18 Pathological consequences of infection Flashcards
What are ways in which a microbe can cause damage?
Direct damage - cytopathic or induce apoptosis
Indirect - activate immune system, which causes inflammation and tissue damage
What are pathological effects of exotoxins?
Lysis of cell membrane and death
pore formation - cell death
inhibition of protein synthesis e.g diptheria
hyperactivation e.g cAMP causing diarrhoea in cholera
inhibit neurotransmitters e.g tetanus
What does term haemolysins mean?
Collective term for enzymes which destroy cell membranes e.g lecithinases/ phospholipases
not limited to RBCs
What are microbial endotoxins?
They are integral to microbial cell wall, and normally released when cell dies. So they are different from exotoxins
particularly characteristic of gram negative bacteria
What is a typical lipopolysaccharide endotoxin composed of?
Lipid A in cell wall
polysaccharide core
O-polysaccharide highly variable region - feature of organisms such as salmonella and shigella
What are effects of lipopolysaccharide endotoxin?
Driven by release of IL-1/ TNF
Fever - IL1/ TNF effect on hypothalamus
circulatory collapse - increased vascular permeability
DIC/ thrombosis
hypoglycaemia
Hypersensitivity occurs due to overactivity of immune system. What are the broad 4 types of hypersenstivity?
Type 1 - allergic/ anaphylactic
Type 2 - cytotoxic
Type 3 - immune-complex mediated
Type 4 - cell mediated
All can be induced by infectious organisms, most commonly II/ III
What is mechanism of Type I hypersensitivity?
Allergen triggers degranulation of mast cells, precoated with specific IgE antibodies
In infectious context
- ruptured hydatid cyst
- ascaris can cause pulmonary eosinophilia
- helminths - schistosome katayama fever
- viral infections
- venom from insect/ snake
What is mechanism of Type II hypersensitivity?
Infection trigger antibody response - IgG is usual culprit for hypersensitivity
Antibody to pathogen, is similar to host signature
IgG binds to cells host cell erroneously, and activates complement, lysing cell.
What are examples of infections which display Type II hypersensitivity reactions?
Autoantibodies -
- mycoplasma
- streptococci - myocardium
- malaria-infected erythrocyte
What is mechanism of Type III hypersensitivity?
Immune complexes cause disease when they become lodged in tissues or blood vessels
What are examples of infections which display Type III hypersensitivity reactions?
Glomerulonephritis - malaria hepatitis B syphilis streptococcal
hypersensitivity pneumonitis - previously called extrinsic allergic alveolitis, but renamed to hypersensitivity pneumonitis as not Type 1 IgE allergy
serum sickness
Serum sickness is Type III hypersensitivity. What is it?
Follow repeated injections of foreign protein, immune complexes form to protein, and are deposited in skin, kidneys, joints
now monoclonal antibodies used, and humanised as much as possible, so less chance of reaction happening
What is mechanism of Type IV hypersensitivity?
activation of T-cells and macrophages, which can cause tissue destruction
What are examples of Type IV hypersensitivity reactions?
Granuloma formation is most common issue
TB/ leprosy toxocara lymphogranuloma venereum shistosoma Histoplasma Viral rashes
