Adaptive Immunity
Overview: The Immune System
• First Line Intrinsic Barriers
o Physical barriers (skin & mucus membranes)
▪ The bodies first line of defence is provided by the physical barriers of the skin and
mucus membranes, as well as other intrinsic barriers of the mechanical, chemical or
microbiological kind
o Mechanical
▪ Expulsive forces help to rid the body of pathogens before they can attach to and breach
the mucus membranes
▪ Ciliary beating helps to sweep pathogens from the upper and lower airways
▪ Tight junctions in the epithelium prevent pathogens from slipping between cells to enter
underlying host tissue
o Chemical
▪ Low pH barriers prevent pathologic bacterial colonization
▪ Proteolytic enzymes breakdown pathogenic components
o Microbiological
▪ Commensal flora competes with pathogens for resources (space and nutrients)
• Second Line Innate Immunity
o Confer protection against a broad spectrum of pathogens through use of surface receptors on
phagocytic cells the recognize evolutionary conserved patterns unique to pathogens
o Phagocytes
▪ Mainly consist of tissue resident and “wandering” macrophages
▪ Ingested pathogens occupy a phagosome which is then fused with a lysosome to
produce a phagolysome where digestion of pathogen occurs
o NK cells
▪ Do not phagocytose pathogens, rather they secrete toxic chemicals or induce apoptosis
in target cells
o Inflammation
▪ Localize response to infection involving vasodilation, increased vascular permeability
and mobilization of phagocytes involving: leukocytosis, margination, diapedesis and
chemotaxis
o Antimicrobial proteins
▪ Interferons
▪ Compliment
o Fever
▪ A systemic response to widespread infection, resulting in an elevated body temperature
▪ Initiated by the release of pyrogens which include bacterial toxins and/or components,
antigen-antibody complexes or substances released by phagocytes
• Third Line Adaptive Immunity
o Goal is to eliminate pathogens that may have circumvented or overwhelmed the first two lines
of defence and to confer protection from new and emergent strains of pathogens
o Cellular response
▪ Involving targeted killing of infected or abnormal cells and a humoral arm involving the
production of soluble immunoglobulins – or antibodies – that confer protection from
specific
o Humoral response
o The characteristics of the adaptive immune response include: specificity and memory
,Module Outline
• Nature of the adaptive response
• Cells of the adaptive response become immunocompetent
o T cell and b cell education (clonal detection)
o Autoimmunity
• Antigen presentation and MHC
• Adaptive Responses
o Cellular immunity
o Humoral immunity
• Disorders of the Adaptive Response
o Autoimmunity
o Hypersensitivity Reactions
▪ Focus: Type I response (anaphylaxis)
o Acquired Immunodeficiency Syndrome
▪ Focus: HIV/AIDS
Adaptive Immunity
• The hallmarks of the adaptive immune response include:
o Specificity (self vs non-self)
▪ The ability to amount a response to a particular pathogen or foreign substance while
being able to discriminate between self vs non-self-antigens
▪ Consequence: the B-cell illustrated here may only be capable of mounting a response to
one particular strain of pathogen without recognizing any of a number of closely related
pathogens
o Memory
▪ Ability to recall past exposures to specific pathogens and provides the adaptive immune
system with the ability to mount an even stronger response to a pathogen upon repeat
exposure
▪ The “immunologic memory” provides the basis for protection offered by vaccinations
• In a vaccinated individual, the immune response may be so quick and roust that
they may not even exhibit signs or symptoms of infection
Innate vs Adaptive Immunity
Innate Adaptive
Broad specificity Narrow specificity
- recognized broadly conserved PAMPs - recognises very specific antigenic
determinants
,- pathogen associated molecular patterns - both B-cell and T-cell receptors recognize
(PAMPs) are often located on structures that very specific antigenic determinants that may
are essential for pathogen survival and be specific for only one particular strain of
accessible to host pattern-recognition pathogen
receptors (PRRs) such as the toll-like - These antigenic determinants can be any
receptors (TLRs) which are present on protein on the pathogen and may not be
phagocytes essential for pathogen survival
- TLRs recognize PAMPs that are common to
broad classes of organisms (e.g. TLR-4
recognizes LPS which is a component of the
outer cell wall of all Gram negative bacteria)
Limited repertoire Vast repertoire
- PRRs are encoded in the host germ line - B-cell and T-cell receptors which recognize
DNA< limiting the absolute number of PAMPs antigenic determinants are produced
for which PRRs are produced through somatic recombination (mixing,
- furthermore, if pathogens modify their matching and recombining) of host gene
PAMPs (e.g. bacterium changes the structure segments, resulting in the generation of T-
of its LPS), then the host PRRS will not mount cell and B0cell receptors that can detect
a response virtually any antigenic determinant
Immediate response Slow response
- components are preformed - initiated by antigen-presenting cells (APC)
which travel from the site of infection to a
nearby lymph node where
immunocompetent cells of the adaptive
