Mech of Bacterial Pathogenosis 2 - Endotoxins Flashcards
Acute Inflammatory Changes
Local Symptoms?
Systemic Symptoms?
Local Symptoms: Redness, swelling, pain, loss of function, pus (pyogenic infection)
Systemic Symptoms: Fever, Rigors, chills, tachycardia, tachypnoea
What is the mechanism behind LOCAL acute inflammatory changes?
Local symptoms - are caused by RESPONSE OF THE LOCAL SMALL BLOOD VESSELS
- increased blood flow (vasodilation)
- increased permeability to fluid and plasma proteins
- increased stickiness of vascular endothelium
- emigration of phagocytes to site of infection
What causes INITIAL acute inflammatory changes?
What AMPLIFIES the release of inflammatory mediators?
release of products from the bacteria : toxins, enzymes
amplification : HISTAMINE, PROSTAGLANDINS, LEUKOTRIENES, KININS
What causes pus in the inflammation response?
Which three organisms cause pyogenic infection?
pyogenic infection is due to ACCUMULATION of phagocytes (mainly neutrophils) - monocytes - complement
Staphlococci
Streptococci
Meningococci
Bacterial Enzymes - HYALURONIDASE
Streptococci : streptococcus pyogenes
action: break down hyaluronic acid
Result: disruption of tissue mosaic allowing bacteria and inflammatory exudate to travel DEEPER AND FURTHER
Bacterial enzymes : Alpha lecithinase
Clostridium perfringens
Action: splits lethicin, found on the surface of many cells
Result: major tissue damage - gas in muscles
Exotoxins
Action?
Made by?
Enzymatic lysis : alpha lecithinase
Pore formation: Type 2
Inhibition of protein synthesis : Type 3
Hyperactivation
Effects on nerve-muscle transmission : botulinum, tetanus
Gram POSITIVE and Gram NEGATIVE
Where are endotoxins found?
When are they released?
gram NEGATIVE - bacteria
in the cell wall : Lipid A (Lipopolysaccharide)
released when BACTERIAL CELL is DAMAGED
Examples of Endotoxin mediated disease?
Neisseria Meningitidis
- meningococcal meningitis
- meningococcaemia
E. Coli
Klebsiella pneumoniae
Pseudomonas Aeruginosa
What are the CONSEQUENCES of endotoxin release.
- Vasodilation
- Increased vascular permeability - BP DROPS
- IL-1, IL-6, IL-8 TNF alpha - CAUSES SEPSIS: 1=hot - 6= CRP - 8= neutrophils TNF-alpha = endothelium leakiness
- PAF - clotting cascade
- migration of phagocytes - increased macrophages
- complement activation
- polyclonal expansion of B cells and secretion of immunoglobulins
What is bacteremia?
What is septicemia?
Bacteria in the BLOOD
Bacteria in the BLOOD - leading to systemic failure
What bacteria tends to cause sepsis?
Staph Aureus
Strep pyogenes
Strep pneumoniae
Toxic Shock Syndrome
Causes?
Action?
Staph Aureus: Toxic Shock Syndrome Toxin (TSST)
Strep pyogenes : streptococcal pyrogenic exotoxin (SPE)
Action: SUPERANTIGENS
What are superantigens?
What is their action?
Example of causative organism and condition?
Superantigens : act simulataneously with MHC class II on APC and specific VB regions of T lymphocytes
Activates MACROPHAGES/MONOCYTES - elicit IL1, IL6, TNF alpha and interferon Y
IL1 - Fever
IL6 - CRP
TNF-a - activates the endothelium (leakiness)
Interferon Y - causes increased macrophages at site of infection
HYPERACTIVATION of T cells
What is unique about T cell stimulation by a superantigen?
Examples of Superantigen and condition?
T cells stimulation via superantigen = does not need to be specific to the antigen - HYPERACTIVATION of T cells !!
Leads to release of IL2, TNFa, IFN-gamma, cytokines
Examples:
Strep Pyogenes - streptococcal pyrogenic exotoxin (SPE)
Staph Aureus - TSST
what is characterised by Type III hypersenstivity reaction?
An example of a type 3 reaction?
Immune complex formation
Impetigo : strep pyogenes
Host = creates antibodies against strep pyogenes antigens
Antibody + Antigen = immune complexes
Antibodies CROSS REACT with antigens of the HOST
Sites: myocardium, synovium, brain
What happens in rheumatic heart disease?
What is the reaction that occurs?
What locations does this reaction take place?
What are the consequences of this?
Cross reactions between the
Group A carbohydrate of streptococcus and structural protein of heart valve
M protein of streptococcus and cardiac muscle
Binding of antibodies to HOST antigen (valve/muscle) - activates complement and leads to an inflammatory response
Granulomas can FORM in the tissue - aschoffs nodules
What happens in the synovium during rheumatic heart disease?
Cross reacting of synovium antibodies - leads to inflammation of the joints - arthritis
What happens in the BRAIN - during rheumatic heart disease?
Cross reacting antibodies - in NEURONS in the caudate and subthalamic nuclei - leads to involuntary movement - sydenhams chorea and St vitus dance
What happens in Type IV hypersensitivity reactions? - Immunopathology of TB
Cell mediated responses
T HELPER CELLS (CD4) react to SPECIFIC ANTIGENS - TB
Release of cytokines that ATTRACT and ACTIVATE MACROPHAGES
Toxic products cause tissue damage acutely and chronically
Forms Granuloma - tubercles and necrosis (caseous necrosis) - looks cheesy!
what are some other infections that cause granulomas
leprosy
shistosomiasis
syphillis
