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Dr Raymond F.

Adebiyi
Dr Marc Bergeron

Basic Concepts in Immunity


Department of Microbiology & Immunology
Ross University School of Medicine
Resources
Required Reading:
Basic Immunology: Functions and Disorders of the Immune
System. 5th edition, 2016. Abbas, AK, Lichtman, AH, & Pillai,
S. Elsevier. St. Louis, MO. Chapter 1, pp 1-25

Suggested Reading:
How the Immune System Works, 6th edition, 2019. Lauren
Sompeyrac. Wiley-Blackwell, Lecture 1
Accessible through Canvas:
Student Resources
Resources
 R2 Digital Library
Immunology & Serology
As the title suggests this is
a quick reference, but it is
by no means complete
enough for this course…

Recommended book:
Immunology at a Glance. 10th edition. Playfair, JHL, & Chain,
BM. Wiley-Blackwell. Hoboken, NJ. 2013.
Learning objectives
1. Name the cells of the immune system. Distinguish which are innate cells and which are adaptive cells.
2. Describe the function of the primary and secondary lymphoid organs.
3. In general terms, how do white blood cells get to the site of infection?
4. Where does activation of adaptive cells occur? How and where do activated adaptive cells perform their function?
5. Define the immune response. Explain how recognition and self-discrimination are important principles related to an
immune response.
6. List the main characteristics of the innate immune response. Name the components of an innate response and
discuss the roles of each component. Describe generally how innate immune cells recognize antigen.
7. List the main characteristics of the adaptive immune system. Contrast these characteristics with those of the innate
immune system. Describe in general terms how innate recognition of antigen differs from adaptive recognition of
antigen. Name the components and the roles of each component of the adaptive immune system.
8. Compare and contrast humoral immunity and cell-mediated immunity.
9. Define the following terms: active immunity; passive immunity; natural immunity; artificial immunity. Recognize
specific examples of each type of immunity.
10. Explain the role of apoptosis in immunity. Describe how Fas/FasL interactions induce apoptosis.
Scope of Immunology
• Infectious disease
• Tissue repair
• Allergy/Hypersensitivity
• Autoimmunity
• Immunotherapy (mAbs)
Journal of Reproductive Immunology 116(2016): 7–12

• Transplantation
• Tumor Immunology/Treatment (CAR Therapy)
• Neuroimmunology

• Rapidly advancing!
DEFINITION

Effort to combat potentially hazardous materials

Restoration of normal structure and function


The Immune system is predicated upon
two central principles
• Recognition
– The body must have the capacity to ‘recognize’ the invading material
– Achieved through cell surface receptors that bind ligands on invaders
• Self-discrimination
– An immune response must implicitly be directed at a ‘foreign’
substance to defend self from harm
– The generation of nonself immune cells occurs by the process of
elimination of self-reactive precursors
Who

How What

Where When
Cells of the immune system Histology:
Lymphoid Tissue
Tissues of the immune system Histology:
Lymphoid Tissue
Lymphocyte Histology:
Lymphoid Tissue

recirculation
Roles of the immune system

Primary immunodeficiencies

Prevention of disease through


vaccination

B cell acute lymphoblastic


leukemia (ALL) - CAR therapy

TNF- mAb for treatment of


rheumatoid arthritis
Histology:

Cells of Immune Responses Lymphoid Tissue

Innate Adaptive
• Natural Barriers • B cells
• Phagocytes • T cells
o Dendritic cells
o Neutrophils
o Macrophages
• Mast cells, Eosinophils,
Basophils
• Complement
Characteristics of Immune Responses
Innate Adaptive
• Group-specific • Antigen-specific
 Multiple, relatively specific  Cells express a unique
antigen receptors per cell antigen receptor
 Recognize antigen based on • Called upon only when
common structural motifs necessary
 Recognize antigen marked • Slow response
by complement • Long-lived
• Always present/Immediate  Second response against
response pathogen is better, faster,
• Short-lived and stronger than first
 No memory  “Immunological Memory”
Phases of immunological action

