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Innate defense acts as first line of defense

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Title: Innate defense acts as first line of defense


1
Innate Defenses Antigen Recognition
  • Innate defense acts as first line of defense
  • The immediate defense of the body against an
    invasion must be in the hands of preformed
    molecules, already present constitutively
  • These molecules must be part of the innate immune
    system.

2
Innate Defenses Antigen Recognition
  • The innate immune system functions by recognizing
    highly conserved sets of molecules
  • These molecular structures are specific to the
    microbes (pathogen-associated molecular patterns,
    or PAMPs) through a limited set of germ line
    encoded receptors called pattern-recognition
    receptors (PRRs)
  • Adaptive immune system uses T -cell receptors
    (TCRs) and B -cell receptors (BCRs) with the
    ability to recognize a large spectrum of antigens
  • There are several distinct classes of PRRs, each
    of which is involved in performing specific tasks
  • These include opsonization, activation of
    complement cascade, phagocytosis, etc.

3
Innate Defenses Antigen Recognition(PRRs)
  • First, PRRs recognize microbial components, known
    as pathogen-associated molecular patterns
    (PAMPs), that are essential for the survival of
    the microorganism and are therefore difficult for
    the microorganism to alter
  • Second, PRRs are expressed constitutively in the
    host and detect the pathogens regardless of their
    life-cycle stage
  • Third, PRRs are expressed on all cells of a given
    type, and independent of immunologic memory
  • Different PRRs react with specific PAMPs, show
    distinct expression patterns, activate specific
    signaling pathways, and lead to distinct
    antipathogen responses
  • The basic machineries underlying innate immune
    recognition are highly conserved among species,
    from plants and fruit flies to mammals

4
Innate Defenses Antigen Recognition (TLRs)
  • A class of PRRs called Toll-like receptors (TLRs)
    has the ability to recognize pathogens or
    pathogen-derived products and initiate signaling
    events leading to activation of innate host
    defenses
  • Signaling by TLRs initiates acute inflammatory
    responses by induction of anti-microbial genes
    and inflammatory cytokines and chemokines
  • Subsequent events, such as recruitment of
    neutrophils and activation of macrophages, lead
    to direct killing of the microbes
  • The notion of TLRs is primary sensors of
    pathogens and responsible for orchestrating the
    innate responses
  • TLRs contribute significantly to activation of
    adaptive immune responses

5
Innate Defenses Antigen Recognition
  • There are 10 TLRs, named TLRs 110, known in
    mammals
  • These receptors recognizes molecules derived from
    a unique class of microbial agents
  • TLR4, for example, recognizes lipopolysaccharide
    (LPS), which is unique to Gram-negative bacteria
  • TLR2 recognizes peptidoglycan, which is abundant
    in Gram-positive bacteria
  • TLR3 recognizes double-stranded RNA from
    double-stranded viruses
  • TLR7 and 8 recognize RNA from single-stranded
    viruses
  • TLR9 recognizes unmethylated CpG DNA found
    abundantly in prokaryotic genomes and DNA viruses

6
Host-Pathogen Interplay
  • Despite this armory of ready-made weapons, the
    fact that specific immune antibody is required to
    prevent some infections
  • Often this is because the invading organism has
    evolved some mechanisms for escaping destruction
  • Examples of this include the capsule of certain
    bacteria which prevents innate recognition. Some
    species of bacteria and protozoa actually welcome
    phagocytosis, having devised means of surviving
    inside the phagosome or cytoplasm of the cell,
    phagocytosis helps hide them from other immune
    mechanisms
  • Because of their short generation times pathogens
    will always hold an advantage in the cat and
    mouse game of immunity.

7
Adaptive immune responseCells Associated
  • T cells
  • B cells
  • Dendritic Cells
  • Other Effector cells

8
Adaptive Defenses T Lymphocytes
  • T lymphocytes constitute the "cellular" arm of
    acquired/specific immunity
  • T lymphocytes play a central role in controlling
    the acquired immune response
  • serve as crucial effector cells through antigen
    specific cytotoxic activity and the production of
    soluble mediators called lymphokines (the
    cytokines produced by lymphocytes)
  • There are two major subsets of T lymphocytes that
    differ in effector function, MHC restriction and
    accessory molecule usage

9
Adaptive DefensesT cell receptors
  • T lymphocytes express a clonal antigen-specific
    receptor
  • Each T cell posses just one type of receptor, so
    that all of the receptors from one cell can only
    recognize one antigen
  • The T cell receptor (TCR) is in fact very similar
    to Immunoglobulin
  • It has 2 paired polypeptide chains both of which
    have constant and variable portions and both of
    which are composed of immunoglobulin-like domains
  • Two important differences are
  • a) TCR is monovalent
  • b) It exists only as a cell surface receptor and
    has no counterpart to secreted antibody
  • Unlike immunoglubolin, they are MHC restricted

10
Adaptive DefensesT cell receptors
11
Adaptive DefensesT cell receptors
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