5. adaptive immune system

ADAPTIVE IMMUNE SYSTEM
PHYSIOLOGY: IMMUNO & HEME

ANTIBODIES
OVERVIEW
‣ Antibodies, or immunoglobulins, are Y-shaped glycoproteins
produced by differentiated B-cells called plasma cells
‣ They are present in bodily fluids, secretions and on the surface of B-
cells
‣ Antibodies recognize and bind to unique epitopes, which are
molecular structures on the surface of their cognate antigens
‣ Learning Goal
‣ To consider antibody structure, function, classes and clinical
relevance

ANTIBODIES
STRUCTURE: HEAVY AND LIGHT CHAINS
‣ Antibody molecules consist of two identical heavy chains and two
identical light chains, which consequently give the antibody
two antigen-binding sites
‣ Disulphide bonds bind the heavy chains to each other and to the light
chains
‣ The heavy and light chains consist of several amino-acid sequences;
each corresponding to a protein domain
‣ Proteins domains are the functional units of the antibody and
correspond to a discrete, folded region of protein structure and so are
relevant in antibody engineering

ANTIBODIES
STRUCTURE: HEAVY AND LIGHT CHAINS
‣ Each light chain has two domains (one variable and one constant), and each heavy
chain has four (one variable and three constant)
‣ There are five heavy chain types:
‣ μ (Mu), γ (Gamma), α (Alpha), ε (Epsilon) and δ (Delta)
‣ Which classify IgM, IgG, IgA, IgE and IgD respectively
‣ There are two light chain types:
‣ κ (kappa) and λ (lambda)
‣ Each antibody can have either two κ or two λ chains but not one of each
‣ The ratio of κ and λ is 2:1
‣ There are no functional differences between the types

ANTIBODIES
STRUCTURE: FC AND FAB REGIONS
‣ Each antibody contains two variable regions and one constant
region
‣ The Fab regions (fragment antigen binding) contain
the variable domains of the light and heavy chains
‣ The variable domains make up the variable regions of the antibody
which give the antibody its antigen specificity
‣ Therefore, these regions differ between antibodies
‣ Each Fab region also contains two constant domains; one from the
heavy chain component and one from the light chain component

ANTIBODIES
STRUCTURE: FC AND FAB REGIONS
‣ The Fc region (fragment crystallizable) consists of the remaining constant domains
from the two heavy chains
‣ The Fc region interacts with different immune cells and mediates various functions
‣ Eg. opsonization
‣ The constant region involves the constant domains from both the Fab and Fc parts
‣ The heavy chain constant domains determine antibody class and are the same for
all antibodies of the same class
‣ IgA and IgG antibodies also have hinge regions, which are flexible amino-acid
chains in the central part of the heavy chains

https://teachmephysiology.com/immune-system/adaptive-immune-system/antibodies/

ANTIBODIES
CLASSIFICATION
‣ Antibodies are classified according to heavy chain type, which is encoded by a gene on
chromosome 14
‣ The different classes are IgG, IgA, IgM, IgD and IgE
‣ (in descending order of abundance in serum)
‣ IgG
‣ IgG is the most abundant antibody class
‣ It is present on the surface of mature B-cells and in serum
‣ There are four subclasses: IgG1, IgG2, IgG3 and IgG4 (in order of serum concentration)
‣ IgG is the only antibody to cross the placenta and so it transfers passive immunity from
mother to fetus
‣ Newborns have high IgG concentrations in the first 3-6 months of life

ANTIBODIES
CLASSIFICATION
‣ IgA
‣ IgA is the most prevalent antibody in secretions, such as saliva and
mucous
‣ There are two subclasses, IgA1 and IgA2
‣ IgA forms a dimer, where a joining chain connects 2 Y-shaped molecules,
giving it four antigen-binding sites in total
‣ IgA antibodies are resistant to enzymatic digestion and act principally
as neutralizing antibodies
‣ Breast milk and colostrum have high levels of IgA which coat the
digestive tract and protect against infections in breast-fed babies

ANTIBODIES
CLASSIFICATION
‣ IgA cont…
‣ In adults, IgA forms a barrier layer at mucosal surfaces to prevent
pathogenic invasion
‣ Plasma cells in the lamina propria produce excessive amounts of polymeric
IgA which then moves by endocytosis through the epithelial layer to be
secreted at the luminal side
‣ IgA neutralizes pathogens and hinders their attachment to epithelial
receptors by binding to their ligands on pathogens or toxins
‣ IgA molecules can also cross-link polyvalent antigens or pathogens,
forming antigen-antibody complexes which are then trapped in the mucus
layer and cleared through peristalsis

