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1. Identify non-immune barriers to infection including the epithelial barrier function of skin
and gastrointestinal system, the acid bath of the stomach, antibacterial enzymes in
secretions.
Epithelial barrier function of skin and gastrointestinal system
- Stratified Squamous Keratinizing epithelia of skin, desmosomes which lock cells
together (keratin creates are hard protective layer and the desmosomes keep
the cells tightly connected)
- Sero-mucous surfaces inhibit adherence to epithelial cells- antibacterial tears,
respiratory mucociliary escalator.
Acid Bath of the stomach
- Acid pH of stomach and the digestive enzymes, bile salts, fatty acids and
lysolipids found in the upper gastrointestinal tract create a substantial chemical
barrier to infection
Antibacterial enzymes in secretions
- Lactic acid and fatty acids in sweat and sebaceous secretions lower pH
- Stomach, skin and vaginal acid secretions have an antibacterial effect
- Other secretions that have with antimicrobial action
o lysozyme and phospholipase A in tears and saliva,
o saliva also contains histatins (histadine-rich peptides with antimicrobial
properities)
o lactoperoxidase in milk,
o acid in gastric juice,
o spermine and zinc in semen
2. Distinguish passive versus active immunity, including maternal IgG in the neonate.
There are 2 ways of achieving immunity:
Active immunization
Passive immunization
These may be naturally acquired or artificially induced
Active Immunity:
Exposure to immunogenic stimulus triggers immune response by
host.
Artificially acquired active immunity: Can be induced by a vaccine, a substance
that contains the antigen. A vaccine stimulates a primary response
against the antigen without causing symptoms of the disease. The
vaccine can contain live organisms, inactivated organisms
(attenuated) or their toxins.
 Slow effects, but long lived.
Artificially acquired passive immunity: A short-term immunization by the injection
of antibodies, such as gamma globulin, that are not produced by the
recipient's cells.
Antibodies may be given as: Human normal immunoglobulin
(prepared from random pools of donated blood), containing Ab’s to
diseases prevalent in community, OR
Human specific immunoglobulin prepared from convalescent
individuals with high titre Ab’s to particular organism (hyperimmune
immunoglobulin)
 Fast effects, but short lived.
Naturally acquired active immunity: Occurs when the person is exposed to a live
pathogen, develops the disease, and becomes immune as a result of
the primary immune response.
Naturally acquired passive immunity: Occurs during pregnancy, in which certain
antibodies are passed from the maternal into the foetal
bloodstream. Of the three main immunoglobulins, IgG, IgA and IgM,
only IgG is small enough to cross the placental barrier. It affords
immunity to specific viral infections. At birth the baby's levels of IgG
are equal to or slightly higher than those of the mother. This
provides passive immunity during the first few months of life.
Passive immunity is short lived because these IgG Ab’s gradually
catabolised (t1/2 = 3 weeks), so protection only lasts ~4 months.
3. Identify the role of cell-mediated immunity, antibodies and complement in defence.
Humoral immunity, also called antibody-mediated immunity, is provided by antibodies
present in the body’s “humors,” or fluids (blood, lymph, etc.). Though they are produced by
lymphocytes (or their offspring), antibodies circulate freely in the blood and lymph, where
they bind primarily to bacteria, to bacterial toxins, and to free viruses, inactivating them
temporarily and marking them for destruction by phagocytes or complement. Antibodies
are fairly useless against infectious microorganisms like viruses and the tuberculosis bacillus
that quickly slip inside body cells to multiply there.
When lymphocytes themselves rather than antibodies defend the body, the immunity is
called cell-mediated immunity or cellular immunity because the protective factor is living
cells. In cases where antibodies provide only partial immunity, cell-mediated arm of
immunity comes into play. Cell mediated Immunity refers to the removal or destruction of
pathogens, cells infected by viruses, intracellular bacteria as well as abnormal or cancerous
cells by T lymphocytes, mf, NK cells, neutrophils.
Complement System
The term complement system, or simply complement, refers to a group of at least 20
plasma proteins that normally circulate in the blood in an inactive state. These proteins
include C1 through C9, factors B, D, and P, plus several regulatory proteins. Complement
provides a major mechanism for destroying foreign substances in the body. Its activation
unleashes chemical mediators that amplify virtually all aspects of the inflammatory process.
