Immunity
Overview of the Immune System
Immune System
Adaptive
Innate
(Specific)
(Nonspecific)
2o line of defense
1o line of defense
Protects/re-exposure
Cellular Components Humoral Components Cellular Components Humoral Components
Interactions between the two systems
Comparison of Innate and Adaptive
Immunity
Innate Immunity Adaptive Immunity
• No time lag • A lag period
• Not antigen specific • Antigen specific
• No memory • Development
of memory
Cells of the Immune System
Immune System
Myeloid Cells Lymphoid Cells
Granulocytic Monocytic T cells B cells NK cells
Neutrophils Macrophages Helper cells
Basophils Kupffer cells Suppressor cells Plasma cells
Eosinophils Dendritic cells Cytotoxic cells
Development of the Immune
System
ery pl neu mφ
nk
CD8+ CTL
CD4+
TH1
thy
TH2
mye
lym
Function of the Immune System
(Self/Non-self Discrimination)
• To protect from pathogens
• Intracellular (e.g. viruses and some bacteria
and parasites)
• Extracellular (e.g. most bacteria, fungi and
parasites)
• To eliminate modified or altered self
Effects of the Immune System
• Beneficial:
• Protection from Invaders
• Elimination of Altered Self
• Detrimental:
• Discomfort and collateral damage (inflammation)
• Damage to self (hypersensitivity or autoimmunity)
Overview of the Immune System
Immune System
Innate Adaptive
(Nonspecific) (Specific)
Cellular Components Humoral Components Cellular Components Humoral Components
Innate Host Defenses Against Infection
• Anatomical barriers
– Mechanical factors
– Chemical factors
– Biological factors
• Humoral components
– Complement
– Coagulation system
– Cytokines
• Cellular components
– Neutrophils
– Monocytes and macrophages
– NK cells
– Eosinophils
Anatomical Barriers - Mechanical Factors
System or Organ Cell type Mechanism
Skin Squamous epithelium Physical barrier
Desquamation
Mucous Membranes Non-ciliated epithelium Peristalsis
(e.g. GI tract)
Ciliated epithelium (e.g. Mucociliary elevator
respiratory tract)
Epithelium (e.g. Flushing action of
nasopharynx) tears, saliva,
mucus, urine
Anatomical Barriers - Chemical Factors
System or Organ Component Mechanism
Skin Sweat Anti-microbial fatty
acids
Mucous Membranes HCl (parietal cells) Low pH
Tears and saliva Lysozyme and
phospholipase A
Defensins (respiratory & GI Antimicrobial
tract)
Sufactants (lung) Opsonin
Anatomical Barriers - Biological Factors
System or Organ Component Mechanism
Skin and mucous Normal flora Antimicrobial
membranes substances
Competition for
nutrients and
colonization
Humoral Components
Component Mechanism
Complement Lysis of bacteria and some viruses
Opsonin
Increase in vascular permeability
Recruitment and activation of phagocytic cells
Coagulation system Increase vascular permeability
Recruitment of phagocytic cells
Β-lysin from platelets – a cationic detergent
Lactoferrin and Compete with bacteria for iron
transferrin
Lysozyme Breaks down bacterial cell walls
Cytokines Various effects
Cellular Components
Cell Functions
Neutrophils Phagocytosis and intracellular killing
Inflammation and tissue damage
Macrophages Phagocytosis and intracellular killing
Extracellular killing of infected or altered self
targets
Tissue repair
Antigen presentation for specific immune
response
NK and LAK cells Killing of virus-infected and altered self targets
Eosinophils Killing of certain parasites
Phagocytosis
and
Intracellular Killing
Phagocytes - Neutrophils (PNMs)
Blood film showing a
monocyte (left) and two
neutrophils © Bristol
Biomedical Image Archive
Used with permission
• Characteristic nucleus,
cytoplasm
• Granules
• CD 66 membrane
marker
Characteristics of Neutrophil
Granules
primary granules secondary granules
azurophilic; specific for mature neutrophils
characteristic of young
neutrophils;
contain cationic proteins, contain lysozyme, NADPH
lysozyme, defensins, oxidase components,
elastase and
lactoferrin and B12-binding
myeloperoxidase protein
Phagocytes - Macrophages