ANTIBODIES
CLASSIFICATION
‣ IgM
‣ IgM antibodies are expressed on the surface of B-cells as monomers
but secreted as pentameters
‣ A pentameter has five antibodies connected by a joining chain,
with ten antigen-binding sites in total
‣ It is the first immunoglobulin produced during fetal development and
the first to be produced by B-cells against a new infection
‣ IgM has high avidity, meaning the antibody-antigen complex is
strong, but low affinity, so the strength of a single epitope-antibody
interaction is weak

ANTIBODIES
CLASSIFICATION
‣ IgD
‣ IgD is present on the surface of B-cells
‣ It has a role in B-cell and antibody production
‣ All naive B cells express IgD and IgM
‣ IgE
‣ IgE is mainly found on mast cells but is also present at low levels in the blood and
extracellular fluid
‣ It is associated with allergy, particularly type I hypersensitivity reactions, including atopic
disease (e.g. asthma and dermatitis) and anaphylaxis
‣ It triggers histamine release from mast cells and basophils
‣ IgE is also part of the body’s response to parasitic infections

ANTIBODIES
FUNCTION
‣ The Fc region binds different immune cell receptors (e.g.
on phagocytes) and mediates various effector functions
‣ Opsonization
‣ Antibodies (mainly IgG1 and IgG3) can act as opsonins
by binding to the pathogen, which allows better
recognition by phagocytes
‣ Phagocytes then bind to the antibodies via their Fc
receptors and initiate phagocytosis

ANTIBODIES
FUNCTION
‣ Neutralisation
‣ Antibodies can prevent pathogens from accessing cells by
blocking different parts of the bacterial or viral cell surface
‣ Consequently, this neutralizes certain viruses and bacterial
toxins
‣ Neutralizing antibodies must have high affinity to be
effective
‣ IgG and IgA antibodies have the greatest effect

ANTIBODIES
FUNCTION
‣ Complement Activation
‣ The classical complement pathway can be activated by
IgM or IgG antibodies when they bind microbial surfaces
‣ This releases C3b, which acts as an opsonin, and other
complement components which make up the membrane
attack complex
‣ MAC punches holes in the pathogen plasma membrane
which leads to cell lysis and death

ANTIBODIES
FUNCTION
‣ Immune Complexes
‣ The binding of multiple antigens and antibodies
together can form immune complexes
‣ Complex formation limits the antigens’ diffusing ability,
making it easier for phagocytes to find and ingest
pathogens through phagocytosis

ANTIBODIES
FUNCTION
‣ Antibody-Dependent Cell-Mediated Cytotoxicity
‣ Antibodies bind and opsonize target cells
‣ Natural killer cells then recognize the Fc portion of the
antibody and release cytotoxic granules (perforin and
granzymes) into the target cell which trigger apoptosis
‣ They also release interferons, which attracts
phagocytes

ANTIBODIES
REVIEW QUESTIONS
‣ What is the most abundant class of antibody?
‣ IgG
‣ IgM
‣ IgA
‣ IgD

ANTIBODIES
REVIEW QUESTIONS
‣ Which class of antibody is secreted in breastmilk?
‣ IgM
‣ IgA
‣ IgE
‣ IgG

ANTIBODIES
REVIEW QUESTIONS
‣ Anti-thyrotropin receptor antibodies are associated with
which autoimmune disease?
‣ Coeliac disease
‣ Rheumatoid arthritis
‣ Graves’ disease
‣ Lupus

ANTIBODIES
REVIEW QUESTIONS
‣ Which two classes of antibodies are expressed by all naïve
B cells?
‣ IgG and IgA
‣ IgM and IgE
‣ IgD and IgA
‣ IgM and IgD

ANTIBODIES
REVIEW QUESTIONS
‣ What is opsonization ?
‣ Preventing pathogens from entering cells
‣ Making pathogens more susceptible to phagocytosis
‣ Attracting natural killer cells to destroy pathogens
‣ Forming a complex with an antigen

ANTIBODIES
REVIEW QUESTIONS
‣ What is opsonization ?
‣ Preventing pathogens from entering cells
‣ Making pathogens more susceptible to
phagocytosis
‣ Attracting natural killer cells to destroy pathogens
‣ Forming a complex with an antigen

