Transcript Study of the Immune System

Study of the Immune
System
Now that we know all about
microbes…..
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What provokes us to fight against microbes?
How do we know that they are foreign?
What initiates the response?
Introduction to Antigens
Antigen (Ag)
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most
antigenic
Any substance that stimulates
an immune response
Requirements for antigenicity
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foreignness (recognition of
nonself)
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large size
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complexity
Characteristics of Antigens
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Epitope
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antigenic determinant
small molecular group that
is recognized by:
 Antibodies
 B cells
 T cells
Defense Mechanisms of the Host
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Immune system
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first line of defense
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any barrier that blocks invasion at the portal of entry
nonspecific
second line of defense
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relies on a multilevel network of physical barriers,
immunologically active cells, and a variety of chemicals
3 main lines of defense:
protective cells and fluids
inflammation and phagocytosis
nonspecific
third line of defense
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acquired with exposure to foreign substance
Stronger immune response
produces protective antibodies and creates memory cells
specific
Physical or Anatomical Barriers:
First Line of Defense
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Skin and mucous membranes:
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outermost layer of skin
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few pathogens can penetrate if intact
flushing effect of sweat glands
mucous coat impedes attachment and
entry of bacteria
blinking and tear production
stomach acid
nasal hair traps larger particles
Vaginal secretions
Structure and Function of the
Organs of Defense and Immunity
Immunology
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study of the body’s second
and third lines of defense
Functions of a healthy
functioning immune system:
1.
Constant surveillance of the
body
2.
Recognition of foreign
material
3.
Destruction of entities
deemed to be foreign
Blood
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Plasma
 Serum - fluid portion
 complement proteins and
antibodies
 Three types of formed elements
 Erythrocytes
 Platelets
 Leukocytes
 Divided into granulocytes
and agranulocytes
White Blood Cells
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Leukocytes
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Housekeeping and defense
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Scavenge dead or worn-out cells
Disease organisms
Squeeze out of blood vessels and enter
tissues
Develop from stem cells in bone marrow
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Granulocytes
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Agranulocytes
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Neutrophils
Eosinophils
Basophils
Monocytes
Macrophages
Lymphocytes
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B-cells
T-cells
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Neutrophils
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Eosinophils
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1-3%
orange granules and bilobed nucleus
destroy eukaryotic pathogens
Basophils, mast cells
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55-90%
lobed nuclei with lavender granules
phagocytes
0.5%
constricted nuclei, dark blue granules
release potent chemical mediators
Lymphocytes
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20-35%
large nucleus
involved in specific immune responses
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Monocytes, macrophages
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B (humoral immunity)
T cells (cell-mediated immunity)
3-7%
large nucleus
Phagocytic
Dendritic cells
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Activate lymphocytes
Produce cytokines
White
Blood Cells
Innate Immunity
“Second” line of defense
Second Line of Defense
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cells and mechanisms that defend the host
from infection by other organisms
genetically-encoded to recognize:
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common pathogenic features
foreign substances
does not confer long-lasting or protective
immunity to the host
provide immediate defense against infection
Actions of the Second Line of
Defense
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Recognition
Inflammation
Phagocytosis
Interferon
Complement
1. Recognition
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Toll-like receptors (TLRs)
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protein receptors within cell
membrane of macrophages
recognize structurally
conserved molecules derived
from microbes
Detect foreign molecules and
signal the macrophage to
produce chemicals
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cytokines
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stimulate an inflammatory
response (nonspecific)
promote the activity of B and
T cells (specific)
2. Functions of inflammation
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Mobilize and attract immune cells to site
Set mechanisms to repair tissue damage
Destroy microbes and block further invasion
2. Inflammatory Response
Classic signs and symptoms
characterized by:
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Redness
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increased circulation and
vasodilation in injured tissue
Warmth
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heat given off by the increased
blood flow
Swelling
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increased fluid escaping into the
tissue as blood vessels dilate
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WBC’s, microbes, debris and fluid
collect to form pus
helps prevent spread of infection
Pain
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edema
stimulation of nerve endings
Possible loss of function
Fever
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Initiated by circulating pyrogens
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cytokines produced by some leukocytes
reset the hypothalamus to increase body temperature
signals muscles to increase heat production and
vasoconstrict
Benefits of fever:
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inhibits multiplication of temperature-sensitive
microorganisms
impedes nutrition of bacteria
increases metabolism and stimulates immune reactions
3. Phagocytosis
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nonspecific defense
mechanism
clear microbes from
infected tissues
capture and digestion of
foreign particles
Phagocytes
3 main types of phagocytes:
Neutrophils
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general-purpose
react early to bacteria and other foreign
materials, and to damaged tissue
Eosinophils
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attracted to sites of parasitic infections and
antigen-antibody reactions
Macrophages
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derived from monocytes
