The Immunology Of Autoimmune Disease

Front 1

What are the four basic compartments of the immune system?

Back 1

Innate, adaptive, cellular, humoral

Front 2

What is innate immunity?

Back 2

Responds to microorganisms with preformed cells and soluble factors. "One size fits all." Quick but not very specific

Front 3

What is adaptive immunity?

Back 3

Requires activations steps for individual cells to proliferate and make specific soluble factors to be effective. Delayed response that is highly specific.

Front 4

What is cellular immunity?

Back 4

Relies on direct contacts between immune cells and pathogens or other cells. Localized and often deadly to the targeted microbe or cell.

Front 5

What is humoral immunity?

Back 5

Mediated by soluble products of immune or accessory cells. Factors can circulate far from the cellular source.

Front 6

What cells are the central command for the immune system?

Back 6

T helper cells

Front 7

What kinds of cells/molecules are used in fighting virus or intracellular bacteria?

Back 7

CD*+ T-cell; NK cell; Macrophage

Front 8

What kinds of cells/molecules are used in fighting worms and parasites?

Back 8

B-2 cell; IgE; IgG; Eosinophil; Mast cell

Front 9

What kinds of cells/molecules are used in fighting fungi or bacteria at the mucosa?

Back 9

Mast cell; NKT cell; B-1 cell; IgA

Front 10

What kinds of cells/molecules are used in fighting fungi or bacteria in blood?

Back 10

IgM; Macrophage; IgG; Neutrophil

Front 11

What are the 4 steps to a balanced immune response?

Back 11

1) Identify what is foreign vs. self
2) Differentiated between benign and harmful
3) Mount an appropriate response to the potentially dangerous threats
4) Recognize when danger has passed and ramp down the response

Front 12

What are the two general processes by which the immune system goes about 'ignoring self'?

Back 12

Central tolerance and peripheral tolerance

Front 13

What is central tolerance?

Back 13

Education process during T and B lymphocyte maturation that eliminates or inactivates those that react against the self

Front 14

What is peripheral tolerance?

Back 14

Usually involves death induction by ligands (e.g. Fas ligand and TRAIL) that are expressed by activated killer cells. This normally occurs after an immune activating event like and infection

Front 15

How does the innate immune system recognize foreign organisms? (name the two ways and define)

Back 15

With pattern recognition receptors (Toll-like receptors expressed by many cell types that bind to commonly produced structures (LPS, dsRNA, flagellin). These receptors are often connected with intracellular pathways (inflammasome, NFkB) that initiate inflammation) and humoral immunity (recognition of microbes by antibodies or complement molecules which then active other immune cells to engulf the invader or release inflammatory mediators)

Front 16

How does the adaptive immune response recognize foreign organisms? (name and define)

Back 16

Adaptive immune response (activation of T lymphocytes and maturation of antibody response through T and B lymphocyte interaction) and antigen presentation (activates T-cells from immune cell phagocytosis)

Front 17

How does the immune system generate the right response? (4 steps and explain)

Back 17

1) Generate inflammation: Increase blood flow to site, attract immune cells (chemokines, complement), slow microbial growth (fever), and activate other protective mechanisms. Mediated by release of proinflammatory cytokines: IL-1, IL-6, and TNF; activation of complement; production of lipid mediators and chemokines.

2) Get APCs activated: activated APCs upregulate MHC and costimulatory molecule expression, and make cytokines that drive T-cell differentiation.

3) Redistribute and recruit: Activated CD carrying antigens travel to local lymph nodes where APCs interact with naive T-cells and drive the immune response based on the signals established by the microbe

4) Th lineage commitment: Naive Th cells (Th0) emerge from the thymus with an antigen-specific receptor but have not reached maturity yet. The final step is determined by the accessory stimuli received at the time of antigen presentation, and they differentiate based on cytokine

Front 18

What Th cell is used to fight virus or intracellular bacteria? What activates it and what does it produce?

Back 18

Th1, activated by IFN-gamma and IL-12, produces IFN-gamma and lymphotoxin-alpha (LT-a)

Front 19

Which Th cell is used to fight worms and parasites? What activates it and what does it produce?

