Immuno Cytokines And Hypersensitivity Diseases

Front 1

BAFF

Back 1

Serves as signal 2 for marginal zone B cells (signal 1 = BCR binding antigen, with crosslinking).

Front 2

C3a

Back 2

Moderate chemokine - attracts macrophages and neutrophils.
Induces local inflammation - vasopermeability, mast cell degranulation and smooth muscle contraction.
Anaphylatoxin.

Front 3

C3b

Back 3

Opsonization.
Formation of active C3 convertase.
Formation of active C5 convertase.

Front 4

C5a

Back 4

Strong chemokine (stronger than C3a) - attracts macrophages and neutrophils.
Induces local inflammation - vasopermeability, mast cell degranulation and smooth muscle contraction.
Anaphylatoxin.

Front 5

C5b

Back 5

MAC formation (recruits C6/C7/C8/C9).

Front 6

CCL18

Back 6

Attracts T cells to dendritic cells in lymph nodes.

Front 7

CCL19/CCL21

Back 7

Attracts B cells and T cells to T cell zone of lymph nodes.
Binds CCR7.

Front 8

CXCL13

Back 8

Attracts naïve follicular B cells to B cell zone in lymph nodes.
Binds CXCR5.

Front 9

CXCL8

Back 9

Attracts neutrophils.

Front 10

FoxP3

Back 10

NOT A CYTOKINE, but important because natural Treg cells express it.

Front 11

GM-CSF

Back 11

Induces macrophage differentiation in bone marrow.

Front 12

IFN-alpha (type 1)

Back 12

Activates NK cells.
IFN-beta is activated first, IFN-alpha is activated later.

Front 13

IFN-beta (type 1)

Back 13

Activates NK cells.
IFN-beta is activated first, IFN-alpha is activated later.

Front 14

IFN-gamma (type 2)

Back 14

Activates macrophages.
Induces activated T cells to differentiate into TH1 cells (signal 3).

Front 15

IL-10

Back 15

Inhibits NK cells.

Front 16

IL-12

Back 16

Activates NK cells.
Induces activated T cells to differentiate into TH1 cells (signal 3).

Front 17

IL-1beta

Back 17

Causes fever.
Activates vascular endothelium.
Activates acute phase response (CRP and MBL).
Activates macrophages/neutrophils.

Front 18

IL-2

Back 18

Induces massive proliferation of activated T cells.

Front 19

IL-3

Back 19

Induces macrophage differentiation in bone marrow.

Front 20

IL-4

Back 20

Activates B cell differentiation into plasma cells.
Induces activated T cells to differentiate into TH2 cells (signal 3).
Production favors allergic response.

Front 21

IL-5

Back 21

Activates B cell differentiation into plasma cells.
Cause basophils/eosinophils to start expressing FC-epsilonRI and binding IgE on surface (in type 1 allergic response).

Front 22

IL-6

Back 22

Causes fever.
Activates vascular endothelium.
Activates acute phase response (CRP and MBL).

Front 23

TNF-alpha

Back 23

Causes fever.
Activates vascular endothelium.
Activates acute phase response (CRP and MBL).
Activates NK cells.
Causes dendritic cells to move to lymph nodes (adaptive response).

Front 24

Type 1 interferons

Back 24

Main antiviral cytokines. Include IFN-alpha and IFN-beta.
Production mediated via IRF-3.

Front 25

Type 1 Hypersensitivity

Back 25

Most important players are Th2 CD4s, mast cells, eosinophils, IgE, IL-4, IL-5, and IL-13. Most people will not have an immune response to innocuous substances (pollen, dust mite feces, nuts, etc). The first time the antigen is encountered, the person undergoes sensitization but does NOT have an allergic reaction.

Front 26

Type II Hypersensitivity

Back 26

Important players here are IgG (or sometimes IgM) antibodies that are produced to and bind to antigens on the surface of cells/tissues.

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examples of Type 1 hypersensitity not considered autoimmune disease:

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Common examples (not considered autoimmune disease) are:
--Penicillin-induced hemolytic anemia
--Hemolytic anemia caused by ABO-mismatched blood transfusions
--Erythroblastosis fetalis
--Hyperacute transplant rejection

Front 28

examples of Type 1 hypersensitity - considered autoimmune disease:

Back 28

Common examples of autoimmune diseases that are mediated by type II hypersensitivity:
--Autoimmune hemolytic anemia
--Idiopathic/autoimmune thrombocytopenia purpura
--Pernicious anemia
--Rheumatic fever (molecular mimicry causes antibodies produced in response to Strep infection to cross-react with self-antigens in heart, kidney, and joints)
--Goodpasture’s syndrome
--Graves’ disease
--Myasthenia gravis
--Bullous pemphigoid
--Pemphigus vulgaris

Front 29

Type III Hypersensitivity

Back 29

Important players here are IgG (or sometimes IgM or IgA) antibodies specific for soluble antigens. When these antibodies and antigens are found in an ~1:1 ratio in the serum, they form immune complexes which overwhelm clearance mechanisms in the spleen and can deposit on tissues throughout the body

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examples of Type III Hypersensitivity not considered autoimmune disease

Back 30

Common examples (not considered autoimmune disease) are:
--Arthus reaction (injection of antigen in individual with pre-existing antibodies can lead to formation of immune complexes and inflammation at site of antigen injection)
--Serum sickness (antibodies to foreign proteins in serum of transfused blood)
--Post-streptococcal glomerulonephritis (antibodies to Strep antigens form complexes and are deposited in kidney vasculature)
--Hypersensitivity pneumonitis (Farmer’s lung)

Front 31

examples of Type III Hypersensitivity - considered autoimmune disease

Back 31

Common examples of autoimmune diseases that are mediated by type III hypersensitivity:
--SLE (lupus)
--Polyarteritis nodosa (a type of vasculitis that is likely autoimmune)
--Rheumatoid arthritis has features of type III hypersensitivity (although in this class we are considering it to be type IV hypersensitivity)

Front 32

example of Type IV Hypersensitivity (Delayed-type hypersensitivity) not considered autoimmune disease:

Back 32

Common examples (not considered autoimmune disease) are:
--Poison ivy/oak (contact dermatitis): Poison ivy contains a hapten called pentadecacatechol
--Nickel (and other metal) “allergy” (these are more properly called contact dermatitis since they are type IV and not type I like true allergies): the small metal ions are haptens
--PPD skin test
--Guillain-Barré syndrome
--GVHD
--Acute transplant rejection
--Chronic transplant rejection (chronic rejection also involves antibody-mediated type II or type III hypersensitivity as well)

Front 33

example of Type IV Hypersensitivity (Delayed-type hypersensitivity) - considered autoimmune disease:

Back 33

Common examples of autoimmune diseases that are mediated by type IV hypersensitivity:
--Type I diabetes
--Multiple sclerosis
--Hashimoto’s thyroiditis
--Celiac disease (response to peptides derived from gluten such as gliadin)
--Rheumatoid arthritis (although it can involve immune complexes, not all patients have Rheumatoid Factor so it is more likely that it is the cellular infiltration of the joints that is causing the symptoms)

Treatment is disease-specific, but in many cases immunosuppression can be helpful.