Mediated by Immune Complexes (IC)

F/M 10:1

ANTI-DSDNA, LEUKOCYTE, PHOSPHOLIPID Abs

systemic and multiorgan (NON-organ-specific) IC are formed in serum and trapped in basement memb. of glomeruli, kidney, joints ANTI-DS-DNA, anti leukocyt Antibodies Anti-phospholipid antibody Polyclonal B cell activation Etiology unknown

Cell mediated and Immune Complex mediated

F/M 3:1

REHEUMATOID FACTOR Abs bind to Fc of IgG

Excessive TYPE 1 Cytokines

Rheumatoid factors IgM or IgG/A to FcgammaG (not essential for disease)

F/M 2:1

ANTI MBP+ CNS Abs Cell Mediated

Organ specific Ab to myelin basic protien (MBP)

Oligoclonal, no polyclonal Ab in CSF Treatment with IFNbeta (inhibits IFNgamma expression of MHCII)

Type IV Hypersensitivity

F/M 50:1 !!

Cell mediated (T-cell)

Thyroid-specific Anti-thyroglobin Ab and anti-microsomal Ab are secondary to thyroid destruction (diagnostic tool) Manifests as goiter/hypothyroidism Peaks 3rd, 4th decade

Type II HypersensitivityReaction

ANTI GBM Abs bind to cell Glomerular Basement Membrane surface antigens

F/M 1:4 2 peaks: young, elderly

LINEAR DEPOSITION Anti-glomerular-basement Abs destroy basement membranes in lungs and kidneys: ROIs destroy cells, elastase and colligenase destroy elastin and colligen Lung, Kidney Anti-glomerular basement memb. Ab LINEAR deposition of IgG and compliment

TWO MODES

1. Ab to PARIETAL cell surface antigens so no IF produced, or

2. BIND DIRECTLY TO INTRINSIC FACTOR blocking B-12 binding Defective RBCs Abs bind to cel surfc Ags and destroy PARIETAL GASTRIC CELLS THAT SECRETE INTRINSIC FACTOR Ab's bind to IF so no B12 binding MEGALOBLASTIC ANEMIA

F/M: 8:1

THYROID ANTI-TSH-R Abs mimic thyroxin stimulating hormone

HYPERthyroidism Goiter, bulging eyes

F/M : 4:1

Abs attack Ach receptors

BLOCK ACH BINDING ON NERVE RECEPTORS

Affects JOINTS

prior infection with Klebisella pneumoniae

NO RHEUMATOID FACTOR

F/M 1:9

Glycophorin (Ii) /Anti-Ii Ab

Ab to RBC surface antigens glycophorin or Ii

ONLY AT TEMPS BELOW 37 DEG. C

Type 1 Hypersensitivity Reaction in NOSE

IgE x-linking causes degranulation of mast cells and basophils, resulting in the release of histamines, prostaglandins, and leukotrienes

Type I Hypersensitivity Reaction LUNGS

IgE cross-linking causes degranulation of mast cells and basophils, resulting in the release of histamins, prostaglandins, and leukotrienes

Type I Hypersensitivity Reaction 

MULTIPLE SYSTEMS

IgE x-linking causes degranulation of mast cells and basophils, resulting in the release of histamins, prostaglandins, and leukotrienes

Type II Hypersensitivity

IgM Isohemagglutins lead to compliment pathway activation + opsonin-mediated phagocytosis + ADCC of RBCs

Rh Factor Incompatibility

Mom develops Anti-Rh+ IgGs, which lead to compliment pathway activation + opsonin-mediated phagocytosis + ADCC of infant's RBCs

Used to prevent Rh negative mom from generating anti Rh+ antibodies following delivery of an Rh+ baby.

Swamps-out the Rh+ antigens by binding them all (IgG) so that mom's immune system doesn't see any.

Type III Hypersensitivity Reaction

Immune complexes all over body

HLA DR2/DR3-related Antibodies to dsDNA

Type III Hypersensitivity Rxn

Immune complexes in LUNG tissue cause damage

Type III Hypersensitivity Rxn

First dose of horse serum sensitizes (DIPTHERIA VACCINATION, etc.)

Second dose causes cute reaction ANAPHYLAXIS

TYPE IV HYPERSENSITIVITY

- Leprae Nerves (?)

- Tuberculosis Lungs -

- Sarcoidosis Skin

Pathogens thrive in MACROPHAGES, form LARGE, MULTI-NUCLEATED CELLS which trigger immune responses

Type IV TB test

Th1-mediated reaction which generates IFNgamma and TNF, acivates macrophages.

Also cytokine reaction.

Localized to point of intradermal injection (wheal and flare)

Type IV (Delayed) Reaction

On second exposure, memory Th1 cells react to presence of URISHIOL HAPTEN.

Reaction may be moderated by Th2's (IL-4)

Type IV (T cell-mediated) CNS demyelination

Unregulated type 1 cytokines cause a ruckus.