ANTIBODIES
REVIEW QUESTIONS
‣ Which type hypersensitivity reaction is IgE associated
with?
‣ Type I
‣ Type II
‣ Type III
‣ Type IV

ANTIGEN PROCESSING
AND PRESENTATION

ANTIGEN PROCESSING AND PRESENTATION
OVERVIEW
‣ T cells can only recognize antigens when they are displayed on cell surfaces
‣ This is carried out by Antigen-presenting cells (APCs), the most important of
which are dendritic cells, B cells and macrophages
‣ APCs can digest proteins they encounter and display peptide fragments
from them on their surfaces for another immune cell to recognize
‣ This process of antigen presentation allows T cells to “see” what proteins are
present in the body and to form an adaptive immune response against them
‣ Learning Goal
‣ To discuss antigen processing, presentation and recognition by T cells

ANTIGEN PRESENTATION
‣ Antigens are delivered to the surface of APCs by Major Histocompatibility
Complex (MHC) molecules
‣ Different MHC molecules can bind different peptides
‣ The MHC is highly polygenic and polymorphic which equips us to recognize a
vast array of different antigens we might encounter
‣ There are different classes of MHC, which have different functions:
‣ MHC class I molecules are found on all nucleated cells (not just professional
APCs) and typically present intracellular antigens such as viruses
‣ MHC class II molecules are only found on APCs and typically present
extracellular antigens such as bacteria

‣ This is logical because should a virus be inside a cell of any
type, the immune system needs to be able to respond to it
‣ This also explains why pathogens inside human red blood
cells (which are non-nucleated) can be difficult for the
immune system to find, such as in malaria
‣ Remember that this is the general rule but in cross-
presentation extracellular antigens can be presented by
MHC class I and in autophagy intracellular antigens can be
presented by MHC class II

ANTIGEN PROCESSING
‣ Before an antigen can be presented, it must first be processed
‣ Processing transforms proteins into antigenic peptides
‣ MHC Class I Molecules
‣ Intracellular peptides for MHC class I presentation are made by
proteases and the proteasome in the cytosol, then transported
into the endoplasmic reticulum via TAP (Transporter associated
with Antigen Processing) to be further processed
‣ They are then assembled together with MHC I molecules and
travel to the cell surface ready for presentation

https://teachmephysiology.com/immune-system/adaptive-immune-system/antigen-processing-presentation/

ANTIGEN PROCESSING
‣ MCH Class II Molecules
‣ The route of processing for exogenous antigens for MHC
class II presentation begins with endocytosis of the antigen
‣ Once inside the cell, they are encased within endosomes
that acidify and activate proteases, to degrade the antigen
‣ MHC class II molecules are transported into endocytic
vesicles where they bind peptide antigen, and then travel
to the cell surface

‣ The antigen presented on MHCs is recognized by T cells using a T
cell receptor (TCR)
‣ These are antigen-specific
‣ T Cell Receptors
‣ Each T cell has thousands of TCRs, each with a unique specificity
that collectively allows our immune system to recognize a wide
array of antigens
‣ This diversity in TCRs is achieved through a process called V(D)J
recombination during development in the thymus

‣ TCR chains have a variable region where gene segments are randomly
rearranged, using the proteins RAG1 and RAG2 to initiate cleavage and
non-homologous end joining to rejoin the chains
‣ The diversity of the TCRs can be further increased by inserting or deleting
nucleotides at the junctions of gene segments; together forming the
potential to create up to 1015 unique TCRs
‣ TCRs are specific not only for a particular antigen but also for a specific
MHC molecule
‣ T cells will only recognize an antigen if a specific antigen with a specific
MHC molecule is present
‣ This phenomenon is called MHC restriction

‣ Co-Receptors
‣ As well as the TCR, another T cell molecule is required for
antigen recognition and is known as a co-receptor
‣ These are either a CD4 or CD8 molecule:
‣ CD4 is present on T helper cells and only binds to
antigen-MHC II complexes
‣ CD8 is present on cytotoxic T cells and only binds to
antigen-MHC I complexes

‣ This therefore leads to very different effects
‣ Antigens presented with MHC II will activate T helper
cells and antigens presented with MHC I activate
cytotoxic T cells
‣ Cytotoxic T cells will kill the cells that they recognize,
whereas T helper cells have a broader range of effects
on the presenting cell such as activation to produce
antibodies (in the case of B cells) or activation of
macrophages to kill their intracellular pathogens

