Introduction to Immunology (text pages: 727-760)
• What happens if some bacterium manages to get through the passive defense
mechanisms like skin and mucous membranes?
• What mechanisms exist to fight a potential infection
o Non-specific immunity
o Specific immunity
Non-specific active immunity
• A resistance to infection mediated by white blood cells
• Derived from bone marrow stem cell and differentiate into
o Myeloid precursors which give rise to
ƒ Mast cells
ƒ Polymorphonuclear leukocytes
ƒ Monocytes
• Which in turn differentiate into macrophages
• And into Dendritic cells
o Lymphoid precursors which give rise to
ƒ T cells (thymus processed)
ƒ B cells (bone marrow processed
• Which in turn give rise to
• Plasma cells
• Memory cells
Some of these cells have the ability to
phagocytize foreign material
• PMNs
o granular appearance due
to the presence of
materials that will attack
foreign material
o found in blood, but can
move out of blood
stream into extravascular areas
(diapedisis)
• Monocytes
o Circulating
o Capable of diapedisis
o Differentiate into
monocyte and dendritic
cells
o All types are found in lymph nodes and spleen
Action of phagocytosis
• Attachment
o Receptors on
phagocyte surface
recognize
molecular patterns
on bacteria or
viruses. For
example a receptor
may recognize the
molecular pattern of LPS and initiate a phagocytosis sequence
• Ingestion
• Phagosome formation
• Phagolysosome formation
• Lysis
This mechanism is not always effective. Some organisms may live within the
phagolysosome. Recall ‘leucocidins’.
Mechanisms of diapedisis improved by events associated with infection or injury
• Damaged connective tissue cells, mast cells, release agents (cytokines) that
promote diapedisis
o Histamine
ƒ Effective vasodilator, increases vascular permeability
o Kinins
ƒ a class of substances with multiple effects
• Actions is to draw phagocytes to the area of injury or infections
• Activate the phagocytes to engulf pretty much everything around.
• Pus…a large accumulation of PMNs and monocytes
Specific Active Immunity
• Phagocytes are the first cells involved with developing some type of immunity.
While their role seems non-specific in that, any foreign material may be attacked.
During degradation of the foreign material, the antigen, is processed, bound to
protein known as the Major Histocompatibility Complex (MHC) and passed
through the cytoplasmic membrane to the surface of the cell.
MHC
•
•
•
•
Proteins present in all vertebrates
The proteins that allow cells to identify self from non-self
They act as a template containing the information that the phagocyte captures
Two types
o Class I are found on the surfaces of all nucleated cells
o Class II are found on the surface of B cells, macrophages, and dentritic
cells
So what happens
• For foreign material phagocytized,
• Some material is combined with the MHC (Type II proteins) in the
phagolysosome and moved to the cell surface
•
For a foreign material originating within cells (viruses or tumor material)
• Proteins processed by the cell itself (the infected cell), imbedded in the MHC
(Type I proteins) and moved to the cell surface
Other cells of the immune system have on their surfaces receptors
• T-Cells
o T-Cell Receptors
ƒ Membrane spanning proteins that extends to the cell surface
ƒ Each T-cell has thousands of copies of the same receptor
ƒ T-cells are different from each other
o the MHC serves as a reference
point for the T-cell receptor
which recognizes the antigen
imbedded within
What happens upon recognition?
• Depends on the type of T cell and the type of
antigen
• Cytotoxic T Cells
o T cells known as T-cytotoxic cells,
produce toxic proteins that kill the cell
containing the antigen
o Active with Class I type antigens
• Natural Killer Cells
o A form of cytotoxic T cells that target cells types lacking MHC
•
•
•
Helper T Cells: Type I
o Secrete agents (cytokines) that stimulate activity of macrophages
Helper T Cells: Type II
o B Cells bind antigens to proteins on their surface and internally process
the foreign material.
o Antigens are presented on the MHC complex
o TH2 cells interact with the MHC-antigen complex and release cytokines
that stimulate the B-cell to
ƒ Proliferate as Plasma Cells
ƒ Produce memory cells
Plasma cells
o Produce antibodies with react specifically
with the antigen
o Short lived
•
Memory cells
o Upon repeated exposure to the antigen these will clone as plasma cells and
produce antibodies
A general summary of events
So…What are antibodies and what role to they play?
• Antibodies or immunoglobulins (Ig) are proteins that are able to combine with
•
•
antigens.
Found in serum and other
body fluids
Proteins have a distinctive
structure
o Variable fragments
o Fixed Fragments
Variable classes of immunoglobins
So what happens during a response to an antigen?
•
•
•
Processing of the antigen by white blood
cells
If processed by B-cells
o Plasma cells and memory cells are
produced
o Initially IgM is active against the
antigen but eventually IgG is
produced
o Review Primary Response and
Seconday Response
Antibodies react with antigens in a variety
of ways
o Causing cell lysis
o Neutralizing toxins
o Opsonizing agents (promote phagocytosis)
o Precipitation soluble antigens
o Agglutination of cells
ƒ Review blood typing and RhoGam
How do vaccinations work?
• Review types of antigens
o Toxoids
o Cellular
o Attenuated
• Why do we vaccinate at
certain times?
Types of Immunity
• Naturally Acquired
o Active: You get the disease
o Passive: in vivo protection (cross placental IgG, colostrums IgA)
• Artificially Acquired
o Active: Vaccination
o Passive: administration of blocking antibody
So what’s deal with allergies?
• Allergies are known as hypersensitivities
• Multi-step events requiring exposure to an antigen followed by a dormant stage
when you become sensitized
• Second exposure is not good.
Immediate type hypersensitivity
• Review events
o Involvement of mast cells
ƒ Connective tissue cells particularly numerous in respiratory and
gastrointestinal tracts near blood vessels
ƒ Upon degranulation skin become swollen, eyes bulge, general hives,
joints swell, cramps
ƒ Very Nasty.
• Event known as Anaphylactic shock
o Compare systemic to localized reactions
• Treatment
o Usually adrenalin for systemic
o Mediators for localized reactions (antihistamine)
• Typical agents
o Bee venom
o Some proteins
o Some drugs
• Review desensitization by blocking antibody
Delayed type hypersensitivity
• Mediated by TH1 cells
• Prior exposure sensitizes T cells
• Second exposure T cells secrete cytokine which
o Draws phagocytes to the area
o Causes localized swelling and redness
o Itchyness
• Commonly known as contact dermatitis
• Examples
o Tuberculin tine test
o Poison ivy reactions
o Animal dander reactions
Autoimmune types
• Usually involve antibody production against “self” tissues
• Result is never good
• Examples include
o Myasthenia gravis (against muscle)
o Goodpasture’s syndrome (against kidney)
o Lupus erythematosis (DNA, blood clotting proteins
o Rheumatoid arthritis (cartilage)
ÆAll figures except where noted, are from Madigan et al. 2002 or Madigan et al. 2000
References:
Madigan, M. T., J.M. Martinko, and J. Parker. 2002. Brock Biology of Microorganisms
10th ed. Prentice Hall.
Madigan, M. T., J.M. Martinko, and J. Parker. 2000. Brock Biology of Microorganisms
9th ed. Prentice Hall.