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Lectures 1 & 2
The immune system
Overview
Grading:
Exam I
Exam II
State Exam
Lecture highlight
Final oral report
25%
25%
35%
5%
10%
LCME 514 Lectures
Core
Textbook
Oral reports:
A student each lecture will take turn to summarize the last
lecture’s highlights for 5 minutes, and take questions from
other students
Experts in Clinical Immunology
On 4/19/05, each student should present for 5 minutes as if he or she is
an expert immunologist on the disease. This presentation accounts for
10% of the final grade.
The students should include following components in their
presentation:
1. What is the immunological mechanism of the disease? Describe the major
immune components (cells, cytokines or molecules) and their functions in
each disease.
2. What are the diagnosis criteria?
3. What are the therapy options?
Before lecture
Read the textbook and try to understand
all the terminologies in bold.
These are building blocks so that we can
build a “nice house of Immunology” in
the class.
Lecture objectives
What components make up the immune system?
Cells, organs, cytokines and molecules involved in the
immune system
What is the goal of the immune system?
To clear pathogens and cancer cells in our body
Innate and adaptive immune responses
Humoral Immunuty and Cell-Mediated Immunity
What are the side effects of the immune system?
Autoimmune diseases, Allergies, Transplantation Rejection
The goal of the immune system
Figure 1-2
goal of the immune system
Plus tumor cells
Figure 1-3 part 1 of 4
Figure 1-3 part 2 of 4
Figure 1-3 part 3 of 4
Figure 1-3 part 4 of 4
The territory to defend by the immune system: the physical barriers
Figure 1-4
The immune system =The defense system of the body
Innate (immediate) and adaptive (late but antigen-specific) immune
responses
Figure 1-7
Innate and adaptive responses work together
Innate
Adaptive
 Antigen independent
 Immediate (hours)
Antigen-dependent
Slower (days)
 Neutrophils
 NK cells
 Macrophages
T cells
B cells
Dendritic cells
*Innate immune responses help form adaptive
immune responses, and
Adaptive immune responses utilize the machinery
of innate immunity for effector function
Cells of Innate Immunity
Neutrophils
NK cells
Macrophages
Mast cells
Eosinophils
Basophils
Cells of Adaptive Immunity
Dendritic cells
B cells
T cells (CD4 or CD8)
Immune cell recognition of pathogens followed by destruction
Figure 1-5
Infection induces inflammation to recruit more immune cells
Figure 1-6
Hematopoiesis generates immune cells
Stem cells: 1. Self renewal
2. Totipotency
They are in bone marrow after
fetal development.
They make all myeloid and
Lymphoid blood/immune cells
T cell progenitors migrate to
thymus and generate T cells
B cell progenitors reside in
bone marrow to make naïve B
cells
Immune cells = Soldiers
Hematopoiesis occurs in the adult bone marrow
Figure 1-10
Myeloid vs. Lymphoid cells
Myeloid cells
Stem cells
Lymphoid cells
T cells: T cell antigen receptor
B cells: B cell antigen receptor
NK cells: no antigen-specific receptor
Monocytes: Macrophage precursors
 Origin : bone marrow
 Antigen receptors: No
 Function: to become macrophages
 Present in blood circulation
Neutrophils: Phagocytes






Origin and maturation: Bone marrow
Antigen receptors: No
Function: Phagocytosis and killing of microorganisms
Where: in blood circulation
Sites of function: infection sites
Short life span
NK cells: natural killers
 Origin : many (bone marrow and thymus)
 Antigen receptors: No
 Function: Kill tumor and virus-infected cells
 Effector machinery (=weapons): perforins and granzymes
Macrophages: Phagocytosis and antigen presentation
 Origin : bone marrow
 Antigen receptors: No
 Function: phagocytosis of microorganisms and antigen
presentation to T cells
 Present in various tissues in various forms
(Kupffer cells, intraglomerular, alveolar, serosal, microglia,
spleen sinus and lymph node sinus macrophages)
Dendritic cells (DC): transport antigens and activate T
