Immunology Final Exam Review

Final Exam Information

• 42 questions on the final exam
• 10 questions cover pre-midterm content, including:
  • Serology
  • Titers
  • Primary and memory antibody responses
  • Seroconversion
  • Incubation period
  • Neonatal immunity
  • Vaccination of neonates
  • Passive immunity
• 5 questions on vaccines
• 15 questions on immunodiagnostics
• 4 questions on sensitivity and specificity of diagnostic tests
• 10 questions on hypersensitivities
• Note: some questions may cover multiple topics
• Review for the final exam will be during class on Thursday, Nov 28
• Submit any remaining questions/topics to the class representative by Wednesday at noon.

Lecture 27 - Hypersensitivities III and IV

• Lecture focusing on hypersensitivity types III and IV.

Type III Hypersensitivity

• Caused by immune complexes
• Immune complexes form constantly, removed by phagocytic cells
• May deposit in blood vessels, causing vasculitis.
• Signs include:
  • Rash
  • Protein in the urine (glomerulonephritis)
  • Joint pain
• Multiple signs may be observed in some cases
• Immune complex formation, deposition, and inflammation
• Acute inflammation due to complement cascade activation
• Timeline for acute inflammation (2-8 hours after priming).
• The wet form of FIP infection is due to this mechanism

Type III Hypersensitivity - Disease due to Immune Complex Formation

• Disease attributed to soluble antigen binding with antibody.
• Immune complexes form frequently, but disease only results when excessive complexes form
• Usually involves IgG
• Local Type III: Immune complexes form in the tissues.
• Generalized Type III: Forming in circulation, depositing in blood vessels (joints and kidnyes) and causing vasculitis
• Localized Type III Mechanism: Local immune complex formation activates inflammation
• Pre-formed antibodies bind to antigens located in the tissues.

Example of Localized Type III Hypersensitivity: Blue Eye in Dogs

• Occurs in a small percentage of dogs infected with canine adenovirus type 1 or vaccinated with modified live adenovirus type 1 vaccine or infected with Infectious Canine Hepatitis virus
• Lesion: anterior uveitis leading to corneal edema and opacity
• Virus-antibody complexes and neutrophils are present in the lesion
• Develops approximately 1-3 weeks after infection or vaccination

Blue Eye (Immune complex formation)

• Immune complex formation following virus release (canine adenovirus type 1 or modified live virus) originating from infected corneal endothelial cells
• Resulting damage/edema of cornea
• Attenuated vaccines can produce temporary corneal opacities

Note:

• Factors other than ICH or CAV-1 vaccination can cause "Blue Eye" due to immune complexes
• Not all corneal opacities are always due to immune complex formation

Examples of Generalized Type III Reactions

• Glomerulonephritis
• Purpura hemorrhagica in horses following Strep equi infection or vaccination.

Glomerulonephritis

• Most glomerulonephritis is caused by immune complex disease in domestic animals
• Immune complexes lodge in glomerular capillaries causing vasculitis and protein loss.
• Associated with the antigens of various infectious agents such as:
  • Borrelia burgdorferi (Lyme disease)
  • Ehrlichia species
  • Canine adenovirus 1 and 2
  • Feline leukemia virus
  • FIP virus (cats)

Diagnosis of Glomerulonephritis

• Histological section of kidney biopsies
• Stained with anti-dog IgG antibody labeled with a fluorochrome

Streptococcus equi Infection and Purpura Hemorrhagica

• Purpura hemorrhagica caused by immune complex mediated type-III hypersensitivity mechanism
• Purpura: hemorrhagic area larger than 3 millimetres in skin or mucus membranes.
• Strep Equi infection = Non-thrombocytopenic Purpura (due to immune complex formation)
• FYI: Purpura hemorrhagica (caused by low platelet count) is called thrombocytopenic purpura (platelet decrease due to many factors)

Strep equi infection: Clinical Signs

• Abscesses of submandibular lymph nodes

Strangles (Streptococcus equi) and Purpura Hemorrhagica

• Strangles (Streptococcus equi) can cause purpura hemorrhagica (vasculitis) 2-4 weeks post-acute infection or vaccination, more likely with modified-live vaccines.
• Immune complexes lead to acute vasculitis

Vasculitis lesions post Strep. Equi infection

• Purpura hemorrhagica: Destruction of blood vessels in the skin (leading to sloughing).
• Edema: Leaky blood vessels.

