Pathology Flashcards
What is pathology?
The study of disease.
What is aetiology?
The cause.
What is the difference between a symptom and a sign?
Symptom is what the patient complains of.
Sign is what the professional detects.
What is an idiopathic pathology?
The cause is unknown.
What is a iatrogenic pathology?
Caused by medial intervention.
What is the pneumonic for the surgical sieve? Describe each step.
VIITAMIN: Vascular, Infective, Inflammatory, Trauma, Auto-immune, Metabolic, Idiopathic, Iatrogenic, Neoplastic.
Name the two lineages of defence cells.
Myeloid and Lymphoid.
What type of cell can come from either lineage?
Dendritic cells
What defence cells are from myeloid origin?
Neutrophils,
macrophages,
mast cells,
eosinophils and basophils.
What defence cells are from lymphoid origin?
T cells, B cells and natural killer cells.
All myeloid cells are?
Granulocytes: Contain antimicrobial enzymes
What is the most numerous myeloid cell in the innate response?
Neutrophil (white blood cell)
What are monocytes?
Macrophage precursor.
What myeloid cells have a role in allergy?
Mast cells and basophils.
What is the function of dendritic cells?
Present antigens directly to T cells. (Sometimes B)
Where are T cells DERIVED from?
Bone marrow.
Where do T cells mature?
Thymus.
Where are mature T cells found?
Lymphoid organs.
What cells are important for immunological memory?
Both B and T cells.
What are the two types of T cells?
CD4 and CD8
What do CD8 T cells interact with?
MHC class 1
What do CD4 T cells interact with?
MHC class 2.
Where do B cells mature?
Bone marrow.
Where are mature B cells found?
In lymphoid organs, close to T cells.
What cells are phagocytic?
Neutrophils, macrophages, tissue dendritic cells and mast cells.
What cells fight parasites?
Eosinophils and basophils.
What is the innate response?
The immediate response.
What does secretory IGA bind to?
Antigens, flagella (preventing motility), toxins (neutralising them), itself (forming a net) and adhesion molecules (prevents adhesive properties of bacteria.
What occurs in the early induced innate response?
Mediators are released, phagocytosis is promoted and the cell is induced to express cytokines and chemokines.
What are cytokines?
Small proteins.
Act as signalling molecules that coordinate immune responses.
Name the 3 ways in which the cytokines can act? (Hint: ‘Crine’)
Autocrine: Alters behaviour of the cell they were secreted into.
Paracrine: Alters behaviour of neighbouring cells.
Endocrine: Enters the circulation and alters the behaviour of distant cells.
What is the purpose of chemokines?
Recruit immune cells and dictate where they travel to.
Where are leukocytes found?
In veins.
Explain neutrophil migration, more specifically the rolling mechanism.
Leukocytes interact with receptors on the endothelium surface of the blood vessel.
Continuous weak binding creates a rolling mechanism.
The leukocyte encounters a different receptor ICAM-1 that creates tighter binding (rolling stops.)
A signal is then sent that loosens the endothelial cell attachment.
Diapedesis occurs - neutrophil pulled though the endothelial cell wall.
Name the roles of neutrophils. (3)
Engulf and destroy pathogens.
Degranulation ( release granules that assist phagocytosis)
Create neutrophil extraceluler traps.
Name the 3 complement initiating pathways.
Classical: Antigen and antibody.
Alternative: Microbial cell wall (foreign cell surface)
Mannose: Carbohydrates on pathogen surface.
What region of a T cell presents an antigen binding site.
Variable region.
With regards to T cell diversity; what are the genes of the alpha section of the variable region?
Variable and joining.
With regards to T cell diversity; what are the genes of the beta section of the variable region?
Variable, diversity and joining.
Explain thymic education of T cells.
T cells move into the thymus expressing CD4 and 8 at low levels.
T cells move to the cortex where there are many epithelial cells expressing MHC class 1 and 2 cells.
Those T cells that can’t bind to to the MHC cells undergo apoptosis. POSITIVE SELECTION.
If the T cell binds to MHC class1 it will produce CD8 and stop producing CD4.
If T cells bind to self antigens they undergo apoptosis.
NEGATIVE SELECTION: If the T cells don’t bind to self antigens they can proceed into the body.
When are T cells deemed mature?
Once they have come into contact with a foreign antigen.
In terms of priming naive CD4 T cells; what dictates the type of T cell produced?
