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The IMMUNE SYSTEM
D-
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Edward Jenner (1798) - Vaccination
The Pox virus - variola
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!!However!!
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Body Defenses Against Invasion
INNATE IMMUNITY Rapid responses to a broad
range of microbes
ACQUIRED IMMUNITY Slower responses to specific
microbes
External defenses
Internal defenses
(3rd line of defense)
(1st line of defense)
(2nd line of defense)
Skin
Phagocytic cells
Humoral response (antibodies)
Mucous membranes
Antimicrobial proteins
Secretions
Inflammatory response
Invading microbes (pathogens)
Cell-mediated response (cytotoxic lymphocytes)
Natural killer cells
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General Anatomy of the Human Lymphatic System
Lymph Node
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Cells involved in the Bodys Defenses
Release histamine (chemoattractant)
5,000,000
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Attack invading parasites.
2750
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Attracted to sites of infection. Attack
microbes.
540
5400
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Body Defenses Against Invasion
INNATE IMMUNITY Rapid responses to a broad
range of microbes
ACQUIRED IMMUNITY Slower responses to specific
microbes
External defenses
Internal defenses
(3rd line of defense)
(1st line of defense)
(2nd line of defense)
Skin
Phagocytic cells
Humoral response (antibodies)
Mucous membranes
Antimicrobial proteins
Secretions
Inflammatory response
Invading microbes (pathogens)
Cell-mediated response (cytotoxic lymphocytes)
Natural killer cells
First line of DEFENSE
The outer layer of the body
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Body Defenses Against Invasion
INNATE IMMUNITY Rapid responses to a broad
range of microbes
ACQUIRED IMMUNITY Slower responses to specific
microbes
(neutrophils, macrophages, natural killer (nk)
cells)
External defenses
Internal defenses
(3rd line of defense)
(1st line of defense)
(2nd line of defense)
Skin
Phagocytic cells
Humoral response (antibodies)
Mucous membranes
Antimicrobial proteins
Secretions
Inflammatory response
Invading microbes (pathogens)
Cell-mediated response (cytotoxic lymphocytes)
Natural killer cells
Second line of DEFENSE
Cells proteins in our blood stream
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Second line of DEFENSE
The bodys way of dealing with non-specific
invasion
A simplified view of the inflammatory response
Chemotaxis
histamine, prostaglandins
tissue heals
Phagocyte migration
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Third line of DEFENSE
Specific Defense Mechanisms
How to deal with specific recurring invasion?
MEMORY
Humoral response (antibodies B-lymphocytes)
3rd line of defense ACQUIRED IMMUNITY Slower
responses to specific microbes
Cell-mediated response (cytotoxic T-lymphocytes)
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Lymphocytes are pivotal cells for dealing with
specific defense mechanisms
Where do they come from? Where do they live?
further differentiation
Helper T cells, TH Cytotoxic T cells, TC
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How do we know that Lymphocytes are required for
adaptive immunity?
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How do we initiate the specific response and get
the lymphocytes involved?
Foreign antigens are presented for
identification
- - but first we have to distinguish self from
foreign
Class I MHC
present on all nucleated cells
Class II MHC
present on macrophages, dendritic cells B cells
Where do these antigenic fragments come from?
MHC major histocompatibility complex
(macrophage or dendritic cell)
APC antigen presenting cell
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What are these antigens?
Where do these antigenic fragments come from?
Native protein
Fragmented protein (showing distinguishing
antigenic epitopes)
Unfolded protein
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The interaction of T cells with MHC molecules
Antigen Presentation
Infected cell
Antigen pre-senting cell
Microbe
(macrophage or dendritic cell)
Antigen fragment
Antigen fragment
Class I MHC molecule
Class II MHC molecule
T cell receptor
CD4 molecule
T cell receptor
CD8 molecule
Helper T cell
(a)
Cytotoxic T cell
(b)
Antigen recognition by TC causes their activation
and killing action
Antigen recognition by TH leads to a great
activation process
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ANTIGEN PRESENTATION
Foreign antigens are presented for
identification
Macrophages or Infected Somatic Cells can be
Antigen-Presenting Cells
Antigen recognition by TC causes their activation
and killing action
Antigen recognition by TH leads to a great
activation process
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 The central role of helper T cells in humoral
and cell-mediated immune responses
Foreign antigens are presented to Thelper cells
for identification
After a dendritic cell engulfs and degrades a
bacterium, it displays bacterial antigen
fragments (peptides) complexed with a class II
MHC molecule on the cell surface. A specific
helper T cell binds to the displayed complex via
its TCR with the aid of CD4. This interaction
promotes secretion of cytokines by the dendritic
cell.
