Chapter 1
Elements of the Immune system and
their Roles in Defense
Introduction
 Immunology is the study of physiological mechanisms that
are used to defend the body from invasion by foreign or
infectious agents
 In response to diseases caused by infectious agents, the
body develops cells dedicated to defense – these form the
immune system
 Protective immunity takes time to develop, while
microorganisms can rapidly multiply and cause disease
 Immunity involves two responses, the flexible but specific
defenses of the adaptive immune response and the fixed
defenses of the innate immune response
Defenses Facing Invading
Pathogens
The Ubiquitous Enemy- Microbes
 Microbes survive on animal & plant products
 Release digestive enzymes
 Grow on living tissues (extracellular) where they are bathed in
nutrients
 Other intracellular microbes infect animal/human cells,
utilizing host-cell sources
 Some microbes are harmless and some even helpful (e.g. E.
Coli in our intestines)
 Many others cause disease (human pathogens)
 There is a constant battle between invading microbes and the
immune system
Immunity-The Immune Response
 People who survive a specific infection become immune to it
– protective immunity
 To provide protective immunity, the immune system must first
engage the microorganism
 There is lag time between infection and protection
 The first infection is the most dangerous one
 This understanding led to the concept of immunization or
vaccination
 Disease is prevented by prior exposure to an attenuated
infectious agent
Historical Perspective
 Origins of immunology attributed
to Edward Jenner
 Discovered in 1796 that cowpox
“vaccinia”
 protected from human smallpox
 Procedure called vaccination
 Prevents severe disease by
exposing the immune system to
the infectious agent in a form that
cannot cause the disease
The Eradication of Smallpox by
Vaccination
 Vaccination was Initiated
in 1796
 WHO in 1979 announces
eradication of smallpox
 What are the risks to the
human population should
the virus emerge again?
 Naturally
 Deliberate act of human
malevolence
The Nature of Pathogens
 Any organism with potential to cause disease is a pathogen
 Opportunistic pathogens cause disease if the body’s
defenses are weakened
 Constant evolutionary struggle between the host and the
pathogen
 REPLICATION TIMES favor the PATHOGEN!!!
The Four Kinds of Pathogen that Cause
Human Disease
Refer to Figure 1.3: The Diversity of
Human Pathogens
Blastophores
(yeast-like cells)
Pseudohyphae
Candida albicans-normal
inhabitant of the human
body, thrush & systemic
infections
Cocci-grape like clusters
Staphylococcus aureus-gram
positive bacterium that
colonizes human skin, pimples
& boils (other strains = food
poisoning)
Mycobacterium
tuberculosis-causes
tuberculosis
Avian Influenza (Bird Flu)
• Bird flu or Avian
Influenza, is a
contagious disease of
animals caused by
viruses that normally
infect only birds
• By the middle of 2005,
some 50 people had
died from bird flu
• Virus can mutate to a
more contagious form,
experts continue to
warn of the potential
for a full-blown
pandemic
Skin and Mucosal Surfaces Physical Barriers Against Infection
 Skin is first line of defense against infection
 Tough impenetrable barrier
 Skin continuous with epithelia lining
 respiratory
 gastrointestinal
 urogenital tracts
The impermeable skin gives way
to specialized tissues that are
more vulnerable to microbe attack;
Known as mucosal surfaces or mucosae
Skin and Mucosal Surfaces Physical Barriers Against Infection
 Mucosal surfaces are bathed in mucus; thick fluid containing
glycoproteins, proteoglycans, and enzymes - protective
 Lysozyme in tears and saliva – antibacterial
 Respiratory tract mucus is continuously removed to clear
unwanted material
 Stomach, vagina, skin acidic – protective
When skin and mucosal barriers are
breached - immune system responds
Secretions at Epithelial Surfaces
Secretions from epithelial surfaces at external sites
of the body are important
for protection against entry of microbes
Site
Source
Specific secretions
Eyes
Lacrimal glands (tears)
Lysozyme, IgA and IgG
Ears
Sebaceous glands
Waxy secretion- cerumen
Mouth
Salivary glands (saliva)
Digestive enzymes, lysozyme, IgA,
IgG, lactoferrin
Skin
Sweat glands (sweat)
Lysozyme, high NaCl, short chain
fatty acids
Stomach
Gastric juices
Digestive enzymes (pepsin, rennin),
acid (low pH, 1-2)
Physical Barriers that Separate the Body
from its External Environment
Strong barriers to infection
provided by the skin, hair,
and nails are colored blue
More vulnerable mucosal
membranes are colored red
Immune Defense-Innate
Versus Adaptive Immunity
 Innate immune system




Is the first line of defense against infections
It works rapidly
Gives rise to the acute inflammatory response
Has some specificity for microbes
 Adaptive immune system
 Takes longer to develop
 Is highly specific for antigens, including those associated with
microbes
 Remembers that it has encountered a microbe previously, (i.e. shows
memory)
Immune Defense-Innate
Versus Adaptive Immunity
 The innate and adaptive immune systems work together….
