Medical Microbiology & Immunology
Guri Tzivion, PhD
tzivion@windsor.edu
Extension 506
MICR 600: Winter 2016
Windsor University School of Medicine
Dr. Guri Tzivion (tzivion@windsor.edu)
 PhD, Immunology and Microbiology, the Hebrew
University, Jerusalem, Israel
 Postdoc, Molecular Cancer Biology, Harvard Medical
School, Boston, MA
 Assistant Professor, Texas A&M Medical School
 Associate Professor, Karmanos Cancer Center &
Pathology, Wayne State University, Detroit, MI
 Associate Professor, Cancer Institute & Biochemistry,
University of Mississippi Medical School, Jackson, MS
Dr. Guri Tzivion
 Research Interests:
Mechanisms of signal transduction involved in cancer
pathogenesis, specifically the Ras-Raf-MAPK
pathway and the PI3K-AKT pathway.
Modulators of the Nicotinamide-sirtuin pathway as
potential therapeutic agents in metabolic disorders
and aging.
Class Outline
Lecture 1: Immunology Introduction: Basic
Concepts and Components of
the Immune System, Innate
Immunity
Lecture 2: Adaptive Immune Responses,
Antigens, Antibodies and Cellmediated Immunity
Class Outline
Lecture 3: Major Histocompatibility
Complex, Transplantation and
graft rejection
Lecture 4: Immunological Methods and
Diagnostics, Hypersensitivity
and Allergy
Class Outline
Lecture 5: The Complement System
Lecture 6: Tolerance and Autoimmune
Diseases
Lecture 7: Cancer Immunity and
Immunodeficiency
NBME Microbiology Exam Topics
Microbiology Module (125 items)
General Principles:
Biochemistry, Molecular Biology, Genetics, Tissue Response to
Disease, Pharmacodynamic/Pharmacokinetic Processes,
Microbial Biology and Infection, Microbial classification and
its basis, Bacteria and bacterial diseases, Viruses and viral
diseases, Fungi and fungal infections, Parasites and parasitic
diseases, Principles of sterilization and pure culture techniques
Immune Responses
Organ Systems:
Hematopoietic & lymphoreticular, Central & peripheral nervous
Skin & related connective tissue, Musculoskeletal, Respiratory
Cardiovascular, Gastrointestinal, Renal/urinary, Reproductive
Immunology Module (25 items):
Immunologic Processes, Immunologic Diseases
NBME Sample Question
11. During an experiment, an investigator gently abrades the
skin from the flank of a mouse, creating a 1 × 2-cm skin
window. A glass cover slip is then placed over the area so
that cells attracted to the site attach to the cover slip for
assessment. Two hours later, an extravasation of cells from
the vasculature is noted on the cover slip. Which of the
following complement components is the direct cause of the
enhanced vascular permeability and chemoattraction in the
abraded skin area in this experiment?
(A) C1q
(B) C4b
(C) C5a
(D) C7
(E) C9
NBME Sample Question
11. During an experiment, an investigator gently abrades the
skin from the flank of a mouse, creating a 1 × 2-cm skin
window. A glass cover slip is then placed over the area so
that cells attracted to the site attach to the cover slip for
assessment. Two hours later, an extravasation of cells from
the vasculature is noted on the cover slip. Which of the
following complement components is the direct cause of the
enhanced vascular permeability and chemoattraction in the
abraded skin area in this experiment?
(A) C1q
(B) C4b
(C) C5a
(D) C7
(E) C9
NBME Sample Question
12. An investigator injects an experimental animal with a
newly discovered bacterial strain to evaluate T-lymphocyte
activation. It is found that bacterial engulfment by
macrophages results in the presentation of bacterialderived peptide ligands to CD4+ T lymphocytes. Which of
the following cell-surface molecules on the macrophage is
most directly involved in the presentation of the processed
peptides?
(A) CD28
(B) Class II MHC
(C) Fcε receptor
(D) Interleukin-2 (IL-2) receptor
(E) Membrane immunoglobulin
NBME Sample Question
12. An investigator injects an experimental animal with a
newly discovered bacterial strain to evaluate T-lymphocyte
activation. It is found that bacterial engulfment by
macrophages results in the presentation of bacterialderived peptide ligands to CD4+ T lymphocytes. Which of
the following cell-surface molecules on the macrophage is
most directly involved in the presentation of the processed
peptides?