Administration of Type-2 cytokines (Il-4, TGF, IL-13) may help (dampen Th1's).

Oral feding of antigen to promote "tolerance" to "switch" Th1 domination to Th2

Progenitor cell disorder

Deficient in ALL LYMPHOID AND MYELOID cells

ANEMIC

Increased susceptibility to ALL agents. Bone marrow xplant

NO lymphoid precursor cells

No B OR T cells

PRIMARY

lack of LYMPHOID PROGENITOR CELLS

SECONDARY:

Lack of ADA or JAK-3 Can also be secondary with lack of ADENOSINE DEAMINASE (ADA), required for PURINE metabilism, so no DNA synthesis, toxic metabolites acumulate . Absence of JAK-3 can also be a SECONDARY cause

Defective/absent Thymus

FEW OR NO CIRCULATIING T CELLS

May improve with age

Lack T-CELL RECEPTORS for CANDIDA

"Hole in Repitorie"

Normal B-cell immunity to Candida still OK.

Block Pre-B to Immature B maturation

LACK ALL TYPES OF Ig

Recurrent bacterial infections

Defect in tyrosine kinase.

Apparant at 6 mo. age when mom-derived Abs degraded

Lack of IgE, IgA, IgG

patients recover with antibiotics

apparant at 6 months.

increased suscep. to bacterial infections

NORMAL NUMBERS OF PERHIPERAL B CELLS

Lack of ALL Igs

Onset at any age

F=M

Increase in sinopulmonary infections.

Missing IgA

Treat with ANTIBIOTICS since other Ig's OK.

(If gave IgA, recipient would form Anti-IgA Abs.)

Defective CD40 (B-cell) / CD40L (T-cell) interaction

  ISOTYPE SWITCHING DOES NOT HAPPEN.

Mom's immunity gone,

but infant's immuno system hasn't yet fully matured.

Accumulation of large cytoplasmic granules in phagocytes which become dysfunctional:

granules won't fuse to lysosomes.

NK also impaired.

LACK OF MELANIN in skin, eyes, hair. SHORT-TERM: anti-fungal, Anti-bact LONG-term: Bone Marrow Xplant

Dysfunction of NADPH OXIDASE

Short-term treatment

: IFNgamma (upregulates ROIs), anti-fungal, anti-bacterial.

Long-term is Bone Marrow Transplant

Imparired trafficking of Leukocytes

CD-18 Deficiency

UNCONTROLLED ACTIVATION OF C1

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proteolysis of C2/C4

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more C2b, vasoactive kinin, C4a, anaphylatoxin. Also make more Kallikrein which cleaves kinnogen to relase BRADYKININ

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Life-threatening edema HERIDITARY ANGIOEDEMA

Affects classical and altternate compliment paths

Increases suscep. to ALL BACTERIAL infections.

Chronic nephritis from deposition of C3 nephritic factor

Can't MAC Attack!

Susceptibility to ONLY to NISSERIA bacteria (memingitis and ghonnorea), which sugests that C3 opsonin phagocytosis is the normal role of compliment-mediated defense, not MAC lysis !!!!!!! Wow!!!!!!!!!!

(DAF facilitates C3 convertase decay)

Less DAF

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activation of MAC, lyses RBCs

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PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (you see RBC wreckage in urine after overnight build-up)

B-cell lymphoma seen in after EPSTEIN-BARR virus (MONONUCLEOSIS)

In immunocompromised patients

Lymphomas

Skin cancers

Kaposi's sarcoma

Causes mononucleosis

Predisposes to B-cell lymphoma

(Burkitt's Lymphoma) in immunocompromised patients

Antigens Found ONLY on tumors

Example: Chronic lymphocytec luekemia (CLL)

Antigens found on tumors

as well asother places

e.g. oncofetal antigens such as CEA, AFB, Beta-HCG

CEA

Cardino-Embryonic Antigen

Onco=fetal antigen

colon, breast, stomach cancers.

High in cigarette smokers, COPD patients, Alchoholics with chirrosis

AFP

Alpha Fetal Protien

High in patients wiht pancreatic, gastric, lung cancers

Seen in patients with ataxia telegectasia and alcoholic cirrosis

colon cancer UNIQUE antigens (TSAs)

used for diagnosis

Unique antigen (TSA)

for OVARIAN cancer

used for diagnosis

Overproduction of LIGHT CHAINS by Myelomas

show up in urine

Examples of

Cancer therapy via enhanced APCs

1. Enhance DC antigen presentation via enhancing migration to spleen

2. adding tumor epitopes to DCs ex-vivo

3. fuse DCs with tumor cells to get more MHCI and II expressed

Add GM-CSF to tumors in-vitro then reinfuse into patient

Other versions of this therapy add

IL-1, IL-12, or IFNgamma

Take a sample of patient's bone marrow

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In-vitro, purge of bone marrow samples: make 'em cancer free.

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Chemotherapy for patient to kill cancer

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inject "clean" marrow back into patient