Transcript Immunity

The Immune
Response
text reference
Chapter 43
Campbell & Reece
Non Specific Defenses
•
•
•
•
Anatomical Barriers- 1st line of defense
skin of mucous membranes and cilia
keratin -avoid rips and tears
epithelium
The Inflammatory Response
• (2nd line of defense)
Lymph/ WBC’s attracted
by release of Histimines
from broken skin.
• WBC’s engulf invaders,
blood clots form, temp.
rises to kill bacteria.
• SWELLING=
inflammatory response
Interferons
• (IFNs) are natural cell-signaling proteins
produced by the cells of the immune system
of most vertebrates in response to infection.
• Are active against parasites, tumors, and
bacteria, and inhibit viruses.
• Do not act directly, but stimulate body’s
defenses
White Blood Cells
•
•
Aka “Leukocytes” - made in bone marrow stem cells
Granulocytes- types of circulating WBC’ s, classified by staining properties;
"granules", actually
– Neutrophils (50 – 70%): 1st to injury site, go out into tissues to phagocytize
invaders
– Eosinophils ( 1-4%) responsible for combating infection by parasites in the
body
– Monocytes- ( 2.8% of WBC’s ) protects against blood-borne pathogens and
moves quickly (aprox. 8-12 hours) to sites of infection in the tissues.
(Wikipedia). These are chemically attracted to site of infection; form
Macrophages which trap/engulf in the tissues. (Wikipedia)
– Basophils (0.1%) store histamine, a chemical that is secreted by the cells when
stimulated in certain ways (histamine causes some of the symptoms of an
allergic reaction). Like all circulating granulocytes, basophils can be recruited
out of the blood into a tissue when needed. (Wikipedia)
Types
Lymphocytes
• Immune response is highly specific; " tailored" to each specific invader
• NK cells are a form of cytotoxic lymphocyte which constitute a major
component of the innate immune system. NK cells play a major role in the
host-rejection of both tumors and virally infected cells.
• B Lymphocytes play a large role in the humoral immune response
(making antibodies).
• T Lymphocytes play a central role in cell-mediated immunity. Have special
receptors on their cell surface that recognize/bind.
• Mammals site of proliferation to differentiation is bone marrow and
thymus gland (in chest)
• Lymph Nodes: clean microorganisms out of lymph (tissue fluid)
• Spleen and Tonsils are rich in lymphocytes and particle-trapping cells
B-Lymphocytes and the formation of
antibodies
• >2 trillion lymphocytes in body (some circulatory,
some sessile) in lymph nodes,etc.
• Plasma cells: antibody factories, live a few days
• Memory cells: make antibodies, live long time
• (ex. smallpox, mumps, measles, polio)
• Antibodies = complex, globular proteins
aka"immunoglobulins"
• Antigen = a molecule (invader) that triggers
antibody production
B cells and T cells work together
Antibody structure and function:
• Action:
– "specificity" may coat the antigen and cause clumping
(agglutination) combine with antigen to disrupt their
action may lyse and destroy foreign cells
– structure: 3-D structure to fit with specific antigen
surface made up of 2 light chains, 2 heavy chains.
Antibody Formation
• Antibodies (immunoglobins) are
made by a group of lymphocytes
(WBC’s)
• they are large protein molecules
that Recognize and combine with
foreign macromolecules (antigens)
• Made up of 2 heavy (long)
polypeptide (AA) chains, and 2
light (short) chains.
• 2 Regions: Constant and Variable
– a) Constant region; characteristics
of the species of organism and class
of antibody
– b) Variable region: highly specific;
interacts with the antigen
Five distinct classes of
immunoglobins:
• IgG: gamma globulin (most
common; circulating)
• IgA: mucosal immunity (tears,
saliva, milk, mucous)
• IgD: found on surface of B
lymphocytes, for initial antigen
binding
• IgM: found on surface of B
lymphocytes, 1st to be secreted,
short term
• IgE: role in expulsion of parasites
(worms); also in allergic reactions
The Clonal Selection Theory of
Antibody Formation:
• Great number of antigens can be fought (mouse can form
antibodies against 10 million different antigens!).
• Each person has a large # of B lymphocytes, each only able
to synthesize one type of antibody (on its surface).
• When an antigen is introduced, only a small # of B-cells can
bind to it and they will proliferate (make plasma and
memory cell).
• The antigen-antibody interaction "selects" particular
lymphocytes.
• General lymphocyte population; few "fit" the antigen, then
"customize"- make more of the specific one that "fits").
• V regions are "variable" in light and heavy chains composed
of 300 DNA sequences= 18 billion combos!!
T Lymphocytes and Cell- Mediated
Immunity
• Made from self-regenerating stem cells in bone marrow
• Thymus Gland causes differentiation, selection, maturation
of T cells
• Not affected by antibodies circulating in fluid, but by cellto-cell interaction
• Circulating antibodies formed, by B lymphocytes are
primarily active against viruses and bacteria
• T-lymphocytes act against other eukaryotic cells (body and
own cells that are infected)
• T cells will LYSE the infected cell (kill it), thus exposing the
viruses to antibody action
• Also the principle agents in immune response to tissue
transplants
Functions of T Cells:
• One kind of T-cell has Cytotoxic function; when exposed to
a certain antigen, it divides and daughter cells become:
active cell or memory cell
• Active cells- release chemicals (lymphokines) that attract
macrophages and stimulate phagocytosis "killer cells"
• T- "helper" cells: necessary for activation of both B
lymphocyte and cytotoxic T cells
• T- "Suppressor"-cells: moderate the activities of B cells and
other T cells , inhibit their differentiation/ multiplication
• "MHC genes"- major histocompatability complex group of
at least 20 different genes (with multiple alleles) coding for
"self" antigens.
Immune Disorders:
• Allergies: exposure to environmental antigens (pollen, dust,
food….) triggers production of IgE antibodies and memory
cells are formed.
• Re-exposure produces more IgE, etc. which bind to
basophils and mast cells, which release histamines and
chemicals which induce inflammation.
• Autoimmune Disease: individual makes antibodies against
his/her own cells; Prominent examples include:
–
–
–
–
–
–
diabetes mellitus type 1 (IDDM)
systemic lupus erythematosus (SLE)
Sjögren's syndrome
Hashimoto's thyroiditis
Graves' disease
rheumatoid arthritis (RA).
Other Medical Ramifications
• Tissue and Organ transplants: MHC genes
must be a close match, or face rejection.
• Blood Transfusion: A, B, AB, O
• Agglutination caused by mixing types
Blood
Antigens
Antibodies
A
Type A
Anti-B
B
Type B
Anti-A
AB
Type A & Type B
none
O
none
Anti-A & Anti-B
• "universal recipient"
• "universal donor"
The Rh factor:
• Rh+
– Dominant allele codes for rhesus protein (called RhD
antigen) in blood
– About 85% of pop.
• Rh– Recessive allele
– Lack this antigen in blood
• Can cause disease during pregnancy.
• Rh- mother may form antibodies against Rh+ fetus;
• The following pregnancy may results in death of the
next baby.
And…
• Inheritance of Blood Type
– Co-Dominant IA, IB
– Recessive io
• Organ Transplants: T-lymphocytes can cause graft rejection (e.g.
skin)
• tutorials:
• http://highered.mcgraw-hill.com/olc/dl/120110/micro38.swf
• - Cytotoxic T-cell Activity Against Target Cells
- Interaction of Antigen Presenting Cells and T-helper Cells
- Monoclonal Antibody Production
- IgE Mediated Hypersensitivity