• Antibody mediated
• Antigen is insoluble
• Antibody is IgG or IgM
• Clasical compliment, Opsonization or ADCC
• Lysis of host cells by NK or macrophges
• (eg) Blood mismatch, AID, Drug reactions

• Glycolipids
• Blood and saliva
• Isohemogglutimin IgM
• O most common, AB rarest

• Protein antigen
• No naturally ocurring AB to RH AG.
• On RBC only
• Genes CDE
• 85% RH+

• used to prevent HDN
• Binds fetal RH⁺ RBc and removes them from mother's circulation before immune response activated

• Mediated by isohemagglutinins IgM
• Release of anaphylatoxins C2a C4a & C5a.
• Fatality 10-40%

Immune transfusion reactions

Hemolitic Major

Hemolitic Minor

Hemolitic delayed

Non hemolitic

Major: Recipient's AB against donor's RBC

Minor: Donor's AB against recipient's RBC

Delayed: Recipient develops AB against donor's RBC

Non hemolitic: AB to WBC.  IGE for anti-IgA (Anti-HLA).  Result in type 1 hypersensitivity.

• Soluble AG
• Immune complex mediated
• (eg) arthus reaction, serum sickness

(eg) Muscle sore after tetanus shot (soluble)

1. Local aggregation of insoluble IC
2. Sensitization due to second shot.  High serum IgG must be achieved.
3. Reaction localized I.D. or I.M.

Earliest onset 1-2 hours after shot.  (depends on # of AB & AG for complexing)

1. Inject soluble AG
2. Insoluble IC form
3. Classical complement pathway & generation of C5a & C3a
4. C5a attracts neutrophils
5. Neutrophils & platelets agregate at vessel wall
6. Neutrophils frustrated phagocytosis
7. retard blood flow, vessel walls rupture

• Systemic response to IV AG. 
• Occur in sensitized individual in hours
• Result of primary immune response
• Result of IC formation in vessels.
• Complement CH₅₀ lvl lowest at peak of disease.
• Symptoms subside when uncomplexed AB in serum

Delayed type hypersensitivity: hypersensitivity IV

• 24-48 hours
• CMI, mostly CD4⁺ T helper cells
• No AB involved

• 1974-1975: 2 kids died within 24 hours of shot
• 1979: Pertusis 1000->13000.  (41 die)
• New acellular pertusis vacine same rates of protection, less alleged offending antigens.

Killed/inactivated whole cell

examples

• Rabies
• Hepatitis A
• Intramuscular Polio virus (IPV)
• Influenza

Killed/inactivated whole cell

+

-

<+>

• Safe to give to immunosupressed & pregnant
• Stable
• AB is sufficient to provide protection

<->

• killed AG is processed differently by body resulting in no protection or more sensitive
• Weakly immunogenic, need boosters.
• killed by phagocytosis.  processed as exogenous, so TH2 and AB response.

Live whole organism

examples

• MMR
• Oral polio Vaccine (OPV)
• Chicken pox
• Live attenuated intranasal influenza vaccine
• Rotavirus
• Typhoid fever
• BCG for TB.
• Yellow fever

Live whole organism

+

-

<+>

• Processed as exogenous & endogenous so AB & CMI.
• Sustained immune response so no booster

<->

• Less stable, need "cold chain"
• Can revert to virulent form

1. Grow in forign organism that it usuay doesnt infect
2. Pathogen loses virulence in humans

(eg) BCG for TB vaccine

Can also develop temperature sensitive mutants.

• Administer toxin produced by pathogen as inactivated.
• (eg) diphtheria, tetanus, botulism

• Capsular polysachurides are virulent, but T independent.
• Don't enduce memory, need many boosters
• (eg) meningococcal, pneumococcal, Bib, typhoid fever polysachuride.

Human Immune serum globulin

(gamma-globulin)

• Gamma globulin collected from donors
• can keep immune compromised safe for a month.
• given IM (IGIM) or IV (IGIV)

Specific human immune globulin

• Donors selected who have high AB (after shot)
• (eg) RhoD, Varicella-Zoster, Hep B, Tetanus,

Monoclonal antibodies

• Single specificity for 1 epitope of an AG (usually IgG)
• Hybridoma Immortal, divides rapidly
• Good because specific.

• Deplete cells expressing AG by activating C'
• Deplete cell population by opsonizing to enhance phagocytosis
• Non depleting, block function of target protein. (eg) Zenapax

• Hep A (pre & post)
• Measles (post)
• Hypogammaglobulinemia (every month)
• IVIG in neonates with roup B strep
• Kawasaki disease

Palivizumab

(Synagis)

• Resperatory syncytial virus (RSV) prophylaxis
• Anti-RSV F protein

• Prevent graft rejection using anti-CD3
• Receptor blockade
• Murine AB

Omalizumab

(Xolair)

• Anti IgE therapy for severe allergies
• Humanized AB

Ibritumomab tiuxetan

(Zevalin)

• Murine AB
• Targets B cell marker CD20
• Targets small tumors

Daclizumab

(Zenapax)

• IL-2 receptor blocker
• Humanized AB
• Prevent renal graft rejection

Trastuzumab

(Herceptin)

• Anti ErbB-2
• prevents HER2+ cancer cell from growing, and lables for destruction

• RA
• Psoriasis
• Crohns
• ulcer

• Remicade (Mouse/human)
• Humera (human)
• Embrel (TNF-α + IgG)

Central T cell tolerance

Peripheral T cell tolerance

Central: Thymus, T cells that strongly recognize self-peptides on MHC molecules die. 