Another effect of complement activation is that certain bacteria and other cell types are
killed by cell lysis. (Luckily our own cells are equipped with proteins that inactivate
complement.) Although complement is a nonspecific defensive mechanism, it
“complements” (enhances) the effectiveness of both innate and adaptive defenses. The
complement is activated via 3 pathways.
Complement can be activated by the two pathways outlined in Figure 21.6. The classical
pathway involves antibodies, water-soluble protein molecules that the adaptive immune
system produces to fight off foreign invaders. The classical pathway depends on the binding
of antibodies to the invading organisms and the subsequent binding of C1 to the
microorganism-antibody complexes, a step called complement fixation (described). The
alternative pathway is triggered when factors B, D, and P interact with polysaccharide
molecules present on the surface of certain microorganisms.
Complement activation by either pathway involves a cascade in which proteins are activated
in an orderly sequence—each step catalyzing the next. The two pathways converge on C3,
cleaving it into C3a and C3b. This event initiates a common terminal pathway that causes cell
lysis, promotes phagocytosis, and enhances inflammation.
The lytic events begin when C3b binds to the target cell’s surface, triggering the insertion of
a group of complement proteins called MAC (membrane attack complex) into the cell’s
membrane. MAC forms and stabilizes a hole in the membrane that ensures lysis of the target
cell by inducing a massive influx of water.
The C3b molecules that coat the microorganism provide “handles” that receptors on
macrophages and neutrophils can adhere to, allowing them to engulf the particle more
rapidly. As noted earlier, this process is called opsonization. C3a and other cleavage products
formed during complement fixation amplify the inflammatory response by stimulating mast
cells and basophils to release histamine and by attracting neutrophils and other
inflammatory cells to the area.
4. Indicate a broad classification of immunodeficiency syndromes, based upon the functions
of the major elements of the immune system.
Primary immunodeficiency (almost always genetic) is classified into five main groups
depending on which element of the immune system is deficient. Affects specific and innate
responses. Usually manifest between 6 months to 2 years with susceptibility to recurrent
infections, pathogens causing infections give clues to which part of the system is lacking.
1. B-lymphocyte deficiency: low levels of antibody is results in inability to clear
extracellular bacteria
2. T-lymphocyte deficiency: both cell-mediated and humoral immunity fail thus hard
to distinguish from B and T cell deficiency (SCID)
3. Both B & T-lymphocyte deficiency both cell-mediated and humoral immunity fail
4. Phagocytic disorders: permit widespread bacterial infections
5. Complement disorders: defective humoral immune function and persistence of
immune complexes (eg membrane attack complex of complement).
Secondary immunodeficiency is an impairment of the immune system resulting from
complications from an illness/infection, malnutrition, aging, or side effects from
immunosuppression, irradiation or chemotherapy for cancer and other autoimmune
diseases in a previously normal person. The impairment may or may not be reversible if the
underlying condition or illness is rectified. Secondary deficiency is more common than
primary.
1. Hereditary and metabolic disease – chromosome abnormalities
2. Immunosuppressive agents – corticosteroids, radiation, immunosuppressive drugs
3. Infectious disease – HIV/AIDS
4. Infiltrative and haematological disease – Leukaemia(Progressive proliferation of
abnormal leukocytes), lymphoma, agranulocytosis, aplastic anaemia.
5. Surgery and Trauma – burns, splenectomy, anaesthesia
SCID (Severe Combined Immunodeficiency Disease)
Absence of both humoral (antibody) and cellular immunity with alymphoplasia or
lymphopenia (both B-type and T-type lymphocytes), associated with marked susceptibility to
infection by bacteria, fungi, protozoa, and viruses, and to progressive disease from live
vaccines.
Death occurs usually before the end of the first year of life, although bone marrow
transplants have been effective in extending life;
SCID can be inherited as either autosomal recessive however there is also an X-linked severe
combined immunodeficiency with a major histocompatability class I and/or class II
deficiency.
Suffer recurrent infections early in life including: Prolonged diarrhoea (rotavirus),
pneumonia (Pneumocystis carinii), oral candidiasis.
In ADA deficiency and receptor mutation (ie the 2 most common types of SCID), the thymus
is small and devoid of lymphoid cells, or absent.
Hypogammaglobulinaemia and failure of antibody production (will see maternal IgG in
infants).
Very low or absent T (CD3) cells; normal NK (CD16) cells
B lymphocytes are usually present (with surface IgM)
Treatment is a bone marrow transplant.