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HC4: Pathology of normal immune response
Techniques to visualize diseased tissue
Pathology always starts with tissue:
- Biopsies
- Resections
- Autopsies
3 techniques can be combined to make a final diagnosis:
- Immunohistochemical techniques
- Possible to make a diagnosis in an hour
- Tissue is frozen
- Light microscopy
- Most important
- A tissue specimen goes into a paraffine block to make very thin slices → the slices are stained
- Glomeruli of a healthy kidney have silver staining
- In case of chronic inflammation, blue dots are present → lymfocytes
- Electron microscopy
- Used to look for details
- For example podocytes
- Used to look for details
Myocardial infarction:
Normal light microscopy of the heart shows that all cells have a nucleus (the heart is a muscle). Many blood vessels and few lymphocytes are present. A myocardial infarction is an ischemic injury, usually caused by a thrombus in a coronary artery:
- Cell death: necrosis of myocytes
- Hours after the incident
- Cardiomyocytes lose their nucleus
- Neutrophils are the first leukocytes to arrive to clean up the necrotic tissue
- Inflammatory reaction with neutrophilic granulocytes
- Days after the incident
- Ischemic tissue is infiltrated massively by cells with lobulated nuclei → neutrophilic granulocytes
- Fibroblast proliferation: remodeling of connective tissue through collagen disposition
- Weeks after the incident
- Fibrotic tissue is starting to replace the dead cells
- Scar formation
- Months after the incident
This is a general mechanism that can be applied in all tissues → the same process can happen in inflamed skin or lung tissue.
Histomorphology of inflammatory cells and their markers
Inflammatory cells have a distinct histomorphology:
- Granulocytes
- Indicate an acute infection or inflammatory process
- Polymorphonuclear cells
- Neutrophils
- Most frequent
- Eosinophils
- Less frequent
- Basophils
- Very rare
- Neutrophils
- Marker: MPO
- Lymphocytes
- Are associated with chronic processes
- Dark nuclei
- Small cytoplasm
- Mononuclear cells
- Markers
- CD3: entire population
- CD8: cytotoxic T-cells
- CD4: T-helper cells
- Plasma cells
- Produce antibodies
- Pericentric nucleus
- B-cells
- Marker: CD20
- Macrophages
- Large cells
- Present to clean up the mess → digest all sorts of things
- May turn into multinucleated cells
- Marker: CD68
- Other cells
- Dendritic cells
- Fibroblasts
- Histiocytes
Visualizing what one cannot directly see
Some questions cannot be answered by "just" looking at light microscopy:
- How can B-cells be distinguished from T-cells?
- Is the complement system involved?
- Are these large cells indeed macrophages or are they tumor-cells?
- Is there a SARS-CoV2 related protein in this cell?
- Are immune complexes involved?
Immunohistochemistry:
Immunohistochemistry is a technique which makes it possible to visualize proteins in tissue. Proteins are stained with a color. This is done by picking an antibody that fits nicely into the protein and then adding color to it.
This technique can be used to visualize B- and T-cells in cases like Hashimoto's thyroiditis:
- Normal thyroid tissue: hormones are made in the pink areas:
- Hashimoto's thyroiditis: many blue dots are visible → these are lymphocytes destructing the thyroid tissue
- By staining a specific antibody in B-cells or T-cells, it becomes possible to see where there are B-cells and where there are T-cells
Immunohistochemistry is also useful in cases of maternal cytomegalovirus infection. This can cause intra-uterine death. The virus, a viral protein, goes through the placental wall. Such a case looks relatively normal under the microscope, but when the CMV-protein is stained, many CMV-infected cells within the placenta that cause the intra-uterine death become visible.
Direct immunofluorescence:
Direct immunofluorescence is another technique to visualize what one can't see. In direct immunofluorescence, an antibody with an immunofluorescent signal is incubated onto a fresh frozen tissue slide, for example against C3 which appears to be present in a glomerulus. This gives a fluorescent signal as result.
Limitation
The main limitation of pathological tissue examination is that a biopsy is always just a snapshot of a dynamic biological process. The pathologist always has to interpret this snapshot in relation to the clinical context.
Mechanisms of Disease 1 2020/2021 UL
- Mechanisms of Disease 1 HC1: Introduction to G2MD1
- Mechanisms of Disease 1 HC2: Introduction to the immune system
- Mechanisms of Disease 1 HC3: Innate and adaptive immune responses & key cytokines
- Mechanisms of Disease 1 HC4: Pathology of normal immune response
- Mechanisms of Disease 1 HC5: B- and T-cell generation and diversity
- Mechanisms of Disease 1 HC6: Mechanisms of adaptive immunity
- Mechanisms of Disease 1 HC7: Effector mechanisms of antibodies
- Mechanisms of Disease 1 HC8: B-cell development and antibodies
- Mechanisms of Disease 1 HC9: Tissue injury and repair
- Mechanisms of Disease 1 HC10: Repair mechanism
- Mechanisms of Disease 1 HC11: Pathology of inflammatory reactions
- Mechanisms of Disease 1 HC12: Introduction to infectious diseases
- Mechanisms of Disease 1 HC13: Bacteria
- Mechanisms of Disease 1 HC14: Viruses
- Mechanisms of Disease 1 HC15: Fungi and parasites
- Mechanisms of Disease 1 HC16: Invaders
- Mechanisms of Disease 1 HC17: Host versus invader
- Mechanisms of Disease 1 HC18: Immune deficiencies and infection risk
- Mechanisms of Disease 1 HC19: Pathology of infectious diseases
- Mechanisms of Disease 1 HC20: Diagnostics of infectious diseases
- Mechanisms of Disease 1 HC21: Essential microorganisms
- Mechanisms of Disease 1 HC extra: Mycobacterial infections (tuberculosis)
- Mechanisms of Disease 1 HC22: Antimicrobial therapy
- Mechanisms of Disease 1 HC23: Principles of antibiotic pharmacotherapy
- Mechanisms of Disease 1 HC24: Introduction MOOC
- Mechanisms of Disease 1 HC25: Epidemiology
- Mechanisms of Disease 1 HC26: Prevention and control
- Mechanisms of Disease 1 HC extra: COVID-19
- Mechanisms of Disease 1 HC27: Mechanisms of hypersensitivity reactions
- Mechanisms of disease 1 HC28: Pathology of allergy
- Mechanisms of Disease 1 HC29: Asthma
- Mechanisms of Disease 1 HC30: Pathology of autoimmunity
- Mechanisms of Disease 1 HC31: HLA and autoimmunity
- Mechanisms of Disease 1 HC32: Vasculitis
- Mechanisms of Disease 1 HC33: Systemic Lupus Erythematosus
- Mechanisms of Disease 1 HC35: Infections and autoimmunity
- Mechanisms of Disease 1 HC36: Immune cells in rheumatoid arthritis
- Mechanisms of Disease 1 HC37+38: Pharmacology: immunosuppression
- Mechanisms of Disease 1 HC39: Pathology of transplantation
Mechanisms of Disease 1 2020/2021 UL
Deze bundel bevat aantekeningen van alle hoorcolleges van het blok Mechanisms of Disease 1 van de studie Geneeskunde aan de Universiteit Leiden, collegejaar 2020/2021.
This bundle contains notes of all lectures from the module Mechanisms of Disease 1, Medicine, Leiden
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