Transcript Immunology.ppt

Overview of the immune system
Immune System
Innate
(Nonspecific)
Cellular
Components
Humoral
Components
Adaptive
(Specific)
Cell
Mediated
Humoral
(Ab)
Differences between:
Non specific
(innate or natural
immunity)
Response is antigenindependent.
There is immediate
maximal response.
Specific Immunity
(acquired or adaptive)
Response is antigendependent.
There is a lag time between
exposure and maximal
response.
Not antigen-specific.
Antigen-specific.
Exposure results in no
immunologic memory
Exposure results in
immunologic memory
Host Defenses
First line of Defense
Mechanical Factors:
Physical barriers to pathogens
Skin
Epidermis consists of tightly packed cells
with keratin which is a protective protein.
Mucous membranes
Lacrimal apparatus: Washes eye
Saliva: Washes microbes off
Urine: Flows out, flushing.
Vaginal secretions: Flow out
Chemical Factors
Fungistatic fatty acid in sebum.
Low pH (3-5) of skin.
Lysozyme in perspiration, tears, saliva, and
tissue fluids except CSF.
Low pH (1.2-3.0) of gastric juice and vaginal
acidity.
Transferrins in blood reduce iron so inhibit
microbial growth.
Normal Microbiota
Microbial antagonism/competitive
exclusion:
Normal microbiota antagonize pathogen:
1-By competing with pathogens for
nutrients, for colonization site by producing
substances harmful to the pathogen.
2- By altering conditions that affect the
survival of the pathogen. e.g. normal
microbiota in vagina alters pH to prevent
overpopulation of C.albicans which is a
pathogenic yeast caused vaginitis.
Second line of Defense
1.Phagocytosis
2.Inflammation
3.Fever
4.Antimicrobial substances
Nonspecific Defenses
Nonspecific defenses deny pathogens access to the body or destroy them
without distinguishing among specific types.
Nonspecific Defenses
Nonspecific defenses deny pathogens access to the body or destroy them
without distinguishing among specific types.
Formed Elements In Blood (note functions)
RBC’s
WBC’s
Agranulocytes
1. Monocytes
and
2. Lymphocytes
Granulocytes
1. Neutrophils (PMNs)
2. Basophils and
3. Eosinophils
Cells of the Immune System
Immune System
Myeloid Cells
Lymphoid Cells
Granulocytic
Monocytic
T cells
B cells
Neutrophils
Basophils
Eosinophils
Macrophages
Kupffer cells
Dendritic cells
Helper cells
Suppressor cells
Cytotoxic cells
Plasma cells
NK cells
Organs of the immune system
During embryonic life, haemopoeitic stem cells
develop in fatal liver and other organs, these
stem cells reside in the bone marrow in
postnatal life.
There is primary lymphoid system which is
responsible for the evolution and maturation
of immune cells (Bone marrow and thymus).
and secondary lymphoid system (tonsils,
peyer patches, spleen and other lymph
nodes all over the body), responsible for
trapping of foreign antigen, residence of
immune cells.
Phagocytosis
.
Inflammation
Redness
Pain
Heat
Swelling (oedema)
In acute-phase proteins are activated
(complement, cytokine, kinins) - chemical
messengers
Vasodilation (histamine, kinins,
prostaglandins, leukotrienes) - bring in more
help
Margination and immigration of WBCs
Tissue repair
Chemicals Released by Damaged Cells
• Histamine
Vasodilation, increased
permeability of blood vessels
• Kinins
Vasodilation, increased
permeability of blood vessels
• Prostaglandins
Intensity histamine and kinin
effect
• Leukotrienes
Increased permeability of
blood vessels, phagocytic
attachment
The Complement System
In serum 30
proteins
produced by the
liver, activated in
a cascade as
previous
catalyzes the
next step.
Outcomes of
Complement
system
1.
2.
3.
Opsonization
Chemotaxic
Cell lysis
Effects of Complement Activation
Opsonization
or immune
adherence:
enhanced
phagocytosis
Membrane
attack complex:
cytolysis
Attract
phagocytes
Classical Pathway
Alternative Pathway
Interferons (IFNs)
Antiviral proteins
Alpha IFN & Beta IFN: Cause cells to
produce antiviral proteins that inhibit viral
replication
Gamma IFN: Causes neutrophils and
macrophages to phagocytize bacteria
Interferons (IFNs)
2 The infecting
virus replicates
into new
viruses.
