Pathoma - Chronic Inflammation & Primary Immunodeficiency

Question 1

What are the 5 stimuli for chronic inflammation?

Answer 1

(1) Persistent infection (2) Infection with virus, mycobacteria, fungus, and parasites (3) Autoimmune disease (4) Foreign material (5) Cancer

Question 2

What is the first step of T cell activation?

Answer 2

Binding to antigen/MHC complex

Question 3

What is the second activation signal of T-cell activation for CD4+ helper T-cells?

Answer 3

B7 on APC binds CD28 on CD4+ cells

Question 4

What are the cytokines secreted by Th1 CD4+ cells and what do they do?

Answer 4

Th1 cells help CD8 cells by secreting: - IL-2 (acts as 2nd activation signal for CD8+ cells) - IFN-y (produced in response to IL-12 from macrophages acting on Th1 cells; activates macrophages)

Question 5

What are the cytokines secreted by Th2 CD4+ cells and what do they do?

Answer 5

Th2 cells help B-cells: - IL-4 (class switching to IgE - IL-5 (class switching to IgA) - IL-10 (calms down inflammation by decreasing expression of MHC II and Th1 cytokines)

Question 6

What is the second activation signal of CD8+ cells?

Answer 6

IL-2 from CD4+ Th1 cells

Question 7

What are the two types of apoptosis performed by CD8+ cells?

Answer 7

(1) Secretion of perforin to create a pore that allows granzyme to enter the target cell (2) Expression of FasL, which binds to Fas on target cell, activating apoptosis

Question 8

What are the 2 ways that B-cell activation can occur?

Answer 8

(1) antigen binding by surface IgM or IgD (results in maturation to IgM or IgD secreting plasma cells) (2) B-cells phagocytose and present antigen on MHC II to CD4+ cells - CD40 receptor on B cells bind to CD40L on CD4+ cells, providing 2nd activation signal - Helper T-cells then secrete IL-4 or IL-5 to mediate class switching

Question 9

What is the defining feature of a granuloma?

Answer 9

Epithelioid histiocyte (macrophage with abundant pink cytoplasm)

Often surrounded by giant cells and a rim of lymphocytes

Question 10

What is the difference between a non-caseating and caseating granuloma?

Answer 10

Non-caseating - lack central necrosis

Caseating - exhibit central necrosis (no nuclei in central cells)

Question 11

What is the differential diagnosis of noncaseating granulomas?

Answer 11

Reaction to foreign material

Sarcoidosis

Beryllium exposure

Crohn disease

Cat scratch disease (will have a stellate-shaped granuloma)

Question 12

What is the differential diagnosis of caseating granulomas?

Answer 12

Tuberculosis

Fungal infection

Question 13

Describe the steps involved in formation of a granuloma

Answer 13

Macrophages eat and present antigen to CD4+ T-cells

The interaction causes macrophages to secreted IL-12

IL-12 induces CD4+ cells to differentiate into Th1 cells

Th1 cells secrete IFN-y, which converts macrophages to epithelioid histiocytes and giant cells

Question 14

Describe DiGeorge Syndrome

Answer 14

Due to failure of 3rd and 4th pharyngeal pouch to develop (absent thymus and parathyroid

CATCH-22:

C - Calcium (hypocalcemia due to parathyroid deficiency - tetany)

A - Appearance

T - Thymus (absent - T-cell deficiency, absent thymic shadow)

C - Cleft palate

H - Heart (tetrolagy of Fallot)

Question 15

What is the deficiency in Severe combined immunodeficiency (SCID)

Answer 15

Defect in both cell-mediated and humoral immunity

Question 16

What are some causes of SCID?

Answer 16

(1) Cytokine receptor defects (e.g. IL-2 receptor)
(2) Adenosine deaminase deficiency (ADA) - buildip of adenosine is toxic to lymphocytes
(3) MHC II deficiency (necessary for CD4+ cells)

Question 17

What is the treatment for SCID

Answer 17

Sterile isolation (“bubble boy”)

Bone marrow transplant

Question 18

What is the deficiency in X-linked agammaglobulinemia (aka Bruton’s)?

Answer 18

Defect in BTK (Bruton tyrosine kinase), which leads to no B-cell maturation

Question 19

What are the most common infections in X-linked agammaglobulinemia?

Answer 19

Enterovirus, Giardia, bacterial

Question 20

What is the deficiency in common variable immunodeficiency (CVID)?

Answer 20

Defect in B-cell differentiation (can be due to either B-cell or helper T-cell defects)

Question 21

What are the increased risks in CVID?

Answer 21

Lymphoma, autoimmune diseases

Question 22

What is the increased risk and associated disease in Selective IgA deficiency?

Answer 22

Mucosal infections (airway and GI)

Associated with Celiac

Question 23

What is the defect in Hyper-IgM Syndrome?

Answer 23

Due to mutated CD40 receptor on B-cells or CD40L on T-cells (leads to class switching defect)

Question 24

What is the defect in Wiskott-Aldrich syndrome?

Answer 24

Mutation in WASP gene so that T-cells are unable to reorganize the actin cytoskeleton

Question 25

What is the classic triad in Wiskott-Aldrich Syndrome

Answer 25

WATER:

Wiskot Aldrich: Thrombocytopenia, Eczema, Recurrent infections

Question 26

What is the result of C1 (complement) inhibitor deficiency?

Answer 26

Will have overactive complement leading to increased vasodilation and vascular permeability

Results in hereditary angioedema (especially peri-orbital edema)

Question 27

What is the mutation in Hyper-IgE (Job’s Syndrome)

Answer 27

Deficiency of Th17 cells due to STAT3 mutation

Leads impaired neutrophil recruitment to site of infection

Question 28

Clinical presentation of Hyper-IgE Syndrome?

Answer 28

FATED:

coarse Facies

Abscesses

Teeth (retained primary)

increased IgE

Derm probz (eczema)