MLSCI 475 Immunology Review September 13, 2004 - PowerPoint PPT Presentation
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MLSCI 475 Immunology Review September 13, 2004
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Email: fchan_at_ualberta.ca. Lecture outline. Innate immunity. nonspecific. Adaptive immunity ... Very important because it is the first line of protection ... – PowerPoint PPT presentation
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Title: 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 492-3945
- 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.
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