 through direct cell contact
 through interactions involving chemical mediators, cytokines and
chemokines
 Many of the cells of the innate immune system are the same
cells used by the adaptive immune system
Principle Characteristics of
Innate and Adaptive Immunity
Immunological Memory
Cells of the Immune System
 Lymphoid cells – 20-40% of white blood cells
 There are 1011 lymphocytes in the human body
 Mononuclear phagocytes – monocytes that circulate in the blood and
macrophages found in tissues
 Granulocytic cells, classified as neutrophils, eosinophils and basophils
based on morphology and cytoplasmic staining characteristics
 Dendritic cells, whose main function is the presentation of antigen to T
cells
Hematopoiesis
 The generation of the cellular elements of blood, including:
 Red blood cells (RBC)
 White blood cells (WBC) or leukocytes
 Platelets
 These cells originate from pluripotent hematopoietic stem
cells (HSC) whose progeny differentiate and divide under the
influence of various hematopoietic growth factors
 HSC give rise to other cells in a process called self-renewal,
becoming more mature stem cells that commit to different
lineages
Types of Hematopoietic Cells
The pluripotent stem
cell divides and
differentiates into more
specialized progenitor
cells that give rise to the
lymphoid lineage
myeloid lineage
erythroid lineage
Types of Hematopoietic Cells
The pluripotent stem
cell divides and
differentiates into more
specialized progenitor
cells that give rise to the
lymphoid lineage
myeloid lineage
erythroid lineage
Types of Hematopoietic Cells
The pluripotent stem
cell divides and
differentiates into more
specialized progenitor
cells that give rise to the
lymphoid lineage
myeloid lineage
erythroid lineage
Abundance of Leukocytes in Blood
 Most abundant leukocytes are the neutrophils, followed by
lymphocytes
Leukocyte Versus Lymphocyte
 Leukocytes- a general term for a white blood cell
Lymphocytes, granulocytes and monocytes are all leukocytes
 Lymphocytes- a class of white blood cells that consist of
small and large lymphocytes, two classes
 Small lymphocyte B lymphocytes (B cells) and
 T lymphocytes (T cells)
 Large granular lymphocytes are
 natural killer (NK) cells, lymphocytes of innate immunity
Figure 1-9 part 1 of 6
Lymphoid Cells
 Lymphocytes are divided into three classes, B cells, T cells and natural
killer cells (NK cells)
 Naïve lymphocytes or small lymphocytes are resting cells that have not
interacted with antigen
 Lymphoblasts are lymphocytes that have interacted with antigen and
proliferate
 Lymphoblasts eventually differentiate into effector cells or into memory
cells
 Effector cells eliminate antigen – plasma B cells that secrete antibody,
cytokine-producing T helper cells (TH) and T cytotoxic cells (TC)
Figure 1-9 part 2 of 6
Natural Killer Cells
 NK cells (large granular lymphocytes) are found throughout
the tissues of the body but mainly in the circulation
 Constitute 5-10% of lymphocytes in human blood
 Contain cytotoxic substances which are important for
protection against viruses and some tumors
 Secrete cytokines which prevent viral replication and helps to
activate T cell mediated immunity
Neutrophils
 Effectors of innate immunity – specialized in the capture,
engulfment and killing of microbes
 Work in the anaerobic conditions found in damaged tissue
 Are short-lived and die at site of infection
 Are phagocytic cells with that contain toxic substances in
intracellular granuales
 Employ oxygen-dependent and oxygen-independent
pathways to destroy pathogens
Figure 1-9 part 5 of 6
Mononuclear Phagocytes
 Granulocyte-monocyte progenitors in the bone marrow
differentiate into pro-monocytes, which enter the blood,
where these differentiate into monocytes
 Monocytes circulate on the blood for about 8 hours, then
migrate into tissues and become tissue specific macrophages
or dendritic cells
Mononuclear Phagocytes
 Differentiation of monocyte into macrophage requires
changes
 Cells enlarge 5-10 times; increased intracellular organelles,
increased phagocytic ability; production of hydrolytic