The cytokines produced (the 3rd signal)
What process results in memory cells being produced?
Priming.
How long do memory cells survive for?
up to 20 years.
In terms of B cell diversity; what is the heavy chain composed of?
Rearrangement of Variable, diversity and joining genes.
In terms of B cell diversity; what is the light chain composed of?
Rearrangement of Variable and joining genes.
What selection do B cells undergo in maturation?
Negative selection.
If they don’t bind to self antigens they can enter the body systems.
Name the 2 activated forms of the B cell.
Thymus dependant:T cells assist.
Thymus indépendant: No help required.
Where does the Thymus dependant stage occur?
In the Thymus.
Where does the Thymus independent stage occur?
The periphery
What is the stronger form of the antibody IgM?
IgG
What do Thymus independent cells differentiate into?
Plasma cells.
What do thymus independent cells lack the ability to do?
Create immunological memory.
Name the 3 processes of accute inflammation.
Vascular dilation.
Increased vascular permeability.
Neutrophil activation and migration.
What occurs in the vascular response? (3)
Small vessels dilate.
Endothelial cells swell and retract. Promotes immune cell passage.
Exudation. Leaky passage of water, salts and proteins.
Name the mediators of acute inflammation.
Histamine and prostaglandins.
What is the function of the histamine mediator?
Acts as a neurotransmitter.
Promotes vasodilation and retraction of endothelial cells.
What is the function of the prostaglandin mediator?
Regulates cytokine and chemokine production.
Acts on nerve fibres to generate pain.
Tissue remodelling.
What enzyme regulates the prostaglandin mediator?
Cyclo-oxygenase 2
What is the role of Bradykinin (plasma factor) in innate immunity?
Vascular permeability.
Stimulates nerves = pain
Expression of cytokines and chemokines.
Production of chemical mediators.
What human factor is active in intrinsic coagulation?
Human factor 12.
blood comes into contact with endothelial connective tissue
What human factor is active in Extrinsic coagulation?
Human factor 7.
Blood vessel damage
What enzyme turns fibrinogen into fibrin?
thrombin.
What deficiency do you have if you have haemophilia A?
Factor 8.
What deficiency do you have if you have haemophilia B?
Factor 9.
What characterises the Von Willebrand disease?
Deficiency in the Von Willebrand protein that stabilises factor 8.
What are the two outcomes of acute inflammation?
Suppuration: Pus formed by pyogenic bacteria.
Resolution: Tissue restored, rapid elimination of the causative agent.
What is pus surrounded by to prevent spread?
Pyogenic membrane.
What process occurs in unison with chronic inflammation.
The healing process.
Name the classes of chronic inflammation. (2 and the subset)
Specific
Non-specific
Granulomatous. (specific subset)
What type of chronic inflammation flares up regularly?
Non-specific.
What is specific chronic inflammation induced by?
Immunological factors:
Asbestos and foreign body reactions.
Non-immunological factors:
Infective organisms, hypersensitivity, autoimmune.
I general; What is specific chronic inflammation driven by? Name the two subsets.
Macrophages.
M1 and M2.
What drives chronic granulomatous inflammation?
Fused epithelioid macrophages. ‘Giant multinucleate cells’
What is oral Crohn’s/ orofacial granulomatosis?
Granulomas of the soft tissue within the oral cavity.
What causes an autoimmune disease?
Breach of tolerance to self antigens; breakdown of immunoregulatory check points.
Give examples of autoimmune diseases.
Psoriasis, Crohn’s, sjogrens syndrome and rheumatoid arthritis.
What are the symptoms of sjogrens syndrome? Why do these symptoms occur.
Xerophthalmia and xerostomia.
Autoantigen attacks lacrimal and salivary gland tissue. (Auto-antibodies against ribonucleoproteins)
In periodontitis; What drives soft tissue destruction?
Metalloproteinases, ROS and RNS.
What is the purpose of metalloproteinases?
Remodel the fibres in the extracellular matrix. Also used for navigation.
What enzyme breaks down the block on pro-MMPs?
Plasmin.
What regulates pro-MMPs?
Cytokines called TIMPS. (Makes MMPs inactive again by putting the block back on)
ROS and RNS are free radical that..
Damage membranes of self cells.
Cause damage to the mitochondria.
Cause damage to DNA within cells.
In periodontitis; what drives hard tissue loss?
Primarily (excessive) RANKL but also (lack of) OPG.
