2. Phylogeny of vertebrate and invertebrate
immunity
(see Fig. JL-1 and Fig. JL-2)
• Self vs not-self:
• Graft rejection:
• CMI - humoral immunity:
• Bi-functional system
• Epithelium from gills of fish-Lymphoid Organ
5. •immunis
•variolation
•vaccine
•2. Vaccination
•1718 - Lady Mary Wortley
Montagu
•1789 - Edward Jenner
•>100 years later - Louis Pasteur
1. Concepts
of immunity
Exp. I. Vaccine vs fowl cholera
“Serendipity”
Attentuation of virulent cultures
Exp. II. Vaccine vs Bacillus anthracis (1881)
Attenuated bacillus cultures
immunized sheep
Exp. III. Immunizing human against rabie
Joseph Meister
Ethics?
6. 3. Discovery of humoral immunity and Cellular
immunity
• cellular immunity
• phagocytosis
• concept of cell-mediated
• immunity (CMI)
• *Nobel Prize for
Metchnifoff in 1908
1883 -
Metchnikoff
1890 -
• von Behring* &
Kitasato
• in serum - humors
• humors = antibodies
• humoral immunity
• *Nobel Prize for von
Behring in 1901
7. •1900 - Paul Ehrlich
•Side chain receptors
•Ag binding
•Cells induced
•more side chains
produced
Selective
Theory
•1930-1940 - Breinl & Haurowitz
•popularized by Linus Pauling
•Ag as template
•Ab would fold, assumes
•configurations complementary
•to that Ag
•more Ab made
Instructional
theory
1950 - Clonal Selectional theory (Fig. 1-11) Burnet,
Nils Jerne, Talmadge & Macfarlane
4. Early theories of Immunity How is specificity achieved?
AntigenAntibody
8. III. INNATE IMMUNITY (non-specific): 4 types
of defensive barriers
1. Anatomic
Barriers
Skin -
epidermis,
physical layer
sebum, fatty
and lactic acid
- low pH
Mucous
membrane -
cilia
mucus -
viscous
secretions
normal flora
12. 1. Cells of the immune system
- developed from
hematopoietic
stem cells
Pluripotent
a) B lymphocytes - mature
in bone marrow
unique Ag-
binding surface
receptors - Abs
encounter Ag
Memory cells
Plasma cells Secret Ab
13. b) T lymphocytes - mature
in thymus
have unique
CD surface
Ags
once mature,
express TCRs
-
heterodimers
of a & b
polypeptides
bind
processed Ag-
MHC
complex
Memory cells
Effector T
cells
c) Antigen presenting
cells (APC’s)
Macrophages
Dendritic
cells
B-Cells
Secrete
cytokines
or exert killing
function
14. 2-Functions of humoral and cell-mediated immune
response
antigen recognition
antigen processing and presentation (Fig. JL-3)
role of MHC
B cell specificity
T cell specificity
Generation of diversity
15. 3. Clonal selection & expansion (Fig. 1-11)
stimulation due to
interaction with antigens
proliferation of
particular clones
provides diversity &
specificity
16. 4. Primary (1°) &
secondary (2°)
immune response
(Fig. 1-12)
1° response - long
lag phase,
modest level
2° response -
shorter lag phase,
higher (heightened)
level
17. B cells - produce Abs
Tc cells (CTLs)
- lyse virus infected cells
TH cellsAPCs
20. Key Concepts of Immunity
The immune system has evolved to protect us from common pathogens.
Innate immunity is the immediate response to commonly shared microbe antigens (LPS, teichoic acid, patterns of
sugars).
Innate immunity includes physical, chemical and mechanical barriers to entry, phagocytes to engulf and digest
extracellular pathogens, and interferons and NK cells to block virus replication and kill virus-infected cells.
Inflammation attracts leukocytes to the infection site, where innate immune responses occur.
Adaptive immunity is the slower response to specific antigens which vary from pathogen to pathogen.
Adaptive immunity includes antibody, cytotoxic T cells, and inflammatory (macrophage-activating) helper T cells.
An active immune response is made to antigen exposure, either naturally acquired during infection or artificially
acquired by vaccination.
Passive immunity is acquired from another individual in the form of antibodies. Humoral immunity is due to antibody
production, while cellular immunity is due to cytotoxic and inflammatory T cell activity.
21. The immune system is composed of circulating leukocytes and lymphoid organs.
Hematopoiesis, the differentiation of stem cells into mature leukocytes, occurs in the bone
marrow. T cell maturation is completed in the thymus. Bone marrow and thymus are the
primary (central) lymphoid organs.
The secondary (peripheral) lymphoid organs bring together antigen and leukocytes to initiate
adaptive immune responses. Secondary lymphoid organs include the lymph nodes, spleen,
and MALT (Peyer's patches, tonsils and adenoids, appendix, and collections of lymphoid cells
in mucous membranes).
Leukocytes recirculate between lymphoid organs and the blood via the lymphatic vessels,
which also collect antigen from the tissues.
Phagocytes include monocyte/mǿ, granulocytes and dendritic cells. They have receptors for
common pathogen antigens and for complement-coated and antibody-coated antigen. In
addition to engulfing and destroying pathogens, macrophages and dendritic cells can make
cytokines that regulate immune responses and can process and present antigen to T cells.
22. Lymphocytes include B cells, T cells, and Natural Killer (NK) cells. B and T cells have
specific antigen receptors which are generated during lymphocyte development by a
specialized gene-splicing process.
BCR bind native antigen, but TCR bind only to antigen peptides presented on MHC. NK
cells do not have antigen-specific receptors, but recognize altered MHC on virus-infected
and cancer cells.
Cytokines are chemical messengers made by leukocytes, primarily T cells, macrophages
and dendritic cells.
Antigen stimulation plus other signals stimulate specific lymphocytes to proliferate and
differentiate into clones of effector cells and memory cells.
B cells are activated to become antibody-producing plasma cells. Antibodies are specific
antigen-binding proteins that neutralize and opsonize antigen and activate complement
to promote inflammation and phagocytosis. Different antibody isotypes have specialized
locations and functions.
23. Cytotoxic T cells identify and kill virus-infected cells that present virus
(endogenous) peptides on Class I MHC.
Inflammatory (Th1) T cells activate macrophages that present antigen
peptide on Class II MHC to more efficiently kill the phagocytosed
(endogenous) pathogens.
Helper (Th2) T cells activate B cells that present exogenous antigen
peptides on Class II MHC to divide and secrete antibody.
Immune memory is the faster, more efficient immune response made
on repeat contact with an antigen. Memory B and T cells can persist
for long times in the body.
Some antigens are polyclonal mitogens that promote lymphocyte
proliferation.