enzymes; secretion of soluble factors
 There are tissue specific “fixed” macrophages and “free”
macrophages
Figure 1-9 part 4 of 6
Dendritic Cells
 Dendritic cells are so called because of their many surface
membrane folds, similar in appearance to dendrites of the
nervous system
 These folds allow maximum interaction with other cells of the
immune system
 There are three main kinds of dendritic cells which are found
in skin and in T cell and B cell areas of lymphoid tissue:
 Langerhans cells (LH)
 Interdigitating cells (IDC)
 Follicular dendritic cells (FDC)
Dendritic Cells (cont.)
 Most dendritic cells
 possess high levels of surface MHC class II molecules
 process and present peptide antigens to T cells
 Their role is to recognize microbial antigens through innate receptors
and process and present them to T cells of the adaptive immune
system
 Follicular dendritic cells hold intact antigens in specialized
areas of lymphoid tissues
Mast Cells
 Mast cells are found in the skin, connective tissue and
mucosal epithelial tissue of the respiratory and digestive
tracts
 The origin of mast cells is uncertain but precursors
differentiate in the bone marrow and mature in tissues
 When activated mast cells degranulate releasing
pharmacological mediators which cause
 vasodilation
 increase vascular permeability and
 attract leukocytes to the site of degranulation
Figure 1-9 part 3 of 6
Eosinophils
 These are granular leukocytes which stain with eosin (red)
 They are present at low levels in the circulation (2-5% of
blood leukocytes
 Eosinophils have some phagocytic activity but are primarily
responsible for extracellular killing of large parasites such as
worms
 They usually bind to an antibody-coated parasite and release
the contents of their granules (degranulate) onto the parasite
surface
Basophils
 Basophils are granulocytes which stain with basic dyes (blue)
and are present in very low numbers in the circulation (<0.2%
of the granular leukocytes)
 Basophils and mast cells are very similar in morphology
 Both contain and release large characteristic electron-dense
granules in their cytoplasm during allergic reactions
 Like all the granulocytes, basophils are produced from stem
cells in the bone marrow
Figure 1-9 part 6 of 6
Erythrocytes
 Erythrocytes bind to immune complexes composed of
antigen and antibody and carry these complexes to the liver
where these are cleared are Kupffer cells
 Erythrocytes have an important immunological role in
clearing immune complexes from the circulation in persistent
infections and in some autoimmune diseases
 Kupffer cells = phagocytic cells of the liver that line the
hepatic sinusoids
Pluripotent Hematopoietic
Stem Cells
 HSCs are multipotent or pluripotent – able to differentiate in
various ways
 There are fewer than one HSC per 5 x104 cells in the bone
marrow
 A normal mouse has 3 x108 bone marrow cells
 A lethal dose of radiation (x-rays, 950 rads) will kill mice
within 10 days unless they receive a bone marrow transplant
from a genetically identical mouse
 Infusion of 104-105 donor bone marrow cells will restore the
hematopoietic system
 HSCs growth is supported by stromal cells, which form the
hematopoietic-inducing microenvironment (HIM), consisting
of cellular matrix and factors
The pluripotent stem cell divides and
differentiates into more specialized progenitor
cells that give rise to the lymphoid lineage,
the myeloid lineage and the erythroid lineage
Figure 1-11
Site Of Hematopoiesis in Humans
Changes During Development
 The site for hematopoiesis
changes with age
 In early embryo, blood cells
are first produced in the yolk
sac and later in the fetal liver
 From months 3-7 of fetal life
the spleen is the major site of
hematopoiesis
 As bones develop (4-5
months) hematopoiesis shifts
to the bone marrow
 In adults hematopoiesis occurs
mainly in the bone marrow
Hematopoiesis is active
throughout life because blood
cells are both vital and shortlived
Innate Immune Response
 Innate refers to the fact that mechanisms are determined by
