Chapter 19

Lymphatic
System and
Immunity

Macrophage
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
 General Objectives:
• To review the basic concepts of
Immunology
• To correlate immunologic principles with
Host – Microbe Interactions
• To apply the knowledge to clinical
conditions of patients
 Specific Objectives
• 1. explain the basic function & make up of
the Immune System
• 2. differentiate the various lines of
defense
• 3. differentiate the types of immunity and
immune response
• 4. explain the types of disorders of the
Immune System
 Laboratory Diagnosis
• 1. explain the principles of serology as
diagnostic aids for infectious diseases
• 2. discuss the basic concepts of antigen –
antibody reactions (serology)
• 3. apply the principles of molecular
diagnostics in infectious diseases
 Chapter 8 Jawetz Medical Microbiology.
McGraw Hill, 27th edition, 2016
• Overview
• Innate Immunity
• Adaptive Immunity
• Complement
• Cytokines
• Hypersensitivity
• Deficiencies of the Immune Response
• Laboratory Diagnosis
 Introduction
• Functions of the Immune System
• “immunitas”
• Edward Jenner
 Natural vs. Acquired
Natural Acquired
• Unaltered on repeated • Improved by repeated
infection infection = memory
• Non Specific - organisms • Specific vs. stimulating
organism
• Phagocytes , NK cells • Lymphocytes
• Lysozyme, complement, • Abs; cytokines from
acute phase proteins, lymphocytes
interferon
 Immune System

• Lymphopoiesis
• Development / Ontogeny
– Morphologic Basis
• Primary – thymus, bone marrow
• Secondary – lymph node, tonsils, spleen,
appendix, MALT/GALT, Peyer’s patches
– Physiologic Basis – processing, recognition,
proliferation, transformation
• Cells of the Immune System
 Immune System

• Lymphopoiesis
• Development / Ontogeny
– Morphologic Basis
• Primary – thymus, bone marrow
• Secondary – lymph node, tonsils, spleen,
appendix, MALT/GALT, Peyer’s patches
– Physiologic Basis – processing, recognition,
proliferation, transformation
• Cells of the Immune System
Primary & Secondary Lymphoid Organs
Figure 14.17
 T Lymphocyte Subsets
• Helper T (Th) lymphocytes
– Th1: Cell-mediated effector mechanisms
– Th2: Regulation of antibody production
– Treg (regulatory T cells): Immunoregulatory type of
Th cell
• Cytotoxic T (Tc) lymphocytes
– Capable of directly destroying virally infected
target cells
• Supressor T (Ts) lymphocytes
– Downregulate actions of other T and B cells

33
 T helper subsets
• TH1
– Stimulate phagocyte mediated defense
against infections, especially with intracellular
microbes
• TH2
– Stimulates IgE and eosinophil/mast cell –
mediated immune reactions; downregulates
TH1 response
• Toll-like receptors (TLRs) are a class of
proteins that play a key role in the first line
of defense in the innate immune response.
They are single, membrane-spanning,
non-catalytic receptors usually expressed
on sentinel cells such as macrophages
and dendritic cells, that recognize
structurally conserved molecules derived
from microbes.
• The T-cell receptor, or TCR, is a
molecule found on the surface of T cells,
or T lymphocytes, that is responsible for
recognizing fragments of antigen as
peptides bound to
major histocompatibility complex (MHC)
molecules. The binding between TCR and
antigen peptides is of relatively low affinity
and is degenerate: that is, many TCRs
recognize the same antigen peptide and
many antigen peptides are recognized by
the same TCR
• The TCR is composed of two different
protein chains (that is, it is a heterodimer).
In humans, in 95% of T cells the TCR
consists of an alpha (α) chain and a beta
(β) chain (encoded by TRA and TRB,
respectively), whereas in 5% of T cells the
TCR consists of gamma and delta (γ/δ)
chains (encoded by TRG and TRD,
respectively). This ratio changes during
ontogeny and in diseased states (such as
leukemia)
Mechanisms of Innate Immunity
I. Physiologic Barriers at the Portal of Entry
A. Skin
B. Mucous Membranes
II. Innate Immunologic Mechanisms
A. Phagocytic Cells
B. Phagocytosis
C. Alternative Pathway of Complement
D. Inflammatory Response
E. Fever
F. Interferons
G. Natural Killer Cells
CYTOKINES - protein molecules that transmit messages
between the cells

