1. Professor of Pathology, Microbiology, and Medicine
ImmunoPathology I
R. Pat Bucy, MD, PhD
Professor of Pathology, Microbiology, and Medicine

3. Type I Hypersensitivity (AKA: Anaphylactic type, immediate hypersensitivity)
Due to activity of IgE
Cross-linkage of Fce resulting in mast cell degranulation
Anaphylaxis - local vs systemic
Skin test peaks in ~10 minutes
Normal function of IgE

4. Immediate Hypersensitivity (Type I)

8. Type II Hypersensitivity (AKA: Antibody mediated cytotoxic type)
Ab coating of cells → phagocytosis & ADCC
Ab + complement → direct lysis
Ab interaction with cell surface receptor → activation or inhibition of bioactivity

11. Type III Hypersensitivity (Immune complex type)
Immune complex physical chemistry and IC deposition
IC deposition in vessel walls and glomeruli
complement deposition and neutrophil activation
Skin test peaks in ~10 hours
Skin test called Arthus reaction

18. Type IV Hypersensitivity (Cell mediated type)
Delayed Type Hypersensitivity (DTH) - CD4+ T cell mediated macrophage and endothelial activation
Granulomatous inflammation - continual T cell drive with lack of complete M digestion of Ag
Cytolytic T Lymphocytes (CTL) - direct lysis of target cells involving TCR recognition at effector phase
NK cell activity - no specific recognition (no TCR). Require IL-2 and perhaps other cytokines.
Technical difficulties in experimental determination of cellular vs Ab mediated immune mechanisms.

23. Granulomatous Inflammation Aggregation of macrophages with fibrosis
Associated with chronic T cell and macrophage activation
Antigen that is resistant to macrophage degradation

25. Relationship of antibody vs cell mediated hypersensitivity
Radical difference in assay/detection methodology
Usually both are present in a strong immune response
Presence of antibody can be a marker of a specific T cell mediated lesion
Passive transfer is the key experimental approach to determine primary cause of response.

26. Classification Scheme Mechanism vs Antigen
Classical system focuses on mechanism
Don’t know all mechanisms (especially early)
Actual disease mechanisms overlap
Alternative system focused on antigen drive
The kinetic course of antigen concentration is the key immunoregulatory entity.
Often don’t know the specific driving antigens
Infection, environmental, tumors, iatrogenic, self.

27. Leprosy Two forms of disease; one bug (Mycobacterium leprae).
Tuberculoid leprosy - intense immune response with low organism load
Lepromatous leprosy - suppressed immune response with high organisms load
Different cytokine patterns in T cell response correlate with forms of disease

31. Contact Dermatitis
Exposure of the skin to multiple agents can cause sensitization. On repeated exposure, an eczematous eruption occurs.
Histologically, the lesion is a mononuclear infiltrate, epidermal spongiosis (intercellular edema), and vesicle formation (bullae).
Depends on ability covalently conjugate to proteins.
Exposure to poison ivy is a common example of this process.

35. Penicillin Allergy
Since penicillin is fairly reactive with proteins, sensitization is common.
Depending on the idiosyncratic nature of the immune response and subsequent exposure, several clinical syndromes may develop.
Formation of IgE can result in systemic anaphylaxis after penicillin therapy (particularly after intravenous administration).
Formation of IgG and drug conjugates of serum proteins (albumin) can lead to a "serum sickness" syndrome, involving fever, skin rash, lymphadenopathy, and edema. Occasionally arthritis, nephritis, and vasculitis may result.
Conjugation to red blood cells with high dose IV therapy and IgG formation can result in development of hemolytic anemia.

36. Tumor Antigens for CD8+ T cells

37. Organ/Tissue Transplants

38. Alloantigen Recognition
Direct
Indirect
Presentation
Presentation
Recipient
APC
Donor T
Many
endogenous
peptides
Donor
peptide
Recipient T cells

39. Mechanisms of transplant rejection (classical)
No “real” physiologic mechanism (evolutionarily selected)
Hyperacute rejection
Acute vascular rejection
Acute cellular rejection
Chronic rejection

40. Mechanisms of transplant rejection
Cytotoxic damage to endothelial cells with coagulation
“DTH” in interstitium - CD4+ T cells & M activation
CTL activity on parenchymal cells (tubules, cardiomyocytes, bile ducts, hepatocytes)
T cell mediated arteritis with intimal proliferation and infarction
ADCC and NK cell activity in interstitium
Antibody mediated injury to endothelia with intimal proliferation and infarction

42. Clinical Monitoring of Allograft Rejection
Kidney - serum creatinine/Biopsy
Heart - Blind Biopsy
Liver - Bilirubin, transaminases/Biopsy
Lung - Pulmonary Function tests/Biopsy
Pancreas - No good method, (urinary amylase, or cytology)

43. Immune
Complex
IgE Ab
T cells