immune system reside
This process involves antigen presentation,
differentiation and clonal expansion of T-cell
and/or B-cells resulting in a cellular or
humoral response
- since many steps are involved in evoking an
adaptive response, this process may take 3-5
days following initial infection
Lack memory Memory
- does not ‘remember’ previous encounters - hallmark
with pathogens - It is conferred by a subset of memory cells
- it will respond to infection with the same that are produced during each adaptive
pathogen in the same manner it has done so response
in the past - these memory cells ensure that there is a
large reservoir of differentiated cells ready to
quell infections mediated by previously
encountered pathogens
, Origin of the Adaptive Response
• Initiation of an adaptive response occurs in the secondary
lymphoid tissues which include:
o Spleen
▪ Acts to filter the blood of pathogens
o MALT (mucosal associated lymphoid tissue)
▪ A loss aggregation of lymphoid tissue that is in
a unique position to eliminate pathogens at
the mucosal surfaces before they spread to
underlying tissues
▪ Includes adenoids, tonsils, and payer’s patches
of the gut
▪ May also be found within the respiratory tract
and genitourinary tracts as well as the
appendix
o Lymph nodes
▪ Provide immune surveillance of lymphatic fluid
returning from the tissues
▪ More than one thousand lymph nodes situated at strategic locations throughout the
body
▪ During infection, lymph nodes may become swollen and can be detected virtually or by
palpation
▪ Extremely important in initiating and coordinating the adaptive immune response as
they facilitate a rapid interaction amongst immune cells and between immune cells and
pathogens
Lymph Nodes
• Lymphatic fluids collected from tissues enter the lymph
nodes via several afferent lymphatic vessels and leave by
a limited number of efferent vessels
• This arrangement acts to slow the flow of lymph, thereby
ensuring that resident T-cells and B-cells have adequate
time to interact with incoming pathogens
• Lymph nodes also contain macrophages and dendritic
cells that have migrated from infected tissues;
representing the point where the innate and adaptive
immune systems interact
• During times of infection, lymph nodes may contain actively proliferating B-ells, which are largely
found within the germinal centers of the cortex
• These b-cells will differentiate into anti-body-secreting plasma cells and migrate to the medulla or
enter body tissues where they carry out their immune functions
Cells of Adaptive Immunity
• The adaptive immune response is mediated by two cells types – namely B-cells and T-cells
Overview: The Immune System
• First Line Intrinsic Barriers
o Physical barriers (skin & mucus membranes)
▪ The bodies first line of defence is provided by the physical barriers of the skin and
mucus membranes, as well as other intrinsic barriers of the mechanical, chemical or
microbiological kind
o Mechanical
▪ Expulsive forces help to rid the body of pathogens before they can attach to and breach
the mucus membranes
▪ Ciliary beating helps to sweep pathogens from the upper and lower airways
▪ Tight junctions in the epithelium prevent pathogens from slipping between cells to enter
underlying host tissue
o Chemical
▪ Low pH barriers prevent pathologic bacterial colonization
▪ Proteolytic enzymes breakdown pathogenic components
o Microbiological
▪ Commensal flora competes with pathogens for resources (space and nutrients)
• Second Line Innate Immunity
o Confer protection against a broad spectrum of pathogens through use of surface receptors on
phagocytic cells the recognize evolutionary conserved patterns unique to pathogens
o Phagocytes
▪ Mainly consist of tissue resident and “wandering” macrophages
▪ Ingested pathogens occupy a phagosome which is then fused with a lysosome to
produce a phagolysome where digestion of pathogen occurs
o NK cells
▪ Do not phagocytose pathogens, rather they secrete toxic chemicals or induce apoptosis
in target cells
o Inflammation
▪ Localize response to infection involving vasodilation, increased vascular permeability
and mobilization of phagocytes involving: leukocytosis, margination, diapedesis and
chemotaxis
o Antimicrobial proteins
▪ Interferons
▪ Compliment
o Fever
▪ A systemic response to widespread infection, resulting in an elevated body temperature
▪ Initiated by the release of pyrogens which include bacterial toxins and/or components,
antigen-antibody complexes or substances released by phagocytes
• Third Line Adaptive Immunity
o Goal is to eliminate pathogens that may have circumvented or overwhelmed the first two lines
of defence and to confer protection from new and emergent strains of pathogens
o Cellular response
▪ Involving targeted killing of infected or abnormal cells and a humoral arm involving the
production of soluble immunoglobulins – or antibodies – that confer protection from
specific
o Humoral response
o The characteristics of the adaptive immune response include: specificity and memory
,Module Outline
• Nature of the adaptive response
• Cells of the adaptive response become immunocompetent
o T cell and b cell education (clonal detection)
o Autoimmunity
• Antigen presentation and MHC
• Adaptive Responses
o Cellular immunity
o Humoral immunity
