Kuby Immunology : Chapter 1

Overview of the Immune System

A historical perspective of immunology

 What is immunity?
 Immunity is the state of protection against
foreign pathogens or substances (antigens)
 Latin term immunis, meaning “exempt,” is the source
of the English word immunity
 Observations of immunity go back over 2000
years
 Thucydides [thoo-sid-i-deez], an ancient historian,
wrote in 430 BC of a plague [pleyg] in Athens where
those who had recovered could safely nurse the
currently ill
 A historical perspective of immunology
 Can we generate immunity
without inducing disease?
YES…through vaccination
 Vaccination prepares the
immune system to eradicate
an infectious agent before it
causes disease
 Widespread vaccine use has
saved many lives
 Classic examples: rabies
vaccine and eradication of
smallpox
A historical perspective of immunology

 A portion of immunity involves both humoral

and cellular components
 Humoral immunity combats pathogens via
antibodies
 Antibodies are produced by B cells
 Antibodies can be transferred between individuals to
provide passive immunity
 Cell-mediated immunity involves primarily T
lymphocytes
 These can eradicate pathogens, clear infected self-
cells, or aid other cells in inducing immunity
A historical perspective of immunology

 Clonal selection
 Individual B and T cells each have an individual
specificity for a single antigen
 This is due to each cell having many copies of a
receptor on their surface that only bind to one type of
antigen
 When a B or T cell interacts with its specific
antigen, it is selected and becomes activated
 Activation results in a proliferation, producing a
large number of clones
 Each clone is reactive against the antigen that initially
stimulated the original lymphocyte
 Important concepts for understanding
the mammalian immune response
 Pathogens fall into four major categories
 Immune responses are quickly tailored to the type of
organism involved
Important concepts for understanding
the mammalian immune response

 Immune responses rely on recognition

molecules
 Germ-line encoded (pattern recognition
receptors, PRRs)
 These bind to pathogen-associated molecular patterns
(PAMPs)―generic molecules found on many different
types of pathogens (e.g., peptidoglycan)
 Randomly generated (B and T cell receptors)
 These bind to very specific antigens, rather than
generic molecules found on many pathogens
Important concepts for understanding
the mammalian immune response

 Humoral and cell-mediated immunity relies

on surface receptors (B and T cell
receptors)
 These are randomly generated by DNA
rearrangements in B and T cells
 Many of these are nonviable and are deleted
during development
Important concepts for understanding
the mammalian immune response

 Tolerance ensures that the immune system

avoids destroying host tissue
 Many of the random rearrangements used to
create B and T cell receptors could be anti-self
 Tolerance helps to keep these anti-self
recognition molecules/cells from circulating in
the bloodstream
 Important concepts for understanding
the mammalian immune response
 In response to pathogens, vertebrate immune
systems use two interconnected systems
 Innate immunity
 Adaptive immunity
Important concepts for understanding
the mammalian immune response

 Innate immune responses

 First line of defense
 Fast, but nonspecific
 Uses germ-line–encoded recognition molecules
 Also uses phagocytic cells
Important concepts for understanding
the mammalian immune response

 Adaptive immune responses

 Humoral and cell-mediate responses
 Using B and T lymphocytes, respectively
 Slower to develop
 5–6 days (or more)
 Use randomly generated antigen receptors
 Highly specific to individual antigen molecules
Important concepts for understanding
the mammalian immune response

 Innate and adaptive immunity work

cooperatively
 Activation of innate immune responses produces
signal molecules (often cytokines)
 These signal molecules stimulate and direct
adaptive immune responses
 Important concepts for understanding
the mammalian immune response
 Memory is the hallmark of adaptive immunity
 Primary response is initiated upon first exposure to an
antigen
 Memory lymphocytes are left
behind after antigen is cleared
 A second exposure to the
same antigen re-stimulates
memory lymphocytes
 Reactivation yields faster,
more significant, better response
 Memory is NOT present in
innate immunity
 The good, bad, and ugly of the
immune system
 Dysfunctions of immunity―two broad
categories
 Overly active or misdirected immune
responses
 Allergies/asthma
 Autoimmune disease (e.g., multiple sclerosis,
Crohn’s disease)
 Immunodeficiency
 Primary (genetic) loss of immune function
 Secondary (acquired) loss of immune function
 Opportunistic infections (e.g., oral thrush) can
occur in people with impaired immune responses
The good, bad, and ugly of the
immune system

 Transplanted tissues
 A rare case where we want to AVOID an
immune response (rejection)
 The body’s natural response to foreign tissue is to
attack it and destroy it
 Cancer
 A situation where the dangerous cells we want
to target are our own self cells
 Generally tolerated and hard to generate immunity
against
Summary
 Immunity is a complex subject, broken down
into many different layers and areas
 This is just a quick summary of the basics of the
field―there’s MUCH more to come!
 Understanding how immunity works allows
us to:
 Exploit it to prevent infections (vaccination)
 Exploit it to treat illness (shutting down
autoimmune disease or ramping up anti-cancer
responses)
 Provide safer organ and tissue transplants