Disorders of immune system
3 categories
- Hypersensitivity
- Over-active, harmful response to foreign antigens - Immunodeficiency
- failure to mount an adequate immune to foreign Ag - Autoimmunity
- harmful response to self antigens (immune response mistakenly directed towards bodys own cells)
Hypersensitivity disorders
Aggressive immune response to antigen
2 stage process that require two exposures to same antigen
- first exposure to AG sensitizes person to the ag
- second exposure to same ag results in strong immune reaction
Sensitizing ag = allergen (harmless foreign antigen trigger strong response)
Two categories of Hypersensitivity disorders
Immediate hypersensitivity = response in minutes to hours (involves antigen, antibody and various cells)
Delayed hypersensitivity = response in 24 hours to days (involves antigen and T-cells only (no antibody)
Immediate Hypersensitivity = Type 1 Hypersensitivity = Anaphylactic reaction
(Mast cells)
Involves IgE antibodies and granulated cells
(basophils, Eosinophils, mainly MAST cells)
Mast Cells:
-carry granules containing inflam. chemicals (histamine, proteases, heparin)
-Found in tissues close to body surfaces (skin, airways, GI tract)
0Involved in would healing
-ABLE TO STRONGLY bind IgE to cell surface
Immediate Hypersensitivity - 2 stages
1st contact = trigger B-cells
-excess amounts of IgE produced (binds to surface of mast cell and sensitizes it)
2nd contact with same allergen
- allergen binds to IgE on sensitized mast cell
- mast cell degranulate and release inflam. chemicals
eg. Histamine
- dilation of blood vessel
- constrict airway
- increase mucus
- stimulate nerve endings (pain, itching)
Types of Immediate Hypersensitivity (Anaphylactic) Reactions
2
- Localized (atopic) anaphylaxis
- reaction only at site where allergen enters body
- hay fever (resp. tract)
- Rashes (skin) - Generalized (systemic) anaphylaxis
-whole body reaction
-massive release of histamine
-anaphylactic shock
(constricted ait ways, leakage of fluid = swelling, drop blood pressure)
Treatment of Anaphylactic Reactions
Atopic &/or mild systemic reactions (esp. respiratory allergies):
- Anti-histamines
- Steroids & bronchodilators = reduce inflammation & open airways
- Drugs which act on mast cells to prevent degranulation, or prevent IgE from binding
Treatment of Anaphylactic Reactions
Anaphylactic shock:
- Epinephrine = relax smooth muscles, reduce vascular permeability
Treatment of Anaphylactic Reactions
De-sensitization immunotherapy:
- Exposure to increasing amts. of allergen over time (months – years)
- Subcutaneous injections or oral pills
Works best for some allergens (wasp venom, grass pollen) but not at all for others (eg. foods)
Mechanism unclear
Allergy testing
20% pop. hypersensitive to allergens, why not everyone?
- give allergen under skin
- check 20-30 mins later
- genetic?
- Failure to regulate IgE prod.
- hygiene hypothesis = lack of childhood exposure (farm kids stronger)
Delayed (type IV) Hypersensitivity
- no antibodies (allergens and T-cells only)
- Delayed reaction (>24 hours) due to time req. for T-cell response)
1st exposure (sensitization) activates T cells 2nd exposure causes T cells to release cytokines which draw macrophage and cytotoxic t cells to site
Example: Tuberculin Skin test (Mantoux test)
Positive only indicates exposure
test see if “sensitized” to Mycobacterium tuberculosis (causative agent of TB)
- inject non-infectious m.tuberculosis under skin
- loon for inflam due to DH reaction (48-72 hours)
Positive skin test can be due to:
- previous disease, fully recovered
- vaccine
- current exposure
Immunodeficiency disorders (immunocompromised pt.)
Age related change
Failure to have good immune response to AG due to defect in innate/ adaptive immune system
Age related change normal:
Elderly = T/b-cell production down
Kids = immune system not fully formed till 12-18 months
-protection via innate defenses
-protection via moms IgG which cross placenta (maternal antibodies)
Abnormal immunodeficiencies:
- congenital (present at birth due to genetic defect)
- acquired (exposure to external agent In life)
Congenital (primary) immunodeficiencies
five types
highly susceptible to infectious diseases
Mutation (spontaneous or inherited) in genes that regulate immune response/code
-mild to severe depending on function of mutated gene
Five types: B-cell deficiencies (most common) T cell deficiencies B and T cell deficiencies defect in phagocytic cell number/function complement deficiencies
Examples of Congenital (primary) immunodeficiencies 3
Agammaglobulinemia
DiGeorge Syndrome
Severe Combined Immunodeficiency (SCID)
Agammaglobulinemia
- B-cell deficiency. (don’t form from precursor cells)
- no humoral response (low/absent antibodies)
Digeroge syndrome
- T cell deficiency (absent/abnormal thymus)
- susceptibility to intracellular microbes (virus)
- poor antibody response (B cells need T cell to make lg)
Severe combined immunodeficiency (SCID)
- precursor cells for B and T cells do not form (1 in 500,000 births)
- Complete absence of all T and B-cells results in lack of both humoral and cell-mediated immunity
- requires isolated
- treated with bone marrow transplant
Acquired Immunodeficiencies
Suppression of immune response due to external agent
microbial
Human immunodeficiency Virus (HIV)
chemical drugs
Suppression of overactive immune response (steroid)
Suppression of immune response for transplant
Other Factors
Temp or permanent
Microbial infections
Human immunodeficiency Virus (HIV)
- attaches to receptor molecule (CD4)found on helper T-cells)
- replicates in and kill T cells
- Decline of Tcells = immunodeficiency= susceptibility to microbial infections and cancers
Drugs
Temp suppression of an overactive immune response (steroids)
-Inhibit synthesis of inflammatory chemicals, suppression of T-cells, B-cells, macrophage, etc.
suppression of immune response following transplantation
other factors = stress, malnutrition, alcoholism
Autoimmunity disease
Damaging immune reason to own cells/tissue due to inability to tell self from non self
- production of antibodies and activated T-cells which recognize antigens on normal host cells/tissue
- AB-AG complexes form, inflammation, tissue dmg
mechanisms unclear
- similarity between foreign Ag and cellular Ag
- mutation = structure change
Risk of developing AI disease:
- genetic (30%)
- Environmental (70%) - Toxins, drugs, diet, hormones
Autoimmunity disease Examples 3
Type 1 (juvenile) Diabetes
Acute Rheumatic Fever
Rheumatoid Arthritis
- Type 1 (juvenile) Diabetes
- Cytotoxic T-cells destroy insulin producing pancreatic cells (lack of insulin = increased blood and urine glucose) - Acute Rheumatic Fever
- Antibodies produced vs. streptococcus cell wall proteins recognize similar antigen on heart valves (cross reactions) = inflamm and dmg to heart/valves - Rheumatoid Arthritis
- T-cells activated by unknown self-antigen
- lg + antigen deposit in joints (inflamm dmg to cartilage in joints)
What about conditions where both over- and under-reactions occur?
Sepsis
Immune system involvement includes extreme inflammation and immuno-suppression
Sepsis
-organ failure/ tissue dmg caused by unregulated immune response
usually microbial infection (triggered by major trauma, circulatory shock)
combination of symptoms, mortality increases 8% every hour
survivors have post-sepsis syndrome
happens to anyone