a. Interferons - glycoproteins that has virus-

nonspecifc antiviral activity
*3 groups of IFN
i. Alpha IFN-aka Leukocyte IFN
ii. Beta IFN - aka Epithelial IFN, Fibroblast
IFN, Fibroepithelial IFN, B-cell stimulating
Factor 2
iii. Gamma IFN - produced by immnunologically
stimulated lymphocytes, primarily T lymphocytes;
- a lymphokine
- aka Immnune IFN
- main fxns: Immunoregulation. Enhance NK
cells and Activate macrophages.
 b. Tumor Necrosis Factor (TNF) - produced mainly by
macrophages/monocytes (a monokine)
- mediator of host reponse to gram (-)
bacteria
c. INTERLEUKINS - means of communication between
leukocytes
i. IL1 - Lymphocyte Activating Factor
ii. IL2 - T-Cell Growth Factor. Activates cytotoxic
cells, NK cells, LAK cells
iii. IL3 - Multicolony Stimulating Factor (MCSF).
Stimulates hematopietic cells.***
iv. IL4 - produced by activated T cells to stimulate
proliferation of B cells
 B and T cells
IL8 - Monocyte-derived
Neutrophil Chemotactic
Factor. Principal inflammatory
cytokine.
IL9 - stimulates proliferation of
T cell and Mast cells
IL10 - inhibits cytokine
synthesis
IL11 - regulates
 Mechanisms of
Specific Host Defense
• Adaptive Response
• Antigens
– Degree of foreignness
– Molecular size
– Accessibility of immunodominant groups
– Chemical & structural complexity
– Genetic Constitution of the Host
– Dosage, Route & Timing of Ag administration
• Cellular Basis of the Immune Response
– T and B cells
• Autologous or autoAg  autoAbs
• Homologous – Ag used in Ab production
• Heterologous – different Ag from that used
in the immunization
• Heterophil / Heterogenetic – Ags that exist
in unrelated plants or animals producing
cross reaction
 Antibody
• Definition – Structure and Function
• Properties
• Classification
• Formation / Production
– Instructive theory / template
– Selective / germ line theory
– Somatic mutation / forbidden clone
• Antibody Response
• primary vs. secondary
 Ig variants
• Isotype – variants in normal persons
• Allotype – genetically controlled alternate
forms – not in all persons
• Idiotype – variable regions
 52
.
Immunoglobulin Variants
 Antibody Synthesis
• Primary antibody response
• Secondary (anamnestic) antibody response

Copyright © 2014, 2009, 2003, 1996, 1990 by Mosby, an imprint of Elsevier Inc. 54
Antibody Synthesis
 Variable region - responsible for
specificity; the antigen binding site

CH2 - binds with complement,

specifically C1q, and initiates
complement pathway

CH3 - responsible for cytotropic

 Complementarity-
determining regions (CDRs)
are part of the variable chains
in immunoglobulins
(antibodies) and
T cell receptors, generated by
B-cells and T-cells
respectively, where these
molecules bind to their specific
C1r C1s

C1q
C1r C1s

C1q
 2o Ag

Ab Titer

1o Ag

Days After Immunization

 Secondary Ab response
• Shorter lag phase
• Longer plateau
• More gradual decline
 Classes of Immunoglobulins
IgG IgA IgM IgD IgE
Molecul 150 T 160-400 T 900 T 180 T 190 T
ar
Weight
Daltons
S Value 7S 11S(SigA) 19S 8S
Halflife 21-23 5-6 days 5 days 2-3 days 2-3 days
days
Subclas 4 2 2 - -
ses
Domains 4 4 5 4 5
Activat Yes, Alternative Yes. Most No. No.
e except pathway only Efficient
Comple IgG4
ment?
 IgG IgA IgM IgD IgE

