ICS 1 Flashcards
Immunology & Pathology
What are the 3 tissues that can’t regenerate?
Cardiac Muscle, Nerve, Skeletal Muscle fibres
- Difference between hypertrophy and hyperplasia?
- Do they generally occur together? Example?
- Exceptions to this rule?
- Hypertrophy = size of cell, Hyperplasia = number of cells
- Yes. Eg, uterus in pregnancy
- Permanent tissues, eg. heart (only hypertrophy)
Endometrium - only hyperplasia
What does pathogenic hyperplasia lead to? Exception to this rule?
Dysplasia (abnormal cells) possibly leading to cancer
Exception: Benign prostatic hyperplasia
Why does atrophy occur? Defintion? Mechanism?
Decrease in stress on an organ
Decrease in both size cell and nunber
Via apoptosis (ubiquitin or autophagy)
Metaplasia definition? Example? Lead to? Is it reversible?
Change in cell type (usually surface epithelium)
Example: Barrett’s Oesophagus, Bronchii of a smoker
It IS reversible (remove the stimulus)
Can lead to dysplasia and cancer
What are the two options after tissue damage has occurred? What determines which of these occurs?
Regeneration or Repair
Determined by tissue type and whether the damaging stimulus is removed
When does tissue regeneration occur? Example? Mechanism?
Occurs with acute inflammation, with removal of damaging stimulus. Eg, liver regenerates using stem cells after tumour
When does tissue repair occur? Example? Mechanism?
Occurs with chronic inflammation, with sustained damaging stimulus. Eg, liver with cirrhosis after excessive alcohol, fibrosis occurs
What occurs in the brain instead of fibrosis?
Gliosis
Healing by 1st intention mechanism? Skin wounds
Sutures - bring skin close together.
Weak fibrin joins wound. Replaced by collagen. Replaced by normal cells with remodelling.
Healing by 2nd intention mechanism? Skin wounds
Skin can’t be brought together. Granulation tissue formed, heals from the bottom up. Larger scar formed.
Two types of blood flow? How does this affect clotting?
Laminar flow: cells move through centre of blood vessel
Turbulent flow: cells move chaotically all around the blood vessel
What is Virchow’s Triad? Definition & categories
3 categories contributing to thrombosis
Endothelial cell damage (endothelial dysfunction)
Change in blood flow (stasis or turbulence)
Change in blood constituents (hypercoagubility)
Define thrombosis
solid mass of blood constituents formed within the vascular system during life
Differences of venous thrombosis?
More commonly due to slow blood flow - especially without muscle use.
5 possible outcomes from thrombosis?
- Lysis and resolution (plasmin)
- Organisation (fibrosis, grows within vessel layer)
- Recanalisation (holes)
- Embolism (dislodges)
- Propagation (growing along the vessel)
Define embolism. Causes? (4)
Mass of material in the vascular system: lodging and blocking a blood vessel:
thrombo-embolism, fat, tumour, air
Definitions of ischaemia and infarction?
Ischaemia: reduction in blood flow
Infarction: cell death due to reduction in blood flow
What is reperfusion injury? Basic mechanism?
Tissue damage caused when blood supply returns to tissue after ischaemia
Lack of antioxidants, ROS released, Damaged further
End-artery vs Dual-artery - definitions and significance
End-artery: artery that is only supply of oxygenated blood to tissue (most organs)
Dual-artery: tissue with two supplies of oxygenated blood (lungs, liver, parts of brain)
End-artery far more likely to undergo infarction and ischaemia
Two classes of anti-thrombotic drugs? Mechanism? 2 examples of each?
ANTICOAGULANTS: slow down clotting
eg:
Heparin - blocks thrombin from allowing: ‘fibrin to fibrinogen’
Warfarin - inhibits production of Vitamin K dependent clotting (10, 9, 7, 2)
ANTIPLATELETS: stop platelet aggregation
eg:
Aspirin - stops thromboxane formation
Clopidogrel - binds to P2Y12 ADP receptors
5 signs of inflammation? (local)
Heat (calor) Redness (rubor) Swelling (tumor) Pain (dolor) Joint Immobility
Acute inflammation: characteristics? main cell involved?
