Immune Injury
• Hypersensitivities
• Autoimmune Disorders
Immune Injury
Autoimmunity
Immature or defective T-cells Exposure to normally sequestered antigens Cross reactions Thyroiditis SLE Rheumatoid Disorders Diabetes Sometimes genetic predispositions to autoimmunity
“Hypersensitivities”
Why in quotes? Some are truly “hyper” reactions, e.g. allergies. Others are due to non-self although not by their nature harmful agents, e.g. transfusion or transplantation reactions Some may be caused by normal immune reactions to infectious agents
Four Types
I anaphylactic type
II
III
cytotoxic type
immune complex type
IV
Delayed-type hypersensitivity
Three are humoral, immediate types can be transferred with serum “passive” hypersensitivities
Type IV is the only cell-mediated type, would require transfer of lymphocytes for “passive” sensitization
They all require a sensitization stage
and time for immune response to develop
Later exposure is called the challenge stage
The term “immediate” refers only to the challenge stage. In the first three types, preformed antibodies cause immediate and usually very obvious reactions
CMI, DTH: even though T-cells are already activated, they do not travel to site as quickly as humoral antibodies. May take a few days before reaction is observable.
Anaphylactic Type
local or regional: hay fever, animal dander, food allergies
Systemic: insect venoms, injected drugs e.g. radio-opaque dyes, foods allergy shots
Sensitization Stage
Effects of Systemic Anaphylaxis
• Vascular changes – dilation and increased permeability lead to shock
• Effects on smooth muscle – constrict bronchioles • Affect heart action
Long-term • Allergy Shots – what’s the theory?
• Testing for and avoidance of allergens
Treatments
Symptomatic: • Antihistamines • Anti-inflammatories • For systemic anaphylaxis, epinephrine
Cytotoxic Type
HDN Transfusion Reactions Autoimmune Hemolytic Anemias Idiopathic Thrombocytopenia Purpura
Which one does not require a sensitization stage???
May also be due to a foreign substance that attaches to a cell, e.g. some drugs, some bacteria
Complex-Mediated Injury
• May occur after some infections • Autoimmune disorders
• Serum Sickness • Arthus Reaction, a local, deliberately caused response
Effects
Inflammation especially in small blood vessels, glomeruli, joints Accumulation of neutrophils and macrophages Tissue damage
Role of Complement
• In which types of immune injury is C’ involved? • Cytotoxic Type
• Complex-Mediated Type Although some damage may be done by antibody-antigen alone, even without C’ activation
Delayed Type Injury
Contact Sensitivity Tuberculin Reaction
Sensitization Stage
Part of Sensitization Stage and also occurs at beginning of Challenge Stage
Activation of Tc may follow Cytotoxic T cell activity is one form of Cell-Mediated Immunity Tuberculin Response is another. This is the one most often called DTH. Contact Hypersensitivity is another
Contact Hypersensitivity
• Formaldehyde, latex gloves, poison ivy, poison oak, material in flea collars
• Material attaches to skin cells. T-cells are activated and attempt to destroy & remove the altered skin cells • Effects: mild erythema to severe inflammation, blister formation. Because of itching, the host causes additional damage
DTH or Tuberculin Rx’n
• Activated T cells • Secrete lymphokines • Recruit many other lymphocytes & macrophages to the area • So only a minority are antigen-specific cells • Tissue Build-up • Granuloma Formation
Conclusions
Immune injuries occur under a variety of circumstances The mechanisms must have derived from protective measures. Else they would not have persisted evolutionarily Some agents may cause several of the types of immune injury, e.g. penicillin Autoimmune Disorders may exhibit a variety of immune injuries
End of our coverage of Immune Injury