Mechanisms of autoimmune
- Molecular mimicry - resemblance between host and pathogen antigen: e.g. Multiple sclerosis
- Epitope spreading: An auto-immune response is triggered by primary autoantigen. This favors the development of Th1. It damages target tissue and releases more autoantigens (Ag2, Ag3, etc.) and hence damage - spread of specificity and chronicity of the disease.
- Autoantibodies made elsewhere enters immunological priveleged sites (e.g. MS: MBP specific Th1 enters BBB
Autoimmunity is normally prevented because
Autoimmune and T cell subtypes
Th1: MS, Type 1 Diabetes Mellitus (macrophage-related?)
Th2: Allergy, asthma, eczema, hayfever
Th17: IBD Inflammatory bowel diasease
Overview of some autoimmune diseases
- MS Multiple Sclerosis
- Goodpasture’s syndrome
- IBD Inflammatory bowel disease
NOD2 mutation in Crohn’s disease
Viral hepaitits: MHC1 x CD8+ -> Cytotoxic T cell -> Kill infected hepatocyte (if chronic - cirrhosis)
PPD Test for TB
purified protein derivative (PPD) of M. tuberculosis is injected intradermally into the flexor surface of the forearm
The interpretation of tuberculin tests depends on BCG vaccination history and immune status. For example, in HIV-positive patients, a negative tuberculin test does not exclude TB tuberculosis as it may be due to general anergy.
The greater the reaction, the more likely it is that an individual is infected or has active TB disease
|Diameter of induration||Positivity (degree of hypersensitivity to tuberculin protein)||interpretation|
|Less than 6 mm||Negative – (no significant hypersensitivity to tuberculin protein)|
|6 - 15 mm||Positive – (hypersensitive to tuberculin protein)||maybe....|
|15 mm and above||Strongly positive – (strongly hypersensitive to tuberculin protein)|
- Systemic autoimmune
- Weight loss
- Raised ESR, CRP
- Leukopenia, thrombocytopenia
- Normochromic normocytic anemia
- ANA (the reason why SLE is SYSTEMIC is because nuclear components are found in ALL CELLS!!!)
History of asthma, hayfever
Onset in first 2 years of life
Summary of GPCRs g protein coupled receptors
(KISS QUICK til your SIQ of SQS - sick of sex); All B-adrenoceptors are Gs
Subtypes of GPCR
Capsule: Made of polysaccharide/polypeptide
BUT eventually, IgG antibodies will attach to capsule protein → Fc on IgG x FcR on phagocyte → phagocytosis
Pili: Shaft (pilin) + adhesive tip (complement to glycoprotein/glycolipid receptor on another cell)
Outer membrane - LPS (endotoxin)
Vasodilation for inflammation (Anaphylactic, septic) and neurogenic shock
Vasoconstriction for hypovolemic, cardiogenic
Quick review of bacteria
Only in Gram + Only in Gram - Cell wall: Thick peptidoglycan, Teichoic acid Outer membrane (LPS, [and its constituents... Lipid A, Polysaccharide)
Cell wall: Thin peptidoglycan
Periplasmic space between inner and outer membrane contain enzymes (e.g. B-lactamase) to break down macromolecule
- Strep. pyogene
- Staph. aureus
Its antigens are presented with MHCII molecules on APC -> POLYclonal Th1 cell stimulation -> IL1, IL6, TNF-alpha release
Rheumatic fever: Antibody vs heart (endocarditis), joint (RA), kidney (glomerulonephritis)
Virulence factors: molecules expressed and secreted by pathogens that enable them to achieve the following:
e.g. bacterial toxin, capsule, hyaluronidase
Source: Where from
Route: Endogenous or exogenous
Exogenous (e.g. Zoonoses - from animals to human)
Endotoxin Exotoxin LPS: Lipid A (toxic) and Polysaccharide on OUTER cell membrane
Fever and shock via TNF-alpha and IL1
Poorly antigenic so always comes about!
Secreted Protein (polypeptide)
Specific - enzymes!
