34

Adaptive Immunity

1
Copyright © McGraw-Hill Global Education Holdings, LLC. Permission required for reproduction or display.
 Overview of Specific
(Adaptive) Immunity
• Three major functions
– recognize nonself
– respond to nonself
• effector response
– eliminates or renders foreign material harmless
• anamnestic response
– upon second encounter with same pathogen
immune system mounts a faster and more
intense response
– remember nonself
2
Acquired Immune System Development
• B and T cells initially
arise in the bone
marrow
– B cells continue to
mature there
– T cells are moved to
the thymus for
further maturation
• Both cell types go
through extensive
screening to avoid
self-reactivity
3
 Four Characteristics of
Specific Immunity
• Discrimination between self and non-self
– usually responds selectively to non-self, producing
specific responses against the stimulus
• Diversity
– generates enormous diversity of molecules
• Specificity
– can be directed against one specific pathogen or
foreign substance among trillions
• Memory
– response to a second exposure to a pathogen is so
fast that there is no noticeable pathogenesis 4
 Types of Specific Immunity
• Humoral immunity
– also called antibody-
mediated immunity
– based on antibody
activity
• Cellular immunity
– also called cell-
mediated immunity
– based on action of
specific kinds of T
lymphocytes

5
 Antigens
• Self and nonself substances that elicit an immune
response and react with products of that response
• Most are large, complex molecules
• Antigenic determinant sites (epitopes)
– site on antigen that reacts with specific antibody or T
cell receptor
– valence is number of epitopes on an antigen
• Antibody affinity
– strength with which antibody binds to its antigen at a
given antigen-binding site
• Avidity of antibody
– overall antigen-binding at all antigen binding sites 6
Haptens
• Small organic molecules
• Not antigenic but may
become antigenic when
bound to larger carrier
molecule
– e.g., penicillin
– may elicit hapten
specific and carrier
specific responses

7
 Types of Specific Immunity
• Naturally acquired active immunity
– type of specific immunity a host develops after
exposure to foreign substance
• Naturally acquired passive immunity
– transfer of antibodies, e.g., mother to fetus across
placenta, mother to infant in breast milk
• Artificially acquired active immunity (vaccination)
– intentional exposure to a foreign material
• Artificially acquired passive immunity
– preformed antibodies or lymphocytes produced by
one host are introduced into another host 8
9
 Recognition of Foreignness
• Distinguishing between self and non-self is
essential for the proper functioning of the
immune system
– this allows for selective destruction of invading
pathogens without destruction of host tissues
– involves major histocompatibility complex

10
 Major Histocompatibility
Complex (MHC)
• Collection of genes that code for self/nonself
recognition potential of a vertebrate
• In humans, called human leukocyte antigen
(HLA) complex
– on chromosome 6
– three classes of MHC molecules
– one paternal allele and one maternal allele

11
 Major Histocompatibility
Complex (MHC)
• Class I molecules found on almost all types of
nucleated cells
– important for organ transplantation
• Class II molecules found only on antigen
presenting cells
– required for T cell communication to
macrophages, dendritic cells, B cells
• Class III molecules include secreted proteins
not required for self/nonself recognition
12
13
 MHC and Antigen Processing
• Class I and Class II bind to antigens in the cell
– endogenous antigen processing
• class I binds to antigen peptides that originate in the
cytoplasm and present antigen to CD8+ T cells
– exogenous antigen processing
• class II binds to antigen fragments that come from
outside the cell and present to CD4+ T helper cells

14
 Cluster of Differentiation Molecules
(CDs)

• Membrane proteins on lymphocytes and other cells

– have specific roles in intercellular communication
– used to identify and differentiate between leukocyte
subpopulations
• e.g., CD4 is the cell surface receptor for HIV 15
 T-Cell Biology
• Major players in cell-mediated immune
response
• Originate from CD34+ stem cells in the bone
marrow but mature in thymus
• Have major role in B cell activation
• Immunologically specific and function in a
variety of regulatory and effector ways