the genes a person inherits from their parents
 There are many families of receptor proteins expressed by
immune cells that recognize pathogens
 These receptors recognize chemically diverse ligands –
peptides, proteins, glycoproteins, proteoglycans,
peptidoglycans, carbohydrates, glycolipids, phospholipids
and nucleic acids – produced by pathogens
Key Elements of Innate Immunity
 Cells and molecules of the innate immunity identify common
classes of pathogen and destroy them
 Four key elements of innate immunity
 Molecules that noncovalently bind to surface macromolecules of
pathogens
 Molecules that covalently bond to pathogen surfaces, forming ligands
for phagocyte receptors
 Phagocytic cells that engulf and kill pathogens
 Cytotoxic cells that kill virus-infected cells
Innate Immune Response
 Recognition that the pathogen is present
 Involves soluble proteins and cell surface receptors that bind
 either to the pathogen and its products (ligands)
 human cells and serum proteins that become altered in the
presence of the pathogen
 Recruitment of destructive effector mechanisms that kill and
eliminate the pathogen
 Effector cells that engulf bacteria, kill virus-infected cells or attack
protozoan parasites
 Complement
 serum proteins that help the effector cells by marking pathogens
with molecular flags
 complement also attack pathogens in their own right
Innate Immune ResponseInflammatory Response
 Cells and proteins in damaged tissue “sense” the presence of
bacteria
 Cells produce soluble proteins called cytokines that interact with other
cells to trigger the innate immune response
 Overall effect of the innate immune response is to induce a
state of inflammation in infected tissue
 Latin: Calor, dolor, rubor and tumor
 Heat, pain, redness and swelling
 Inflammation is due to the innate immune response not the
infection!!!
Inflammation
 Cytokines induce the local
dilation of blood capillaries
 This increases blood flow
and causes skin to warm
and redden
Inflammation
Vasodilation increases leak of plasma into tissues, causing
expansion of local fluid volume leading to swelling and pain
Phagocytosis/Endocytosis
 If a microorganism crosses an epithelial barrier and begins
to replicate, it is recognized by phagocytes- macrophages
and neutrophils
 Phagocytes can distinguish surface molecules on
microorganims from surface molecules on host cells – called
pattern recognition
 Ingestion of microorganisms is called phagocytosis
 A cell’s membrane expands around particles to forms
vesicles called phagosomes
 Upon phagocytosis, phagocytes produce toxic products that
kill microorganisms, which include nitric oxide, superoxide
anion and hydrogen peroxide
Phagocytes- Neutrophils- PMN
 The most abundant mobile phagocyte (eating cell) is the
neutrophil (polymorphonuclear cell, PMN)
 Phagocytosis is coupled to release of cytokines and other
inflammatory mediators
 Cytokines recruit neutrophils and other immune cells
 Granular leukocytes comprise the majority of white blood cells
 Patrol the blood stream in search of invading microbes
 Neutrophils are specialized killing machines, short-lived, when they
die they produce pus
 Eventually mopped up by macrophages
Neutrophils are Mobilized from the Bone
Marrow, and Target (home) to Infection Sites
Mononuclear Phagocyte System
 Mononuclear phagocyte system
 System of phagocytes located mainly in the organs and tissues
 Monocytes are present in the blood stream and settle in the tissues as
macrophages
 Macrophage-like cells in the liver – Kupffer cells
 Macrophage-like cells in the brain – Microglia
Process of Phagocytosis
Macrophage (pink)
E. Coli (green)
Phagocytic process
 Several stages




Phagocyte attraction to the site of infection
Phagocyte contact with the microbe
Ingestion (endocytosis)
Killing of the ingested microbe by means of oxygen and oxygenindependent mechanisms
 Opsonization
 Way of making microbes more palatable to the phagocyte
 Molecules coating a microbe, such as complement or antibody
facilitate contact and ingestion of the microbe
Macrophages are Key Players in the
