Orientation… Immunology can be studied at the level of molecules, cells, tissues & organs, organ systems & organisms. Can it be studied at the level of populations of organisms? Today, we will be looking at: –( overlooked ) cells, e. g., “natural killer cells –immunological behaviors we have taken for granted, e. g., How do CTL’s kill? –special cellular activities, and e. g., what type of T-cell mediates delayed hypersensitivity e. g., what type of cells participate in “antibody-dependent cell-mediated cytotoxicity” (ADCC) –localization of immunological reactivity in tertiary tissue. i. e., How do cells know where to be present… where they are needed? –physiological responses…

Natural killer cells (aka NK cells)… Related to other lymphocytes Natural killer cells function early Respond to INF-  and INF-  –But not INF- 

Natural killer cells (aka NK cells)… What is the signal –(as opposed to mechanism) Target does not display critical peptide that signals “I am self.” NK cell is stage to kill: –If critical “self” peptide is not present, killing is not suspended; –If critical “self” peptide is present, killing is suspended.

How do CTL’s kill? What is a CTL? –Are there “precursor” forms? –How are they activated? –What is their “target”? Where do they function? i. e., where is their target?

How do CTL’s kill? Distinguish three types of CTL’s –naïve –effector –memory

How do CTL’s kill? ( Finally ), the mechanism….

How do CTL’s kill? CTL’s recirculate: Sequence: association (aka “conjugate formation”) coup de gr  ce go gunning for other targets

“Special” cellular activities…. Delayed-type hypersensitivity An odd mix of specificity and non-specificity… Antigen driven ( thus, specific ) Macrophage is principal mediator ( thus, non-specific ) Granuloma develops…

“Special” cellular activities…. A ntibody D ependent C ell-Mediated C ytotoxicity Specific or non- specific? What is the nature of the “target” cell? ADCC

Localization in the tertiary… There is a series of events: –Stimulus (some sort of offense in some tissue) –Arrival of non- specific effectors (viz. neutrophils) –Arrival of specific effectors (viz. T- lymphocytes.)

Localization in the tertiary… A similar mechanism works with T-cells…

Localization in the tertiary… But how do the T-cells know where to go?

Inflammatory response… In the tertiary sites, an inflammatory response can be mounted. The gross signs of inflammation are: heat, redness, swelling, and pain. If the inflammatory response is properly directed toward a target, the response is beneficial. If inflammation is not controlled, tissue damage may ensue. The damaged tissue contributes to the inflammatory response by signaling that effector cells are needed at that location. Tissue damage leads to the break down of membrane components and, by this means, produces arachidonic acid – CH 3 (CH 2 ) 4 (CH=CHCH 2 ) 4 (CH 2 ) 2 COOH – “[Arachidonic acid] is further metabolized by one of two enzyme pathways into various prostaglandins (by cyclooygenase) or leukotrienes (by lipooxygenase). Both prostaglandins and leukotrienes are highly pro-inflammatory, bronchospastic and vasodilatory.”

Inflammatory response… arachidonic acid (1913) : a liquid unsaturated fatty acid C 20 H 32 O 2 that occurs in most animal fats, is a precursor of prostaglandins, and is considered essential in animal nutrition prostaglandins (1936): any of various oxygenated unsaturated cyclic fatty acids of animals that perform a variety of hormonelike actions (as in controlling blood pressure or smooth muscle contraction. leukotrienes (1980): any of a group of eicosanoids that participate in allergic responses (as constriction of bronchial air passages in asthma) eicosanoid [eicosa- containing 20 atoms (fr. Gk eikosa- twenty) + -noic, suffix used in names of fatty acid...] (1980): any of a class of compounds (as the prostaglandins) derived from polyunsaturated acids (as arachidonic acid) and involved in cellular activity.

Inflammatory response… What’s happening here? What are these “lipid inflammatory mediators”? Answer: products from the membranes of cells in tissues damaged by inflammation. Arachidonic acid metabolites

Extra slide….

spectacular Concluding overview!