16
 T-Cell Receptors
(TCRs)
• Reside in the plasma
membrane surface
• Recognize and bind
fragments of antigens
• Antigen fragments must be
presented by antigen-
presenting cells (APCs) on
the ends of MHC molecules

17
 T Cell Activation
• Requires binding a specific
antigen
– occurs through antigen
presentation bridging MHC
class II on the APC to the
TCR on the T cell
– initiates signaling cascade
involving other membrane-
bound proteins and
intracellular messengers
– second signal required for
lymphocyte proliferation,
differentiation, and
expression of specific
cytokine genes 18
• Mature T cells are Types of T Cells
naïve until activated by
antigen presentation
• Once activated they
proliferate into effector
cells and memory cells
– effector cells carry out
specific functions to
protect host
– three types
• T helper (TH),
cytotoxic T
lymphocytes (TCs),
and regulatory T
cells 19
 T-Helper Cells
• Also known as CD4+ T cells
• Activated by antigen presentation with class II
MHC
• Subdivisions of T helper cells
– TH0 – undifferentiated T cells
– TH1 – help activate macrophages
– TH2 – help B cells produce antibodies
– TH17 – assist in antibacterial responses
– Treg – help control lymphocyte responses

20
 T Helper Cells
• TH1 cells
– promote cytotoxic T cell activity and activate
macrophages
– mediate inflammation and delayed hypersensitivity by
producing a specific set of cytokines
• IL-2, IFN-γ, tumor necrosis factor (TNF)-β
• TH2 cells
– stimulate antibody responses and defend against
helminth parasites
– involved in promoting allergic reactions
– produce a specific set of cytokines
• IL-5, IL-6, IL-10, and IL-13 21
 Cytotoxic T Cells (TCs)
• Are CD8+ T cells that have been activated by
antigen presented on MHC-1 molecules of
nucleated cells
• Once activated these CTLs can kill target
cells that have the same antigen-MHC-1
combination that originally activated the CTL
• After bind target, CTL kills target cell via the
perforin pathway and CD95 pathway

22
 Regulatory T Cells
• Treg cells
– derived from approximately 10% of CD4+ T
cells and 2% of CD8+ T cells
– IL-10 induces regulatory function by inhibiting
T helper cell function
– Tregs also suppress/regulate functions by
secretion of IL-9 and TGF-β

23
24
 Superantigens
• Bacterial and viral proteins
– staphylococcal enterotoxin B
– the toxin that causes toxic shock syndrome
– mouse tumor virus superantigen
– putative proteins from Epstein-Barr and rabies viruses
• Stimulate stronger immune response than normal
antigens by “tricking” T cells into activation although
they have not been triggered by a specific antigen
• Stimulate T cells to proliferate nonspecifically
• Contribute to microbial pathogenicity
• stimulate release of massive quantities of cytokines
from T cells
– may result in circulatory shock and multiorgan failure 25
 B-Cell Biology
• B cells must be activated by a specific
antigen to continue mitosis
– cells then replicate and differentiate into
plasma cells which secrete antibodies
• B cells have immunoglobulin receptors for the
specific antigen that will activate that
particular B cell
– these receptors associate with other proteins
and are called B-cell receptors (BCRs)
• Interaction with that antigen is communicated
to the nucleus via a signal transduction
pathway similar to that described for T cells
26
27
 B-Cell Activation
• Leads to proliferation and differentiation into
plasma cells
– some cytokines produced by helper T cells
can act on B cells and assist in growth and
differentiation
• Typically antigen-specific
• Two mechanisms for antigen-specific
activation
– T dependent
– T independent

28
 T-Dependent
Antigen Triggering
• Like T cells, require
two signals
– antigen-BCR specific
interaction
– activated T helper 2
binds B cell
presented antigen
and secretes B cell
growth factors
• B cell differentiates
into plasma cell and
memory cell 29
 T-Independent Antigen
Triggering
• T-independent antigens
– polymeric antigens with large number of
identical epitopes (e.g., bacterial
lipopolysaccharides)
• Less effective than T-dependent B cell
activation
– antibodies produced have a low affinity for
antigen
– no memory B cells formed

30