Gram + and -
Antigenic so vaccine is available
Denatured by boiling
LPS binds to TLR4 (toll like receptor) on macrophage → Proinflammatory cytokines released → Pyrexia, inflammation
Examples of Exotoxin
Prion - vCJD
Virus - Measle, polio, HIV
Rotavirus: Fecal oral source
Enter enterocyte via VP4, replicates and secretes NSP4 (nonstructural protein: viral enterotoxin)
NSP4 causes osmotic diarrhea
Virus invasion of the infected villi → Cell death → Villi atrophy → Malabsorption
Poliomyelitis: Fecal-oral source
Binds to CD155 of nerve → Cause cell death especially anterior horn
Bacteria - Pneumonia, Cholera
Mannitol salt agar: Selective media (encourage growth of certain bacteria and inhibiting others)
Blood agar: Differential media
β-hemolytic(yellow) - complete lysis of RBC by colony - Streptococcus haemolyticus
α-hemolysis (green) - partial lyse - Streptococcus viridans
Contain bile salt to inhibit gram +
And to see if lactose fermenting
Staph grow as grapes
Strep grow as pairs
inner membrane periplasmic space peptidoglycan outer membrane
Transpeptidase aka pencillin-binding protein
gram -: periplasmic space
gram +: periplasm only
nam + nag in cell membrane and then sent to periplasm
nam + amino acid
Nam x nam crosslinked via opposing aminoacids via transpeptidase (PBP) thus forming many layers!
b-lactam: cephalosporin and penicillin
Eukaryotes have 80S ribosomes, each consisting of a small (40S) and large (60S) subunit.
Prokaryotes have 70S ribosomes, each consisting of a small (30S) and a large (50S)
Buy AT 30, CELL at 50
Drugs acting on 30s ribosome subunits :
Drugs acting on 50s ribosome subunits :
Gram-negative rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms (endotherms).Most E. coli strains are harmless, but some, such as serotype O157:H7, can cause serious food poisoning in humans, and are occasionally responsible for product recalls. The harmless strains are part of the normal flora of the gut, and can benefit their hosts by producing vitamin K2, and by preventing the establishment of pathogenic bacteria within the intestine.
Food poisoning caused by E. coli is usually caused by eating unwashed vegetables or undercooked meat.
E. coli can harbour both heat-stable ST and heat-labile LT enterotoxins. The latter, termed LT, contains one A subunit and five B subunits arranged into one holotoxin, and is highly similar in structure and function to cholera toxins. The B subunits assist in adherence and entry of the toxin into host intestinal cells, while the A subunit is cleaved and prevents cells from absorbing water, causing diarrhea. LT is secreted by the Type 2 secretion pathway. If E. coli bacteria escape the intestinal tract through a perforation (for example from an ulcer, a ruptured appendix, or due to a surgical error) and enter the abdomen, they usually cause peritonitis that can be fatal without prompt treatment. However, E. coli are extremely sensitive to such antibiotics as streptomycin or gentamicin.
fimbrial adhesins (projections from the bacterial cell surface) to bind enterocyte cells in the small intestine.
Damage to endothelial cells is the primary event in the pathogenesis of hemolytic-uremic syndrome (HUS). The cardinal lesion is composed of arteriolar and capillary microthrombi (thrombotic microangiopathy [TMA]) and red blood cell (RBC) fragmentation.
red blood cells are destroyed and the kidneys fail
E. coli O157:H7 is believed to cause more than 80 percent of the STEC infections that lead to hemolytic uremic syndrome.12 This microorganism is not a normal part of the human intestinal flora13 but is present in the intestines of 1 percent of healthy beef cattle; the meat can become contaminated during the slaughter and processing of the anima
.E. coli bacteria also may be transmitted by contact with persons who inadequately wash their hands, resulting in fecal and oral contamination and transmission.14
The classic triad of features for hemolytic uremic syndrome consists of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure
Hematologic findings include destruction and fragmentation of erythrocytes that result in microangiopathic hemolytic anemia.
Ninety-two percent of patients with hemolytic uremic syndrome develop thrombocytopenia, which results from entrapment of platelets in the organs
Acute renal failure results when micro-thrombi are deposited in kidney parenchyma. This manifests in the form of hypertension associated with oliguria and anuria, which are early signs of acute renal failure.