1 Viral RNA from an
infecting virus
enters the cell.
5
New viruses released
by the virus-infected
host cell infect
neighboring host
cells.
6
AVPs degrade viral
m-RNA and inhibit
protein synthesis
and thus interfere
with viral replication.
3 The infecting virus also
induces the host cell to
produce interferon on
RNA (IFN-mRNA), which
is translated into alpha
and beta interferons.
4 Interferons released by the virus-infected host cell bind to plasma
membrane or nuclear membrane receptors on uninfected neighboring
host cells, inducing them to synthesize antiviral proteins (AVPs). These
include oligoadenylate synthetase, and protein kinase.
Specific Defenses of the Host:
The Immune Response
*Antigen (Ag) : A substances that causes the body to produce
specific antibodies or sensitized T ells, also
called immunogen.
*Antibody (Ab): A proteins produced by the body in response to
an antigen, and capable of combining specifically
with that antigen.
Serology: Study of reactions between antibodies and
antigens.
Antiserum: Generic term for serum because it contains Ab.
Globulins: Serum proteins
Gamma () globulin: Serum fraction containing Ab.
Serum Proteins
The Immune Response
Two arms
Acquired immunity:The ability obtained and
developed during an individual's lifetime, to
produce specific antibodies or T-cell.
The factors involved in this immunity known as:
1. Humoral immunity: from humors, because they
were found in the body fluid, it Involves Ab
produced by B cells (B lymphocytes).
2. Cell-mediated immunity: Involves specialized
lymphocytes T cells or T lymphocytes
Acquired Immunity
Natural Acquired:( Active and passive).
Artificially Acquired:( Active and passive).
*Naturally acquired active immunity
Resulting from Antigen enter the body naturally
(infection).
*Naturally acquired passive immunity
Antibodies via transplacental or via colostrum
*Artificially acquired active immunity
Injection of Antigen (vaccination)
*Artificially acquired passive immunity
Injection of performed Antibody.
Antigenic Determinants
A specific region on the surface of an antigen to which
antibodies recognize and react with, it is called epitopes.
Haptens
it is a molecule too small to stimulate the antibody
formation by itself but only when combine with a
carrier molecule. e. g. penicillin antibiotic.
Factors Influencing Immunogenicity
A. The Immunogen
1- Foreignness The immune system normally
discriminates between self and non-self such that
only foreign molecules are immunogenic.
2- Size: the larger the molecule the more
immunogenic it is likely to be.( generally substances
with mol.wt.> 100,000 dalton are potent
immunogenic).
3- Chemical Composition: The more chemical
complexity of the substance is the more
immunogenic it will be.
4- Physical form - In general particulate antigens are
more immunogenic than soluble ones and denatured
antigens more immunogenic than the native form.
5. Degradability - Antigens that are easily
phagocytosed are generally more immunogenic. This
is because for most antigens (T-dependant antigens)
the development of an immune response requires that
the antigen be phagocytosed, processed and
presented to helper T cells by an antigen presenting
cell (APC).
CHEMICAL NATURE OF IMMUNOGENS:
A. Proteins -The vast majority of immunogens are
proteins. These may be pure proteins or they may
be glycoproteins or lipoproteins. In general,
proteins are usually very good immunogens.
B. Polysaccharides - Pure polysaccharides and
lipopolysaccharides are good immunogens.
C. Nucleic Acids - Nucleic acids are usually poorly
immunogenic. However, they may become
immunogenic when single stranded or when
complexed with proteins
.D. Lipids - In general lipids are non-immunogenic,
although they may be haptens.
In an antigen, the same antigenic determinant
repeated many times .
TYPES OF ANTIGENS
T-independent Antigens - T-independent antigens
are antigens which can directly stimulate the B
cells to produce antibody without the requirement
for T cell help .
In general, polysaccharides are T-independent
antigens.
T-dependent Antigens - T-dependent antigens
are those that do not directly stimulate the
production of antibody without the help of T cells.
Proteins are T-dependent antigens.
LYMPHOCYTES
Both B cells and T cells originate from stem
cells in adult red bone marrow or in the
fetal liver. (RBCs, macrophages,
neutrophiles, and other WBCs also
originate from these same stem cell).
Some cells pass through the THYMUS and
emerge as mature T-cells.
Other cells probably remain in the Bone
marrow and become B-cells.
Both types of cells then migrate to lymphoid
tissues, such as lymph nodes or spleen.