• Characteristic nucleus
• Lysosomes
• CD14 membrane marker
Large Lymphocyte, giemsa stained peripheral blood film © Dr Peter Darben,
Queensland University of Technology clinical parasitology collection. Used with
permission
Phagocyte Response to Infection
• The SOS Signals
– N-formyl methionine-
containing peptides
– Clotting system peptides
– Complement products
– Cytokines released by
tissue macrophages
• Phagocyte response
– Vascular adherence
– Diapedesis
– Chemotaxis
– Activation
– Phagocytosis and killing
Initiation of Phagocytosis
Attachment via Receptors:
IgG FcR
Complement R
ScavengerR
Toll-like R
Phagocytosis
• Attachment
•Pseudopod extension
•Phagosome formation
•Granule fusion
•Phagolysosome formation
Respiratory Burst
Oxygen-Dependent Myeloperoxidase-Independent
Reactions
+
G-6-P-dehydrogenase
Glucose +NADP Pentose-P + NADPH
NADPH oxidase -
NADPH + O2 NADP++ O2
Cytochrome b558
- Superoxide dismutase
2O2 + 2H+ H2O2 + 1O2
- -
2O2 + H2O2 OH* + OH + 1O2
Toxic compounds – Superoxide anion (O2 -), Hydrogen peroxide (H2O2),
Singlet oxygen (1O2) and Hydroxyl radical (OH*)
Respiratory Burst
Oxygen-Dependent Myeloperoxidase-Dependent
Reactions
- myeloperoxidase -
H2O2 + Cl OCl + H2O
- 1O -
2OCl + H2O 2 + Cl + H2O
Toxic compounds – Hypochlorous acid (OCl-), and Singlet oxygen (1O2)
Respiratory Burst
Detoxification Reactions
-
Superoxide dismutase
2O2 + 2H+ H2O2 + O2
Catalase
2 H2O2 H2O + O2
Oxygen-Independent Killing in
the Phagolysosome
Effector Molecule Function
Cationic proteins (cathepsin) Damage to microbial
membranes
Lysozyme Hydrolyses mucopeptides
in the cell wall
Lactoferrin Deprives pathogens of iron
Hydrolytic enzymes (proteases) Digests killed organisms
Summary of Intracellular Killing
Pathways
Intracellular Killing
Oxygen Oxygen
Dependent Independent
Myleoperoxidase Myleoperoxidase
Dependent Independent
Nitric Oxide Dependent Killing
TNF
TNF
Nitric Oxide
Nitric Oxide
Non-specific Killer Cells
NK and Lymphokine activated
killer (LAK) cells They all kill foreign
ADCC (K) cell [antibody- and altered self
dependent cellular cytotoxicity
(ADCC) ] targets
Activated macrophages
Eosinophils
Natural Killer (NK) cells
also known as large granular
lymphocytes (LGL)
kill virus-infected or
malignant cells
identified by the presence of
CD56 & CD16 and absence
of CD3
activated by IL2 and IFN-γ to
become LAK cells
Lymphokine Activated Killer (LAK)
cell
kills
kills
transformed
malignant
and malignant
cells
cells
Regulation of NK Cell Function
•MHC I •KIR •KAR •KAL
•No Killing •Killing
K Cells
morphologically undefined
mediate ADCC
have Fc receptor
recognize antibody
coated targets
could be NK cells (IgG),
macrophages (IgG),
eosinophils (IgE) or other
cells (IgG)
Complement system
• The complement system consists of a number of
small proteins C1 to C9
• synthesized by the liver
• Circulate in the blood as inactive precursors.
1. Membrane attack – by rupturing cell wall of bacteria.
(Classical Complement Pathway)
2. Phagocytosis – by opsonizing antigens. C3b has most
important opsonizing activity. (Alternative Complement
Pathway)
3. Inflammation – attracting macrophages and neutrophils.
(Lectin pathway)- opsonin, mannose-binding lectin (MBL),
and ficolins- serine proteases
Classical & alternative Complement Pathway
Major Histocompatibility Complex (MHC)
• the surface of all nucleated cells of the body. In humans
• the MHC genes are also referred to as human leukocyte
antigen (HLA) genes.
• Mature red blood cells, No MHC
• two classes of MHC molecules involved in adaptive
immunity, MHC I and MHC II
• MHC I molecules are found on all nucleated cells; they
present normal self-antigens as well as abnormal or
nonself pathogens to the effector T cells involved in cellular
immunity.
• MHC II molecules are only found
on macrophages, dendritic cells, and B cells; they
present abnormal or nonself pathogen antigens for the initial
activation of T cells.
