Orientation

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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 CTLs 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

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Natural killer cells (aka NK cells)

• Related to other lymphocytes
• Natural killer cells function early
• Respond to INF-? and INF-?
• But not INF-?

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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.

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How do CTLs 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?

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How do CTLs kill?

• Distinguish three types of CTLs
• naïve
• effector
• memory

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How do CTLs kill?

• (Finally), the mechanism.

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How do CTLs kill?

• CTLs recirculate

• Sequence
• association
• (aka conjugate formation)
• coup de gr?ce
• go gunning for other targets

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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
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Special cellular activities.

• ADCC

• Antibody Dependent Cell-Mediated Cytotoxicity
• Specific or non- specific?
• What is the nature of the target cell?

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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.)

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Localization in the tertiary

• A similar mechanism works with T-cells

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Localization in the tertiary

• But how do the T-cells know where to go?

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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
  CH3(CH2)4(CHCHCH2)4(CH2)2COOH
• 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.

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Inflammatory response

• arachidonic acid (1913) a liquid unsaturated
  fatty acid C20H32O2 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.

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Inflammatory response

• Whats happening here?
• What are these lipid inflammatory mediators?
• Answer products from the membranes of cells in
  tissues damaged by inflammation.

Arachidonic acid metabolites
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Extra slide.
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spectacular Concluding overview!