3: Immunology - role of mucosal immunity in disease

Question 1

Which cells initiate presentation of antigen to T cells in lymph nodes to start the adaptive immune response?

Answer 1

Dendritic cells

Macrophages

Question 2

Which signal molecules trigger activation of immune cells following a cellular insult?

Answer 2

Cytokines

Chemokines

Defensins

Question 3

The appropriate immune response to a pathogen tends to have a ___ effect for the host.

The inappropriate immune response to a pathogen ___ the host’s cells.

Answer 3

protective

damages

Question 4

Which pathogen is notable for causing mucosal immune dysregulation?

Answer 4

HIV

Question 5

Upon HIV infection of the mucosa, which immune cell takes it up for presentation and inadvertently spreads it throughout the gut and lymphoid tissue?

Answer 5

Dendritic cells

Question 6

Which T cells are infected and killed by HIV?

Answer 6

CD4+ T cells (helper / memory)

someone says this in Trainspotting

Question 7

In which types of tissue is HIV infection common?

Answer 7

Mucosal tissue

Question 8

What is primary immunodeficiency?

Answer 8

Part of the immune system is missing from birth

Question 9

HIV infection is a (primary / acquired) immunodeficiency.

Answer 9

acquired

Question 10

What immunoglobulin is the most common in the mucosal immune response?

Answer 10

IgA

Question 11

Which primary immunodeficiency is responsible for Coeliac disease?

Answer 11

IgA deficiency

Question 12

What is CVID?

Answer 12

Collection of immunodeficiencies which causes sinopulmonary and GI infections

Question 13

If someone presents with recurrent infections, what should you check?

Answer 13

Immunoglobulin levels

Question 14

What is XLA?

Answer 14

X-linked agammaglobulinaemia

Question 15

What immunodeficiency is seen in people with XLA?

Answer 15

No B cells

No IgG

Question 16

What will you see in someone with XLA?

Answer 16

Recurrent infection

Question 17

XLA is only present in (males / females).

Answer 17

males

Question 18

What is used to treat XLA patients?

Answer 18

Immunoglobulin infections

Question 19

What is the phagocyte respiratory burst?

Answer 19

Phagocytes produce reactive oxygen species (superoxide) to kill pathogens

Question 20

What is CGD?

What is the primary immunodeficiency?

Answer 20

Chronic granulomatous disease

Failure of phagocytes to produce superoxides for respiratory burst

Question 21

What does SCID stand for?

What is the immunodeficiency?

What will the patient present with?

Answer 21

Severe combined immunodeficiency

No B cells; No T cells

Constant infection (pulmonary and GI), opportunistic

Question 22

What immunoglobulin is associated with allergy?

Which immune cell is activated and degranulates due to the action of this antibody?

What symptoms present after?

Answer 22

IgE

Mast cells

Allergy symptoms - bronchoconstriction, increased permeability of blood vessels, runny nose, anaphylaxis

Question 23

Mast cell activation by IgE is self-perpetuating because:

Activated ___ ___ produce ___ which stimulates B cells to produce more IgE.

(mast cells, IL-4)

Answer 23

mast cells , IL-4 , T_H2

Question 24

What immune cells are activated by allergens?

What happens systemically if this isn’t treated?

Answer 24

Mast cells, Basophils, Eosinophils

Anaphylaxis

Question 25

Which diseases causes small intestine damage leading to malabsorption ⇒ malnutrition?

Answer 25

**Coeliac disease** **IBD** (Crohn's, UC)

Question 26

Which foods does **gluten** come from?

Answer 26

**Wheat** **Barley** **Rye**

Question 27

Is **coeliac disease** an allergy?

Answer 27

**No** **Genetically linked autoimmune disorder** which can develop at any time

Question 28

Which foodstuff triggers the symptoms of coeliac disease?

Answer 28

**Gluten**

Question 29

Which genes trigger the development of Coeliac disease?

Answer 29

***HLA-DQ2*** HLA-DQ8

Question 30

Is Coeliac disease **antibody-mediated** or **T cell mediated**?

Answer 30

**T cell mediated**

Question 31

**Gluten specific T cells** produce **IFgamma** which triggers other T cells. Which T cells are triggered? What happens?

Answer 31

**Intraepithelial lymphocytes** (CD8+ T cells) ## Footnote **Killing of epithelial cells**

Question 32

What will patients with undiagnosed Coeliac disease present with?

Answer 32

**Abdominal pain** **Bloating** **Diarrhoea** - steatorrhoea **Weight loss**

Question 33

What components of epithelial cells **atrophy** in Coeliac disease?

Answer 33

**Villi**

Question 34

The immune response associated with Coeliac disease ___ the intestinal epithelium.

Answer 34

**damages**

Question 35

Patients with Coeliac disease will have a ___ epithelium on endoscopy.

Answer 35

**flattened**

Question 36

Why do **damaged villi** and a **flattened epithelium**, associated with Coeliac disease, cause **malnutrition**?

Answer 36

**Loss of villi -** less absorption **Smaller surface area** - less absorption

Question 37

What structures, usually found between villi on intestinal epithelium, are the only things visible on someone with damaged epithelium due to Coeliac disease?

Answer 37

**Crypts**

Question 38

**Coeliac disease** is caused by an **adaptive T-cell mediated** reaction to **gluten**. Which genes are responsible for the protein which activates the T cells?

Answer 38

***HLA-DQ2*** **/** HLA-DQ8

Question 39

How do you treat **Coeliac disease**?

Answer 39

**Stop eating gluten** the gut then returns to normal

Question 40

How is Coeliac disease diagnosed?

Answer 40

**Positive tTG-IgA** **antibody test with the patient still eating gluten** ## Footnote **Then positive biopsy (flattened epithelium)**

Question 41

What is the usual method of **diagnosing Coeliac disease**? Who's excluded from this?

Answer 41

**Biopsy to confirm damage to small intestine** Children

Question 42

What are the symptoms of **Coeliac disease**?

Answer 42

**Weight loss** **Anaemia** **Diarrhoea** - steatorrhoea **Abdominal pain** **Bloating** i.e all of them, impossible to do serology on ALL of these people

Question 43

Which test is done to confirm **Coeliac disease** instead of **biopsying** or doing serology on every patient who has GI symptoms?

Answer 43

**tTG-IgA test** tissue transglutaminase test

Question 44

Under what circumstances will the IgA autoantibody test give a false negative?

Answer 44

**If the patient is complying with "no gluten" before they're officially diagnosed** catch 22 because you can only be formally diagnosed if you eat gluten, which causes your symptoms

Question 45

What is the gold standard method of diagnosing Coeliac disease?

Answer 45

**Duodenal biopsy** AFTER positive tTG-IgA test

Question 46

Why may a person with diagnosed Coeliac disease experience symptoms again?

Answer 46

**Non-compliance with gluten-free diet**

Question 47

Which enzyme **modulates** gluten when it enters the gut to form a complex with it?

Answer 47

**Tissue transglutaminase**

Question 48

Are **B cells** specific for the **gluten** itself or **tTG** enzyme which has formed a complex with it?

Answer 48

**tTG**

Question 49

The more **gluten** you eat, the more **\_\_\_** that will be presented to **B cells** and the more epithelial damage which will be done.

Answer 49

**tTG**

Question 50

Which inflammatory bowel disease can appear anywhere from the rectum to the mouth?

Answer 50

**Crohn's disease**

Question 51

What inflammatory bowel disease tends to move progressively from the **rectum** up the GI tract?

Answer 51

**Ulcerative colitis**