Back 19

Th2, IL-4 activates it, and it produces IL-4, IL-5, and IL-13

Front 20

Which Th cell is used to fight fungus or bacteria at the mucosa? What activates it and what does it produce?

Back 20

Treg

Front 21

Which Th cell is used to fight fungus or bacteria in the blood? What activates it and what does it produce?

Back 21

Th17, activated by IL-6 (and IL-23), produces IL-17 (A, F) and IL-6

Front 22

How do Th1 cells mediate cellular immunity?

Back 22

Activate macrophages, NK cells, CD8+ T cells, and B cells to produce IgG2 antibodies; increase antigen presentation through MHC; viral clearance and destruction of intracellular microbes

Front 23

What inhibits Th1 cells?

Back 23

IL-4 and IL-10

Front 24

What kind of diseases are Th1 cells pathogenic in?

Back 24

Autoimmune

Front 25

How do Th2 cells mediate an immune response?

Back 25

Production of cytokines (IL 4, 5, 13); activate B cells to produce IgG4 and IgE, increased production of eosinophils, and mast cell arming

Front 26

What inhibits Th2 cells?

Back 26

IL-10 and IL-12

Front 27

What kind of disease is Th2 pathogenic in?

Back 27

allergies and asthma

Front 28

How do Th17 cells mediate an immune response?

Back 28

Cytokine production (pro-inflammatory); activation of monocytes, neutrophils, and synovial fibroblasts

Front 29

What inhibits Th17 cells?

Back 29

IL-4 and IFN-gamma

Front 30

What kind of disease is Th17 implicated in?

Back 30

RA and MS

Front 31

How do Treg cells mediate an immune response?

Back 31

Down-regulate Th1 and Th2 immune responses; thought to protect against autoimmunity

Front 32

What inhibits Treg?

Back 32

TNF-a

Front 33

What are the three broad ways that the immune system returns to baseline?

Back 33

Clearing the threat, passive suppression, and active suppression

Front 34

How does active suppression by the immune system work?

Back 34

1) Regulatory cells (Treg and Breg) produce immunosuppressive cytokines (TFG-B and IL-10) and suppress immune cell responses in an antigen-dependent way, most often by affecting APCs

2) Anergy: Some effector cells persist but are resistant to re-activation. This mainly happens from antigen-stimulation without co-stimulation or with CTLA4 stimulation

3) Apoptosis: activated lymphocytes become sensitive to death ligands (FasL, TRAIL) expressed by killer cells

Front 35

What are the killer cell populations and how do they work?

Back 35

Cytotoxic T lymphocytes: eliminate virus infected cells through MHC class 1 activation

Natural killer cells: recognize nucleated cells that don't express MHC class 1 and kill them. This controls viruses that suppress MHC class 1 presentation to evade the immune system

Killer B lymphocytes: A type of B lymphocyte that expresses FasL and MHC class II that interacts and kills T helper cells (BOSS)

Front 36

Describe the process of autoimmunity in SLE.

Back 36

Pathogenic autoantibodies against DNA and other nuclear antigens (ANAs) cause accumulation of immune complexes in skin and kidney. This immune complex deposition leads to activation of complement, release of inflammatory mediators, and tissue damage.

Front 37

Describe the process of autoimmunity in RA.

Back 37

Immune system led by Th17 cells attacks cartilage and bone leading to cartilage degradation, accumulation of synovial fluid, synovial hyperplasia, and resorption of bone

Front 38

How could autoimmunity form (3 ways) from a failure of the immune system to differentiate self and foreign?

Back 38

Failed self tolerance: defects in central or peripheral tolerance, which allow survival of self-reactive cells (e.g. APECED, ALPS)

Molecular mimickry: foreign antigens kind of look like self, so self gets attacked

Altered self proteins: modifications to self proteins (glycosylation, citrullination) can confuse immune recognition. Certain MHC molecules may seelctively present these altered self antigens and account for genetic associations in some diseases (RA association with smoking and HLA-DR4 MHC class II)

Front 39

What is APECED?

Back 39

Mutation in AIRE transcription factors involved in central tolerance of Th cells in the thymus.

Can contribute to autoimmunity

Front 40

What is ALPS?

Back 40

Mutations affection the Fas/FasL apoptosis pathway and peripheral tolerance