REVIEW QUESTIONS
‣ Which cells do MHC class II molecules stimulate?
‣ T helper cells
‣ Cytotoxic T cells
‣ Plasma cells
‣ B memory cells

REVIEW QUESTIONS
‣ Which MHC Class molecule is found on all nucleated
cells?
‣ MHC Class I
‣ MHC Class II
‣ MHC Class III
‣ MHC Class IV

REVIEW QUESTIONS
‣ Which MHC class molecules do cytotoxic T cells interact
with?
‣ MHC class II
‣ MHC class V
‣ MHC class I
‣ MHC class IV

REVIEW QUESTIONS
‣ Why does the immune system struggle to detect
pathogens such as malaria?
‣ It is encapsulated
‣ It mutates rapidly
‣ It resides in red blood cells
‣ It replicates too quickly

REVIEW QUESTIONS
‣ Why does the immune system struggle to detect pathogens such
as malaria?
‣ It is encapsulated
‣ It mutates rapidly
‣ It resides in red blood cells
‣ It replicates too quickly
‣ Pathogens such as malaria reside in red blood cells, which are non-
nucleated and therefore do not possess MHC Class I molecules.

REVIEW QUESTIONS
‣ Which of these correctly describes MHC restriction?
‣ A situation in which extracellular antigens can be presented by
MHC class I
‣ T cells will only recognize an antigen if a specific antigen with a
specific MHC molecule is present
‣ A situation in which intracellular antigens can be presented by
MHC class II
‣ TCR chains have a variable region where gene segments are
randomly rearranged, using the proteins RAG1 and RAG2

REVIEW QUESTIONS
‣ Which of these correctly describes MHC restriction?
MHC class I
‣ T cells will only recognize an antigen if a specific antigen
with a specific MHC molecule is present
MHC class II
‣ TCR chains have a variable region where gene segments are
randomly rearranged, using the proteins RAG1 and RAG2

REVIEW QUESTIONS
‣ Autophagy is:
MHC class I
‣ Important for assembling intracellular peptides for MHC class I
presentation
MHC class II
‣ The transport of MHC molecules to the cell surface via
endocytosis

REVIEW QUESTIONS
‣ Autophagy is:
MHC class I
‣ Important for assembling intracellular peptides for MHC class I
presentation
‣ A situation in which intracellular antigens can be presented
by MHC class II
‣ The transport of MHC molecules to the cell surface via
endocytosis

REVIEW QUESTIONS
‣ What is the self-antigen implicated in Grave’s disease?
‣ Thyroid Stimulating Hormone
‣ Thyroid Stimulating Hormone Receptor
‣ T3
‣ T3 Receptor

T CELL MEMORY
OVERVIEW
‣ T cells/T lymphocytes are white blood cells produced in the thymus gland
‣ They play an important role in adaptive immunity
‣ There are several subtypes of T cells
‣ These include: T helper cells, T regulatory cells, T memory cells and cytotoxic T
cells
‣ These cells have distinct functions and they work together in a complex network
involving other immune cells to combat disease
‣ Learning Goal
‣ To cover the role of the T memory cell and how they help to protect against
infection in the long term

T CELL MEMORY
INITIAL EXPOSURE - INNATE T CELL IMMUNE RESPONSE
‣ When an antigen first enters the body it encounters cells of the innate immune system
‣ e.g. macrophages and dendritic cells
‣ These cells capture and present the antigen (antigen presenting cells/APCs) and release a
variety of cytokines and inflammatory mediators to recruit other immune cells and to stimulate
the innate immune response
‣ The antigen presenting cells then drain into local lymph nodes where they encounter naïve T
helper cells and B cells
‣ These initiate the more specialized, adaptive immune response
‣ The antigen exposure causes the naïve T helper cells to differentiate into memory helper T
cells
‣ These then proliferate and specialize into Th1 or Th2 roles –> leading to activation of cytotoxic
T cells and B cell differentiation