Other Serum Ig Secretory Ig Pentameri ___ Reagenic

Name c Ig Ig
Other -can -predominant - -involved - asso. w/
Notes cross the Ig in secretion predomina in B cell Immediat
placenta -with J chain nt Ig in 1º activation e
except -exist as immune - Hypersens
IgG2 monomer in response susceptib itivity
-major Ig serum and -has J le to - binds
in 2º dimer in chain enzyme basophils
Immune secretion degradati and mast
response on cells
-Heat & - elevated
Acid during
Labile parasitic
infections
 Protective Functions of
Antibodies:
• 1. enhanced phagocytosis
• 2. virus neutralization (blocking
attachment to its cellular receptor)
• 3. toxin neutralization
• 4. complement mediated lysis
• 5. ADCC – Ab-dependent cell cytotoxicity
 Complement
• Pfeiffer 1894
• Pathways
• Destruction of complement –
anticoagulant, heating, normal serum
inhibitor, storage
• Hypocomplementemia
 COMPLEMENT SYSTEM
• a set of proteins that play a role in cytolytic
destruction of cellular antigens by specific
antibody
 Complement Proteins
Serum protein Molecular Weight (kD) Concentration (ug/ml)
C1q 410 150
C1r 85 50
C1s 85 50
C4 205 300 – 600
C2 102 25
C3 190 1,200
C5 190 80
C6 110 45
C7 100 90
C8 150 55
C9 70 60
Factor B 93 200
Factor D 24 2
Properdin 55 15 - 25
Biologic Effects of Complement
• 1. cytolysis of bacteria, viruses, infected
cells and tumor cells via MAC which leads
to loss of osmotic integrity and cell lysis
• 2. chemotaxis
• 3. opsonization – organisms & Ag-Ab
complexes become coated with molecules
that bind to receptors on phagocytes
• 4. anaphylatoxins promote vasodilation
and increased vascular permeability
 Complement
• Classical – triggered after Abs bind to microbes
or other Ags; component of humoral arm of
adaptive immunity
• Alternative/properdin – complement proteins
activated on microbial surfaces; component of
innate immunity
• Lectin – binding to terminal mannose on surface
glycoproteins of microbes; component of innate
immunity
 its active form Bb with the
participation of C3
-Bb will cleave C3 into C3a
and C3b and will combine
with C3b to form C3bBb
b. Factor D - cleaves Factor
B into Bb in the presence of
C3 and Mg++ ions
Therefore,
dFactor B + Factor D + C3
. C5, C6, C7, C8, C9 - MEMBRANE ATTACK PHASE
UNITS
-
 Classical Pathway
• Recognition Unit
– C1 (w/ 3 subunits – C1q,r,s) particularly C1q
binds to Ab
– Stabilized by Ca++ (C1r, C1s remain
associated w/ C1q)
• Activation Unit
– The formation of C5 convertase : C4,C2, C3
• MAC
– C5-C9
 The Alternative Pathway
 Recognition unit
 Does not require Abs
 Triggers include:
 Bacterial cell walls (esp. w. LPS)
 Fungal cell walls
 Yeast
 Viruses
 Virally infected cells
 Tumor cell lines
 Some parasites (esp. trypanosomes)
 Activation Unit
 C5 convertase: C3bBbBb
 MAC
 C5- C9
 Lectin Pathway
 Recognition unit
 Does not require Abs
 MASP-1,-2,-3 complex attaches to:
 MANNOSE/MANNAN
 Others include glycoproteins or CHO on bacteria,
yeasts, viruses, some parasites
 Calcium dependent
 Activation Unit
 C5 convertase: C3b4b2a
 MAC
 C5- C9
 The Complement Proteins
Lectin Pathway (Stevens, 2010)

Serum MW, kD Conc Function

Protein (µg/mL)
MBL 200-600 0.0002-10 Binds to mannose

MASP-1 93 1.5-12 Unknown

MASP-2 76 Unknown Cleaves C4 & C2

VATING FACTOR: MANNOSE GROUP
GROU
CHO IN MICROBIAL CE
EFFECTORS:
P/MBL- MANNAN-BINDING PROTEIN
SP – MBP-ASSOCIATED SERINE PR
 CLASSICAL ALTERNATIVE LECTIN