COGNITIVE PHASE

ACTIVATION PHASE

EFFECTOR PHASE
INNATE IMMUNITY
COGNITIVE phase – INNATE immunity

Cognitive functions mediated by Pattern Recognition


Receptors (PRRs):
– Limited in number (dozens)
– Specificity is predetermined and fairly
broad (generally respond to groups of organisms)
– Same for all cells
– Little or no expansion upon stimulation
Cognitive phase –
Innate immunity
Type 1 PRRs – Secreted PRRs:
• Circulate in blood and lymph
• Mannan binding lectin, a collectin – binds
to CHO on bacteria to initiate complement
activation
• Other C-type lectin receptors and C-
reactive protein function similarly
• Produced by the liver
• Induced by IL-6
Cognitive phase –
Innate immunity
Type 2 PRRs – Phagocytosis PRRs/Scavenger Receptors:

• High affinity for mannose residues


• Bind to bacteria
• Facilitate phagocytosis
• Pathogen-derived proteins are presented to T cells (antigen
processing and presentation)
Cognitive phase –
Innate immunity
Type 3 PRRs – Signaling receptors:
TLRs (Toll-like receptors):
– Homologous to toll receptors
– On macrophages, dendritic cells, and epithelial cells (cell membrane and on
endosomes)
– Binding to pathogens results in activation of signal transduction and expression of
cytokine genes

NLRs (Nod-like receptors):


– Nucleotide oligomerization domain-like receptors (cytosolic)

RLRs (RIG-like receptors):


– Retinoic acid-inducible gene-like receptors (cytoplasmic)
Microbial ligands recognized by PRRs
PRRs bind to unique microbial structures:
– Pathogen-Associated Molecular Patterns – PAMPs
– Microbe-Associated Molecular Patterns – MAMPs
– Bacterial-Associated Molecular Patterns – BAMPs
– Damage-Associated Molecular Patterns – DAMPs
PAMPs:
– Not shared with the host
– Common to many pathogens
– Invariant
PRRs recognize specific PAMPs
ADAPTIVE IMMUNITY
COGNITIVE phase –
ADAPTIVE immunity

Cognitive functions mediated by unique cell surface receptor:


– Specific to each cell (each B cell and T cell express
receptors of only one specificity)
– Receptor is generated by recombination of genes
encoding the receptor (germline gene rearrangement)
– Rearrangements are random, and are antigen
independent
– Allows for high degree of diversity in antigen receptors
(many lymphocytes of only one specificity)
– Expanded upon stimulation
COGNITIVE phase –
ADAPTIVE immunity

Take home message:


– Specificity is guaranteed by having each cell only
carry receptors specific for one antigen
– Diversity is ensured by the staggering number of
lymphocytes, each possessing specificity for only
one antigen
COGNITIVE phase –
ADAPTIVE immunity

To illustrate:
Adaptive immune recognition
Cognitive phase
Comparison of BCR vs TCR

Recognizes many
different kinds of antigen Recognizes only peptides

B cell receptor T cell receptor


B cells and T cells express
a unique antigen receptor

The Immune System Fig 3.4 Garland Science 2009


Characteristics of Receptors
Adaptive Immunity
T cells
• How do they recognize antigen? • How do they recognize antigen?

• What do they do in response to


• What do they do in response to antigen?
antigen?
• Cytokines
• Cell-surface interactions
Types of adaptive immunity
Properties of adaptive immune system

1. Specificity
2. Diversity
3. Clonal expansion
4. Anamnestic reaction
(Secondary response)
(Booster response)
5. Memory
Time course of adaptive immune response
Types of immune responses
(Refinements)
The Immune Response
Lectures on B cells,
antigen & antibodies
INTEGRATIVE
Lecture on INTERACTIVE
Cytokines SESSION AT
THE END

Lecture on
Innate
Immunity

Lecture on
complement

Lecture on antigen
presentation & T cells
Overview
Lymph drains
antigen and innate
Innate cells to secondary
Recognition lymphoid tissue
Activation of B
cells and T cells

Antibodies & Killer T cells kill


cytokines trigger infected cells
additional
T cells become
functions
effector cells, B
cells secrete
antibodies
Effector T cells and
antibodies traffic
to site of infection
THE END

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