Once in these organs, B cells recognize
antigens by means of antigen receptors
which are antibody molecules on their
surface (IgD).
After antigen exposure, B-cells changed to
memory cells and antibody-secreting plasma
cells.
Once re-exposure to antigen, memory cells quickly
proliferate to produce more plasma cells.
Further differentiation of the activated B-cell into
clone occurs, resulting in the formation of large
antibody-secreting cells called plasma cells.
Plasma cells are relatively short-lived
(less than 1 week) but excrete large
amounts of antibody during this
period.
Memory cells, in contrast, are very
long-lived cells, and on re-exposure to
the initial stimulating antigen, they
quickly transform into plasma cells
and begin secreting antibody.
Antibody Structure
IgG antibodies
Monomer
80% of serum antibodies
Fix complement
In blood, lymph, intestine
Cross placenta
Enhance phagocytosis;
neutralize toxins &
viruses; protects fetus &
newborn
Half-life = 23 days
IgM antibodies
Pentamer
5-10% of serum
antibodies
Fix complement
In blood, lymph, on
B cells
Agglutinates
microbes; first Ab
produced in
response to
infection
Half-life = 5 days
J
Chain
C4
IgA antibodies
Secretory
Piece
Dimer
10-15% of serum
antibodies
In secretions
Mucosal protection
Half-life = 6 days
J
Chain
IgD antibodies
Monomer
0.2% of serum
antibodies
In blood, lymph, on B
cells
On B cells, initiate
immune response
Half-life = 3 days
IgE antibodies
Monomer
0.002% of serum
antibodies
On mast cells and
basophils, in blood
Allergic reactions;
lysis of parasitic
worms
Half-life = 2 days
Clonal Selection
Bone marrow gives rise to B cells.
Mature B cells migrate to lymphoid
organs.
A mature B cells recognizes
epitopes.
Clonal Selection
Self-tolerance
Body doesn't make Ab against self
Clonal deletion
The process of destroying B and
T cells that react to self antigens
The Results of Ag-Ab Binding
Antibody titer
Is the amount of Ab in serum
Monoclonal Antibodies
Hybridomas are produced by fusing a cancer
cell with an Ab-secreting plasma cells
Ideally, if an antibody-producing B cell could
be grown by standard cell-culture method , it
would produce the Highly specific, only
desired antibody in unlimited amounts.
Chemical Messengers of immune cells:
CYTOKINES
CYTOKINES
Cytokines are a diverse group of non-antibody
proteins released by immune cells that act as
intercellular mediators, especially in immune
processes.
A. Cytokines are clinically important as
biological response modifiers. :
1. Monokines - produced by mononuclear
phagocytes
2. Lymphokines - produced by activated T
cells, primarily helper T cells
3. Interleukins - name given to many cytokines,
abbreviated as IL and given a number, serve as
Communicator between leukocytes.
Classification of T Cells according to
function
Helper T Cells (TH)
TH1
TH2
Activate cells related to cell-mediated
immunity
Activate B cells to produce, IgM, and IgE
Cytotoxic T Cells ( TC)
Destroy target cells with perforin
Delayed Hypersensitivity T Cells (TD)
Associated with allergic reaction, transplant
rejection.
Suppressor T cells (TS)
Turn off immune response when Ag no longer
present.
Classification of T-cells according
to cell-surface receptor
(CD)
CD4 : A molecule found on human helper T
cells and delayed hypersensitivity T cells. It is
involved in the interaction with MHC Class II
molecules. CD4 is the 'receptor' by which the
AIDS virus enters T cells.
CD8: A molecule found on most cytotoxic and
suppressor T cells. It is involved in interacting
with MHC Class I molecules.
Major histocompatibility complex
Tissue cells of each individual possess:
Uniqueness that is a function of certain
surface glycoprotein molecules known as
MHC or human leukocyte antigens (HLA),
since they are also identified on the
surface on WBCs.
Histocompatibility genes that are found on
the short arm of chromosome No 6 in
humans encodes such glycoprootein.
Class I MHC : encoding 2 polypeptide chains
found on the surface of all nucleated cell. Tc
and Ts (CD8) recognize antigens associated
with MHC class I.
Class II MHC: encoding 2 polypeptide chains
found on the surface of B cells,
T cells and macrophage (APC) .
The (CD4) recognize antigens in association
with MHC class II.
T-independent Antigens
B cell