scavenge and process foreign substances to
prepare them for reactions with B and T
lymphocytes
4. Interferon
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Type of cytokine
Produced in response
to viruses, RNA,
immune products, and
various antigens
Bind to cell surfaces
and induce expression
of antiviral proteins
Inhibit expression of
cancer genes
5. Complement (C)
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Consists of 26 blood proteins
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proteins are activated
work in concert to destroy
bacteria and viruses
Adaptive Immunity
“Third” line of defense
Adaptive Line of Defense
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acquired immunity
stronger immune response as well as
immunological memory
Production of specific antibodies
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dual system of B and T lymphocytes
in response to an encounter with a foreign molecule
allows for the generation of responses that are
tailored to specific pathogens or pathogeninfected cells
Specific Immunity – Adaptive
Line of Defense
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Two features that characterize specific
immunity:
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specificity
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antibodies produced
function only against the antigen that they were
produced in response to
memory
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lymphocytes are programmed to “recall” their first
encounter with an antigen
respond rapidly to subsequent encounters
Classifying Immunities
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Active immunity
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Passive immunity
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preformed antibodies are donated to an individual
does not create memory, acts immediately, and is short
term
Natural immunity
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person is challenged with antigen that stimulates production
of antibodies
creates memory, takes time and is lasting
acquired as part of normal life experiences
Artificial immunity
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acquired through a medical procedure such as a vaccine
Combinations of acquired immunity
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Natural active immunity
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Natural passive immunity
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acquired by a child through
placenta and breast milk
Artificial active immunity
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acquired upon infection and
recovery
acquired through inoculation
with a selected Ag
Artificial passive immunity
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administration of immune
serum or globulin
Development of the Immune
Response System
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Cell receptors or markers confer specificity and
identity of a cell
Major functions of receptors are:
1. perceive and attach to nonself or foreign
molecules
2. promote the recognition of self molecules
3. receive and transmit chemical messages
among other cells of the system
4. aid in cellular development
Acquired Immunity Generates Two
Responses to Most Pathogens
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B lymphocytes
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(B cells)
involved in producing
antibodies against
epitopes
Humoral immune
response
T lymphocytes
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(T cells)
provide resistance through
lysis of infected or
abnormal cells
Cell-mediated immune
response
Lymphocyte Receptors
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Lymphocyte’s role in surveillance and
recognition is a function of their receptors
B-cell receptors
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bind free antigens
T-cell receptors
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bind processed antigens
Antibody Structure and Functions
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Immunoglobulins
Large Y-shaped protein
Contains 2 identical fragments (Fab) with ends
that bind to specific antigen
Fc binds to various cells and molecules of the
immune system
Classes of Antibodies
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IgD
 important in B cell activation
IgM
 released by plasma cells during the primary immune
response
IgG
 crosses the placenta and confers passive immunity
IgA
 helps prevent attachment of pathogens to epithelial cell
surfaces
IgE
 causing histamine release when activated
B-cell Activation and Antibody
Production
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Antibodies in Serum (Antiserum)
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The 1st introduction of an Ag to the immune system
 produces a primary response
 gradual increase in Ab titer
The 2nd contact with the same Ag
 produces a secondary, or anamnestic, response
 due to memory cells produced during the initial
response
T Cells & Cell Mediated Immunity
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Cell mediated immunity requires the direct
involvement of T lymphocytes
T cells act directly against Ag and foreign cells when
presented in association with an MHC carrier
T cells secrete cytokines that act on other cells
Sensitized T cells proliferate into long-lasting memory
T cells
Antibody-Antigen Interactions
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Opsonization
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Agglutination
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process of coating microorganisms or other particles with
specific antibodies
 more readily recognized by phagocytes
Ab aggregation
cross-linking cells or particles into large clumps
Neutralization
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Abs fill the surface receptors on a virus or the active site on a
microbial enzyme
 prevent it from attaching
Antitoxins
 special type of Ab that neutralize a bacterial exotoxin
Immunization
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Passive immunization
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patient is given preformed antibodies
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form of immunotherapy
Active immunization
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patient is vaccinated with a microbe or its
antigens
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providing a form of advance protection
Vaccines
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Type of active immunity
Provide an antigenic stimulus
that does not cause disease
Most vaccine preparations are
based on one of the following
antigen preparations:
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Killed whole cells or inactivated
viruses
Live, attenuated cells or viruses
Antigenic molecules derived
from bacterial cells or viruses
Genetically engineered
microbes or microbial antigens
Disorders in Immunity
Immunopathology
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Allergy, hypersensitivity
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Autoimmunity
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abnormal responses to
self Ag
Immunodeficiency
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misdirected expression
of immune responses to
an allergen (antigen)
deficiency or loss of
immunity
Four types…..