(A) CD28
(B) Class II MHC
(C) Fcε receptor
(D) Interleukin-2 (IL-2) receptor
(E) Membrane immunoglobulin
Student evaluations
Block Exam 1: 30% (10 Immunology questions)
Block Exam 2: 30% (no Immunology questions)
NMBE Exam: 30% (has up-to 20% questions
related to Immunology topics)
Class assignments quizzes and lab: 10%
Textbook and other recommended readings:
1. Textbook: Kuby Immunology, 7th Edition.
Judy Owen, Jenni Punt and Sharon Stranford.
Publisher: Freeman, W. H. & Company
2. Alternative textbook: Cellular and Molecular
Immunology, 8th Edition.
Abul K. Abbas, Andrew H. H. Lichtman, Shiv Pillai
publisher: Elsevier Health Sciences.
3. Review of Medical Microbiology and Immunology,
14th Edition
Warren Levinson
Publisher: McGraw-Hill Professional Publishing.
MICR 600 MDIII Immunology
Class 1
Immunology Introduction
Basic Concepts and Components
of the Immune System
Innate Immunity
Two kinds of the immune system:
 Innate immunity
 Adaptive immunity
Innate Immunity or Nonspecific Immunity
 Is present before any exposure to pathogens and
is effective from the time of birth
 Involves nonspecific responses to pathogens
 Consists of external barriers plus internal cellular
and chemical defenses
Adaptive Immunity
 Also called specific immunity or acquired
immunity
 Develops only after exposure to inducing agents
such as microbes, toxins, or other foreign
substances
 Involves a very specific response to the pathogen
The Immune Response
INNATE IMMUNITY
(all animals)
• Recognition of traits shared
by a broad range of
pathogens using a small
set of receptors
• Rapid response
ADAPTIVE IMMUNITY
(vertebrates only)
• Recognition of traits
specific to particular
pathogens using a large
array of receptors
• Slower response
Pathogens
(such as bacteria,
fungi, and viruses)
Barrier defenses:
Skin
Mucousal membranes
Secretions
Internal defenses:
Phagocytic cells
Natural killer cells
Antimicrobial proteins
Inflammatory response
Humoral response:
Antibodies defend against
infection in body fluids
Cell-mediated response:
Cytotoxic cells defend
against infection via cells
Innate Immunity of Invertebrates
● In insects for example, an exoskeleton made of
chitin forms the first barrier to pathogens
● Their digestive system is protected by a chitinbased barrier and secreted lysozyme that helps
in breaking down bacterial cell walls
● They also have hemocytes circulating within
their hemolymph that carry out phagocytosis
Phagocytosis
Pathogen
PHAGOCYTIC
CELL
Vacuole
Lysosome
(contains
degrading
enzymes)
Innate Immunity of Vertebrates
● Innate defenses include barrier defenses,
phagocytosis and antimicrobial proteins and
peptides
● The vertebrate-specific defenses include:
natural killer cells, interferons and inflammatory
responses
Components of Innate Immunity:
 Physical barriers
 Phagocytic cells
 Immunological surveillance
 Interferons and and other cytokines
 Complement system
 Inflammation
 Fever
Barrier Defenses
● Barrier defenses include the skin and mucous
membranes of the respiratory, urinary, and
reproductive tracts
● Mucus traps microbes and promotes their
removal
● Various body fluids including saliva, mucus, and
tears provide hostile environment to microbes
● The low pH of skin and the digestive system
prevents growth of many bacteria
First line barriers to infection
 Intact skin is a barrier that cannot normally be
penetrated by bacteria or viruses although even
very small abrasions may allow their passage
 Likewise, the mucous membranes that line the
digestive, respiratory, and genitourinary tracts bar
the entry of potentially harmful microbes
First line barriers to infection: secretions
 Secretions from sebaceous and sweat glands give the
skin a pH ranging from 3 to 5, which is acidic enough
to prevent colonization by many microbes
 Microbial colonization is also inhibited by the
washing action of saliva, tears and mucous secretion
 All these secretions contain antimicrobial proteins
 One of these, lysozyme, digests the cell walls of
bacteria, helping in their destruction
Second line barriers
 Microbes that penetrate the first line defenses face
the second line defense, which depends mainly on
phagocytosis (the ingestion of invading organisms
by certain types of white blood cells).
 Phagocyte function is intimately associated with an
effective inflammatory response and also with
certain antimicrobial proteins.
 Phagocytic cells recognize groups of pathogens by
surface receptors called Toll-Like Receptors (TLRs).
