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Introduction
of
Immunology
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Immunology
Immunity : means protection against infections
Immune system: collection of cells and moleculesthat defend us against microbes
Immune deficiencies infections
Immune excesses autoimmune diseases
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Immunology Overview
Types of immunity: Innate and AdaptiveImmunity
Cells and Tissues of the Immune System
Lymphocytes Effector cells
Antigen-presenting cells Lymphoid tissues
Normal Immune Responses
The innate immune response
Capturing and displaying antigens Cell-mediated immunity
Humoral immunity
Immunologic memory
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Innate and Adaptive Immunity
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Innate (Natural) Immunity
Always present (innate); doesnt change over time
First line of defense
Major components:
Epithelial barriers (skin, GI, respiratory) NK cells
Complement
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Second line of defense
More specific (adaptive) and powerful than innate
Major components:
Lymphocytes
Lymphocyte products
Two types of adaptive immunity: Humoral immunity (mediated by antibodies)
Cellular immunity (mediated by T cells)
Adaptive (Acquired) Immunity
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Cells and Tissues of the Immune System
Lymphocytes
Antigen-presenting cells
Effector cells
Lymphoid tissues
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Lymphocytes
Present in blood and in lymphoid organs
Groups
T-lymphocytes (grow up in thymus)
B-lymphocytes (grow up in bone marrow)
Each one has receptors for a specific antigen
Recognize millions of different antigens!
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Live in blood, bone marrow, lymphoid tissues
Two basic functions:
kill stuff
help other cells do their jobs
T-cell receptor (TCR) complex recognizes antigens
binds antigen
sends signals to the T cell
Antigens must be:
displayed by other cells and bound to an MHC(Major Histo-Compatipility) receptor
T- lymphocytes
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The T-Cell Receptor
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The T-Cell Receptor
T cell
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Helper T cells
CD4+ (and CD8-)
help B-cells make antibodies
help macrophages
decreased in patients with AIDS
Cytotoxic T cells
CD8+ (and CD4-)
kill virus-infected cells and tumor cells
T- lymphocytes
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CD8+ T cells surrounding tumor cell
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Collection of genes on chromosome 6
Three types: class I, class II, class III
Highly polymorphic!
Gene products:
class I molecules
class II molecules
class III molecules (and other stuff)
MHC (Major Histo-Compatipility) complex
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class I MHC moleculeclass II MHC molecule
class II MHC genes class I MHC genesclass III MHC genes
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Display antigens from within the cell (e.g.,
viral antigens) to CD8+ T cells.
Present on all nucleated cells!
Class I MHC molecules
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Display extracellular antigens (e.g., bacterial
antigens the cell has eaten) to CD4+ T cells
Present mainly on antigen presenting cells, like
macrophages!
Class II MHC molecules
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Live in blood, bone marrow, lymphoid tissues
Basic function: make antibodies (Immunoglobulins)
B-cell receptor complex recognizes antigens
binds antigen
sends signals to T cells
Antigens can be free and circulating (dont have to be bound to
MHCs or displayed by other cells to be recognized!)
B - lymphocytes
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The B-Cell Receptor
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Belong to innate immunity system
Main job: recognize and kill damaged or infected
cells
Antigens dont have to be bound to MHCs or
displayed by other cells!
Natural Killer Cells
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Natural killer cell
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Natural killer cell (top) killing infected cell (bottom)
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Antigen-presenting cells
Main job: catch antigens and display them to lymphocytes
Dendritic cells
Have fine cytoplasmic projections
Present all over body: skin, lymph nodes, other organs
Capture microbial antigens, display to B and T cells
Other APCs
Macrophages eat microbe and present antigens to Tcells, which tell macrophages to kill microbe
B- cells present antigens to helper T cells, which tell B
cells to make antibodies
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dendritic cells APCs
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Effector cells
These cells carry out the ultimate immune system function:eliminate infection.
Types of effector cells
NK cells
Plasma cells
T cells (both CD4+ and CD8+)
Macrophages
Other leukocytes (e.g., neutrophils)
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Lymphoid tissues
Lymphocytes grow up in primary organs, then travel
to secondary organs, searching for antigens.
Primary organs
Thymus bone marrow
Secondary organs
lymph nodes spleen
Mucosal and Cutaneous lymphoid tissues
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The Innate Immune Response
Main barriers: skin, mucosa
If microbes go through epithelium, they encounter
innate immune system
What happens in the innate immune system?
Phagocytes eat microbes, kill them
Cytokines are released
Complement is activated
The adaptive immune system is activated
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Capturing and displaying antigens
Dendritic cells in epithelium capture microbe antigens,transport them to lymph nodes
APCs in lymph nodes eat antigens, display them to T-cells
B-cells in lymph nodes also recognize antigens
Antigens and molecules produced during innate immune
response trigger proliferation and differentiation of B and T
cells
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Cell-mediated immunity
T cells are activated by antigen and co-stimulators in
lymph nodes
then they proliferate and differentiate into effectorcells that go find the antigen.
CD4+ T cells help macrophages eat microbes
CD8+ T cells kill infected cells directly
All these steps are dependent upon cytokines
How does the process work?
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Cell-5Mediated Immunity
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Polypeptides that do lots of different things:
help leukocytes grow and differentiate
activate T cells, B cells and macrophages
help leukocytes communicate
recruit neutrophils
Made by lymphocytes and macrophages
Examples: TNF, the interleukins, interferon
What are cytokines?