Innate and Adaptive Immune Response
Phagocytosis
Bacterial Killing
Release of Inflammatory Mediators
T Cell Activation
Macrophages Respond to Pathogens by
Using Different Receptors to Stimulate
Phagocytosis & Cytokine Secretion
 Bacterium (red) binds to cellsurface receptors of the
macrophage (blue)
 Bacterium is engulfed into an
endocytic vesicle called a
phagosome
 Fusion of the phagosome with
lysosomes forms an acidic
vesicle called a phagolysome
 - Contains toxic molecules and
hydrolytic enzymes that kill the
bacterium
Macrophages Respond to Pathogens by
Using Different Receptors to Stimulate
Phagocytosis & Cytokine Secretion
 Bacterial component binding to a cellsurface receptor sends a signal to the
macrophage’s nucleus
 this initiates the transcription of genes
for inflammatory cytokines
 The cytokines are synthesized and
secreted into the extracellular space
Macrophages Recognize a Array of
Patterns, then
Microbe
Virulence = the
disease-evoking
power of a
pathogen
Macrophage
Cytokine
production
activate defense mechanisms including cytokine production
 There are 10 expressed
TLR genes in mice
 Each recognizes a distinct
set of molecular patterns not
found in normal vertebrates
 TLRs have limited specificity
but can recognize a broad
range of pathogenic
microorganisms
Soluble Proteins also
Mediate Innate Immunity
 Plasma leaking into tissues brings in plasma proteins,
including the
 mannose-binding protein (MBP) and
 complement proteins
 Complement activation leads to covalent binding of
complement proteins to bacterial surfaces
 Complement receptors on macrophage cells promote
phagocytosis of opsonized bacteria
 Complement kills bacteria
 Complement recruits additional phagocytes
Complement
 Complement was discovered as a component of normal
plasma that augments killing of bacteria by antibodies
 Complement can be also be activated early in infection in the
absence of antibodies
The Complement System
 Serum proteins of the complement system are activated in
the presence of a pathogen, forming a bond between
complement protein and the pathogen
 The attached piece of complement marks the pathogen as
dangerous
 The soluble complement fragment attracts a phagocytic white
blood cell to the site of complement activation
 The effector cell (macrophage) has a surface receptor that
binds to the complement fragment attached to the pathogen
 The receptor and its bound ligand are taken up into the cell
by endocytosis, which delivers the pathogen to an
intracellular vesicle called a phagosome, where it is
destroyed
The Complement System
Mechanisms of Protection
 Antigens: Substances that can trigger an immune response –
more specifically a substance that the immune system can
recognize
 Can be proteins, lipids, or sugers
 Can be found on the surface or secreted by microorganisms
 Antibodies (immunoglobulins): Proteins molecules
synthesized by cells of immune system that recognize
antigens
Adaptive Immunity
 Occasionally the infection outruns the innate immune
response
 Innate immunity has a restricted number of receptors to recognize
pathogens
 This activates the adaptive immune system
 The adaptive immune system is mediated by lymphocytes
which expand into effector cells and also persist as memory
cells
 The adaptive immune system generates a huge diversity of
immunoglobulins (Ig) and T cell receptors
 Upon infection, only the B cells with specific Ig or T cells with
specific receptors are stimulated to proliferate and
differentiate into effector cells
Clonal Expansion in the Adaptive
Immune System:
Selection of
lymphocytes by a
pathogen
Organs of the Immune System
 Distinguished by function – primary and secondary lymphoid
organs
 Thymus and bone marrow are primary organs where
maturation of lymphocytes takes place
 Lymph nodes, spleen and mucosal-associated tissues are
secondary organs which trap antigen and promote
lymphocyte maturation
Lymphocytes and Lymphoid Tissues
 Lymphocytes are
 Found in lymphoid tissues
 Activated in the secondary
lymphoid tissues
 Arise from stem cells in bone
marrow