ACTIVATING IMMUNE LPS (bacterial Mannose groups

SUBS. COMPLEXES capsule) on microbial cell
(IgG OR IgM) IgA
RECOGNITION C1q, C1r, C1s C3, Factor B, MBP, MASP-1,
UNIT Factor D MASP-2

C3 CONVERTASE C4b2a C3bBb C4b2a

C5 CONVERTASE C4b2a3b C3bBb3b C4b2a3b

MAC C5b6789 C5b6789 C5b6789

END RESULT CELL LYSIS

 Functions
• Chemotaxin – C5a, C5b, C6, C7
• Immune Adherence – C3b
• Kinin Activator – C2b
• Anaphylotoxins – C3a, C4a, C5a(most
potent)
• Opsonins – C3b, C4b, C5b
• Virus neutralization – C4b, C1
Plasma Complement Regulation
 C1 inhibitor (C1INH) – dissociates C1r and
C1s from C1q
 Factor I – cleaves C3b and C4b
 Factor H – competes for factor B
 C4 binding protein – acts as a cofactor with I
to inactivate C4b
 S protein (vitronectin) – prevents attachment
of the C5b67 complex to cell membrane
 Decay accelerating factor (DAF) –
accelerates dissociation of C3 convertase
 Inhibitors of MAC
• HRF – Homologous Restriction Factor
• CD 59 or MIRL (Membrane Inhibitor of
Reactive Lysis)
 Deficiencies of Complement
Components
 C1 LE-like syndrome
 C2 LE-like syndrome, recurrent infections
 C3 severe recurrent infection
 C4 lupus like syndrome
 C5 Neisseria Syndrome
 C6 Neisseria Syndrome
 C7 Neisseria Syndrome
 C8 Neisseria Syndrome
 C9 no known disease
 C1INH Hereditary Angioedema (HANE)
 DAF and HRF PNH
 Factor H or I recurrent bacterial infections
C1-inhibitor deficiency:
hereditary angioedema
 Disorders of the Immune
System
• Hypersensitivity – types, mechanisms &
examples
• Autoimmunity
• Immunodeficiency – primary vs. acquired
• Amyloidosis
T
INIT
Y
DESCRIPTIVE IATI MECHANISM EXAMPLES
P
ON
E

TIM
NAME
E

Ag induces cross-linking of IgE Systemic anaphylaxis, Local

IgE-mediated 2-30
I bound to mast cells with release anaphylaxis, Hay fever, Asthma,
hypersensitivity mins
of vasoactive mediators Eczema

Ab directed against cell-surface Blood transfusion reactions,

Antibody-mediated
5- antigens mediates cell Haemolytic disease of the
II cytotoxic
8hrs destruction via ADCC or newborn, Autoimmune
hypersensitivity
complement Haemolytic anaemia

Ag-Ab complexes deposited at

Arthus reaction (Localised);
Immune-complex various sites induces mast cell
II 2- Systemic reactions disseminated
mediated degranulation via FcgammaRIII,
I 8hrs rash, arthritis,
hypersensitivity PMN degranulation damages
glomerulonephritis
tissue

