Class #10 - Autoimmune/immunodeficiency

Question 1

Gene associated with Autoimmune diseases (AD) regarging immune signaling?

Answer 1

PTPN22

Question 2

Microbial role in AD (2)?

Answer 2

1-Induction of costimulants

2-Molecular mimicry

Question 3

Sx of Systemic Lupus Erythematosis (SLE)?

Answer 3

Butterfly rash
hair loss
swollen joints
light sensitivity
glomerulonephritis

Question 4

SLE autoantibodies attaches to?

Answer 4

dissolved nuclear content like DNA (Hypersensitivity type 4)

Question 5

Pathogenesis of SLE?

Answer 5

Susceptibility genes + External triggers (UV light) ->apoptotic bodies -> Ig against apoptotic bodies ->

Question 6

Rheumatoid Arthritis (RA) pathogenesis?

Answer 6

{Susceptibility genes (HLA)} + {Envir. Factors that may trigger the conversion of arginine to citrulline (citrullination)} -> creation of anti-citrullinated protein ab (antibody) and other autoantibodies (all of them called rheumatoid factor)

Question 7

Panus?

Answer 7

Infiltration of immune cells and hyperplasia of synovial cells.

Question 8

RA and bones?

Answer 8

RANKL and expressed on T cells stimulating bone resorption by osteoclast.

Question 9

Multiple sclerosis (MS) pathogenesis?

Answer 9

T cells/monocyte cross the BBB by expressing the right combination of integrins -> Diapedisis -> They then attack oligodendrocytes (making myelin sheath) -> Discoloration of white matter in the brain

Question 10

MS course (4)?

Answer 10

1-Relapsing-remitting MS (most common type)
2-Primary progressive
3-Secondary progressive
4-Progressive-relapsing

Question 11

Inflammatory Bowel Disease (IBD) types?

Answer 11

Crohn’s: throughout GIT in discontinuous matter, lesion into musc. layer
Ulcerative colitis: Only colon, only mucosal layer

Question 12

T cell association in IBD?

Answer 12

Crohn = Th1

Ulcera.: Th2

Question 13

Genes involved in Crohn?

Answer 13

NOD2: Encode p+ that binds to intracellular bacteria and then activate NF-kB ->prod. cytokines -> promote barrier function of epithelial cells.
NOD2 - defective = defective epi. barrier

Question 14

Ulcerative Colitis autoantibodies?

Answer 14

A) Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA)
B) Molecular mimicry

Question 15

“Transplant”, 2 types of reactions?

Answer 15

1-Direct alloantigen recognition: Host recognize MHC on graft as non-sefl. Scene of battle vasculature.
2-Indirect alloantigen recognition: Graft cells react. Scene of battle = skin,GIT,liver

Question 16

3 types of Direct alloantigen recognition

Answer 16

1-Hyperacute: type 2 hypersensitivity. Preformed Ig. Blood incompatibilities.
2-Acute:
2.1 Type 4 hypersensitivity. Involve T cells. CD4+ recruiting macrophage that will cause damage to parenchymal cells. Result in wavy appearance of basement membrane.
2.2 Type 2 hypersensitivity. Ig form within the capillaries and induce complement activation.
3. Chronic rejection: Slow inflammation of vessel walls (type 4 hypersensitivity). Manifesting in hyperplasia of smooth musc. resulting in occlusion of blood vessels

Question 17

Indirect alloantigen recognition also called. Reasons?

Answer 17

Graft vs Host Disease (GVHD).
1-Immunocompetent tissues in immunocompromised host.
2-T cell from transplant recognize the host as non-self and attack.

Question 18

Primary vs 2nd immunodeficiency?

Answer 18

1-genes

2-infections, cancer, drugs, malnutrition

Question 19

Primary immunodeficiency types?

Answer 19

Specific: Ig deficiency, cell-mediated

Non specific: complement, neutrophils defect

Question 20

Primary immunodeficiency : What is X-linked severe combined immunod.?

Answer 20

Pro-T cell -> gamma chain not expressed, cannot become Immature T-cell.

Question 21

Primary immunodeficiency: What is X linked gamma globulemia (BTK)?

Answer 21

Pro-B cell -> Pre B cell -> Defect in tyrosine kinase, cannot become Immature B cell.

Question 22

Primary immunodeficiency: Severe Combined Immunod. (scid)?

Answer 22

Absence functional T-cell

Question 23

Secondary immunodeficiency : AIDS pathogenesis?

Answer 23

gp120 (HIV) -> CD4 ->gp120 -> CCR5/CXCR4 coreceptors (t-cell) ->gp41(HIV) allows it to enter cytoplasm

Question 24

Proliferation of HIV?

Answer 24

RNA converted to DNA by reverse transcriptase then enter nucleus and binds to DNA of cell. Cell needs to be undrergoing proliferation.

Question 25

Ways HIV kill CD4+ T-cells?

Answer 25

1) Direct killing: membrane permeability defect
2) Killed by CD8+ by MHC 1 HIV antigen recognition
3) Infected CD4+ can trigger apoptosis of uninfected CD4+

Question 26

Treatment of AIDS

Answer 26

Drug combination: Anti-Retroviral Therapy (ART)