Type
Systems
involved
Examples
IgE
Mast cells
Hay fever
Asthma
I
Immediate
Hypersensitivity
II
Antibody Mediated IgG Ab
IgM Ab
Blood group
incompatability
III
Immune Complex
Mediated
IgG
Ab-mediated
inflammation
Arthritis
Serum sickness
IV
T-cell Mediated
Delayed
hypersensitivity
Cytotoxic rxns
Injection rxns
Contact
dermatitis
Graft rxns
1. Type I Hypersensitivity
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Two levels of severity:
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Atopy
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any chronic local allergy
Ex: hay fever or asthma
Anaphylaxis
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a systemic, often explosive reaction that involves
airway obstruction and circulatory collapse
Contact With Allergens
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Generalized predisposition to allergies is
familial
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not to a specific allergy
Allergy can be affected by age, infection,
and geographic area
Atopic allergies may be lifelong or may be
“outgrown”
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may also develop later in life
Mechanism of Type I Allergy
Develop in stages:
 Sensitizing dose
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on first contact with
allergen
specific B cells form IgE
which attach to mast cells
and basophils
generally no signs or
symptoms
Provocative dose
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subsequent exposure with
the same allergen
binds to the IgE-mast cell
complex
Chemical Mediators and Allergic Symptoms
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General targets include:
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skin, upper respiratory tract,
GI tract, and conjunctiva
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Responses
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rashes, itching, redness,
rhinitis, sneezing, diarrhea,
shedding tears
Systemic targets
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smooth muscles, mucous
glands, and nervous tissue
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Responses
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vascular dilation and
constriction resulting in change
in blood pressure and
respiration
Specific Diseases
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Atopic disease
 hay fever, rhinitis; seasonal, inhaled plant
pollen or mold
 asthma
Food allergy
 intestinal portal can affect skin and
respiratory tract
 vomiting, diarrhea, abdominal pain
 possibly severe
 eczema, hives, rhinitis, asthma, occasionally
anaphylaxis
Drug allergy
 common side effect of treatment
 reaction from mild atopy to fatal anaphylaxis
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Sudden respiratory and circulatory disruption
that can be fatal in a few minutes
Bee stings, antibiotics or serum injection
Treatment and Prevention
General methods include:
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Avoiding allergen
2.
