7. Immune-Mediated Diseases

What is immunologic tolerance?

Unresponsiveness to an antigen induced by prior exposure

What are the two types of self-tolerance?

Central tolerance and peripheral tolerance

What is anergy?

Functional T cell unresponsiveness resulting from antigen recognition without co-stimulatory signals from APCs

What is autoimmunity?

Failure of self-tolerance leading to immune attack against self-tissues

What are tolerogens?

Antigens that induce tolerance

What are immunogens?

Antigens that induce immunity

What are the four main categories of immune-mediated disorders?

Immunodeficiencies, hypersensitivities, autoimmune diseases, and immune system neoplasms

What is the principal consequence of immunodeficiency?

Increased susceptibility to infection

What are the two major groups of immunodeficiency diseases?

Congenital (primary) and acquired (secondary) immunodeficiencies

What causes congenital immunodeficiencies?

Genetic mutations or mother's exposure to environmental agents

What are some causes of acquired immunodeficiencies?

Microbes, nutritional deficiencies, drugs, stress, and aging

What is Leukocyte Adhesion Deficiency (LAD)?

A congenital immunodeficiency characterised by recurrent bacterial infections, impaired pus formation, and delayed wound healing

What is Chédiak-Higashi syndrome?

A congenital immunodeficiency characterised by defects in secretory granule exocytosis and lysosomal function

What is Severe Combined Immunodeficiency Disease (SCID)?

A congenital immunodeficiency where both humoral and cell-mediated immune responses are deficient

What are three viral agents that can cause acquired immunodeficiencies?

Feline immunodeficiency virus (FIV), feline leukemia virus (FeLV), and feline panleukopenia virus (FPV)

What are hypersensitivity reactions?

Antigen-specific reactions that rely on adaptive immunity and its immunological memory

How many types of hypersensitivity reactions are there?

4

Which types of hypersensitivity reactions are antibody-mediated?

Types I, II, and III

Which type of hypersensitivity reaction is cell-mediated?

Type IV

What is the immune reactant in Type I hypersensitivity?

IgE

What is the immune reactant in Type II and III hypersensitivity?

IgG

What are the immune reactants in Type IV hypersensitivity?

Th1 cells and CTL

What is an example of a Type I hypersensitivity reaction?

Allergic rhinitis, asthma, or systemic anaphylaxis

What is an example of a Type IV hypersensitivity reaction?

Delayed-type hypersensitivity (DTH) or contact dermatitis

What are the two main mechanisms of central tolerance?

Clonal deletion and clonal anergy

What is peripheral tolerance?

Mechanisms that maintain self-tolerance in mature lymphocytes in peripheral tissues

What is a key mechanism of peripheral tolerance?

Suppression of self-reactive lymphocytes by regulatory T cells

What are the three main causes of autoimmunity?

Genetic factors, environmental factors, and breakdown of regulatory mechanisms

What is an example of a Type II hypersensitivity reaction?

Autoimmune hemolytic anemia

What is an example of a Type III hypersensitivity reaction?

Serum sickness or Arthus reaction

What are the two main types of effector mechanisms in Type IV hypersensitivity?

Macrophage activation and cytotoxicity

What cells are primarily involved in Type I hypersensitivity reactions?

Mast cells and basophils

What is the role of IgE in Type I hypersensitivity?

It binds to Fc receptors on mast cells and basophils, triggering degranulation when cross-linked by allergens

What are the two phases of Type I hypersensitivity reactions?

Sensitisation phase and activation/effector phase

What cytokine promotes IgE production in Type I hypersensitivity?

IL-4

What are the main mediators released in the early phase of Type I hypersensitivity?

Histamine and other preformed mediators

What are the main mediators in the late phase of Type I hypersensitivity?

Leukotrienes and other newly synthesised mediators

What is anaphylaxis?

A severe, potentially life-threatening systemic allergic reaction

How do genetic factors contribute to autoimmunity?

They can predispose individuals to autoimmune diseases by affecting immune regulation or self-antigen presentation

How can environmental factors trigger autoimmunity?

Through molecular mimicry, bystander activation, or exposure to cryptic antigens

What is molecular mimicry in the context of autoimmunity?

When foreign antigens share structural similarities with self-antigens, leading to cross-reactive immune responses

What is bystander activation in autoimmunity?

When tissue damage from infection leads to release and exposure of self-antigens, triggering autoimmune responses

What are cryptic antigens in autoimmunity?

Self-antigens that are normally hidden from the immune system but become exposed due to tissue damage or altered processing

How can a breakdown in regulatory mechanisms lead to autoimmunity?

Through defects in regulatory T cells or other suppressive mechanisms that normally prevent autoimmune responses