How does osteoclastogenesis operate?
RANK on infant osteoclasts becomes activated when it binds to a ligand. Starts tp resorb bone.
How does osteoblastogenesis operate?
OPG inhibits the RANKL molecule. Once molecule inhibited the osteoblast comes in to repair the lost bone.
What is an opportunistic pathogen?
Micro-organism will cause disease if exposed to the appropriate environmental stimuli.
Define an endogenous infection.
Microbe originates from the patients own flora.
Define an exogenous infection.
Microbe originates from outside the patients body.
What protein helps E.coli bind?
Tamm-Horsfall
What feature of bacteria help them attach to mucosa (i.e. bladder) regardless of the immune response?
Pili
Name some encapsulated infections.
Meningitis, pneumonia.
List what benefits microbes have from being encapsulated. (3)
Capsule prevents immune response from taking action.
Uses the capsule to adhere to surfaces.
Antibodies can’t detect the capsulated organisms.
What is an endotoxin?
A toxin that is released from the cell wall of the bacteria.
Endotoxins are released from what type of bacteria?
Gram negative
What is an exotoxin?
A toxin that is released from the bacteria.
Exotoxins are released from what type of bacteria?
Gram postive.
What toxin is far more dangerous? (Ends/Exo)
Exotoxin
What is LPS: Lipopolysaccharide?
An endotoxin released by gram negative bacteria.
How does LPS cause toxic shock syndrome?
LPS recognised by white blood cells, the cells release signals that cause unregulated coagulation.
What are the two healing outcomes?
Healing by regeneration.
Healing by repair.
What occurs in healing by regeneration?
Replaced with functional cells, exact same tissue/structure restored.
What occurs in healing by repair?
Forms a scar, normal structure permanently altered.
What does the outcome of acute inflammation healing depend on?
Severity, location and tissue type.
What does chronic inflammation result in?
Fibrosis.
What cells shrink the wound?
Myofibroblasts, have contractile properties.
Describe the process of wound healing.
Hemostasis: Clot formation.
Inflammatory response.
Proliferate: Granulation tissue creates the foundation for new tissues.
Remodelling: Maturation.
What kind of wounds can result in healing by primary intentions?
Neat cuts.
What kind of wounds can result in healing by secondary intentions?
less neat, ‘raggy’ cuts
Describe healing by secondary intentions.
Larger scab
More inflammation due to larger amounts of necrotic tissue.
Larger amounts of granulation tissue (foundation tissue)
Wound contraction by myofibroblasts.
Name and describe the 2 stages of the proliferation phase.
1: Vascular.
New capillaries produced.
2: Fibrous
Mature fibroblasts lay down collagen. (forms the early scar)
What is angiogenesis?
Formation of new capillaries.
Name the 2 mechanisms of capillary formation.
Sprouting
Intussusceptive
What are both mechanisms of angiogenesis controlled by?
VEGF
Explain fracture healing.
Inflammation: Blot clot forms, inflammatory cells migrate to remove debris.
Soft callus: Chondrocytes lay down collagen. Cell division and blood vessels form.
(Triggered by inflammation)
Hard callus: Odontoblasts activated. Lay down mineralised bone.
(woven bone: spongy and hard bone)
Remodelling: Cortical bone replaces softer bone. No scar on the bone due to constant remodelling.
Define chronic inflammation.
Extensive deposition of collagen and formation of extra fibrous connective tissue.
What can chronic inflammation be caused by?
Dysregulated healing.
Repeated damage.
Substantial damage.
Define hypersensitivity.
Exaggerated immune response to a foreign agent.
Define allergen.
Antigen that causes a reaction.
Define allergy.
Immunological reaction.
How many types of hypersensitivity is there?
4
What type(s) of hypersensitivity are mediated by IgE?
Type 1
What type go hypersensitivity causes anaphylaxis?
Type 1
What is the function of a Hapten?
When bound to proteins can stimulate antibody formation.
Name an example of a drug that can act as a hapten.
Penicillin
What are the 2 steps in IgE mediated reaction? (hypersensitivity 1)
Sensitisation: Primed to response to the allergen.
Elicitation: Response is degranulation.
Name the 2 responses in IgE mediated hypersensitivity (1).
Cutaneous atrophy:
‘wheal and flare’
Systemic anaphylaxis:
Degranulation all over the body.
Describe the 3 fatal reactions of systemic anaphylaxis.
