Inflammatory Diseases + Immune Deficiencies

Question 1

what is IBD and what are the 2 types

Answer 1

chronic, relapsing inflammation in the digestive tract

1. Ulcerative colitis-inflammation and ulcers in the mucosa/submucosa (superficial) of Large intestine/Rectum- continuous
2. Chrons Disease- Inflammation in the bowel walls (mucoa to serosa). Any area from mouth to anus- patchy

Question 2

symptoms of IBD

Answer 2

Abdominal pain, diarrhea, rectal bleeding, severe internal cramps and weight loss

Question 3

IBD risk factors

Answer 3

Diet- high animal pro
fam hx (NOD2 mutation)
Cigarette smoking
Northen climate
Age (>65)

Question 4

IBD pathogenesis

Answer 4

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

Question 5

What innate cells primarily mediate the inflammatory response in IBD

Answer 5

macrophages/neutrophils

Question 6

What can ulcetieris collitis and churns disease lead to (s/s)

Answer 6

-difficulty absorbing nuts, abdominal pain, diarrhea

UC- toxic megacolon, increased incidence of cancer
CD- Fitsula which connects the intestine to another organ or tissue

Question 7

tx of IBD

Answer 7

biologics- anti TNF a monoclonal antibodies
immunomodulators
corticoster

Question 8

overall picture of Gout

Answer 8

recurring inflammatory arthritis

• chronic deposition of uric acid crystals in jt tissues
• inflammatory response of host tissue to deposited uric acid crystals

Question 9

where is gout mc

Answer 9

1st metatarsophalangeal jt

Question 10

gout risk factors

Answer 10

• hyperuricaemia (high bmi, kidney disease)
• diet (alcohol)
• genetics
• M>F
• > 35

Question 11

s/s of gout

Answer 11

• jt inflammation
• gout flares
• asymetrical arthritis
• nodules

Question 12

pathogenesis of gout (steps)

Answer 12

uric crystals interact w macrophages and activate NLRP3 inflammasome

-NLRP3 catalyzes activation of caspase 1 which generates inflammatory cytokines IL1B IL18

Question 13

Pathogenesis of OA

Answer 13

• exfoliation of cartilage fragments leading to delimitation and exposure of underlying bone
• DAMPS/Alarmins activate local macrophages (produce inflammatory factors)
• monocytes and neutrophils recruited

Question 14

How does atherosclerosis damage the epithelium of blood vessels (3)

Answer 14

hypertension: trauma from turbulent blood flow

Hyperlipidemia: diet (LDLs), genetics

Chronically elevated blood glucose levels

Question 15

Pathogenesis of athersclerosis

Answer 15

1. LDLs accumulate in the innermost layer of vessels (intima)
2. monocytes enter intima and engulf LDLs
3. Die and form Foam cells
4. plauques continue to develop and eventually hardens and encroaches the arterial lumen impeding blood flow

Question 16

S/S of athersclerosis

Answer 16

• CVD leading cause of death worldwide

- Occlusion, plaque rupture, thrombosis (leading to coronary symptoms, angina, stroke etc)

Question 17

Risk factors of atherosclerosis

Answer 17

• genetics
• high BP
• elevated blood lipids
• diabetes
• BMI
• Smoking
• sedentary lifestyle

Question 18

tx of atherosclerosis

Answer 18

• Lipid lowering meds
• Diet/life mods
• BP meds
• Blood thinners

Question 19

What is sepsis and what causes it

Answer 19

inflammatory response to microbial products in the blood (systemic)

-primaily induced by bac in blood

Question 20

General pathogenesis of sepsis

Answer 20

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)

Question 21

Consequences of sepsis

Answer 21

• mito dysfunction
• apoptosis and necrosis
• endothelial dysfunction
• metabolic acidosis
• capillary leakage (hypotension)*
• Disteminated intravascular coagulation*