Cytotoxic T cell
Dendritic cell
Peptide antigen
Helper T cell
Cell-mediated immunity (attack on infected cells)
Class II MHC molecule
Bacterium
TCR
Humoral immunity (secretion of antibodies
by plasma cells)
Interleukin-2 activates TH, TC and B cells
CD4
Dendritic cell
B cell
Interleukin-1 activates TH
The cells in this clone secrete other cytokines
that help activate B cells and cytotoxic T cells.
Called cytokines (lymphokines)
Proliferation of the T cell, stimulated by
cytokines from both the dendritic cell and the T
cell itself, gives rise to a clone of activated
helper T cells (not shown), all with receptors
for the same MHCantigen complex.
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Cell-mediated Immune Response
Cytotoxic T cells (TC) get the message
PORE
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Humoral response to a T-dependent antigen
Dendritic Cell or
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Humoral response to a T-dependent antigen
Dendritic Cell or
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Humoral response to a T-dependent antigen
Dendritic Cell or
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(No Transcript)
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How do we get long- term protection
(IMMUNIZATION)?
Almost always requires IL-2 interaction with
activated TH-cells
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What is an antibody?
A protein (immunoglobulin), made by plasma cells,
that has two very specific and very tight antigen
binding sites
Variable regions (bivalent)
How is that we have so many antibodies
(proteins)? theoretically, as many as 1011!!
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What is an antigen?
A foreign molecule that does not belong to the
host and elicits an IMMUNE RESPONSE
Fragmented protein (showing distinguishing
antigenic epitopes)
Unfolded protein (antigen)
Native protein
Epitopes
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T-cell and B-cell receptors are similar to (yet
different from) antibodies
antigen binding sites
T-cell receptor
B-cell receptor
(remember, these receptors are different from the
MHC (I II) molecules)
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Hypervariability is a function of recombinational
rearrangement
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How do Antibodies Protect?
MAC Attack Membrane Attack Complex
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IgMs are the first Abs made by plasma cells and
first to appear in blood stream. Presence of IgM
usually indicates a current infection.
IgGs are the most abundant Abs in blood tissue
fluids. Also crosses placenta, so can provide
passive immunity to fetus.
IgAs usually found in bodys secretions, e.g.,
saliva, milk, even bile..
IgDs are mostly on B cell surfaces serving as
antigen receptors
IgEs have somewhat longer tail than IgG and
attach to mast cells. When triggered by antigen,
they cause histamine release. Allergic response
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Immunological Memory
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Figure 43.10 An overview of the immune responses
(Layer 1)
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Figure 43.10 An overview of the immune responses
(Layer 2)
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Figure 43.10 An overview of the immune responses
(Layer 3)
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What are the consequences of exaggerations and
failure of the Immune System? 1. Allergic
reactions 2. Autoimmune diseases 3.
Immunodeficiency diseases
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Allergic Reactions
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SOME AUTOIMMUNE DISEASES (immune system
attacks your own tissues)
Lupus erythematosus -
develop immune reaction against normal breakdown
of skin and other tissues
Rheumatoid arthritis -
inflamation damages cartilage and bone of joints
Insulin-dependent diabetes (type 1 diabetes) -
destruction of ones own pancreatic insulin
producing cells
Rheumatic fever -
antibodies produced to Streptococcal infection
react with heart valvular tissue
Graves disease -
antibodies bind to TSH and greatly stimulate
thyroid hormone output
Chronic atrophic gastritis -
antibodies against parietal cell H,K-ATPase
destruction of gastric epithelium
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DEFEAT OF THE IMMUNE SYSTEM
IMMUNODEFICIENCY
SCID - severe combined immunodeficiency
congenital disorder
Hodgkins disease
cancer that damages lymphatic system depresses
immune system (also, a whole series of lymphomas
and leukemias)
Aquired ImmunoDeficiency Syndrome - AIDS
viral infection - HIV - human immunodeficiency
virus attacks T helper cells (recognizes
CD-4) immune response is to produce antibody
against HIV (HIV-positive) TH cells disappear -
greatly compromises the immune response individual
s become susceptible to opportunistic diseases
cancer
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Early Stage of HIV Infection
HIV virus concentration
Antibody against HIV
T cell concentration
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The Stages of HIV Infection