24- Memory TH1 cells release

I cell-mediated Contact dermatitis, Tubercular
72hr cytokines that recruit and
V hypersensitivity lesions
s activate macrophages
Primary Immunodeficiencies
 Immunodeficiency Diseases
• T lymphocyte disorders – DiGeorge
• B lymphocyte disorders – Xlinked agmma
• Combined T & B lymphocyte disorders
– Wiskott Aldrich
• Phagocytic disorders
– CGD, Chediak Higashi, Job’s syndrome
• Complement disorders
– PNH, C2 and C3 deficiency
• Job’s – defective mobility of phagocytes;
random movement is normal; directional
motility is impaired
• Lazy Leukocyte syndrome – both random
and directed movement of phagocytes are
defective – failuree to respond to
chemotactic stimuli
 Autoimmunity
• Breakdown of the immune system’s ability
to discriminate between self and non self
• Persistent activation of immunologic
effector mechanisms that alter the function
and integrity of individual cells and organs
 The bar graph shows the
prevalence of the top 10
autoimmune diseases in the
 Autoimmune Diseases
• Organ Specific
– Thyroid – Hashimoto’s, primary myxedema,
thyrotoxicosis
– Stomach – pernicious anemia
– Adrenal – Addison’s
– Pancreas – juvenile RA
• Non organ specific
– Muscles – dermatomyositis
– Kidney – SLE
– Skin – scleroderma
– Joints - RA
 Factors:
• Genetic – HLA, inheritance, females >
• Age – peak = 60 – 70 y/o
• Exogenous – uv rays, drugs, viruses,
chronic infectin, altered Ags (perceived as
non self)
• Immune complex deposition
• Complement activation – release of
mediators of inflammation
 Immunogenic stimuli:
• Hidden / sequestered Agens = Ags that
don’t normally circulate in the blood / fails
to establish immune tolerance
• Altered antigens arise – mutation
• Foreign antigen shared or cross reactive
w/ self antigens or tissue components
 Main autoantibodies:
• Anti – GBM
• ANA
• Anti platelet Abs = ITP
• Anti – Sm (1/3 of SLE)
• Anti sperm
 SYSTEMIC AUTOIMMUNE DISEASES

SYSTEMIC LUPUS
ERYTHEMATOSUS (SLE)

- dse of the connective tissue

- expresses itself as a vasculitis
- it is an IMMUNE COMPLEX
disease characterized by
 SYSTEMIC AUTOIMMUNE DISEASES

SYSTEMIC LUPUS
ERYTHEMATOSUS (SLE)

- dse of the connective tissue

- expresses itself as a vasculitis
- it is an IMMUNE COMPLEX
disease characterized by
Sunlight exposure accentuates this erythematous
rash ("photosensitivity").
 homogenous cytoplasmic
mass that often fills the
cytoplasm of the phagocyte)
- often, LE bodies
are not engulfed by
neutrophils producing
“rosette
formation”
- LE FACTOR - a
7s IgG Antibody which
reacts with
Anti-Centromere Antibody
(ACA) - highly selective for
the CREST variant of
scleroderma

*CREST- calcinosis cutis,

Raynaud’s phenomenon,
Here is a patient with the taut and shiny skin typical of
sclerodactyly. The skin becomes inelastic and it is hard to move
the fingers.
A serious consequence of the "R" in the CREST syndrome
(limited scleroderma) is seen here. The fingertips are blackened
and additional portions of the hand purplish with early
gangrenous necrosis from vasospasm with the Raynaud
phenomenon.
 Rheumatoid Factor (RF)

- group of immunoglobulins that

interact specifically with the Fc portion of
IgG molecules (anti-antibodies)

- primarily, are of the IgM class

 RF
• Felty’s syndrome – RA, splenomegaly,
leukopenia, HLA DR4
 T & B cell assays
• Ficoll Hypaque
• T & B cell function
 Tumor Markers
• AFP
• CEA
• HCG
• PSA
• CA – 125
 Transplantation Immunology
• Autograft
• Syngraft
• Allograft / Homograft
• Xenograft / Heterograft
 Lymphatic System
• Consists of two semi-independent parts
– A network of lymphatic vessels
– Lymphoid tissues and organs scattered throughout
the body
• Lymphatic nodules
• Lymph nodes
• Tonsils
• Spleen
• Thymus
• Returns interstitial fluid and leaked plasma
proteins back to the blood
– Lymph: interstitial fluid once it has entered
lymphatic vessels
Functions of the Lymphatic System

1. Maintains fluid balance in tissues

– Returns three liters of fluid a day back to
the circulation
2. Absorbs fats from the small intestine
– Lacteals: specialized lymph capillaries
present in the intestinal mucosa
• Absorb digested fat and deliver chyle (fatty
lymph) to the blood
3. Defends against microorganisms and
foreign substances
 Lymphatic Vessels
• One-way system
• Lymph flows toward the heart
• Lymph vessels include
– Microscopic, permeable, blind-ended
capillaries
– Lymphatic vessels
– Ducts
• Lymphatic capillaries → Lymphatic
vessels → Lymphatic ducts (largest of
them all)
Lymphatic System