SEPTIC SHOCK- low BP

Question 22

tx of sepsis/septic shock

Answer 22

• infection control (antibiotics)
• Hemodynamic stabilization (control BP)
• Modulation of septic response

Question 23

what is celiac disease and what is changed in individuals that are susceptible

Answer 23

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

Question 24

what does the immune responses in celiac disease lead to

Answer 24

structural changes in the gut

1. villous atrophy (flattening of the villi)
2. Crypt hyperplasia (elongation of the crypts- malabsorption)

Question 25

s/s of celiac disease

Answer 25

diarrhea, fatigue, weight loss, bloating, gas etc

Question 26

pathogenesis of celiac disease (types of cells activated etc)-4

Answer 26

1. Gluten antigens bypass tight junctions of gut epithelium (more apcs) 2. APCs activate T cells (Th1, CTLs) 3, IEL numbers increase 4. Inhibition of Treg function

Question 27

Which alleles lead to genetic suseptibility to celiac disease

Answer 27

HLA DQ2 and/or HLA DQ8

Question 28

What is the difference between celiac disease, gluten intolerance, wheat allergy

Answer 28

Celiac disease- T cells, IgG (structural changes) Gluten intolerance- IgG Wheat allergy- IgE

Question 29

What is an immunodeficiency disease + types

Answer 29

- 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

Question 30

Reoccurence of bacterial or fungal/viral infections indicate what type of immunodeficiency

Answer 30

bacteria- defects in antibody, complement or phagocytic function Fungal/viral- defect in t cell responses

Question 31

Features of primary immunodeficiencies

Answer 31

- most are x linked (males always show) | - failure in b cell development or antibody secretion

Question 32

Brutons X linked Agammaglobulinemia- cause and what occurs

Answer 32

Mutation in Brutons tyrosine kinase -B cells can’t progress past pre b cell stage (absence in antibody)

Question 33

Hyper IgM syndrom- cause and what happens

Answer 33

Mutation in CD40L Tcells can’t provide CD40L signal required for class switching- elevated IgM but no IgA IgG IgE

Question 34

Common variable immunodeficiency- cause and what happens (what type of inf)

Answer 34

mutations of a variety of genes that encode cell surface proteins and cytokine receptors - reoccuring bacterial inf - decreased lvls of IgG igA IgM

Question 35

Selective IgA deficiency- cause and what happens

Answer 35

B cells cannot secrete IgA - most common immunodeficiency disease in NA - recurring mucosal inf

Question 36

what does defects in C3 pro lead to

Answer 36

higher risks of reoccurring extracellular bac inf

Question 37

What is neutropenia

Answer 37

Deficiencies in neutrophil prod

Question 38

What is cyclic neutropenia and what causes it

Answer 38

neutrophil numbers fluctuate from near normal to very low every 21 days -Mutatuons in neutrophil elastase (ELA2)

Question 39

what causes defects in phagocytic cell migration

Answer 39

Leukocyte adhesion deficiency- deficiency in b subunit of integrin molecules (LFA1) impairing diapedesis

Question 40

What is chronic granulomatous disease

Answer 40

Form granulomas as a result of inability to kill bacteria (defects in respiratory burst)

Question 41

What is SCID

Answer 41

Impairment of both arms of adaptive immunity (t and b cells) | -usually affected by severe bacterial, viral or fungal infections

Question 42

What causes X linked SCID and what does it result in

Answer 42

Mutations in the IL2 receptor | t cells/ NK cells fail to develop normally and B cell numbers normal but dysfunctional

Question 43

What causes Recombination activating gene deficiency SCID

Answer 43

Mutations in RAG1/2 enzymes resulting in arrested lymphocyte development due to inability to perform VDJ recombination

Question 44

Bare lymphocyte syndrome SCID and what does it result in

Answer 44

Defects in expression of MHC 1/2 molecules | -T cells can’t be pos selected and few develop, b cell dysfunction