Immuno: EXAM 3- Ch. 6: Effector Mechanisms of Cell-Mediated Immunity

All content from Ch. 6 Slideshow from Basic Immunology Textbook 7th edition

Define Cell-mediated immunity (CMI); How can it be transferred?

immunity to phagocytosed or intracellular bacterial infections which can be transferred from immune to naive syngeneic animal by T cells, but NOT by antibodies

What is responsible for microbe specificity in CMI; What is responsible for the elimination of those microbes?

Lymhocytes are specific for microbes, but activated Macrophages do the eliminating

What are the 4 subsets of CD4 HTL effector cells? What is the difference between them?

Th1, Th2, Th17, Tfh who all produce different sets of cytokines

What is the main cytokine for Th17?

IL-17

What is the main cytokine for Th1?

IFN-y

What is the main cytokines for Th2? (3)

IL-4, IL-5, IL-13

What are the main cytokines for Tfh? (3)

Main is IL-21, but also has IFN-y and IL-4

What is the principle target cell for Th1?

Macrophages

What is the principle target cell for Th2?

Eosinophils

What is the principle target cell for Th17?

Neutrophils

What is the principle target cell for Tfh?

B cells

What are the main reactions/ functions for Th2? (2)

Eosinophil and mast cell activation

What does Th1 mainly defend against?

Intracellular pathogens

What does Th2 mainly defend against?

helminths

What does Th17 mainly defend against?

extracellular bacteria and fungi

What does Tfh mainly defend against?

extracellular pathogens since it prepares B cells

What Th T cell is involved in allergies?

Th2

Where are the 3 sources of cytokines in an immune response?

Th subsets of HTLs, CD2+ regulatory T cells, CD8 T cells

How/why do CD4+ T cell subsets develop?

In response to types of microbes each subset is best at eradicating

What are the 4 general properties of T cell cytokines?

Produced transiently in response to antigen, usually autocrine or paracrine, pleiotropism, redundancy

What is Pleiotropism in cytokines?

The fact that each cytokine has multiple biological actions which produces diversity of actions

What is Redundancy in cytokines?

the fact that multiple cytokines share the same or similar biological activities

When are Th1 cells induced and by who? Why?

Induced by APCs upon ingestion of microbes to stimulate killing of ingested microbes

What does IFN-y do?

Activates macrophages via classical pathway and stimulates isotope switching to IgG

What interaction alongside with the release of IFN-y causes the activation of macrophages to become microbicidal?

CD40L with CD40

What are the steps in classical macrophage activation? (What initiates it, what does it express & secrete, what does this cause?)

Th1 cells encounter an antigen on an APCs, the Th1 cell will express CD40L and secrete IFN-y which activates transcription factors and increases the expression of lysosomal enzymes causing macrophages to become strongly microbicidal

What stimulates isotope switching and what does this cause? How does this work?

IFN-y stimulates isotope switching to IgG to promote microbe killing via phagocytosis b receptor-mediated endocytosis and compliment activation

What are the 3 ways activated macrophages respond?

Killing phagocytosed bacteria, secreting cytokines (TNF, IL-1, and IL-2), and increasing expression of MHC and costimulators (B7 molecules)

What can inherited defects in Th1 cell development/ function cause?

susceptibility to intracellular microbial infections

Define delayed type hypersensitivity reactions

leukocyte recruitment and activation by injecting a microbial Ag into skin of individual previously exposed to microbe prior infection or vaccination, like the tuberculin test

What cytokines drive the differentiation of CD4+ T cells into Th1 effector cells? What is this in response to?

IL-12 and IFN-y in response to intracellular bacteria and viruses

What releases IL-12 to activate CD4+ T cells into Th1 effectors?

phagocytic APCs like NK and macrophages

What releases IFN-y to activate CD4+ T cells into Th1 effectors?

NK cells

What do Type I IFNs from viral infections do?

promote Th1 differentiation

What are the specific functions of Th2 cells? (3)

Promote IgE, mast cell, and eosinophil mediated parasite destruction

What does IL-4 stimulate in Th2 cells? What does this do?

IgE production which opsonizes helminths

What does IL-5 stimulate in Th2 cells? What does this do?

activates eosinophils to bind to IgE via FceRs which causes them to release their granule content which is toxic to parasites

What does IL-13 from Th2 cells stimulate ? Why?

mucus secretion and intestinal peristalsis to expel parasites from the intestines

What do IL-4 and IL-13 inhibit? Why? (Th2 Cells) What do they activate instead

classical pro-inflammatory Macrophages to terminate damaging reactions and instead stimulate the alternative pathway of macrophage activation

What is the alternative pathway of macrophage activation triggered by? What does it do?