Fig. 19.1
 Lymphatic Vessels
• Lymphatic Capillaries
– Similar to blood capillaries, with modifications
• Very permeable
• Loosely joined endothelial mini-valves
• Withstand interstitial pressure and remain open
– Join to form lymphatic vessels
• Lymphatic vessels have valves that ensure the
one-way flow of lymph
• Lymph is moved by
– Contraction of lymphatic vessel smooth muscle
– Skeletal muscle action
– Thoracic pressure changes
Lymph Formation and Movement

Fig. 19.2
 Lymphatic Vessels
• Lymph is delivered into
one of two large trunks
– Right lymphatic duct:
drains the right upper
arm and the right side
of the head and thorax
– Thoracic duct: arises
from the cisterna chyli
and drains the rest of
the body
Fig. 19.1
 Lymphatic Tissue
• Reticular connective tissue that contains
lymphocytes and other cells
• Can be surrounded by a capsule (lymph
nodes, spleen, thymus)
• Can be non-encapsulated (diffuse lymphatic
tissue, lymphatic nodules, tonsils)
• Diffuse lymphatic tissue consists of dispersed
lymphocytes and has no clear boundaries
• Lymphatic nodules are small aggregates of
lymphatic tissue (e.g., Peyer’s patches in the
small intestines)
Lymphatic Tissue and Organs
• Peyer’s patches:
– Isolated clusters of lymphoid tissue, similar to
tonsils
– Found in the wall of the distal portion of the small
intestine
– Similar structures are found in the appendix
• Peyer’s patches and the appendix:
– Destroy bacteria, preventing them from breaching
the intestinal wall
– Generate “memory” lymphocytes for long-term
immunity
Fig. 19.3
Lymphatic Tissue and Organs
• Tonsils
– Simplest lymphoid organs
– Form a ring of lymphatic tissue around the pharynx
– Location:
• Palatine tonsils: either side of the posterior end of the
oral cavity
• Lingual tonsils: lie at the base of the tongue
• Pharyngeal tonsil: posterior wall of the nasopharynx
– Epithelial tissue overlying tonsil masses
invaginates, forming blind-ended crypts
– Crypts trap and destroy bacteria and particulate
matter
Fig. 19.4
Lymphatic Tissue and Organs
• Lymph nodes
– Principal lymphoid organs of the body
– Embedded in connective tissue and clustered
along lymphatic vessels
– Aggregations of these nodes occur near the body
surface in inguinal, axillary, and cervical regions of
the body
– Two basic functions:
• Filtration: macrophages destroy microorganisms and
debris
• Immune system activation: monitor for antigens and
mount an attack against them
Lymph Node

Fig. 19.5
Lymphatic Tissue and Organs
• Lymph nodes (cont.)
– Nodes are bean shaped and surrounded by
a fibrous capsule
– Trabeculae extended inward from the
capsule and divide the node into
compartments
– Nodes have two
histologically
distinct regions:
a cortex and a
medulla

Fig. 19.5
 Lymphatic Tissue and Organs
• Lymph nodes (cont.)
– Cortex contains follicles with germinal
centers, heavy with dividing B cells
– Dendritic cells nearly encapsulate the
follicles
– T cells circulate continuously among the
blood, lymph nodes, and lymphatic stream
– Deep cortex
houses T cells in
transit

Fig. 19.5
Lymphatic Tissue and Organs
• Spleen
– Is in the left superior side of the abdomen
– Two distinct areas:
• White pulp: contains mostly lymphocytes
suspended on reticular fibers and are involved
in immune functions
• Red pulp: remaining splenic tissue concerned
with disposing of worn-out RBCs and
bloodborne pathogens
– The spleen is a limited reservoir for blood
Fig. 19.6
Lymphatic Tissue and Organs
• Thymus
– A bilobed organ that secretes hormones
(thymosin and thymopoietin) that cause T
lymphocytes to become immunocompetent
– Size of the thymus varies with age:
• In infants, it is found in the inferior neck and
extends into the mediastinum where it partially
overlies the heart
• It increases in size and is most active during
childhood
• It stops growing during adolescence and then
gradually atrophies
Lymphatic Tissue and Organs
• Thymus (cont.)
– Differs from other lymphoid organs in
important ways
• It functions strictly in T lymphocyte maturation
• It does not directly fight antigens
– The stroma of the thymus consists of star-
shaped epithelial cells (not reticular fibers)
– These thymocytes secrete the hormones
that stimulate lymphocytes to become
immunocompetent
Thymus

