D’YOUVILLE COLLEGE
BIOLOGY 307/607 - PATHOPHYSIOLOGY
Lecture 6 - IMMUNE DISORDERS
Chapter 5
1.
Hypersensitivities:
- hypersensitivity involves inappropriate immune response (much more
vigorous than needed) to harmless antigenic stimuli, to self-antigens, deposited
immune complexes, or cell-mediated attack against infections or persistent
immune complexes
- four patterns are recognized; these are not totally independent and may
overlap (fig. 5 – 14):
1. immediate hypersensitivities (type I) (fig. 5 – 15 & ppts. 1 & 2): include
certain allergies (atopic immune sensitivities)
- responses are characterized by anaphylaxis (= ‘without protection’) a
damaging response that may be localized or systemic
- mast cells - main vehicles for this hypersensitivity
- relatively innocuous antigens (allergens) provoke sensitization, which
entails proliferation of IgE type antibodies that bind to receptors on mast cells
('primed' mast cells)
- subsequent antigen encounters instigate a disproportionately strong
response involving mast cell degranulation that releases histamine and other
mediators of inflammation (especially eosinophil chemotaxins) (ppts. 3 - 6)
- histamine promotes acute inflammation, provokes bronchial muscle
spasm and increases secretory activity of mucous membranes resulting in urticaria
(hives), rhinitis (hay fever), eczema, conjunctivitis, & allergic asthma (fig. 5 – 16 &
ppts. 3 - 6)
- application of desensitization treatments may alleviate the
hypersensitivity but may carry the risk of systemic anaphylaxis
- antihistamines, epinephrine (that competes for histamine receptors)
may be used for immediate reactions
- steroids & NSAIDS block second phase responses, which take longer to
develop (several hours compared to minutes for immediate response)
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2. cytotoxic hypersensitivities (type II)
- NK cells (antibody dependent cellular cytotoxicity – ADCC) activated by
antibodies often against ‘self’ antigens (autoimmunity) or antibodies against red
blood cell antigens (transfusion reaction) (ppts. 7 & 8)
- diseases (table 5 – 4): myasthenia gravis (cytotoxic attack of muscle motor
end plates); severe muscular weakness results
- Goodpasture’s syndrome (attack on glomerular or lung tissues);
nephritis possibly leading to kidney failure or restrictive pulmonary disease (due to
hemorrhage and fibrosis of lung tissue)
- Graves disease - antibodies against TSH receptors provoke
thyrotoxicosis
- multiple sclerosis (attack on myelin of brain & spinal cord), type I
diabetes (attack on pancreatic beta cells) & systemic lupus erythematosus (attack on
connective tissues of various organs)
- transfusion reactions and other blood incompatibility disorders, e.g.,
erythroblastosis fetalis
3. immune complex hypersensitivities (type III) – imbalance between antigen
level and antibody level produces departure from normal immune response:
formation of numerous circulating antigen-antibody complexes (immune
complexes) that settle on vascular walls instigating vessel damage, formation of
small clots, inflammation (fig. 5 – 17 & ppts. 9 & 10)
- immune complex deposits can afflict various tissues: nerve (neuropathies),
kidney (glomerulonephritis), skin (rashes), systemic distribution (serum sickness),
joints (rheumatoid arthritis) & heart (valve damage)
4. cell-mediated (delayed) hypersensitivities (type IV)
- delivered by the cells of CMI: T lymphocytes (both TH & TC),
macrophages & NK cells (including ADCC – NK) (fig. 5 – 18 & ppts. 11 & 12)
- instigated by persistent offending agents: intracellular bacteria
(tuberculosis, leprosy), allergens from poison ivy, poison oak (contact dermatitis) or
foreign tissue (graft rejection)
- viral infections may elicit type II response (NK cells) or type IV (TC
cells)
- anaphylactic reactions may result with type IV as well as types I & II:
allergens such as insect venoms, plant resins (see above), drugs (e.g., penicillin),
Bio 307/607 lec 6
