Two Types of Immunity

 Innate
– “possessed at birth, possessed as an
essential characteristic”
– Always present
 Adaptive
– “to make suitable to or fit to a specific
use or situation”
– Created and modified
Innate Immunity
 Protection by Skin and Mucous
Membranes
 Phagocytic Cells
– Remove debris (garbage men)
– Macrophages, Neutrophils, Monocytes
 Natural Killer Cells
– Lymphocytes that kill virally infected cells and
tumours
 Complement System
– “complements antibody in the killing of bacteria”
– A group of >30 proteins found in the blood
Lymphocytes

 Two types of lymphocytes

– T-Cells (Thymus derived)
 Natural Killer Cells (Innate Immunity)
 CD4+ T-Cells (helper cells)

 CD8+ T-Cells (cytotoxic cells)

– B-Cells (Bone Marrow derived)

Adaptive Immunity

 Two Components of Adaptive Immune

System
 Humoral (humoral mediated immunity)
– B-Cells  Plasma Cells  Antibodies
 Cellular (cellular mediated immunity)
– CD8+ T-Cells  Direct Cellular Killing
– CD4+ T-Cells  Recruitment of other
immune cells (inflammatory response)
Immune Response
Antigen
 Antigen – “any substance when
introduced into the body stimulates
the production of an antibody”
– Bacteria, fungus, parasite
– Viral particles
– Other foreign material
 Pathogen – an Antigen which causes
disease
Immune Response
Antibodies
 Antibody – “a Y-shaped protein,
found on the surface of B-Cells or free
in the blood, that neutralize antigen by
binding specifically to it”
 Also known as an Immunoglobulin

Antigen
Humoral Mediated
Immunity
Cellular Mediated
Immunity
 Via T-Cells
 CD8+ T-Cell
– Stimulated  Direct Killing
 CD4+ T-Cell
– Th1  Stimulated  Macrophage Activation
– Th2  Stimulated  B-Cell Activation
Cellular Mediated
Immunity
 Remember B-Cells have direct surface
receptors (immunoglobulins) for
antigen!
 T-Cells do not possess these receptors
 Instead, T-Cells need to have antigen
presented to them (like on a silver
platter)
 Antigen is presented to T-Cells by …
Antigen Presenting Cells
 Cellular Mediated
Immunity
 TwoGeneral
Types of Antigen Presenting
Professional
Cells
(APCs)APC APC
All Cells B-Cells, Macrophages,
Dendritic Cells
Present antigen found inside Present antigen found
the cell outside the cell
Use an MHC class I Use an MHC class II
molecule to present antigen molecule to present antigen
Interact with CD8+ T-Cells Interact with CD4+ T-Cells
 Cellular Killing T-Cell Help
General APCs
 All cells in the body are always
“cleaning” themselves
 When they find some “dirt” (viral
protein, normal cellular debris) 
Need to make sure it is not something
harmful
 Attach the “dirt” to an MHC-I molecule
 Present this “dirt” to a CD8+ T-Cell
General APCs &
CD8 T-Cells
+
Professional APCs

 Professional APCs have the ability to

take up (endocytosis) extracellular
proteins (self or foreign)
 Break down this protein into peptides
and attach it to an MHC-II molecule
 Present the peptide to a CD4+ T-Cell
Professional APCs
CD4 Th1-Cells
+
Professional APC
CD4+ Th2-Cells
Summary of Adaptive
Immunity
 Humoral
– Antibody Production – B-Cells
 Cellular
– CD8+ T-Cells  MHC-I  Cytotoxic
– CD4+ Th1-Cells  MHC-II  Activate
Macrophages
– CD4+ Th2-Cells  MHC-II  Activate
B-Cells to produce Antibody
What Prevents the Body
from Attacking Itself?
 Two Concepts
– Central Tolerance
– Peripheral Tolerance
Central Tolerance
 Occurs during lymphocyte (T & B Cells)
maturation in the primary lymphoid organs
(thymus & bone marrow)
 The body presents immature lymphocytes
with self-antigen
 Lymphocytes which react with high affinity
to this self-antigen are deleted (apoptosis)
 Lymphocytes which react with low affinity
are positively selected to mature
Central Tolerance
Peripheral Tolerance
 During maturation, lymphocytes cannot be
presented with every self-antigen
– Some antigens are found in low concentrations
in specific locations
– New antigens are formed during life
 Therefore, lymphocytes come in contact
with new antigen
 Particular importance to the cytokine
environment present when lymphocytes
encounter this new antigen
Rheumatoid Arthritis (RA)

 RA is thought to be T-Cell mediated

 Most widely accepted hypothesis:
– Professional APC encounters some
“unknown” antigen
– It presents this “unknown” antigen to a
CD4 T-helper Cell
– In a genetically predisposed individual,
this starts an immune chain reaction
Cellular components of synovial inflammation

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Mechanisms in Rheumatology ©2001

Rheumatoid Arthritis
 Certain cytokines are important in
driving the inflammatory process in RA
 Two important cytokines are
– Tumour Necrosis Factor – alpha (TNF-α)
– Interleukin-1 (IL-1)
 Rheumatologists have developed new
medications which target these
cytokines
Rheumatoid Arthritis

 Drugs which inhibit TNF-α

– Infliximab (Remicade®) – Chimeric
monoclonal antibody directed against
TNF-α
– Etanercept (Enbrel®) – Soluble receptor
which “floats” around and mops up any
TNF-α
Infliximab (Remicade®)
Infliximab: Mechanism of action

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Mechanisms in Rheumatology ©2001

Etanercept (Enbrel®)
Etanercept: Mechanism of action

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Mechanisms in Rheumatology ©2001

Ankylosing Spondylitis

 Up to 90% of white patients with AS

are positive for HLA-B27
 HLA-B27 is an MHC Class I molecule
HLA-B27
Ankylosing Spondylitis

 Remember – MHC is part of the

adaptive immune system – so
everybody is different
 Those people with HLA-B27 type of
MHC Class I are at higher risk for
developing AS
 But Why?
Ankylosing Spondylitis

 The HLA-B27 molecule has a specific

binding groove
 Only certain peptide fragments will fit
into this binding groove
 Big Question: What peptide fragment
could be responsible for the initiation
of Ankylosing Spondylitis?
 Summary

 Innate and Adaptive Immunity

 B-Cells
– Act as Professional APCs for Th2-Cells
– Turn into plasma cells and synthesize
antibody
 T-Cells
– Natural Killer Cells – Innate Immunity
 Summary

 CD8 T-Cells
– Interact with MHC Class I (any cell)
– Direct Cellular Killers
 CD4 T-Cells
– Interact with MHC Class II (professionals)
– Th1– Cellular activation - Macrophages
– Th2– B-Cells - Antibody