Fig. 19.7
 Fig. 19.8
Overview of
the Lymphatic
System
 Immunity
• The ability to resist the harmful effects of
microorganisms and other foreign
substances
– Adaptive immunity exhibits specificity and
memory
– Innate immunity does not show specificity
or memory
 Innate Immunity
• Responds quickly and consists of:
– Mechanical mechanisms
• Skin and mucosae prevent entry of
microorganisms
• Tears, saliva, and mucus remove them
– Chemical mediators
– Cells
– Inflammatory Response
 Innate Immunity
• Chemical mediators promote phagocytosis
and inflammation (Tab. 19.1)
 Innate Immunity
• Complement
– Each complement pathway involves a
cascade in which compliment proteins are
activated in an orderly sequence. The end
result is cell lysis, phagocytosis, and
inflammation
– Refers to a group of 20 or so proteins that
circulate in the blood in an inactive form
– Provides a major mechanism for destroying
foreign substances in the body
– Amplifies all aspects of the inflammatory
response
– Kills bacteria and certain other cell types (our
cells are immune to complement)
 Innate Immunity
• Complement (con’t.)
– Can be activated by either the classical or
the alternative pathway
• Classical pathway is part of adaptive immunity
– Depends on the binding of antibodies to invading
organisms
– Subsequent binding of C1 to the antigen-antibody
complexes (complement fixation)
• Alternative pathway is part of innate immunity
– Triggered by interaction among factors B, D, and
P, and polysaccharide molecules present on
microorganisms
Fig. 19.9
 Innate Immunity
• Interferons
– Leave the infected cell and enter
neighboring cells
– Stimulates the neighboring cells to produce
proteins to prevent the replication of viruses
– Activate macrophages and natural killer
cells
 Innate Immunity
• Cells
– Chemotaxis is the ability of white blood cells to
move to tissues that release certain chemicals
– Phagocytosis is the ingestion and destruction of
materials.
– Neutrophils are small phagocytic cells
– Basophils and mast cells release chemicals that
promote inflammation
– Eosinophils release enzymes that reduce
inflammation
– Natural killer cells lyse tumor cells and virus-
infected cells
 Innate Immunity
• Cells
– Macrophages are large phagocytic cells
• Can engulf more than neutrophils can
• In connective tissue they protect the body at
locations where microbes are likely to enter,
and macrophages clean blood and lymph
• Some macrophages have specific names
– Dust cells in the lungs
– Kupffer cells in the liver
– Microglia in the CNS
Tab. 19.2
 Innate Immunity
• Inflammatory Response
– Can be initiated in many ways
• Chemical mediators cause vasodilation and
increase vascular permeability, which allows
the entry of other chemical mediators
• Chemical mediators attract phagocytes
• The amount of chemical mediators and
phagocytes increases until the cause of the
inflammation is destroyed. Then the tissue
undergoes repair
 Innate Immunity
• Inflammatory Response Fig.
– Local inflammation produces the 19.10