Toll-Like Receptors and select pathogen targets
EXTRACELLULAR
Lipopolysaccharid
FLUID
Helper e
protein
Flagellin
TLR4
PHAGOCYTIC
CELL
TLR5
VESICLE
CpG DNA
TLR9
TLR3
ds RNA
Innate immune
responses
Innate immune response to injury
Pathogen
Mast
cell
Splinter
Macrophage
Signaling
molecules
Capillary
Red
Neutrophil
blood cells
Movement
of fluid
Phagocytosis
● There are several types of phagocytic cells:
o Neutrophils engulf and destroy pathogens
o Macrophages are found throughout the body but
accumulate at injury sites and secrete inflammatory
cytokines
o Dendritic cells stimulate development of adaptive
immunity
o Eosinophils discharge destructive enzymes
Neutrophils
 Constitute about 60 - 70% of all leukocytes (white
blood cells)
 Cells damaged by invading microbes release
chemical signals that attract neutrophils from the
blood
 The neutrophils enter the infected tissue, engulf the
microbes and destroy them
 Neutrophils tend to self-destruct as they destroy
foreign organisms, and their average life span is
only few days
Eosinophils
 About 1.5% of all leukocytes
 Contribute to defense against large parasitic
invaders, such as the blood fluke, Schistosoma
mansoni
 Eosinophils position themselves against the
external wall of a parasite and discharge
destructive enzymes from cytoplasmic granules
Monocytes & Macrophages
 Constitute
about
5%
of
leukocytes
 Provide an effective phagoytic
defense
 They migrate into tissues from
the blood and develop into
macrophages
 They extend long pseudopodia
that can attach to polysaccharides
on the microbe’s surface,
engulfing the microbes by
phagocytosis, and fusing the
resulting vacuole with a lysosome
Monocytes vs M
DENDRITIC CELLS
• Originate in the bone
marrow
• Function as antigen
presenting cells (APC).
• Four types of dendritic
cells are –
Langerhan’s cells
Interstitial dendritic cells
Myeloid cells
Lymphoid dendritic cells
Classes of innate
immune cells
- Monocyte/Macrophage
- Dendritic cell (DC)
- Polymorphonuclear
granulocytes (PMN): Neutrophil,
Eosinophil, Basophil
- Mast cell
The various types of
immune cells
● Cellular innate defenses in vertebrates also
involve natural killer cells
● These cells circulate through the body and detect
abnormal cells (cancer or virus-infected cells)
● They release chemicals leading to target cell
death, inhibiting the spread of virally infected or
cancerous cells
THE INFLAMMATORY RESPONSE
 Damage to tissue by a physical injury or by the
entry of a microorganisms triggers a localized
inflammatory response
 One of the chemical signals is histamine
 Histamine is released by circulating leukocytes
called basophils and by mast cells in connective
tissues
1. Cells of a tissue injured by physical damage or bacteria release
chemical signals such as histamine and prostaglandin
2. In response to the signals, nearby capillaries dilate and became more
permeable. Fluid and clotting elements move from the blood to the
site and clotting begins.
3. Chemokines released by cells attract phagocytic cells from the blood
4. Phagocytic cells absorbe pathogens and cell debris promoting tissue
healing
Antimicrobial Peptides and Proteins
● Peptides and proteins function in the innate
immune system by attacking pathogens or
impeding their reproduction
● Interferon promotes innate defenses by
interfering with virus reproduction and activating
macrophages
● About 30 proteins make up the complement
system, which causes lysis of invading cells
and triggers inflammation
Inflammatory Responses
● The inflammatory response, such as pain and
swelling, is brought about by molecules released
upon injury or infection
● Mast cells release histamine, which triggers
blood vessels to dilate and become more
permeable
● Activated macrophages and neutrophils release
cytokines, signaling molecules that enhance
the immune response and induce fever
● Inflammation can be either local or systemic
(throughout the body)
● Fever is a systemic inflammatory response
triggered by pyrogens released by
macrophages and by toxins from pathogens
● Septic shock is a life-threatening condition
caused by an overwhelming or unbalanced
inflammatory response
Evasion of Innate Immunity by
Pathogens
● Some pathogens avoid destruction by modifying
their surface molecules to prevent recognition by
the immune system or by resisting breakdown
following phagocytosis
The lymphatic system
Blood
capillary
Interstitial
fluid
Adenoid
Tonsils
Thymu
s
Peyer’s
patches
(small
intestine)
Lymphatic
vessels
Tissue
cells
Spleen
Lymphatic
vessel
Lymphatic
vessel
Lymph
nodes
Appendix
(cecum)
Lymph
node
Masses of
defensive