- p. 3 -
certain foods (e.g., glutens – celiac disease); systemic anaphylaxis may cause
widespread tissue damage and/or shock (anaphylactic shock)
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- p. 4 -
• MHC proteins – of major importance in inducing cell-mediated
hypersensitivities
- cell surface recognition molecules produced from major
histocompatibility complex (MHC) region of genome; immense variability of
products ensures no two people (other than monozygotic twins) will have the same
MHC
- involved in antigen presentation (fig. 5 – 19 & ppt. 13)
- all body cells (except red blood cells) display MHC class I proteins; only
antigen presenting cells (APC) also display MHC class II proteins
• tissue transplants (graft rejection) – instigated by introduction of MHC
incompatibility between donor and recipient causing cell-mediated rejection of foreign
tissue; AMI rejection (complement fixation) may occur in previously sensitized
recipients (fig. 5 – 21 & ppt. 14)
- improving graft survival (fig. 5 – 22 & ppt. 15) – tissue-typing for best
match; purge donor tissue of APC; purge host’s TH cells to weaken immune
response
- post transplant immunosuppression therapy (patient isolation to avoid
exposure to exogenous pathogens)
- administration of antibiotics to minimize vulnerability to opportunistic
infections
- graft vs. host reactions possible with transplanted tissues containing
components of foreign immune system, e.g., bone marrow; donor lymphocytes may
attack host tissues
Bio 307/607 lec 6
2.
- p. 5 -
Immunodeficiencies:
• primary - B cell, T cell, SCID (severe combined immunodeficiency – both B
& T cell) (table 5 - 7)
- usually genetically derived
- increased vulnerability to virus infections and especially yeast/fungal
infections (normally held at bay by TC cells - fig. 5 - 23 & ppt. 16)
- bone marrow transplants are used to treat, but may be rejected by NK
cells or instigate a graft vs. host disease (quite often fatal)
- recent use of gene therapy shows promise for SCID treatment
• secondary - HIV/AIDS (human immunodeficiency virus infection followed
by acquired immunodeficiency syndrome)
- enveloped virus with RNA genome + reverse transcriptase (retrovirus) (
fig. 5 – 24 & ppt. 17)
- many genetically diverse subtypes of HIV render it elusive to
immunization measures
- infects target cells via CD4 receptors and certain chemokine receptors
- first on macrophages/monocytes and often much later on T4
lymphocytes; enters target cell by endocytosis and produces a DNA genome (from
RNA template) that inserts into host DNA (provirus)
- ‘cycling’ of host cell (stimulated by an interleukin in host) triggers
virus reproduction and infection of other target cells (fig. 5 – 25 & ppt. 18)
- disease progresses from flu-like symptoms (acute phase) to
seroconversion (appearance of HIV antigens in blood)
- infection may be held at bay for variable length of time (chronic phase) by
T8 cells until T4 cell numbers decline to a point of paralyzing the T8 response
- disease then progresses to ARC (AIDS related complex) then to AIDS
(crisis phase) (fig. 5 - 26 & ppt. 19)
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- decline of T4 cell population leads to widespread breakdown of immune
defenses (fig. 5 – 27 & ppts. 17 & 18): neuropathies in brain tissue, neoplasms, e.g.,
Kaposi sarcoma (due to deficient tumor surveillance), opportunistic infections (PCP –
Pneumocystis pneumonia)
- transmission via exposure to body fluids containing infected T cells (less
likely free virus) – sexual activity, IV drug use with shared needles, transfusion with
contaminated blood, accidental needle stick or other exposure to fluids of infected
patient
- reverse transcriptase inhibitors (AZT) and other drugs that block reverse
transcription + protease inhibitors are among contents of ‘cocktails’ administered to
HIV infected patients; while not a cure, they appear effective in delaying progression
to AIDS (fig. 5 – 25 & ppt.15)