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CD4+ T cells differentiate into two kinds of effector
cells:
TH1 cells (activate macrophages, cause B cells to
secrete Ab)
TH2 cells (activate eosinophils, cause B cells tosecrete IgE)
These cells go to the site of infection, and with the
help of macrophages and cytokines, do their job.
CD8+ T cells differentiate into cytotoxic T cells
These cells kill cells that have microbes in their
cytoplasm.
Types of effector T cells
C ll M di t d I it
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Cell-Mediated Immunity
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Humoral immunity
B cells get activated by exposure to antigens
(sometimes with the help of CD4+ T cells)
B cells differentiate into plasma cells (that make
antibodies)
The antibodies do nasty things to microbes.
How does the process work?
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Plasma cell
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Y-shaped glycoprotein
2 light chains 2 heavy chains
Constant regions of heavy chain form theFc fragment
binds to APCs defines isotype (immunoglobulin
class: IgA, IgE, etc.)
Variable regions of both chains form theFab fragments
binds to antigen
defines idiotype
What is an antibody?
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What do antibodies do?
Bind to and neutralize microbes, so they cantinfect cells.
Coat (opsonize) microbes, making them tasty tomacrophages and neutrophils (which have receptors
for the Fc portion of IgG!
Activate complement.
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The complement
Its a bunch of proteins that poke holes in cells. Consists of about 20 plasma proteins (C1, C2, etc.)
Can be activated in a few different ways
by antigen-antibody complexes
by bacterial Lipo-proteins
End results:
cell lysis
chemotaxis
opsonization
Complement
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Complement,
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Humoral Immunity
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Immunologic memory
Most effector lymphocytes die after killing the
microbes.
A few memory cells live on for years.
expanded pool of antigen-specific lymphocytes
respond faster, better than nave cells
vaccines depend on these cells
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Summary of the Adaptive Immune Response
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Immune Disorders:
Immunodeficiency disorders
AIDS, antibody deficiency
Hypersensitivity Disorders (allergy)
Type-I (IgE), Type-II (IgG), Type-III
(Immunecomplex), Type-IV (Cell mediated).
Autoimmune disorders
SLE, Rhematoid, Rheumatic fever.
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Introduction
Immune response against self antigen resulting in Tissue
damage.
Single organ or systemic multi organ.
Common in females.
Normally immune system is tolerant to self antigens
(learns during fetal development).
Autoimmune disorders result from Defective tolerance,
cross reacting antibodies or antigenic mimicry.
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Rheumatic fever:
Autoimmune disorder.
Group A, streptococcal pharyngitis.
Antibody cross react with connective tissue in
susceptible individuals*
Inflammation - T lymphocytes, macrophages.
Affected organs: Heart, skin, brain & joints.
M h l
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Morphology:
Acute Rheumatic Fever
Acute Inflammatory Phase
Heart: Pancarditis
Skin: Erythema Marginatum
CNS: Sydenham Chorea
Joints: Migratory polyarthritis
Chronic Rheumatic Fever
Deforming fibrotic valvular disease.
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Fish mouth Mitral stenosis:
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Asthma
HypersensitivityAllergy , Type I
Narrowing of airways of lungs - Bronchi
Allergens in the air will stimulate mast cell - IgE antibody.
Inflammation of airwaysBronchitis.
Causes: Genetic, Environmental, Race, Age.
High in industrial cities
Increasing incidence in smokers
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Pathogenesis - Atopic Asthma:
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Asthma Mechanism:
Allergy
Inflammation Of Bronchi
Obstruction
Mucous Plugs
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INFLAMMATION
TRIGGERSExercise
Cold Air, diseases,
AirwayHyperresponsivenessGenetic*
INDUCERS
Allergens,pollutants
Airflow Limitation
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AsthmaNormal
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Lung in Asthma with Mucous plugs
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Mucous plug in asthma:
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Asthma Microscopic Pathology
Obstructed
Inflammed
Bronchi
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Systemic Lupus Erythromatosis (SLE)
Typical patient: young woman with butterfly rash
Symptoms unpredictable (relapsing/remitting)
Multisystem (skin, kidneys, joints, heart)
Antinuclear antibodies
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Autoantibodies!
Antinuclear Ab present in all patients with SLE... but
found in other autoimmune diseases too
Anti-RBC, -lymphocyte, -platelet, orphospholipidantibodies may be present.
Underlying cause unclear
Genetic predisposition
plus triggers (UV radiation, drugs)
Etiology
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They cause tissue injury!
Form immune complexes
Cause destruction, phagocytosis of cells
Multi-system effects:
Kidney (renal failure)
Skin (butterfly rash)
CNS (focal neurologic deficits) Joints (arthritis)
Heart (pericarditis, endocarditis)
Whats so bad about having these autoantibodies?
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Young woman with polyarthritis and a butterfly (or
other) skin rash
Sensitivity to sunlight
Headaches, seizures, or psychiatric problems
Unexplained fever
Clinical presentation of SLE
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Variable! Some have few symptoms, rare patients die within
months.
Most patients: relapses/remissions over many years.
Acute flare-ups controlled with steroids
80% 10-year survival
Most common cause of death: renal failure
Prognosis of SLE