 B cells - mature bone
marrow
 T cells - mature thymus
 Primary lymphoid tissues
 Bone marrow and thymus
 Secondary lymphoid tissue
and lymphatics
 Spleen and lymph nodes
Thymus
 Site of T cell
development and
maturation
 T cells in the
thymus are called
thymocytes
 It is a flat,bilobed
organ situated
above the heart
 Function is to
generate a diverse
repertoire of T cells
to protect the body
from infections
Bone Marrow
 Site of B-cell origin and development
 B cells proliferate and differentiate by interacting with stromal
cells and cytokines
Lymphatic System
 Plasma from blood (interstitial
fluid) seeps through to tissues
and a portion (lymph) flows into
lymphatic capillaries and
lymphatic vessels
 Antigens are carried to lymph
nodes, as are lymphocytes,
enabling interactions
Secondary Lymphoid Organs
 Meeting place where
lymphocytes circulating blood
encounter antigens brought
from sites of infection
 Antigens derived from infections
originating in connective tissues
(as a result of skin wounds) are
carried by the lymphatics to the
nearest lymph node
 Dendritic cells activated by
infection also carry antigens
Circulating Lymphocytes
Encounter Lymph-borne Pathogens in
Draining Lymph Nodes
 Lymphocytes leave blood and
enter lymph nodes where they
are activated by pathogens
 Pathogens drain from site of
infection (example: foot) to LN via
afferent lymphatic vessels
 Activated lymphocytes stay in LN
and divide and differentiate into
effector cells, while non-activated
cells leave through efferent
lymphatics
 Lymphocytes recirculate at a rate
of 5 X 106 cells/min
Architecture of the Lymph Node
 Kidney-shaped; packed
with lymphocytes &
macrophages through
which lymph percolates
 Pathogens and dendritic
cells carrying pathogens
arrive in afferent lymph
 Pathogens are degraded
and used to stimulate
lymphocytes
 Lymphocytes arrive at LN
in arterial blood;
extravasate from
capillaries
Lymph is the mixture of extracellular fluid and
cells that is carried by the lymphatic system
Architecture of the Lymph Node
 In LN, there are discrete
sites where B cells and T
cells congregate
 Effector B cells; plasma
cells -secrete antibodies
 LN increases in size due
to dividing lymphocytes “swollen glands”
 Expansion occurs in
lymphoid follicles
 As lymphocyte
development proceeds,
follicle shape changes germinal center
Lymph is the mixture of extracellular fluid and
cells that is carried by the lymphatic system
2.
Cytotoxic T cells
3.
Helper T cells
5.
B cells
4.
1.
6.
7.
The Spleen
 Filter for blood that removes old or damaged cells
 Site where blood-borne pathogens encounter lymphocytes
The Spleen
 White pulp of spleen
consists of sheath of
lymphocytes called the
periarteriolar lymphoid
sheath (PALS)
surrounding a central
arteriole (CA)
 T cells are closest to
the CA, while B cells
are more peripheral,
forming a B cell corona
Germinal centers form between the T and B cell zones
The marginal zone contains differentiated B cells
Mucosal-Associated Lymphoid Tissue (MALT)
 Mucosal surfaces lining digestive, respiratory and urogenital
tracts are the major sites of entry for pathogens and are
defended by MALT
 Range from loosely organized clusters of lymphoid cells to
well-organized structures – tonsils, appendix
 The gut associated lymphoid tissues (GALT) include tonsils,
adenoids, appendix and Peyer’s patches that line the gut
 Bronchial-associated lymphoid tissues (BALT)
Tonsils
 Found in three locations
 Nodular structures of reticular cells and fibers interspersed
with lymphocytes, macrophages, granulocytes and mast cells
 B cells are organized in follicles surrounded by T cells
A Region of GALT
Pathogens arrive through
direct delivery across mucosa mediated
by specialized cells called M cells
Principles of
Adaptive Immunity
 Receptors that uniquely bind to a pathogen are selected and
then amplified
 Millions of different immunoglobulins and T cell receptors are
made by B and T cells
 Each receptor recognizes a different molecular structure
Immunoglobulins and T cell Receptors
are Variable Recognition Molecules
