1 / 43

ImmunoPathology I

ImmunoPathology I. R. Pat Bucy, MD, PhD Professor of Pathology, Microbiology, and Medicine. Type I Hypersensitivity (AKA: Anaphylactic type, immediate hypersensitivity). Due to activity of IgE Cross-linkage of Fc e resulting in mast cell degranulation Anaphylaxis - local vs systemic

bevis
Download Presentation

ImmunoPathology I

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

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

  2. 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

  3. Immediate Hypersensitivity (Type I)

  4. 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

  5. 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

  6. 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.

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

  8. 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.

  9. Classification SchemeMechanism 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.

  10. 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

  11. 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.

  12. 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.

  13. Tumor Antigens for CD8+ T cells

  14. Organ/Tissue Transplants

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

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

  17. 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

  18. 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)

  19. Immune Complex IgE Ab T cells

More Related