• Disorders of the Adaptive Response
o Autoimmunity
o Hypersensitivity Reactions
▪ Focus: Type I response (anaphylaxis)
o Acquired Immunodeficiency Syndrome
▪ Focus: HIV/AIDS
Adaptive Immunity
• The hallmarks of the adaptive immune response include:
o Specificity (self vs non-self)
▪ The ability to amount a response to a particular pathogen or foreign substance while
being able to discriminate between self vs non-self-antigens
▪ Consequence: the B-cell illustrated here may only be capable of mounting a response to
one particular strain of pathogen without recognizing any of a number of closely related
pathogens
o Memory
▪ Ability to recall past exposures to specific pathogens and provides the adaptive immune
system with the ability to mount an even stronger response to a pathogen upon repeat
exposure
▪ The “immunologic memory” provides the basis for protection offered by vaccinations
• In a vaccinated individual, the immune response may be so quick and roust that
they may not even exhibit signs or symptoms of infection
Innate vs Adaptive Immunity
Innate Adaptive
Broad specificity Narrow specificity
- recognized broadly conserved PAMPs - recognises very specific antigenic
determinants
,- pathogen associated molecular patterns - both B-cell and T-cell receptors recognize
(PAMPs) are often located on structures that very specific antigenic determinants that may
are essential for pathogen survival and be specific for only one particular strain of
accessible to host pattern-recognition pathogen
receptors (PRRs) such as the toll-like - These antigenic determinants can be any
receptors (TLRs) which are present on protein on the pathogen and may not be
phagocytes essential for pathogen survival
- TLRs recognize PAMPs that are common to
broad classes of organisms (e.g. TLR-4
recognizes LPS which is a component of the
outer cell wall of all Gram negative bacteria)
Limited repertoire Vast repertoire
- PRRs are encoded in the host germ line - B-cell and T-cell receptors which recognize
DNA< limiting the absolute number of PAMPs antigenic determinants are produced
for which PRRs are produced through somatic recombination (mixing,
- furthermore, if pathogens modify their matching and recombining) of host gene
PAMPs (e.g. bacterium changes the structure segments, resulting in the generation of T-
of its LPS), then the host PRRS will not mount cell and B0cell receptors that can detect
a response virtually any antigenic determinant
Immediate response Slow response
- components are preformed - initiated by antigen-presenting cells (APC)
which travel from the site of infection to a
nearby lymph node where
immunocompetent cells of the adaptive
immune system reside
This process involves antigen presentation,
differentiation and clonal expansion of T-cell
and/or B-cells resulting in a cellular or
humoral response
- since many steps are involved in evoking an
adaptive response, this process may take 3-5
days following initial infection
Lack memory Memory
- does not ‘remember’ previous encounters - hallmark
with pathogens - It is conferred by a subset of memory cells
- it will respond to infection with the same that are produced during each adaptive
pathogen in the same manner it has done so response
in the past - these memory cells ensure that there is a
large reservoir of differentiated cells ready to
quell infections mediated by previously
encountered pathogens
, Origin of the Adaptive Response
• Initiation of an adaptive response occurs in the secondary
lymphoid tissues which include:
o Spleen
▪ Acts to filter the blood of pathogens
o MALT (mucosal associated lymphoid tissue)
▪ A loss aggregation of lymphoid tissue that is in
a unique position to eliminate pathogens at
the mucosal surfaces before they spread to
underlying tissues
▪ Includes adenoids, tonsils, and payer’s patches
of the gut
▪ May also be found within the respiratory tract
and genitourinary tracts as well as the
appendix
o Lymph nodes
▪ Provide immune surveillance of lymphatic fluid
returning from the tissues
▪ More than one thousand lymph nodes situated at strategic locations throughout the
body
▪ During infection, lymph nodes may become swollen and can be detected virtually or by
palpation
▪ Extremely important in initiating and coordinating the adaptive immune response as
they facilitate a rapid interaction amongst immune cells and between immune cells and
pathogens
Lymph Nodes
• Lymphatic fluids collected from tissues enter the lymph
nodes via several afferent lymphatic vessels and leave by
a limited number of efferent vessels
• This arrangement acts to slow the flow of lymph, thereby
ensuring that resident T-cells and B-cells have adequate
time to interact with incoming pathogens
• Lymph nodes also contain macrophages and dendritic
cells that have migrated from infected tissues;
representing the point where the innate and adaptive
immune systems interact
• During times of infection, lymph nodes may contain actively proliferating B-ells, which are largely
found within the germinal centers of the cortex
• These b-cells will differentiate into anti-body-secreting plasma cells and migrate to the medulla or
enter body tissues where they carry out their immune functions
Cells of Adaptive Immunity
• The adaptive immune response is mediated by two cells types – namely B-cells and T-cells