It is triggered by IL-4 and IL-13 from Th2 cells and causes macrophages to secrete fibroblast growth factors leading to collagen synthesis which causes fibrosis

What does repeat exposure to allergens trigger? (2)

mast cell and eosinophil activation

What are Type I Hypersensitivity reactions?

Allergies caused by Th2 T cells

What are IL-13 antagonists effective against? (2)

severe asthma and atopic dermatitis who have a severe Th2 response

What cytokine receptor blocking drugs are currently being tested for use in reducing asthma and other allergic disorders?

IL-4 or IL-5 receptors

What is Leishmania major? What is required to clear it?

protozoal parasite that lives inside macrophages whose elimination requires the activation of the classical pathway of macrophage activation by Th1 cells

What is mycobacterium leprae?

the bacteria that causes leprosy which lives inside macrophages and is eliminated by CMI

What is Lepromatous leprosy?

Leprosy that the body responded to using a Th2 dominated response that is in now in a destructive form

What is tuberculoid leprosy?

A response to mycobacterium leprae with Th1 CMI via M1 Macrophages that cause less serious infection and will be eradicated

What Th T cell response is most effective in removing Mycobacterium leprae infection?

Th1

What stimulates the development of Th2 T cells? Where does this signal come from?

IL-4 that is released by other Th2 cells, mast cells, or tissue cells

What effects do Th17 cells achieve? (4)

enhance inflammation, increase recruitment of neutrophils and monocytes/ innate immunity and destroy extracellular bacteria/ fungi, maintain the inebriety of epithelial barriers

What does IL-17 do? (Th17 Cells)

stimulate the production of chemokines from other cells which is responsible for leukocyte recruitment

What does IL-22 do? (Th17 Cells) How? (2)

helps maintain the integrity of epithelial barriers by stimulating the production of defensins and promoting repair of damaged epithelia

What 3 cytokines promote the development of naive CD4+ cells into Th17 cells? What produces them? In response to what?

IL-1, IL-6, and IL-23 produced by APCs in response to recognition o fungal glycans or extracellular bacterial peptidoglycans

What is TGF-B?

a powerful inhibitor of immune responses who when present together with IL-6 or IL-1, it promotes the development of Th17 cells

What do rate inherited defects in Th17 responses cause? (2)

Bacterial abscesses in the skin and chronic mucocutaneous candidiasis

What are the inflammatory diseases associated with Th17 cells?

Psoriasis and Inflammatory Bowl Disease

What is required for Naive CD8+ T cells to differentiate into effectors?

Antigen recognition WITH costimulation and help from activated CD4 HTLs

How do Activated CD8+ T cells differentiate into fully active CTLs?

By synthesis of cytotoxic molecules

What do Effector CD8+ T cells (CTLs) do?

eradicate cytoplasmic microbes like viruses and ingested bacteria

What are the two types of granule proteins that are critical for cytotoxicity?

Perforin and granzymes

What are the two types of granule protiens that make holes in cell membranes to do apoptosis?

Perforin and caspases

What do perforins do?

disrupt the integrity of target cell plasma and endosomal membranes to facilitate delivery of granzymes into cytosol

What are granzymes (granule enzymes)?

Granule proteins that cleave and activate cascades present in the cytosol of target cells to induce apoptosis

What is Fas ligand (FasL)?

a membrane protein on activated CTLs that bind to Fas on target cells to induce death by activating cascades in target cells

What does FasL —> Fas binding do?

Activates caspases in target cells to induce apoptosis without the requirement for granule exocytosis

Do CTLs die after killing cells? How do they kill cells?

They can kill one target cell at a time by attaching and detaching and can go on to kill more cells after

Why is a greater number of CD8+ CTLs needed relative to CD4+ HTLs in immune responses? (2)

Attachment and detachment takes time and cytokines from each CD4_ HTL can affect multiple cells simultaneously

What is a hallmark of apoptosis? What happens along with it?

DNA fragmentation within a target cell which allows microbial DNA to be broken down with it

How do CD4+ and CD8+ T cells work together to destroy intracellular microbes?

phagocytosed microbes in macrophage vesicles can be eradicated by the action off IFN-y from CD4+ T on macrophages, but microbes that escape the vesicles can trigger CTL mediated cytotoxicity

What are NK cells activated by and what do they do?

Activated by class I MHC deficient cells and kill infected cells?

How are virus infected cells detected by NK cells?

Viruses inhibit class I MHC expression and NK cells detect the absence of class I MHC molecules

What is T cell exhaustion?

initial immune response being prematurely terminated by inhibitory receptors induced on CD8+ T cells by viruses who establish chronic infections by stimulating expression of these inhibitory CTLs

How does HIV evade the immune system?

By directly killing CD4+ T cells