Sudden onset, short duration, usually resolves
Main cell: Neutrophil polymorph
Chronic inflammation: characteristics? cells involved?
Slow onset, long duration, usually doesn’t resolve
Cells: Plasma, Macrophage, Lymphocyte, Giant cells (granuloma)
Granulomas: name of cell, how the cell is made, disease list
Giant cells - made from epitheliod cells (macrophage) and lymphocytes.
Eg: TB, Sarcoidosis, Leprosy, Crohn’s Disease, Rheumatic Fever
Acute Inflammation: 4 outcomes
Resolution
Suppuration (abcess/pus)
Repair and Organisation
Chronic Inflammamtion
How do you treat inflammation? 2 methods and mechanism
- NSAIDS - aspirin, ibuprofen, inhibit prostaglandin synthesis
- Corticosteroids: upregulate inhibitors and down regulate chemical mediators by binding to DNA
Two parts of the definition of atherosclerosis?
Hardening of arteries
Narrowing due to plaque
Atherosclerosis mechanism steps.
Endothelium damage due to irritants, causes LDL deposition, where it is oxidised
oxLDL is taken in by macrophage, becomes FOAM cells
FOAM cells promote migration of smooth muscle from media and more WBC migration
Plaque forms with FOAM cells, collagen, dead cell centre - RUPTURES and causes THROMBOSIS
Apoptosis - mechanism
Cell shrinkage, caspases act, vesicles formed (apoptotic vesicles), phagocytes clean up
Apoptosis - how is it regulated control
BAX (+ve)
Bcl2 (-ve)
Fas receptor and ligand
6 types of necrosis
Coagulative necrosis (infarction)
Liquefactive necrosis
(bacteria, fungal, infection)
Caseous necrosis
(mycobacteria - TB)
Fat necrosis
(lipases)
Fibrinoid necrosis.
(immune complexes)
Gangrenous necrosis
(gangrene)
Difference between thrombosis and a clot?
Thrombosis: within the vascular system during life
Clot: blood coagulation outside of the vascular system or after death
Carcinogenesis definition?
Difference between carcinogenesis and oncogenesis?
Carcinogenesis: ‘the transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations’
Oncogenesis: ‘benign and malignant’
3 characteristics of a neoplasm?
Structure of a neoplastic tumour?
Neoplasms (new growths) are autonomous, abnormal, persistent.
Contain neoplastic cells (monoclonal, nucleated, secreting) and stroma (mechanical support, nutrition, fibroblasts/collagen)
How big can tumour get before angiogenesis/blood vessel recruitment is needed?
1-2mm^3
Carcinogen definition and categories (+ examples)
Carcinogens - ‘agents known or suspected to cause tumours’
Chemical (polycyclic aromatic hydrocarbons) Viral (HPV) Radiation (UV light) Hormones/Parasities/Mycotoxins Miscellaneous (asbestos)
Most common cancers in UK?
Which cancers kill the most?
Breast (F) / Prostate (M)
Lung
Bowel
Lung
Bowel
Breast/Prostate
Which carcinomas most commonly spread to bone? (5)
Breast Prostate Lung Thyroid Kidney
3 types/stages of a carcinoma?
Carcinoma in situ
Micro-invasive carcinoma
Invasive carcinoma
Stages of metastasis?
• Invasion of basement membrane • Tumour cell motility • Intravasation • Evasion host immune defence • Extravasation • Growth at metastatic site • Angiogenesis
Two types of chemotherapy? Mechanism? Example?