Purpura Hemorrhagica associated with recent Strep equi infection

• Most likely result of antibody ELISA test: High antibody titer to Strep equi

General Approach to Treatment of Immune Complex Conditions

• Treat underlying conditions
• If pathogen present, administer antimicrobials
• Suppress immune system (e.g., glucocorticoids)

FYI: ZUKU review MCQ

• A horse presents with distal limb edema in all four limbs, petechial mucous membranes, depression, and low-grade fever
• Multiple horses in the stable recently suffered from upper respiratory infection
• Likely responsible immune reaction type for vasculitis
• Answer: Antigen-antibody complex (Type III)

Type IV Hypersensitivity

• General components include: Antigen-sensitized Th1 CD4 lymphocytes & CD8 lymphocytes, Th1 cytokines (mainly IFN-ɣ), activated macrophages.
• Response peaks at 72 hours.

Delayed-Type Hypersensitivity (DTH)

• DTH with TB testing in cattle and humans is an example of Type IV hypersensitivity mechanism involving T-helper 1-specific T cells that produce IFN-ɣ, activating macrophages.

Type IV Hypersensitivities (DTH response)

• Mediated by Th-1 cells against antigens
• Antigen-activated Th-1 cells produce IFN-y.
• IFN-y activates macrophages
• Often caused by haptens, such as poison ivy and some medications (especially antibiotics)
• Can cause contact dermatitis

Allergic Contact Dermatitis

• General approach to prevention and treatment involves avoidance

Mechanism of poison oak IV hypersensitivity

• Specific T-helper-1 cells reacting to poison oak antigen

Poison Ivy

• Hypersensitivity to poison ivy (toxicodendron) due to haptens (pentadecacatechol) binding to skin proteins
• Often characterized by pruritis (itching) and inflammation
• Treatment may include steroids, topical ointments, and/or medications, followed by avoidance.

FYI (Poison Ivy)

• Not everyone is sensitive to poison ivy
• Reaction usually within 2 days of sensitization, but can take up to 10 days, or even as early as 8 hours
• Hyposensitization is often ineffective

Drug-induced contact dermatitis

• Drug acts as a hapten, binding skin proteins
• Examples include neomycin, penicillin, and local anesthetics (e.g., novocaine)
• Common cause (in humans) is Neomycin, often in antibiotic creams

Topical penicillin

• Topical penicillin can cause dermatitis in ears and nose.

Formaldehyde and Nickel

• Formaldehyde: found in cosmetics, textiles, furniture, and paper
• Nickel: dissolves in weakly acidic environments of sweat
• Both cause hypersensitivity in humans and possibly animals, manifested through contact dermatitis

Type IV Hypersensitivities in Tissue Transplants

• Host vs Graft rejection: T cells recognize foreign MHC molecules in graft tissue, activating cytotoxic T lymphocytes (CTLs) leading to acute rejection
• Chronic rejection (months later): involves Th1 and macrophages activated by foreign MHC II molecules.
• Graft VS Host rejection: occurs when foreign lymphocytes in a bone marrow transplant destroy the recipient's cells and tissues.

Matching Disease Descriptions with Hypersensitivity Types

• Match descriptions of diseases (e.g., vasculitis, blood transfusion reaction, immune-mediated hemolytic anemia, wet form of FIP) with the hypersensitivity type most likely associated with them (types I, II, III, and IV).

Prepare for the final exam covering essential immunology topics such as serology, vaccines, and hypersensitivities. This quiz includes questions on primary antibody responses, immunodiagnostics, and the sensitivity and specificity of diagnostic tests. Make sure to review your notes and clarify any doubts before the exam!