David Sadava H. Craig Heller Gordon H. Orians
William K. Purves David M. Hillis
Biologia.blu
C – Il corpo umano
Immune System and
Lymphatic System
Immune System and Lymphatic System
• What are the major defense systems of
humans?
• What are the characteristics of the non-specific
defenses?
• How does specific immunity develop?
• What is the humoral immune response?
• What is the cellular immune response?
• How does immunological memory work?
• What happens when the immune system
malfunctions?
Immune System and Lymphatic System - What are the major defense systems of humans?
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Two general types of defense
mechanisms:
• nonspecific defenses, or innate, act
rapidly; include skin, phagocytic cells,
and molecules toxic to invaders;
• specific defenses, or adaptive, are
aimed at specific pathogens, e.g.,
antibodies, slow to develop and longlasting.
Immune System and Lymphatic System - What are the major defense systems of humans?
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The lymphatic system
Immune System and Lymphatic System - What are the major defense systems of humans?
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White blood cells, leukocytes, have
nuclei; they can leave closed circulatory
system and enter extracellular spaces if
non-self molecules or cells are present.
The number of white blood cells may
increase in response to pathogens,
providing a clue for detecting infections.
Immune System and Lymphatic System - What are the major defense systems of humans?
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Two types of white blood cells:
• granular includes histamine-producing
signaling cells and phagocytes that engulf
foreign cells and debris, phagocytes include
dendritic cells and macrophages;
• lymphocytes participate in specific defenses –
T cells the immature cells migrate from the
bone marrow to the thymus where they mature,
and B cells leave bone marrow and circulate in
blood and lymph, make antibodies.
Immune System and Lymphatic System - What are the major defense systems of humans?
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Proteins involved in the defensive cell-cell interactions:
• antibodies are proteins that bind to substances
identified as non-self, secreted by B cells;
• T cell receptors are integral membrane proteins,
recognize and bind non-self molecules on other cells;
• major histocompatibility complex (MHC), on the
surface of most mammalian cells, they are selfidentifying labels;
• cytokines are signal proteins released by T cells,
macrophages, and other cells, bind to target cells
and alter their activity.
Immune System and Lymphatic System - What are the characteristics of the non-specific
defenses?
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Inflammation is a response to injury.
Cells adhering to skin and organ linings - mast cells –
and basophils release histamine, a chemical
signal.
Symptoms of inflammation: redness, swelling, heat,
and pain.
Blood vessels in the area are dilated, induced by
histamine.
The capillaries become “leaky” and plasma moves
into tissues (causes swelling), along with
complement proteins and phagocytes.
Immune System and Lymphatic System - What are the characteristics of the non-specific
defenses?
- Interactions of cells and chemical
signals result in inflammation (part 1)
Immune System and Lymphatic System - What are the characteristics of the non-specific
defenses?
- Interactions of cells and chemical
signals result in inflammation (part 2)
Immune System and Lymphatic System - How does specific immunity develop?
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Cellular immune response detects and
destroys virus-infected cells and
mutated cells.
Carried out by T cells in blood, lymph,
and extracellular spaces in tissues.
T cell receptors bind to specific antigenic
determinants, which initiates an immune
response that results in destruction of
the foreign cell.
Immune System and Lymphatic System - How does specific immunity develop?
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Clonal selection:
• diversity is generated by DNA changes
just after B and T cells are formed;
• each B cell is able to produce only one
kind of antibody;
• antigen binding selects a B or T cell for
proliferation—divides to form a clone of
cells.
Immune System and Lymphatic System - How does specific immunity develop?
Cell signaling and defense
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Immune System and Lymphatic System - How does specific immunity develop?
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Primary immune response: when
antigen is first encountered, “naïve”
lymphocytes proliferate to produce
clones of effector and memory cells.
Secondary immune response: when
antigen is encountered again, memory
cells proliferate and launch an army of
plasma cells and effector T cells.
Immune System and Lymphatic System – What is the humoral immune response?
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B cells are the basis of the humoral
immune response.
First make an antibody that is expressed
as a receptor protein on the cell surface.
If an antigen binds to the receptor, the B
cell becomes a plasma cell, which
makes antibodies secreted to the blood
stream. Also gives rise to a clone of
plasma and memory cells.
Immune System and Lymphatic System – What is the humoral immune response?
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For B cell to develop into a plasma cell, a
helper T cell (TH) with the same
specificity must also bind to the antigen.
Division and differentiation of the B cell is
stimulated by signals from the TH cell.
As plasma cell develops, ER and
ribosomes increase—for synthesis of
antibody proteins.
Immune System and Lymphatic System – What is the humoral immune response?
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Antibodies belong to protein group called
immunoglobulins.
All contain a tetramer of four polypeptides—two
light chains and two heavy chains, held together
with disulfide bridges.
Each polypeptide chain has a variable region,
specific for each immunoglobulin, thus
responsible for antibody specificity, and a
constant region, which determines the class of
antibody - the function and destination.
Two antigen-binding sites are identical - bivalent.
Immune System and Lymphatic System – What is the humoral immune response?
-The structure of immunoglobulins (part 1)
Immune System and Lymphatic System – What is the humoral immune response?
-The structure of immunoglobulins (part 2)
Immune System and Lymphatic System - What is the cellular immune response?
Cellular immune response—mediated by
T cells—directed against any factor that
changes a normal cell into an abnormal
cell.
