MLSCI 475 Immunology Review September 13, 2004

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MLSCI 475Immunology ReviewSeptember 13, 2004

• William Chan, B.Sc. (MLS)
• 1071 Dentistry/Pharmacy Centre
• Tel [phone]
• Email fchan_at_ualberta.ca

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Lecture outline

• Innate immunity
• nonspecific
• Adaptive immunity
• specific
• References
• Goldsby et al, Kuby Immunology, 4th ed, 2000
• Currently 5th ed, 2003
• Janeway et al, Immunobiology, 5th ed, 2001
• Currently 6th ed, 2005

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Hematopoiesis
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Innate immunity
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What is innate immunity?

• Pre-existing, nonspecific host defense mechanisms
• Does not lead to memory
• Very important because it is the first line of
  protection against pathogens
• Collaborates with adaptive immunity

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Cells of innate immunity
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Innate defense mechanisms

• Skin (epidermis, sebum) and mucous membranes
  (mucus, cilia, normal flora)
• Saliva, mucous secretions, tears
• Physiological (fever, acid/basic pH)
• Phagocytes, natural killer cells and interferons
• Inflammation
• Complement system

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Natural killer cells

• Large granular lymphocytes
• responsible for nonspecific killing of virally
  infected cells and tumors

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Missing self hypothesis

• NK cells are activated to kill target cells
  expressing no, few or altered self-MHC molecules
  on cell surface (missing self).

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Interferons
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Inflammation

• Redness, heat, swelling and pain
• Results from tissue damage due to a wound or
  invasion by a pathogen
• Release of cytokines and inflammatory mediators
  causes vasodilation and increases vascular
  permeability, leading to movement of fluids and
  proteins and recruitment of phagocytes into
  tissues

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The inflammatory response
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Importance of inflammation

• Recruitment of additional leukocytes (neutrophils
  and monocytes) to site of injury or infection to
  enhance killing
• Localizes injury/infection
• Promotes tissue repair

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Summary

• Innate immunity is our immune systems first line
  of defense.
• Innate immune responses are nonspecific and do
  not generate memory, but are highly effective.

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Adaptive immunity
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What is adaptive immunity?

• Specific, diverse immune responses that lead to
  memory
• Memory response occurs more quickly and is
  stronger
• Is initiated when a pathogen eludes or is not
  cleared by innate immunity and works in concert
  with innate immunity
• Comprises humoral and cell-mediated immunity
• Response takes several days to develop

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Clonal selection

• Both T and B cells undergo this process
• Specificity of each T and B cell is
  pre-determined prior to antigen exposure
• Antigen exposure leads to clonal expansion, each
  clone sharing the same specificity as the parent
  cell

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Diversity of antigen specificities

• Random gene rearrangement during maturation in
  the bone marrow or thymus helps to create a large
  repertoire of immunoglobulins and T cell
  receptors of unique specificities.

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Importance of gene rearrangement

• Diversity generated from limited gene segments
• Each cell assembles together one set of gene
  segments and therefore has a single specificity
• Rearrangement is irreversible, and the same
  specificity is inherited by all progeny of the
  parent cell

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Antigen recognition

• T cells
• Cannot recognize soluble antigens
• Requires MHC
• B cells
• Able to recognize soluble antigens
• MHC involvement is unnecessary

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Major histocompatibility complex (MHC)

• Important in initiating T cell mediated immune
  responses because T cells recognize antigens
  displayed on MHC molecules

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MHC expression

• Each individual inherits one set of MHC genes
  (ie. a haplotype) from each parent.
• MHC genes are expressed codominantly.

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Antigen presentation
Antigen

• Critical aspect of adaptive immunity
• Endogenous peptides (viruses) are presented via
  MHC class I molecules
• Exogenous peptides (bacteria) are presented via
  MHC class II molecules

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Costimulation
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Anergy

• State of functional unresponsiveness to an
  antigen
• Important as a protective mechanism to prevent
  inappropriate response to an antigen (ie. self
  antigens)

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Humoral immunity

• Depends on activation of B cells, leading to
  their differentiation into plasma cells and
  antibody production
• Type and degree of antibody production depend on
  whether the response is primary or secondary, and
  whether the antigen is T-dependent or
  T-independent

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Functions of antibodies
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Immunoglobulins

• An immunoglobulin molecule is Y-shaped consisting
  of two heavy and two light chains
• Fives classes of immunoglobulins based on
  composition of heavy chain (g, a, m, d and e)
• Light chains are either k or l (21)

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Antibody classes
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B cell activation
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Primary versus secondary antibody responses
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T-independent antigens

• Recognition of antigen (eg. bacterial
  polysaccharides) by B cell provides sufficient
  signaling to trigger B cell activation and
  ultimately antibody production
• Limited response with production of IgM
• No class switching and no memory

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T-dependent antigens

• Antibody production requires two signals
• Production of IgM and IgG (class switching)
• Memory cells are generated

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Summary

• Humoral immunity depends on antibody production
  by B cells.
• Different antibody responses can be generated
  depending on the type of antigen and the type of
  infection.

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Cell-mediated immunity

• Important in host immune response towards viral
  infections and tumors

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T cell activation
T
CD28
TCR
B7
MHC
APC
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T cell help

• CD4 (helper) T cells provide help to certain CD8
  T cells to drive their activation

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Effector function
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Mechanisms of killing

• Perforin/granzymes
• Fas/Fas ligand pathway
• Production of cytokines (IFN-g, TNF-a etc)

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Memory
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Summary

• Cell-mediated immunity is a collaborative effort
  by APCs, helper T cells and cytotoxic T cells.
• Helper T cells are the glue of adaptive immune
  responses.