Use drugs
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block the action of the
lymphocytes, mast cells
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antihistamines
Desensitization
therapy
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injected allergens
2. Type II Hypersensitivity
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Involve antibodies and complement
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leading to lysis of foreign cells
Transfusion reactions
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ABO blood groups
Rh factor
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hemolytic disease of the newborn
Human ABO Antigens and Blood Types
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Genetically determined RBC
glycoproteins
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inherited as 2 alleles of A, B, or O
4 blood types: A, B, AB, or O
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type O persons lack both A and B
antigens
Tissues other than RBCs also
carry A and B antigens
Antibodies Against A and B Antigens
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Serum contains pre-formed antibodies
that react with blood of another antigenic
type-agglutination
Type A
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Type B
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contains Abs that react against A antigens
Type O
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contains Abs that react against B antigens
contains Abs that react against A and B
antigens
Type AB
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contains no Abs that react against A or B
antigens
Rh Factor
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Rhesus factor
RBC antigen
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Either there or not
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type results from combination of 2 alleles
RhRh+
Inheriting one dominant gene results in
the production of the Rh antigen
Rh Factor and Hemolytic
Disease of the Newborn
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Hemolytic Disease of the
Newborn (HDN)
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Rh mother forms antibodies to her
Rh+ fetus
requires subsequent exposure to
the antigen to be hemolytic
Prevention
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use of passive immunization with
antibodies against the Rh antigen
prevents sensitization of mother
3. Type III Hypersensitivity
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Large quantity of foreign Ag
stimulates Ab
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produce small, soluble Ag-Ab
complexes
Immune complexes become
trapped in tissues and incite
a damaging inflammatory
response
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arthus reaction
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local reaction to series of
injected Ag to same body
site
serum sickness
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systemic disease resulting
from repeated injections of
foreign proteins
4. Type IV Hypersensitivity
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T cell-mediated
Delayed response to Ag involving activation of and
damage by T cells
Delayed allergic response
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skin response to allergens
tuberculin skin test, contact dermititis from plants, metals,
cosmetics
Graft rejection
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reaction of cytotoxic T cells directed against foreign cells of
a grafted tissue
 MHC markers of donor tissue (graft) are different
host may reject graft; graft may reject host
Immunodeficiency Diseases
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Components of the immune response system are absent
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B and T cells, phagocytes, and complement
2 general categories:
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primary immunodeficiency
 Congenital
 usually genetic errors
 T-cell or B-cell defect
 severe combined immunodeficiency (SCID)
secondary diseases
 acquired after birth
 caused by natural or artificial agents
 Chemotherapy
 AIDS
Evasion of the Immune
System by Pathogenic
Microorganisms
Why develop a strategy for
evasion?
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Pathogen evolution
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Microorganism capable of causing disease
Must subvert host immune system
Successful pathogens = effective evasion
Defenses against human host
responses
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Antiphagocytic factors
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Host cell invasion
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Glycocalyx / Capsules (Encapsulation)
Grow intracellularly
Neighbor cell transfer
Syncytium
Latency
Genetic changes
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Antigenic shift
Antigenic drift
Antiphagocytic
Factors
The Bacterial Surface
Coating Glycocalyx
Coating of molecules
external to the cell wall
Functions:
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attachment
inhibits killing by WBCs
Talaro, 2008
Capsules
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Formation correlates with pathogenicity
Encapsulated cells protect against WBCs
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Chemicals similar to those in human body
Negative charges on capsule and
phagocyte surface
Slippery
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Pseudopodia cannot grip them
Bauman, 2011
“Some Killers Have Pretty Nice Capsules”
S. pneumoniae
K. pneumoniae
H. influenzae
P. aeruginosa
N. meningitidis
C. neoformans
http://medicineworld.org/stories/lead/2-2009/how-a-deadly-fungus-evades-the-human-immune-system.html
Streptococcus pyogenes
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GAS
Most serious
streptococcal
pathogen
Many surface
antigens that enable
virulence and evasion
Talaro, 2008
S. pyogenes….
“There’s an app for that”
Capsule made of
hyaluronic acid (HA)
M-protein
Chemically masked from HA in human
tissues
C-carbohydrates
Protect bacterium from being dissolved by
lysozyme
C5a protease
Catalyzes cleavage of C5a protein
(hinders C-associated aspects & neutrophil
response)
Makes surface projections that resist
phagocytosis
Host Cell Invasion
Survive inside phagocytes after
ingestion
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Ingested by alveolar
phagocytes
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Prevent fusion with
lysosomes
Multiply intracellularly
After cell death, attract
more phagocytes and
continue cycle
Mycobacterium
Bauman, 2011
Neighboring cell transfer
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Can escape out of
phagosomes
Transfer to neighbor
cells w/o leaving host
cell
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Not exposed to Ab
Listeria
monocytogenes
Pommerville, 2007
Syncytium
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Induces cells to fuse
Multinucleate giant cell
Allows pathogen to move
from cell to cell
HIV
RSV
Paramyxoviruses
Talaro, 2008
Latency
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Pathogen remains
inactive for period of
time
Reactivate at later
date
Herpes
Bauman, 2011
Genetic Changes
Viruses
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Glycoprotein spikes
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Adherence
Recognized by host
immune system
Influenza A & B
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Contains two types of
spikes
Hemagglutin (HA)
Neuraminidase (NA)
Pommerville, 2007
Genetic changes of viruses
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Antigenic drift
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Mutation in spikes
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Change their aa composition
Small changes
Single strain
Antigenic shift
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Shift of gene strand with one
from another host
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Human, pig, birds, etc.
Abrupt, major change
Reorganization of strains
H1N1
Bauman, 2011