T cell receptors are glycoproteins, with
two polypeptide chains. The two chains
have different amino acid sequences.
Immune System and Lymphatic System - What is the cellular immune response?
A T cell receptor
Immune System and Lymphatic System - What is the cellular immune response?
T cell receptors bind to a piece of an
antigen displayed on the surface of an
antigen-presenting cell.
When T cell is activated, it forms a clone
and descendents differentiate into two
types of effectors:
• cytotoxic T cells (TC) recognize
abnormal cells and kill them by lysis;
• helper T cells (TH) assist both humoral
and cellular responses.
Immune System and Lymphatic System - What is the cellular immune response?
Major histocompatibility complex
(MHC) proteins: plasma membrane
glycoproteins.
Main role is to present antigens to T cell
receptors so that the T cell can
distinguish between self and non-self.
Immune System and Lymphatic System - What is the cellular immune response?
There are two classes of MHC proteins.
Class I - on surface of every nucleated cell. Bind to
polypeptide fragments, travel to membrane and
“present” the fragments to TC cells. TC cells have a
surface protein CD8 that binds to MHC I.
Class II - on surfaces of B cells, macrophages, and
other antigen-presenting cells. When a non-self
antigen is ingested, fragments bind to MHC II and
are carried to the membrane and presented to TH
cells. TH cells have a surface protein CD4 that
binds to MHC II.
Immune System and Lymphatic System - What is the cellular immune response?
Macrophages are antigenpresenting cells APC
Immune System and Lymphatic System - What is the cellular immune response?
MHC I and MHC II proteins have an
antigen binding site, which holds a
polypeptide fragment.
T cell receptor recognizes not just the
antigenic fragment, but the fragment
bound to MHC I or II.
C6 - Immune System and Lymphatic System - What is the cellular immune response?
The interaction between T cells and
antigen-presenting cells
Immune System and Lymphatic System - What is the cellular immune response?
Phases of the humoral immune responses (part 1)
Immune System and Lymphatic System - What is the cellular immune response?
Phases of the humoral immune responses (part 2)
Immune System and Lymphatic System - What is the cellular immune response?
Phases of the cellular immune responses (part 1)
Immune System and Lymphatic System - What is the cellular immune response?
Phases of the cellular immune responses (part 2)
Immune System and Lymphatic System - What happens when the immune system malfunctions?
Immediate hypersensitivity:
• when exposed to an allergen, large
amounts of IgE are produced;
• IgE constant end binds to mast cells
and basophils—large amounts of
histamine are released;
• histamines produce symptoms such as
inflammation, blood vessel dilation,
difficulty in breathing.
Immune System and Lymphatic System - What happens when the immune system malfunctions?
An allergic reaction
Immune System and Lymphatic System - What happens when the immune system malfunctions?
These reactions can be treated with
antihistamines.
Severe allergic reactions can lead to death.
Allergy to pollen can be treated by
desensitization—small amounts of allergen are
injected under the skin, stimulates IgG
production, but not IgE production.
Delayed hypersensitivity begins hours after
exposure to the allergen. The antigen is taken
up by antigen-presenting cells and a T cell
response is initiated.
Immune System and Lymphatic System - What happens when the immune system malfunctions?
Autoimmunity: clones of B and T cells are
produced that are directed against self antigens.
Possible causes:
• failure of clonal deletion;
• viral infection - if virus has an antigenic
determinant that resembles a self antigen;
• molecular mimicry - self has antigens that
resemble non-self and are recognized by T
cells.
Immune System and Lymphatic System - What happens when the immune system malfunctions?
Some autoimmune diseases:
• systemic lupus erythematosus (SLE);
• rheumatoid arthritis;
• Hashimoto’s thyroiditis;
• insulin-dependent diabetes mellitus (type
I).
Immune System and Lymphatic System - What happens when the immune system malfunctions?
Immune deficiency disorders can be
inherited or acquired.
T or B cells never form, or B cells lose
their ability to become plasma cells.
TH cells (crucial to both humoral and
cellular responses), are the targets of
HIV retrovirus that results in AIDS—
acquired immune deficiency syndrome.
Immune System and Lymphatic System - What happens when the immune system malfunctions?
HIV can be transmitted by:
• blood—e.g., needle contamination;
• exposure through broken skin, wounds,
mucus membranes;
• through blood of infected mother to
baby during birth.
Immune System and Lymphatic System - What happens when the immune system malfunctions?
HIV initially infects TH cells (in the lymph nodes and
spleen), macrophages, and dendritic cells. These
cells carry the virus to the lymph nodes and spleen.
Symptoms abate as T cells mount an immune
response.
But antibody-complexed viruses can still infect TH
cells—secondary infection.
The rate of secondary infection reaches a low, steady
state level—the set point.
Set point level varies in individuals, and determines
rate of progress of the disease..
Immune System and Lymphatic System - What happens when the immune system malfunctions?
The course of an HIV infection
Immune System and Lymphatic System - What happens when the immune system malfunctions?
Gradually, TH cells are destroyed, and the
person is susceptible to many infections.
Opportunistic infections:
• Kaposi’s sarcoma, a rare skin cancer
caused by a herpesvirus;
• pneumonia caused by fungus
Pneumocystis carinii;
• lymphoma tumors caused by EpsteinBarr virus.
Immune System and Lymphatic System - What happens when the immune system malfunctions?
Relationship between TH cell count and opportunistic infections