Laryngeal oedema = suffocation
Bronchiole constriction = suffocation.
Peripheral oedema = hypertension/heart attack.
How is type 1 allergy tested?
Skin prick: ‘wheal’ appears
Patch test
Blood test: IgE levels tested
Food challenge
How do you treat type 1 hypersensitivity reactions? (3)
Antihistamines.
Adrenaline injections: Relaxes muscles. Reduces effect of degranulation.
Hyposensitisation: Repeated injection of the allergen cause IgE to change to IgG.
Describe how anti-histamines work.
(Histamines constantly switching from the active form to the inactive form.)
Anti-histamines stabilise the inactive form.
What are type 2 sensitivity reactions mediated by?
IgM or IgG.
Where do type 3 hypersensitivity reactions occur?
In the vasculature.
What occurs in the vasculature in type 3 reactions.
Anti-body antigen clumps deposit in vessels.
To eradicate the clumps there is an influx of immune cells.
Immune cell influx damage the blood vessels.
Arthur reaction is an example of a type 3 reaction, what causes this?
Insect bit or injecting the antigen.
Serum sickness is an example of a type 3 reaction, what causes this?
Hypersensitivity reaction to penicillin.
Oral erythema multiform is an example of a type 3 reaction, what causes this?
Response to drugs that act as a Hapten.
Causes blistering of the mucosa.
What is Type 4 hypersensitivity mediated by?
Not antibody mediated. Mediated by T cells.
What does type 4 involve?
CD4 and CD8 (from T cells)
What is caused by type 4 hypersensitivity?
Crohns and TB. (granuloma formation)
Name the anaphalatoxins from the complement pathway?
C3a and C5a (byproducts)
List the 5 cardinal signs of inflammation.
Redness: Rubor Swelling: Tumor Heat: Calor Pain: dolor loss of function
Name 2 cells with antigen presenting capabilities.
Macrophages
Dendritic cells
What is the major role of natural killer cells?
Kill abnormal self-cells (tumour/virus infected)
Name 2 constituents of healthy saliva that have anti-microbial properties.
Lactoferrin
Cystitis
Antimicrobial peptides.
Name a pattern recognition receptor capable of recognising and responding to bacterial antigens.
Toll-like receptors.
What is diapedesis?
Blood cells squeeze through tight endothelial cell junctions.
What are the 3 specific signals CD4 T lymphocytes require to become activated?
1: Peptide antigen, presented by MHC class 2, intetacts with cognate T cell receptor.
2: CD28 interacts with CD80/86 expressed on mature dendritic cells.
3: Cytokines (differentiation)
What class of antibody is predominant in a secondary immune response?
IgG.
Where does T cell tolerance occur/maturation?
Thymus
What is the term for the leaking of inflammatory exudate from blood vessels to surrounding tissues?
Oedema.
In chronic inflammation; what molecule inhibits RANKL and derives osteoblast function?
Osteoprotogerin (OPG)
In which stage of wound healing is granulation tissue formed?
Proliferative.
In fibrosis; what is there extensive deposition of?
Collagen
Name 2 microscopical characteristics of a cellular reversible injury.
Cloudy swelling
Fatty changes
Which virus can induce epithelial hyperplasia?
HPV
Name the 4 enzymatic cascades.
Complement.
Kinin
Coagulation
Fibrinolysis.
In the complement cascade (plasma factor) what is the role of MAC: membrane attack complex?
Creates a pore in the cell membrane.
In CD4 T cell priming; What signal determines the subset?
Signal 3/last signal.
Name the 5 CD4 T cell subsets and their functions.
TH1: Supports innate immune response at the site of infection.
TH17: Supports innate response. Release-inflammatory cytokines.
TH2: Communication between T and B cells.
TFH: Communication between T and B cells.
Treg: Switch off T cell responses. Growth factors released that drives healing.
Both TH2 and T follicular help cells allow communication between T and B cells, how do we distinguish between them?
TH2: Communication occurs OUTWITH the lymph node.
TFH: Communication occurs within the lymph node.
Name 2 differences between acute and chronic inflammation.
Acute:
Generalised response, no long lasting immunity.
Name 2 organisms responsible for periodontitis.
P.Gingivalis.
T.Forsythia.
List the roles of macrophages.
Phagocytosis, clear debris.
Antigen presentation.
What is the main function of a plasma cell?
Antibody secretion.
