Chapter 6: Effector Mechanisms of Cell-Mediated Immunity

Pleiotropism

Ability of one cytokine to produce multiple biological effects on different target cells

Th1

• Main cytokine is IFN-gamma, and IL-12

• Activates macrophages by providing CD40 ligand, and IFN-gamma

• Macrophage responses by producing ROS, NO. Secreting cytokines TNF, IL-12. Increasing B7 costimulators

Th2

• Main cytokine is IL-4 (IgE), IL-5 (eosinophils), IL-13 (peristalsis, mucus secretion)

• Promotes IgE, mast cell, and eosinophils, helminth response (too large for phagocytosis)

Th17

• Main cytokine is IL-17 and IL-22

• Induces inflammation, stimulates secretion of chemokines that attract neutrophils, and monocytes to sites of infection from bacterial or fungal, enhances innate immunity

• Defect in response cause bacterial abscesses in the skin

• Target microorganism in the extracellular space

Tfh

• Main cytokines is IL-21

• Enhances B cell activation in germinal centers

Receptor-Mediated Endocytosis (RME)

Mediates phagocytes by opsonins C3b, and IgG (by IFN-γ) that coat the microbes

Tuberculin Test

Risk category	Positive cutoff	Reason
High risk	≥5 mm	HIV positive, recent contact with TB patient, organ transplant
Increased risk	≥10 mm	IV drug user, children, high-prevalence countries
No known risk factors	≥15 mm	Person with no known risk factors for TB

Type IV Hypersensitivity/Delayed Type Hypersensitivity

Leukocyte recruitment and activation by injecting microbial antigen into skin of individual previously exposed to microbe

Alternative Macrophage (M2)

• Facilitates by IL-4, and IL-13

• Anti-inflammatory effects, wound repair, fibrosis (collagen synthesis)

Atopy

• IgE mediated reaction (type I hypersensitivity) against allergen environment

• Blocking IL-13 is effective in treating severe asthma, and atopic dermatitis (eczema)

Leishmania Major

• Protozoal parasite that lives inside macrophage

• Eliminated by activation of M1 macrophage by Th1 cells, Th2-M2 response is ineffective

Lepromatous Leprosy

• Mycobacterium leprae lives inside macrophage

• Associates with Th2 response that are ineffective so infection cannot be eradicated

Tuberculoid Leprosy

• Associates with Th1 facilitates M1 macrophage response that ultimately eradicated infection

IL-17

• Th17 cytokine

• Leukocyte recruitment

IL-22

• Th17 cytokine

• Maintains integrity of epithelial barriers, stimulates production of defensins (antimicrobial substances)

IL-1, IL-6, IL-23 & TGF-β (Transforming Growth Factor Beta)

Differentiates HTL to Th17

Psoriasis

• Autoimmune and inflammatory skin condition

• Excessive activity of IL-17 (Th17), and IL-23 (Th1)

Inflammatory Bowel Disease (IBD)

Treat with IL-12/IL-23 antagonist (Th1)

Naive CD8 T Cell

• Recognize but cannot kill infected APC

• Requires costimulation, antigen recognition on MHC, and cytokines from HTL

• synthesis of cytotoxic molecules to become activated

Perforin

• Granule proteins that disrupt target cell plasma and endosomal membranes

• Facilitates delivery of granzymes into cytosol

Granzymes

• Granule proteins that cleave and activate caspases (present in cytosol) to induce apoptosis

Fas Ligand (FasL)

• Membrane protein on activated CTL that binds to Fas receptor on target cells

• Activates caspases to induce apoptosis that produces DNA fragmentation

• Does not require granule exocytosis and rarely involves

Pathogen Resistance Mechanisms

• T cell exhaustion: chronic infections leads to CD8 expressing inhibitory receptors to terminate immune response

• HIV virus directly eliminates CD4 cells

• NK cells recognize absence of class I MHC molecules and participates

Factors Determine Differentiation of HTL Subsets

• Type of microbe that triggers

• Area/tissue of the body where the initial exposure occurred

• Cytokines & costimulators

IL-5

• Cytokine of Th2

• Activates eosinophils

IL-4

• Cytokine of Th2

• Stimulates IgE production