Conventional chemotherapy:
Antimicrotubule, topoisomerase inhibitors, DNA synthesis inhibitors
Non-selective - cause myelosuppresion, hair loss, diarrhoea
Good for fast dividing tumours (leukaemia, lymphoma, choriocarcinoma)
Targeted chemotherapy:
exploits difference between cancer cells and normal cells, often blocking growth factor receptors
Herceptin in breast cancer, CetuxiMAB (monoclonal antibody)
Benign epithelial cell neoplasm nomenclature? Examples
Papilloma: benign tumour of non-glandular, non-secretory epithelium
Example: squamous cell papilloma and transitional cell papilloma
Adenoma: benign tumour of glandular or secretory epithelium
Example: colonic adenoma, thyroid adenoma
Malignant epithelial cell neoplasm nomenclature? Examples?
Carcinoma: malignant tumour of epithelial cells
Example: transitional cell carcinoma
Adenocarcinoma: malignant tumour of glandular epithelum
Example: adenocarcinoma of prostate, adenocarcinoma of breast
Connective tissue neoplasm nomenclature? Examples (7)
Lipoma, Liposarcoma (adipocytes) Rhabdomyoma, Rhabdomyosarcoma (skeletal/striated muscle) Leiomyoma, Leiomyosarcoma (smooth muscle) Chondroma/Chondrosarcoma (cartilage) Osteoma/Osteosarcoma (bone) Angioma/Angiosarcoma (vascular)
Exceptions to neoplasm nomenclature?
Have ‘-oma’ but are malignant
Melanoma - malignant neoplasm of melanocytes
Mesothelioma: malignant tumour of mesothelial cells, eg pleura or peritoneum
Lymphoma: malignant neoplasm of lymphoid cells
TNM classification of tumours? Will lead to?
T - primary tumour size
N - number of lymph nodes affected
M - amount and distance of metastases
Will lead to a cancer STAGE
Significance of p53 protein? What chromosome?
Significance of RB1 gene?
p53: Gatekeeper to the cell: inhibits proliferation or promotes cell death, responds to DNA damage
Chromosome 17
RB1: transcriptional regular, controlling G1/S checkpoint.
Association with retinoblastoma
TUMOUR SUPPRESSOR GENES:
Two types?
Gatekeepers: p53, RB1
(inhibits proliferation or promotes cell death)
Caretaker: BRCA1/2
(maintain the integrity of the genome, by repairing DNA damage)
Tumour grade: what is it?
Assessment of its degree of malignancy or aggressiveness, from histology (mitotic activity, nuclear size, differentiation)
What would come out of centrifuged blood?
Plasma 55% - water, electrolytes, proteins
Buffy Coat <1% - leukocytes + proteins
Erythrocytes 45% - haematocrit
How are bradykinin’s formed?
Activated factor XII (Hageman factor)
Prekallikrein turns to Kallikrein
Kinninogen to Bradykinin
How does damaged cells lead to inflammatory cytokines?
Damage to lipid membrane
Arachadonic acid goes through:
1. Lipoxygenase: Leukotrienes
2. COX 1,2: Prostaglandins
3 endothelial cell receptors presented to enhance margination of WBC? When are they shown?
P-selectins (initially)
E-selectins (IL-1/TNF-alpha)
ICAMs, VCAMs (IL-1/TNF-alpha)
Systemic signs of inflammation? (due to TNF-alpha, IL-1)
Fever (via hypothalamus and PGE2)
Leukocytosis (in bone marrow)
Liver acute phase reactants due to IL6
(CRP, complement, fibrinogen)
Two mechanisms of killing in phagocytosis?
4 free radicals
- Oxygen independent (lysozymes, defensins, pH)
2. Oxygen-dependent (O2-, H2O2, OH-, HOCl)
What does PRRs stand for?
What do they do?
Two main types and examples
Pattern Recognition Receptors
Recognise PAMPs and DAMPs
Cell associated: TLRs, NLRs, RLRs
Secreted + circulating: Defensins, Cathepsins, Lectins, Collectins, Pentraxins (CRP)
Primary and Secondary lymphoid tissues?
