Transcript ppt

Immunity to Infection 101:
A superficial overview
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Why do you need a “course” in
Immunology in order to understand
parasitology?
Because parasites invest a great deal of energy in
avoiding the host immune response
Trypanosoma brucei
Trypanosoma cruzi
Crash course in Immunology: Major points:
The immune system is a complex but
understandable network of cells and secreted factors.
This system is most easily understood by
breaking it down into it component parts – keeping in
mind that the parts all work together.
The immune system has choices; an effective
response to a pathogen requires that the immune
system make the correct choices.
Pathogens, including parasites, invest a great
deal of energy in avoiding the host immune response.
Defining Characteristics of
the Immune System
• Discriminates between self and non-self
• Essentially unlimited capacity to respond
specifically to non-self
• Remembers non-self and responds more
vigorously on subsequent encounters
Immune system is probably evolved to deal with infections, to rid the body
of infectious agents, and to prevent reinfection. Pathogens that it cannot
get rid of are trouble.
Immune system: Components
Innate:
macrophages: phagocytosis
complement-mediated lysis
skin, mucosa: barrier
NK cells: altered or missing MHC
neutrophils, eosinophils, mast cells
dendritic cells
Adaptive:
T cells and B cells
dependent on innate to get activated
but much more complex in part because of specificity
often uses the innate as an end effector
Innate Immunity
innate immunity is the initial
response to microbes that
prevents infections and in some
cases eliminates pathogens
the effector mechanisms of
innate immunity are often used to
eliminate microbes even in the
adaptive response (innate often
the first AND the end
responders/effectors)
innate immunity stimulates and
directs adaptive responses
Epithelial Barriers
e.g.
gamma/delta T
cells, NK-T cells
Exceptions – dead
or dying cells
Features of Innate
Immune Recognition
components of the
innate immune response
recognize structures unique to
microbes and required for
their survival (molecular
patterns; pathogen associated
molecular patterns = PAMPs)
these “pattern
recognition receptors” (PRR)
of innate system are germ-line
encoded (therefore not
variable)
Trinchieri and Sher Nature Reviews Immunology 7, 179–190 (March 2007) | doi:10.1038/nri2038
Phagocytosis
Effector functions of macrophages
Role of innate immune responses in defense
1. Local reaction to infection - inflammation - to bring effectors
to the sites of infection
2. Systemic: endocrine actions of cytokines (e.g. fever, increased
leukocyte production)
note: both responses can be damaging
Role of innate immune responses in stimulating adaptive
responses
activate and direct T cell and B cell response
provide the “second signals”
(pathogens which fail to activate innate responses
generate poor acquired response)
Innate and adaptive responses to intracellular pathogens
Exceptions – dead
or dying cells
Phases of an adaptive immune response
Proliferation
Types of
Adaptive
Immunity
cellular and humoral adaptive immunity
humoral immunity: initiated by antigen
recognition by B cells, mediated by antibodies and
effective against extracellular pathogens or their
(toxic) products
cell-mediated immunity: initiated by antigen
recognition by T cells, mediated by T cells and other
downstream effectors (e.g. macrophages), effective
against intracellular pathogens (also important in
transplant rejection and tumor immunity)
Effector
functions of
antibodies
Overview of
Immune
Responses in vivo
Effector function of antibodies
Review points
antibodies are produced by B cells and
plasma cells and perform their effector functions
at sites distant from their production - systemic
prior antigen exposure results in the
activation of long-lived plasma cells that continue
to produce antibodies for many years, and memory
cells which can be reactivated for increased
production upon re-exposure.
cellular and humoral adaptive immunity
humoral immunity: initiated by antigen
recognition by B cells, mediated by antibodies and
effective against extracellular pathogens or their
(toxic) products
cell-mediated immunity: initiated by antigen
recognition by T cells, mediated by T cells and other
downstream effectors (e.g. macrophages), effective
against intracellular pathogens (also important in
transplant rejection and tumor immunity)
Types of CMI: Different types of microbes elicit distinct T cell
responses
1. T cell mediated macrophage activation (Th1 and CD8+ T cells):
activation of phagocytes to kill vaculolarized microbes. Cytokine production
recruits cells (monocytes) and activates them in the site of infection. Final
effector is macrophage. DTH
2. Cytolytic T lymphocyte (CTL): lysis of cells with cytosolic pathogens:
- final effector is the CTL itself. Purpose is to destroy cells harboring
intracellular microbes - viruses, bacteria, protozoans. Cytokines production also
important in many cases.
3. Th2 cells: response to helminth parasites: - especially mast/basophil
and eosinophil mediated responses (allergy)
4. NK cell response - especially early in viral and other infections - role
in destruction of infected cells prior to expansion of CTL. Also important in
destruction of target cells which have down-regulated class I MHC.
Antigens must be “presented” to T cells
Pathways for Class II and Class I presentation of antigens
Immunity to Microbes
• Defense against microbes is mediated by innate
and adaptive immunity
• Response is specialized for particular pathogens
• Survival of pathogens is dependent on immune
evasion
• Tissue injury may result from response to
microbe