symptoms of
• Redness
• Heat
• Swelling
• Pain
• Loss of function
– Symptoms of systemic
inflammation include
• An increase in neutrophil numbers
• Fever
• Shock
Tab. 19.3
 Adaptive Immunity
• The adaptive immune system is a functional
system that:
– Recognizes specific foreign substances
– Acts to immobilize, neutralize, or destroy foreign
substances
– Amplifies inflammatory response and activates
complement
• The adaptive immune system is antigen-
specific, systemic, and has memory
• It has two separate but overlapping arms:
– Antibody-mediated immunity (provided by
antibodies in the blood and lymph)
– Cell-mediated immunity (lymphocytes are involved)
 Adaptive Immunity
• Antigens are large molecules that
stimulate an adaptive immune system
response
• Foreign antigens are not produced by the
body (self-antigens are)
• B cells are responsible for antibody-
mediated immunity
• T cells are involved with cell-mediated
immunity
 Adaptive Immunity
• Origin and Development of Lymphocytes
– B cells and T cells originate in red bone marrow
• B cells are processed in bone marrow
• T cells are processed in the thymus
– Positive selection ensures the survival of lymphocytes that can
read against antigens
– Negative selection eliminates lymphocytes that react against
self-antigens
– A clone is a group of identical lymphocytes that can respond to
a specific antigen.
– B cells and T cells move to lymphatic tissue from their
processing sites
• They continually circulate from one lymphatic tissue to another
 Fig.
19.11
 Adaptive Immunity
• Activation of Lymphocytes
– The antigenic determinant (epitope) is the specific
part of the antigen to which the lymphocyte
responds
• The antigen receptor (T-cell receptor or B-cell receptor)
on the surface of lymphocytes combines with the
antigenic determinant
– MHC class I molecules display antigens on the
surface of nucleated cells, resulting in the
destruction of the cells
– MHC class II molecules display antigens on the
surface of antigen-presenting cells, resulting in the
activation of immune cells
 Fig.
19.12
 Adaptive Immunity
• Activation of Lymphocytes
– MHC antigen complex and costimulation are
usually necessary to activate lymphocytes
• Costimulation involves cytokines and certain surface
molecules
– Antigen-presenting cells stimulate the proliferation
of helper T cells which stimulate the proliferation of
B or T effector cells
 Fig.
19.13
 Adaptive Immunity
• Inhibition of Lymphocytes
– Tolerance is suppression of the immune
system’s response to an antigen
– Tolerance is produced by
• The deletion of self-reactive cells
• The prevention of lymphocyte activation
• Suppressor T cells
Tab. 19.4
 Fig.
19.14
 Adaptive Immunity
• Antibody-Mediated Immunity
– Antibodies are proteins
• The variable region of an antibody combines with
the antigen
• The constant region
activates complement or
binds to cells
• Five classes of antibodies
exist: IgG, 1gM, IgA, IgE,
and IgD

Fig. 19.15
 Fig.
19.15
Tab. 19.5
 Adaptive Immunity
• Antibody-Mediated Immunity
– Antibodies affect the antigen in many ways
• Bind to the antigen and interfere with antigen
activity or bind the antigens together
• Increase phagocytosis by binding to the antigen
and to macrophages
• Can activate complement through the classical
pathway
• Attach to mast cells or basophils and cause the
release of inflammatory chemicals when the
antibody combines with the antigen
 Fig.
19.16
 Adaptive Immunity
• Antibody-Mediated Immunity
– Antibody Production
• The primary response results from the first
exposure to an antigen
– B cells form plasma cells, which produce antibodies and
memory B cells
• The secondary response results from exposure to
an antigen after a primary response
– Memory B cells quickly form plasma cells and additional
memory B cells
 Fig.
19.17
 Adaptive Immunity
• Cell-Mediated Immunity
– Cells infected with intracellular microorganisms
process antigens that combine with MHC class I
molecules
– Cytotoxic T cells are stimulated to divide,
producing more cytotoxic T cells and memory T
cells, when MHC class I/antigen complexes are
presented to T-cell receptors
– Cytokines released from helper T cells also
stimulate cytotoxic T cells
 Adaptive Immunity
• Cell-Mediated Immunity
– Cytotoxic T cells lyse virus-infected cells, tumor
cells, and tissue transplants
– Cytotoxic T cells produce cytokines, which promote
phagocytosis and inflammation
 Fig.
19.18
 Fig.
19.19
 Fig. 19.20
• Immune interactions
• Innate immunity,
antibody-mediated
immunity, and cell-
mediated immunity
can function together
to eliminate an
antigen
Acquired Immunity

Fig. 19.21
Page
595