T CELL MEMORY
INITIAL EXPOSURE - ADAPTIVE T CELL IMMUNE RESPONSE
‣ The cytotoxic T cells help with pathogen removal
‣ They recognize and bind to the antigens expressed by pathogens via MHC
I molecules
‣ Upon binding to the antigen/pathogen the cytotoxic T cell releases a variety of
mediators to destroy the pathogen
‣ The T helper cells release a variety of cytokines which activate cytotoxic T cells and
macrophages and induce B cell differentiation into plasma cells to produce
antigen specific antibodies
‣ These antibodies help to fight the infection through binding to the antigen
‣ Once bound, the antibody prevents the antigen from binding to other targets and
also facilitates antigen recognition and removal

T CELL MEMORY
SECONDARY EXPOSURE
‣ T Memory Cells
‣ These cells serve to ‘remember’ the specific antigen involved in
this encounter, so that should this antigen enter the body again
the T helper cells would be able to activate B cells much faster
‣ Subsequently, antigen-specific antibodies are produced
‣ The T helper cells would also stimulate faster expansion
of cytotoxic T cells to hasten pathogen clearance from the body
‣ This would lead to a far quicker immune response and faster
infection clearance

T CELL MEMORY
CLINICAL RELEVANCE - T CELL IMMUNODEFICIENCIES
‣ DiGeorge Syndrome
‣ DiGeorge (or 22q11.2 deletion) syndrome is autosomal dominant and caused by a
deletion of the q11.2 portion of chromosome 22
‣ The clinical features can vary, but can be remembered with the CATCH-22 acroynm:
‣ Cardiac abnormalities
‣ Abnormal facial features
‣ Thymic hypoplasia
‣ Cleft palate
‣ Hypocalcaemia
‣ Chromosome 22 affected

T CELL MEMORY
‣ DiGeorge Syndrome cont…
‣ As T cells usually mature in the thymus after being
produced in the bone marrow, thymic hypoplasia causes a
reduction in mature, functional T-cells
‣ Most cases are partial, meaning there is only mild to
moderate thymus dysfunction which is not life threatening
‣ In complete DiGeorge syndrome, the immunodeficiency
can be fatal

T CELL MEMORY
‣ Severe Combined Immunodeficiency
‣ Severe combined immunodeficiency (SCID) is caused by
mutations which cause the impaired development of B and T cells
‣ It is the most severe primary immunodeficiency, presenting in
early life with severe bacterial, viral and fungal infections
‣ Infants may also present with chronic diarrhea and failure to
thrive
‣ The two most common causes are X-linked and autosomal
recessive adenosine deaminase deficiency

T CELL MEMORY
REVIEW QUESTIONS
‣ Where do T cells mature in the body?
‣ The thymus
‣ The spleen
‣ The bone marrow
‣ Mucosally Associated Lymphoid Tissue (MALT)

T CELL MEMORY
REVIEW QUESTIONS
‣ Which of the following is NOT a subclass of T helper cell?
‣ Cytotoxic T cell
‣ Th1 cell
‣ Th2 cell
‣ Th17 cell

T CELL MEMORY
REVIEW QUESTIONS
‣ Which MHC class molecules do cytotoxic T cells interact
with?
‣ MHC class II
‣ MHC class V
‣ MHC class I
‣ MHC class IV

T CELL MEMORY
REVIEW QUESTIONS
‣ Which of these is an antigen presenting cell?
‣ Dendritic cell
‣ Plasma cell
‣ Eosinophil
‣ Mast cell

T CELL MEMORY
REVIEW QUESTIONS
‣ A vaccine:
‣ directly provides antigen-specific antibodies to a
pathogen
‣ releases cytokines at the site of injection to stimulate a
response
‣ proliferates into Th1 cells once inside the body
‣ contains weakened or dead forms of a pathogen and is
designed to mimic the initial exposure response

T CELL MEMORY
REVIEW QUESTIONS
‣ What do plasma cells produce?
‣ MHC class I molecules
‣ Antigen specific antibodies
‣ Chemotaxins
‣ Antibody specific antigens

References
These slide reflect a summary of the contents of
TeachMePhysiology.com and are to be used for educational
purposes only in compliance with the terms of use policy.
Specific portions referenced in this summary are as follows:
‣ https://teachmephysiology.com/immune-system/adaptive-immune-system/
antibodies/
‣ https://teachmephysiology.com/immune-system/adaptive-immune-system/
antigen-processing-presentation/
‣ https://teachmephysiology.com/immune-system/adaptive-immune-system/t-cell-
memory/
Additional sources are referenced on the slide containing
that specific content.

5. adaptive immune system

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5. adaptive immune system