 Igs expressed on B cells -- bind pathogens
 Plasma cells (effector B cells) secrete antibodies (Igs)
 T cell receptors (TCRs) are not secreted
 Antigen (Ag) is any molecule detected by Ig or TCR; Igs and
TCRs have specificity for Ags
 Epitope (or antigenic determinant) is that part of the antigen
bound by Ig or TCR
Gene Rearrangement in Immunoglobulin
& T-cell Receptors
 In the unrearranged DNA there
are three alternative ‘red’
segments and three alternative
‘yellow’ segments
 A functional gene consists of one
red segment joined to one yellow
segment
 This rearrangement is achieved
by a process of ‘cut and paste’ in
which the intervening DNA is
removed
Gene Rearrangement in Immunoglobulin
& T-cell Receptors
 Different combinations of red
and yellow segments can be
brought together
 The second red segment is
brought together with the third
yellow segment (L to R), but
other combinations of a red and
a yellow segment would have
been equally possible
Antigen Presentation
 Major histocompatibility
complex (MHC) is a cluster
of genes on the short arm of
human chromosome 6
 That encodes a set of
polymorphic membrane
glycoproteins call the MHC
molecules
 Which are involved in
presenting peptide antigens
to T cells
Antigen Processing
and Generic Antigen
Presentation to T Cells
 MHC class I presents antigens derived
from the cytosol; intracellular pathogens
like viruses and some bacteria
 Most cells can present via MHC class I
 MHC class II presents peptides derived
from extracellular milieu (environment)
by endocytosis and phagocytosis
 Antigens are broken down within Ag
presenting cells
 Assembled into a complex with the
MHC
 Transported to cell surface
 Presented to TCR
MHC Class I
Antigen Presentation To T Cells
MHC Class I Antigen Presentation
to T Cells (cont.)
MHC Class II
Antigen Presentation to T Cells
Cell-Mediated Immunity
(the Effector Functions of T Cells)
 Two main T Cell Classes
 CD8 T Cells
 CD4 T Cells
 CD8 T cells –
 cytotoxic;
 kill virally infected cells
 CD8 binds MHC class I
CD8 T Cell
Virally Infected Cell
CD4 T Cells
 CD4 T cells secrete cytokines that modulate other immune
cells
 CD4 T binds MHC class II
 Two classes of CD4 T cells;
 TH1 cells mainly activate macrophages
 TH2 cells chiefly help B cells
Antibody –
Based Adaptive Immunity
Antibody – Based Adaptive Immunity
Antibody Production
Antibody Specificity
Mechanisms by
Which Antibodies
Combat Infection
Immunological Memory
 Lymphocytes that expand persist, providing long term
memory
 First time infection results in a primary response
 Subsequent infections elicit a secondary response
 This is the basis of vaccination
Comparison of a Primary
and Secondary Immune Response
Successful Vaccination Campaigns
 Diphtheria, poliomyelitis and measles
have been virtually eliminated from
the USA
 Sub acute sclerosing panencephalitis
(SSPE) is a brain disease that is a
late consequence of measles
 Reduction of measles was paralleled
by a reduction in SSPE 15 years later
 Because these disease have not
been eradicated worldwide,
immunization must be maintained in
much of the population to prevent
disease recurrence
Immunodeficiency: Inherited or Infectious
 Mutation in immune function genes leads to
immunodeficiency -- different kinds….
 Only one aspect of immune response is affected
 In others, adaptive immunity is completely absent
 Leading to devastating vulnerability to all infections
 Extreme example of immunodeficiency due to disease is the
acquired immune deficiency syndrome (AIDS)
 Caused by infection with the human immunodeficiency virus (HIV)
The Misguided Immune System
 Allergy:
 IgEs made against innocuous substances (foods, pollen, dust);
 constant regions bind to mast cells
 encounter allergen; triggers degranulation
 Autoimmune disease:
 Immune response directed against normal host tissue
 Examples: autoimmune diabetes and reheumatoid arthritis
 Transplantation:
 Organ transplantation stymied by tissue rejection
 Tissue rejection caused by extensive polymorphism of MHC class I
and II genes
Adaptive Immune Responses
can be both Beneficial & Harmful