cells
 Origin : bone marrow
 Antigen receptors: No
 Function: antigen presentation to T cells
 Mechanisms: phagocytosis, cytokines (IL-4, IL-10, IL-12)
and antigen-presentation through MHC molecules
 Migration: From tissue infection sites to 2o lymphoid tissues
Mast cells: parasite killers
 Origin : bone marrow
 Antigen receptors: No
 Function: to kill parasites
 Sensor: IgE receptor
 Effector machinery:cytotoxic granules, lipid mediators,
cytokines and chemokines
 Present in connective tissues
Eosinophils: worm (parasites) killers
 Origin : bone marrow
 Antigen receptors: No
 Function: killing of antibody-coated parasites through
release of killing mix (granule contents)
 Effector machinery:cytotoxic granules, lipid mediators,
cytokines and chemokines
Basophils: relatives of mast cells and eosinophils
 Origin : bone marrow
 Antigen receptors: No
 Function: important effector cells in allergic disorders and
immune responses to parasites
 Sensor: IgE receptor
 Effector machinery:cytotoxic granules, lipid mediators,
cytokines and chemokines
T lymphocytes: master regulators of the immune system
 Origin: Bone marrow
 Maturation: Thymus
 Differentiation to effector cells: secondary lymphoid tissues
(Lymph nodes, spleen, Peyer’s patch, and tonsils)
 Antigen receptors: Yes
 Function: regulates humoral and cell-mediated immune
responses
 Mechanisms: cytokines, cell surface molecules,
granules (cytotoxic T cells)
B lymphocytes: antibody producers
 Origin and maturation: Bone marrow
 Differentiation to plasma B cells: secondary lymphoid
tissues (Lymph nodes, spleen, Peyer’s patch, and tonsils)
 Antigen receptors: B cell receptor (cell surface
immunoglobulins)
 Function: Production of antibodies (IgM, IgE, IgA, and IgG)
 Regulated by T cells
B lymphocytes
Antigens+ T cell help
Circulating blood cells
Figure 1-12
Neutrophils: disposable phagocytes to clear pathogens
Figure 1-13
Macrophages engulf bacteria and produce inflammatory
cytokines
Figure 1-14
The lymphatic system
Figure 1-15
Naïve lymphocytes encounter pathogens’ antigens in lymph nodes
Figure 1-16
Activates lymphocytes
Beginning of adaptive response
Antigens+DCs
T cells
Figure 1-17
B cells undergo differentiation to PC
Figure 1-18
Figure 1-19
Spleen does not have
Afferent Lymphatics
Spleen filters blood
to search for
antigens
Figure 1-20
Antigen receptors of B cells and T cells
Figure 1-21
Antibodies neutralize pathogens in an antigen-specific manner
Figure 1-22
Gene rearrangement to form antigen receptors on lymphocytes
(immunoglobulins and T cell receptors)
Figure 1-23
Antibodies (B cells) bind whole
proteins while TCR (T cells)
binds small peptides
Figure 1-24
Peptides are presented to TCR by MHC class I or II molecules on
APC (antigen presenting cells: B cells, dendritic cells and
macrophages)
Figure 1-25
Viral antigen presentation to CD8+ T cells via MHC class I molecules
Figure 1-26
Bacterial antigen presentation to Th1 or Th2 CD4+ cells
Figure 1-27
Selection and expansion of antigen specific T and B cells
Figure 1-8
Generation and selection of T cells
Figure 1-28
The thymic selection processes are to
generate T cells with functional TCRs
that are not autoreactive.
Antibodies neutralize and opsonize
Figure 1-29 part 1 of 2
Figure 1-29 part 2 of 2
Typical time course of adaptive immune responses
Primary response
Slow (2 weeks)
Weak
Secondary
Fast (several days)
Vigorous
The impact of vaccination
Unwanted immune response: allergies
Unwanted immune response: autoimmune diseases
The goal of a balanced immune system
Immunity
[Pathogens]= 0
[tumor cells]= 0
Allergy and hypersensitivities
Immune response
to allergens
[Pathogens]= 0
[tumor cells]= 0
Cancer
[tumor cells] >> 0
Immune response
to tumor cells
Autoimmune diseases
Immune response
to self antigens
[Pathogens]= 0
[tumor cells]= 0
Immunodeficiency
[Pathogens] >> 0
[tumor cells] >> 0
Immunity to
pathogens and
cancer cells
e.g. AIDS patients
Immune responses can be both beneficial and harmful
Figure 1-34