Inflammatory Diseases + Immune Deficiencies Flashcards
what is IBD and what are the 2 types
chronic, relapsing inflammation in the digestive tract
- Ulcerative colitis-inflammation and ulcers in the mucosa/submucosa (superficial) of Large intestine/Rectum- continuous
- Chrons Disease- Inflammation in the bowel walls (mucoa to serosa). Any area from mouth to anus- patchy
symptoms of IBD
Abdominal pain, diarrhea, rectal bleeding, severe internal cramps and weight loss
IBD risk factors
Diet- high animal pro fam hx (NOD2 mutation) Cigarette smoking Northen climate Age (>65)
IBD pathogenesis
inappropriate inflammatory response to normal gut microflora in ppl with a genetic predisposition (NOD2)
-defective immune signalling fails to clear invading commensal bacteria which trigger inflammation leading to damage
What innate cells primarily mediate the inflammatory response in IBD
macrophages/neutrophils
What can ulcetieris collitis and churns disease lead to (s/s)
-difficulty absorbing nuts, abdominal pain, diarrhea
UC- toxic megacolon, increased incidence of cancer
CD- Fitsula which connects the intestine to another organ or tissue
tx of IBD
biologics- anti TNF a monoclonal antibodies
immunomodulators
corticoster
overall picture of Gout
recurring inflammatory arthritis
- chronic deposition of uric acid crystals in jt tissues
- inflammatory response of host tissue to deposited uric acid crystals
where is gout mc
1st metatarsophalangeal jt
gout risk factors
- hyperuricaemia (high bmi, kidney disease)
- diet (alcohol)
- genetics
- M>F
- > 35
s/s of gout
- jt inflammation
- gout flares
- asymetrical arthritis
- nodules
pathogenesis of gout (steps)
uric crystals interact w macrophages and activate NLRP3 inflammasome
-NLRP3 catalyzes activation of caspase 1 which generates inflammatory cytokines IL1B IL18
Pathogenesis of OA
- exfoliation of cartilage fragments leading to delimitation and exposure of underlying bone
- DAMPS/Alarmins activate local macrophages (produce inflammatory factors)
- monocytes and neutrophils recruited
How does atherosclerosis damage the epithelium of blood vessels (3)
hypertension: trauma from turbulent blood flow
Hyperlipidemia: diet (LDLs), genetics
Chronically elevated blood glucose levels
Pathogenesis of athersclerosis
- LDLs accumulate in the innermost layer of vessels (intima)
- monocytes enter intima and engulf LDLs
- Die and form Foam cells
- plauques continue to develop and eventually hardens and encroaches the arterial lumen impeding blood flow
S/S of athersclerosis
- CVD leading cause of death worldwide
- Occlusion, plaque rupture, thrombosis (leading to coronary symptoms, angina, stroke etc)
Risk factors of atherosclerosis
- genetics
- high BP
- elevated blood lipids
- diabetes
- BMI
- Smoking
- sedentary lifestyle
tx of atherosclerosis
- Lipid lowering meds
- Diet/life mods
- BP meds
- Blood thinners
What is sepsis and what causes it
inflammatory response to microbial products in the blood (systemic)
-primaily induced by bac in blood
General pathogenesis of sepsis
innate cells induce pro inflammatory state (complement, free rads etc) than an antiinfammatory state occurs to try to combat it (IL 10, poor phagocytosis etc)
Consequences of sepsis
- mito dysfunction
- apoptosis and necrosis
- endothelial dysfunction
- metabolic acidosis
- capillary leakage (hypotension)*
- Disteminated intravascular coagulation*
SEPTIC SHOCK- low BP
tx of sepsis/septic shock
- infection control (antibiotics)
- Hemodynamic stabilization (control BP)
- Modulation of septic response
what is celiac disease and what is changed in individuals that are susceptible
Chronic inflammatory condition of the small intestine caused by immune response directed at gluten proteins
*modification of a gliadin by tissue transglutaminase (tTG) may make gluten more immunogenic
what does the immune responses in celiac disease lead to
structural changes in the gut
- villous atrophy (flattening of the villi)
- Crypt hyperplasia (elongation of the crypts- malabsorption)
s/s of celiac disease
diarrhea, fatigue, weight loss, bloating, gas etc
pathogenesis of celiac disease (types of cells activated etc)-4
- Gluten antigens bypass tight junctions of gut epithelium (more apcs)
- APCs activate T cells (Th1, CTLs)
3, IEL numbers increase
- Inhibition of Treg function
Which alleles lead to genetic suseptibility to celiac disease
HLA DQ2 and/or HLA DQ8
What is the difference between celiac disease, gluten intolerance, wheat allergy
Celiac disease- T cells, IgG (structural changes)
Gluten intolerance- IgG
Wheat allergy- IgE
What is an immunodeficiency disease + types
- one or more components of the immune response are defective or lacking
Primary- caused by mutations in genes that are involved in immune system
Secondary- acquired because of another underlying illness/disorder
Reoccurence of bacterial or fungal/viral infections indicate what type of immunodeficiency
bacteria- defects in antibody, complement or phagocytic function
Fungal/viral- defect in t cell responses
Features of primary immunodeficiencies
- most are x linked (males always show)
- failure in b cell development or antibody secretion
Brutons X linked Agammaglobulinemia- cause and what occurs
Mutation in Brutons tyrosine kinase
-B cells can’t progress past pre b cell stage (absence in antibody)
Hyper IgM syndrom- cause and what happens
Mutation in CD40L
Tcells can’t provide CD40L signal required for class switching- elevated IgM but no IgA IgG IgE
Common variable immunodeficiency- cause and what happens (what type of inf)
mutations of a variety of genes that encode cell surface proteins and cytokine receptors
- reoccuring bacterial inf
- decreased lvls of IgG igA IgM
Selective IgA deficiency- cause and what happens
B cells cannot secrete IgA
- most common immunodeficiency disease in NA
- recurring mucosal inf
what does defects in C3 pro lead to
higher risks of reoccurring extracellular bac inf
What is neutropenia
Deficiencies in neutrophil prod
What is cyclic neutropenia and what causes it
neutrophil numbers fluctuate from near normal to very low every 21 days
-Mutatuons in neutrophil elastase (ELA2)
what causes defects in phagocytic cell migration
Leukocyte adhesion deficiency- deficiency in b subunit of integrin molecules (LFA1) impairing diapedesis
What is chronic granulomatous disease
Form granulomas as a result of inability to kill bacteria (defects in respiratory burst)
What is SCID
Impairment of both arms of adaptive immunity (t and b cells)
-usually affected by severe bacterial, viral or fungal infections
What causes X linked SCID and what does it result in
Mutations in the IL2 receptor
t cells/ NK cells fail to develop normally and B cell numbers normal but dysfunctional
What causes Recombination activating gene deficiency SCID
Mutations in RAG1/2 enzymes resulting in arrested lymphocyte development due to inability to perform VDJ recombination
Bare lymphocyte syndrome SCID and what does it result in
Defects in expression of MHC 1/2 molecules
-T cells can’t be pos selected and few develop, b cell dysfunction
