Immune Injury

• Hypersensitivities

• Autoimmune Disorders

Immune Injury

AutoimmunityImmature 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 cytotoxic type

III immune complex type

IV Delayed-type hypersensitivity

Three are humoral, immediate typescan 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, foodsallergy 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

TreatmentsLong-term

• Allergy Shots – what’s the theory?

• Testing for and avoidance of allergens

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 TypeAlthough 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