Primary:
Thymus (t-cells)
Bone marrow (b-cells)
Secondary:
Spleen/Lymph nodes/MALT
3 types of antigen presenting cells? What receptor do they present specifically?
• Dendritic Cells
• Macrophages
• B Cells
Will have Major Histocompatibility Complex II
How do antibodies act? (4)
Neutralisation
Opsonisation
Complement Activation
Agglutination
3 actions of complement?
Cause lysis of pathogens using ‘membrane attack complex’ (MAC)
Increases chemotaxis via C3a, C5a
Opsonisation via C3b
3 complement pathways? What complement proteins binds first in each pathway?
Classical pathway - antibody-antigen immune complexes (C1)
Alternative pathway - foreign surfaces, directly to antigen (C3b)
Lectin pathway - mannose-binding lectin on pathogen surface (C4)
What are interferons?
What cells make them?
Different types?
What is their action?
Signalling molecules
Made by infected host cells
Alpha, Beta (platelets), Gamma (immune cells)
Enhance inflammation and tell healthy cells to produce anti-viral peptides
Basic humoral immunity process?
Free antigen uptaken by naive B-cell, becomes activated.
Naive CD4+ T-helper is activated my APC with MHC II via co-stimulation
T-helper 2 cells, produce cytokines to allow B-cells to undergo clonal expansion and differentiation. Memory cells formed
Plasma cells with produce antibodies.
T-helper 1 vs T-helper 2 model:
What determines which is produced?
What do each perform?
T-helper 1: high IL-12
Help cell-mediated immunity
T-helper 2: low IL-12
Help humoral immunity
Basic cell mediated immunity process?
CD8+ cytotoxic T-cell recognize non-self antigens, and viral antigens on MHC I. Kill via perforins and granzymes.
Function of T-reg cells
Function of NK cells.
T-regulatory cells:
Suppresses autoimmunity, down-regulates other T-cells
Natural Killer Cells:
Innate immunity, killing pathogens via perforins and granzymes
Antibody structure? Draw and then mark on:
Structure of antigen-antibody complex
Heavy Chains, Light Chains
Disulfide bonds
Variable Region, Constant Region
FAB fragment: region on antibody that binds
Epitope: region on antigen that binds
How do B-cells and T-cells randomly assemble genes?
Somatic (VDJ) recombination:
Forms massive variety of TCRs and BCRs
IgG antibody: How abundant? Monomer, Dimer, Pentamer? Can it cross placenta? Normal role?
IgG antibody: 80% in plasma Monomer Can cross placenta Normal antibody functions
IgA antibody: How abundant? Monomer, Dimer, Pentamer? Where is it found? Can it cross placenta?
IgA antibody: 10% in plasma Dimer Found in secretions and mucosa No. Transferred in breast milk
IgM antibody: Monomer, Dimer, Pentamer? How is it linked? When is it made? Main roles?
IgM antibody:
Pentamer
Linked by J protein
Made in primary immune response (first exposure)
Good at fixing complement and agglutination
IgE antibody: Monomer, Dimer, Pentamer? Where is it found? On what cell? Roles? Abundant?
IgE antibody: Monomer Found in respiratory mucosa, urogential, lymphatic tissue Binds to mast cells, for inflammation. Allergy and anti-parasitic activity Very rare - not abundant
IgD antibody:
Monomer, Dimer, Pentamer?
Role?
IgD antibody:
Monomer
Acts as a B cell receptor (BCL) - binds to antigens in humoral immunity
5 kinds of arteries affected by atherosclerosis?
Carotid Aorta Coronary Cerebral Common Iliac/Femoral
3 routes of metastasis?
Haematogenous (blood)
Lymphatic (lymph)
Transcoelomic (cavities - abdo, chest)
Histological findings of a malignant tumour? (3)
Pleomorphism
Hyperchromatic nuclei
Poorly defined border