Peripheral: Lymph nodes, primary T cells (MHC/Peptide-TCR) without secondary stimulation (B7-CD28) causes T cell anergy.

• Inflammatory lesion in eye that appears 2-6 weeks after wound to contralateral eye.
• If severely injured in 1 eye, remove it before other eye gets inflamed. 

• AG on Klebsiella induce AB that cross-react with self
• Inflammation, Fibrosis & ossification of spine.
• 90% victims HLA-B27 positive (MHC I molecule)

• Streptococcal pharyngitis 
• AB cross react with heart valve tissue

• Infection by campylobacter in GI
• AB against lipopolysachurides (anti-LPS) cross react with gangliosides of motor nerves
• Paralysis.  resolves slowly.

• AB against ACH receptors @ Neuromuscular
• Organ specific type II hypersensitivity
• Can't maintain muscle tension
• Genetic disposition HLA-DR3

Systemic lupus erythematosus

(SLE)

• Systemic hypersensitivity III
• AB against DS DNA  (ANA)
• ANA form soluble IC in basement of kidney, arterial walls, synovium cause inflammation.
• Activates C' attracts WBC, local acute inflammation
• Linked to complement deficiency: C1 C4 C2
• Lack of C3b so can't be cleared up by phagocytes.
• Remissions, more common in women
• HLA-DR3 & DR2 (MHC II molecules)
• Test with fluorescent AB on hep-2 cell

• Progressive systemic
• Fibrosis (skin thickening), & arthritis due to excess production of extracellular matrix molecules like collagen
• AB against proteins for RNA/DNA synthesis

• Systemic, destruction of exocrine glands
• symptoms dry eyes, dry mouth
• AB against SS-A (Ro) & SS-B (La).  Cytoplasmic protein-RNA complexes
• tested by ELISA/Western

• AB mediated type II
• AB against TSH receptor binds, and activates.  Hyperthyroidism
• Genetically associated with HLA-DR3 
• can be transferred by placenta
• TSI binds & activates TSH receptor, more thyroid hormone, less TSH

• T cell mediated demyelinazation of CNS tissue.  loss of nerve transmission.
• CD4⁺ CD8⁺ & MHC II involved
• Class IV hypersensitivity
• Genetically HLA-DR2
• Epstein-Barr virus, Adenovirus 2, Hep B

• T cell mediated
• CD8⁺ & CTL destroy beta cells of pancreas
• HLA DR3 DR4 DQw8

• systemic AB and T cell mediated inflammation of synovium
• HLA DR4
• CD4+ T cells cause B cells to release Rheumatoid factors forming pannus that destroy cartilage
• IgM against IgG Fc portion. (rheumatoid factor)

• T cell mediated, specific
• Thyroid function destroyed, hypothyroidism
• Type IV hypersensitivity
• Dry skin, puffy face, brittle hair, feel cold
• HLA-DR5, HLA-DR3 & HLA-B8

• Treatment with antimitotic drugs, cyclosporine, NSAID
• dampen immune response, or delay tissue damage
• Bad because immune suppression
• Treat end state disease, not reverse process.

• TSH-binding inhibitor Immunoglobulin (TBII)
• Block TSH receptor, prevent from activating

Leukocyte adherence disease

(LAD)

• (eg) lack of CD18 inhibits netrophil adherence to endothelial cells.
• Abnormal inflamation, defective wound healing, can't form pus
• Cure is allogeneic stem cell transplant

• Chemotactic defect
• Primary deficiency of neutrophil response to signals or deficiency in production of chemotactic factors  (eg) C3a or C5a

• Killing defect
• X linked recessive 
• less H2O2 production during phagocytosis so bacteria can live in neutrophil
• cured by Actimmune or bone marrow transplant
• Myeloperoxidase deficiency has similar manifestations

• Quantitative B cell deficiencies
• when acquired maternal IgG ↓ infant gets severe recurrent capsule bacterial infections
• Normal # pre B cells, low B cell count
• Treat with injection of HISG

• Qualitative B cell deficiency
• low IgG, IgE, IgA, high IgM
• deficiency in isotype switching mechanism.  Cant turn IgM into IgG IgE or IgA.
• High autoAB against neutrophils, platelets & RBC
• Recurrent pyogenic infections

• normal # B cells, defect in maturation of functional plasma cells
• Defect in cytokine receptor expression & TH2 cytokine production (eg) IL-5

DiGeorge Syndrome

Congenital thymic aplasia

• Deficiency in development of parts of thymus
• Low T cell CD3⁺ counts
• Low DTH reaction to common skin test AG

• Secondary T cell immunodeficiency
• HIV infects cells that have CD4 marker

1. Latent: HIV⁺ for P24 AG or AB found by ELISA & Western.  No symptoms, normal CD4⁺
2. Progressive reduction in CD4⁺.  Low WBC, RBC, many AB, but non specific, less immune response
3. AIDS: HIV⁺ , prone to autoimmune phenomena, opportunistic infection
4. Death

Type 1: No HLA I expression

Type II: No HLA I or II expression.  faulty AG presentation to T cells.  Opportunistic infections

Severe combined Immunodeficiency

(SCID)

• Low B T cell counts
• Can't make T dependent AB & CMI
• "Bubble baby syndrome"
• X linked
• Treat with bone marrow transplant

• Defect in C1 inhibitor

• No T B or PMN cells
• congenetal myeloid and and lymphoid stem cells fail to differentiate during hematopoiesis