2. Immune system
▶ the exogenous microscopic life forms
▶ the defective, damaged, malignantly transformed cells
= complex set of tissues + mobile elements
self/non self discrimination
organism protection
3. Immune cells
form the major immune organs circulate through the lymphatic and blood vessels
recirculate
circulate
extravascular
space
Modulating leukocyte recruitment in inflammation
Margaret Kelly et al.
J Allergy and Cl Immunology, 2007
http://www.sciencedirect.com/science/article/pii/S0091674907009864
4. Immune system responses to pathogens
Innate immune system Adaptive immune system
▶ first line of defense ▶ second line of defense
▶ exists before ▶ adaptive – specific
exposure to microbes response
▶ non-specific immune ▶affords protection
system against re-exposure to
the same pathogen
has cellular and humoral components by which
they carry out their protective function
5. Non-specific Immunity Specific Immunity
Response is antigen-independent Response is antigen-dependent
There is immediate maximal There is a lag time between
response exposure and maximal response
Not antigen-specific Antigen-specific
Exposure results in no Exposure results in immunologic
immunologic memory memory
6. Innate Immune System
http://thyroid.about.com/library/immune/blimm12.htm
Anatomical barriers Defense mechanisms
Skin (1st line of defense) sweat – desquamation – flushing
– organic acids
Nasopharynx mucus – saliva – lysozyme
Eyes tears – lysozyme - phospholipase
Respiratory system mucociliary elevator – surfactant
– defensins (low molecular weight proteins)
GI tract peristalsis – gastric acid – bile
– digestive enzymes – gut flora
7. Inflammation
one of the first responses stimulated by chemical factors released by injured cells
h"p://bio1152.nicerweb.com/Locked/media/ch43/inflamma:on.html
Macrophages and mast cells Local inflammatory response: Phagocytic cells
release chemical signals such Capillaries widen. Fluid digest pathogens,
as Histamine. containing antimicrobial and the tissue
proteins enter the tissue. heals.
More phagocytes invade the
site.
Symptoms: redness, heat, swelling, pain and possible dysfunction
of the organs or tissues involved
8. Complement system - a biochemical cascade
Alternative pathway Lectin pathway Classical pathway
Pathogen surface creates local C-reactive protein or antibody
Mannose-binding lectin binds
environment conducive to binds to specific antigen on
to pathogen surface
complement activation pathogen surface
First to act Second to act Third to act
COMPLEMENT ACTIVATION
Cleavage of C3 to C3a and C3b
C3b covalently bound to surface components of pathogen
Opsonization of pathogens,
Recruitment of Perforation of pathogen
facilitating uptake and
inflammatory cells cell membranes
killing by phagocytes
Death of pathogen
9. Cells of the innate immune response
Leukocytes:
are the products of multipotent hematopoietic stem
cells from the bone marrow
are able to move freely and interact with and capture
cellular debris, foreign particles, or invading
microorganisms
Include: natural killer cells
mast cells
eosinophils
basophils
phagocytes: macrophages,neutrophils,
dendritic cells
Hierarchies of organization in the innate immune system - sciencemag.org
10. Adaptive (specific) immune system
a pathogen that evades
Trigger
the innate immune system
an$gen-‐specific
defense
mechanisms
major functions ▶ recognition of specific “non-self” antigens
▶ response to eliminate specific pathogens
▶ development of immunological memory
11. Adaptive (specific) immune system
Active immunity Passive immunity
is
produced
by
the
person’s
own
immune
the
transfer
of
an:body
produced
by
one
system
–
highly
adaptable human
or
other
animal
to
another
is
usually
permanent
(immunologic provides
protec:on
against
some
infec:ons
memory) –
is
temporary
12. Lymphocytes. A scanning electron micrograph showing lymphocytes
(yellow, like cotton candy), red blood cells, and platelets.
(Copyright Dennis Kunkel Microscopy, Inc.)
Foreign substance (non self)
= antigenes (infectious agents X noninfectious substance:
pollens, foods, transplant tissue)
Specific immune cells
Lymphocytes B and T
13. Lymphoid tissues - Sites of B cells and T cells
differentiation
Immature lymphocytes migrate through primary
lymphoid tissues:
bone marrow – for B lymphocytes
thymus – for T lymphocytes
Mature B and T lymphocytes rich the
secondary lymphoid tissues
14. The peripheral lymphoid organs
contain a mix of B and T cells in different
stages of differentiation:
1 2 3
▶ naive – mature cells ▶ effector cells ▶ memory cells
– they didn’t encounter the – they have been – long-lived survivors
cognate antigen activated by their of past infections
cognate antigen →
active in pathogen
elimination
15. Immunogen
= a molecule or molecular fragment
CAN bind with antibodies or antigen B and T cells receptors
induce an immune response
ALL Immunogens = Antigens
NOT ALL Antigens = Immunogens
(ex: urushiol from the ivy poison)
16. Immunogenicity includes:
foreignness to the host
adequate size
sufficient quantity
Criteria used in developing vaccines
=> which must be highly immunogenic to
produce protective immune responses against
pathogenic microorganisms
17. Humoral and Cell-Mediated Immunity
Humoral immunity
deals with infectious agents in the blood and body tissues
managed by B-cells
(with help from T-cells)
Cell-Mediated immunity
deals with body cells that have been infected
managed by T-cells
18. Humoral immune system
= the antibody-mediated system because of its use of specific immune-
system structures called antibodies
19. Humoral immune system
Activation phase
Ingestion (phagocytosis) of foreign matter by macrophages
Digest the infectious agent and then display some of its components on their
surfaces
Cells called helper-T cells - recognize this presentation, activate their immune
response, and multiply rapidly
Effector phase
Activated helper-T cells use chemical signals to contact B-cells
B-cell descendants become either plasma cells or B memory cells
The plasma cells manufacture huge quantities of antibodies that will bind to the
antigen and prime it for destruction
20. The Cell-Mediated System
killer-T cells recognize components of the
foreign matter material on the surfaces of
the infected body cells
destroy the invaders (primary response)
T memory cells
secondary response
http://www.trinity.edu/lespey/biol1307/lectures/lect1/lect1.html
24. Immunity as an Adaptation
The Human Immune System
= important evolutionary adaptation
allows humans to better cope with an
often hostile environment
a highly favorable adaptation for the human
to protect the human cellular machinery
from benefiting parasitical organisms
instead of human cells
25. Disorders of human immunity
Immunodeficiency
= one or more of the components of the immune system are inactive:
Humoral immune deficiency – hypogammaglobulinemia
T cell deficiency – acquired immune deficiency syndrome
Granulocyte deficiency – granulocytopenia/agranulocytosis
Asplenia
Complement deficiency
26. Disorders of human immunity
Autoimmunity
= overactive immune response
the immune system fails to properly distinguish
between self and non-self, and attacks part of the body
27. Disorders of human immunity
Hypersensitivity
Occasionally – inappropriate response of immune system to the presence
of antigen
Four different types of hypersensitivity:
Type I: Immediate Hypersensitivity
Ex: Allergies to penicillin, insect bites,etc
Type II: Cytotoxic Hypersensitivity
Ex: Pemphigus, Autoimmune hemolytic anemia (AHA),
Goodpasture's syndrome
Type III: Immune Complex Hypersensitivity
Ex: Serum sickness
Type IV: Delayed Hypersensitivity
