dendritic cell binds to a CD8 cell and a CD4 cell.

The dendritic cell expresses a costimulator

The CD4 cell releases cytokines which allow the CD8 cell to be activated.

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14
Q

Steps of clonal expansion due to IL-2

A

Before a T cell encounters an antigen, its IL-2R is in a low affinity, dimeric state.

T cell is activated by antigen and costimulator

IL-2 is secreted

Another subunit of the IL-2R is expressed due to activation and the trimeric IL-2R is in a high affinity state.

Cell proliferation ensues.

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15
Q

What are general characteristics of TH1 and what are the steps in its response?

A

Th-1 cell uses IFN-gamma, it activats macrophages and produces IgG, it fights intracellular microbes, and is involved with autoimmune diseases and tissue damage associated with chronic infections

Bacteria binds to APC, APC binds to naive T cell, Naive T cell releases IFN-gamma which:

Activates macrophages, causes complement binding and opsonizing IgG antibodies, and activates CD8 T cell

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16
Q

What are general characteristics of TH2 and what are the steps in its response?

A

IL-4, mast cell/eosinophil activation, IgE production, alternative macrophage activation, fights helminthic parasites, and is involved with allergic diseases

Helminths bind APC, which binds T cell, T cell proliferates and secretes IL-4, which causes:

Antibody production, mast cell degranulation, intestinal mucus secretion and peristalsis, eosinophil activation, and alternative macrophage activation (enhanced fibrosis/tissue repair)

17
Q

What are general characteristics of TH17 and what are the steps in its response?

A

IL-17/22, neutrophillic, monocytic inflammation, fights EC bacteria and fungi, is involved in autoimmune and inflammatory diseases (potent inflammator)

18
Q

How are CD4 cells differentiated to become Th1/2/17?

A

Cytokines!

When an APC binds, it releases certain cytokines depending on which helper t would best fight the microbe.

If an IC bacteria is bound, IFN-gamma and IL-12 are released which causes signal transduction and ultimately T-bet aids in producing TH1 cells.

With Helminths, IL-4 is released and ultimately GATA-3 produces TH2 cells.

With EC bacteria and fungi, TGF-beta and IL-6 are secreted and ultimately ROR-gamma t helps produce TH17 cells

19
Q

What are the steps of T cell migration to infected site?

A

T cell activated

Activated T cell expresses different adhesion molecules which allows it to migrate.

It leaves the LN and largely travels in circulation

Adhesion molecules on T cell and endothelial wall are responsible for this process.

Macrophage in infected tissue releases cytokines into the blood which causes these adhesion molecules to be expressed on the endothelial wall.

These adhesion molecules first slow the t cell down so it is rolling

Then it adheres more tightly until it is helped through the endothelial wall (extravasion or diapedesis) and to the infected area by chemokines (which were also released by infected macrophages).

This occurs in a non-antigen specific manner, not specific to a certain kind of T-cell activated for a certain antigen.

20
Q

What are the steps of macrophage activation by CD4 t cells?

A

Macrophage ingests bacteria and binds to CD4 cells.

Macrophage is only slightly activated but expresses CD40.

CD4 cell expresses CD40L. When they bind together, the t cell releases IFN-gamma, which activates the macrophage

21
Q

What is the response of an activated macrophage?

A

Produces ROS and NO, increases lysosymal enzmes–>killing of microbes

Secretes cytokines (TNF, IL-1, IL-12) and chemokines–>inflammation, TH1 differentiatoin, IFN production

Increased Class II MHC molecules and costimulators–>increased T cel activation.

22
Q

What kind of feedback occurs between macrophages and TH1 cells

A

IL-12 creates differentiated TH1 cell. It can be released by semi-activated or activated macrophage.

IFN gamma leads to enhance macrophage killing.

23
Q

What kind of feedback occurs between NK cells and macrophages

A

A similar process occurs with IL-12 from macrophage causing NK cells to release IFN-gamma which causes macrophage to kill microbes.

24
Q

What is the role of TH2 cell in CMI

A

Negative regulation: It limits the injurious consequences of macrophage activation

25
Q

General process of effector function of CD8 t cell

A

Binds to target cell and recognizes antigen (costimulator not required for an activated CD8 t cell (CTL, cytolytic t lymphocyte).

Perforin is released which forms pores in the target cell membrane, then granzymes are released into the pores which activates apoptosis (controlled death…no inflammation).

26
Q

How are the granules focused?

A

Once a contact occurs and adhesion is made, many constituents of the cytoplasm are moved elsewhere. Perforin monomers are only released at the binding area (similar to immune synapse) and granzymes too.

27
Q

How does FasL-Fas initiate apoptosis

A

FasL on t cell binds to Fas on target cell forming a Fas trimer. FADD then binds, then DED then procaspase 8–>apoptosis

28
Q

How does granzyme lead to apoptosis?

A

granzyme binds to BID which eventually opens of the outer mito. membrane which releases cytochrome c

It also binds to procaspas-3 making it caspase 3 which helps form CAD which leads to DNA fragmentation.

Cytochrome c binds to apaf-1 and the complex activates pro-caspase 9 and 3, which also cleaves I-CAD to CAD which enters the nucleus and cleaves DNA.

29
Q

How do NK cells kill?

A

They can kill by releasing IFN-gamma which activates macrophages

They can also kill in a manner similar to CD8 cells but with different recognition. In this case, the NK cell has an activating and inhibitory receptor. The inhibitory receptor may bind to MHC class I molecules. If a virus has down-regulated the MHC class I self molecules, the inhibitory receptor won’t be active and the NK cell will kill the target cell.

30
Q

What is antibody-dependent cell mediated cytotoxity?

A

Antibodies bind to target cells and many cells (macrophages, eosinophils, NK cells, etc.) can bind to the FC portion of the antibody. Upon doing so, they are programmed to perform an action; in the case of NK cells, it kills the target cell.

31
Q

What are some ways microbes have evolved to evade the CMI?

A

Mycobacteria prevent phagosome/lysosome fusion and survive in phagosome.

Cytomegalovirus, ebstein barr virus and herpes simplex virus prevent antigen from being presented on MHC

Epstein barr virus inhibits macrophage activation

pox virus bloacks cytokine activation of effector cells