-Secreted by MPhage

-Causes acute inflammation

-Induces Chemokine Production

-Activates endothelium to express adhesion molecules

-Endogenous pyrogen

Hot TBone stEAk

IL1 - Hot

Cytokines - IL2

- Secreted by Th cells

- Stimultes growth of helper and cytotoxic T cells

(Hot T-Bone stEAk)

IL2 - T cells

- Secreted by activated T cells

- Supports growth and differentiation of bone marrow stem cells

- Fxn similar to GM - CSF

Hot T-Bone steEAk

IL3 - stimulates bone marrow

- Secreted by Th2 cells

- Promotes growth of B cells

- Enhances class switching to IgE and IgG

Hot T-Bone stEAk

IL4- stimultes IgE (and G)

-Secreted by Th2

-Promotes differentiation of B cells

-Enhances class switching to IgA

-Stimulates production and activation of eosinophils

Hot TBone stEAk

-stimulates IgA production

Cytokines - IL6

- Secreted by Th cells and macrophges

- Stimulates production of acute-phase reactants and immunoglobulins

- Secreted by macrophages

- Major chemotactic factor for neutrophils

"Cleanup on IL-8" - recruited to clear infections

- Secreted by regulatory T cells.

- Inhibits actions of activated T cells.

- Activates Th2, Inhibits Th1

- Secreted by B cells and macrophages

- Activates NK and Th1 cells

(a natural born 12 year old killer)

- Secreted by Th1

- Stimulates macrophages

- Activates Th1, inhibits Th2

- Secreted by macrophages

- Mediates septic shock

- Causes leukocte recruitment, vascular leak

Type III Hypersensitivity

Arthus Reaction

- What size precipitates? Mediated by what? Symptoms?

- Medium

- Compliment activated chemotactic factors, PMN, plts

- Thrombi, hemorrhageic, necrotic lesions

Type III Hypersensitivity Reaction

Serum Sickness

Etiology? Sxs? Populations?

- Injection of foreign serum or its products

- Drugs (sulfonamides, PCN, cephalosporisn, phenytoin, thiourea)

- Fever, pruritic rash, LAD, joint pain

- Serum used only in a few dzs - hepatitis, tetanus, immunosupression

Type III Hypersensitivity

Polyarteritis Nodosa

Etiology? Sxs? Associated Dz?

- Continuous insult of arteriolar wals by deposition of circulating Ag-Ab complexes

- Thrombosis, obliteration of blood flow

- Hep B antibody complexes

Type III Hypersensitivity

Glomerulonephritis

Etiology? Antigens? Path?

- Ag-Ab complexes deposit on and behind renl GBM

- DNA, insulin, thyroglobulin, group A nephritogenic strep, foreign serum

- Fluorescent antibody against either the antigen antibody, or complement - Lumpy-bumpy pattern

Type III Hypersensitivity

SLE

Antigens? Inflammatin mediated by? Signs/Sxs? DX?

- dsDNA, RBC, WBC, plt, ANA

- Complex lodges in kidney - GMN

- Inflammation med by C'5a induced influx of NP - lysosomal damage

- polyarthralgia, arthritis, malaar rash, pleurisy, pericarditis, vasculitis

- lumpy bumpy pattern, LE cell (macrophage with phagocytized nucleus)

Type III Hypersensitivity

RA

Pathogenesis? Haplotype? Dx?

- Antigen and antibody alteres 3 structure of antibody

- Anti against Fc of IgG

- IgG-IgM (RF)- complexes in synovial fluid - lysosomal enzymes released

- Delayed-type hypersensitiity effector cells, (IL1, IL6, TNF), macrophages, osteoclasts

-Pannus inflammation and loss of cartilage

Immunodeficiency

Transient physiologic hypogamaglobulinemia

- When? Reason?

- 3-6 months, low IgG from low rate of sxs

Immunodeficiency

Congenital agammaglobulinemia

- Normal thymus and CMI

- Recurrent pyogenic infecions, digestive tract d/os

- loss of pre-B to B cell - loss of tyrosine kinase gene - pre-B cells are normal

- No tonsils, B cells, germinal centers

- Serum IgG <10%

- passive transfer of adult IgG

Immunodeficiency

Dysgamaglobulinemia

- Selective class deficiency - generally IgA

- Failure of IgA bearing cells to differentiate into plasma cells

- Increased susceptibility to autoimmune dz

Immunodeficiency

DiGeorge

Cause (week? pouches?) Fxs? Infxns?

- Unknown intrauterine injury, wk 12, pouches 3-4

- Depressed CMI - infxn with opportunitistic bugs

- Normal germinal centers, plasma cells, serum immunoglobulin

- Tx: No vaccination with live vaccine

Immunodeficiency

Chronic mucocutaneous candidiasis

- absence of immunity to Candida

- Normal T cell and B cell number and function

- 50% with endocrine dysfxn

Immunodeficiency

Wiskott-Aldrich

Triad??? Features? Cause? Tx?

- Thrombocytopenia, Infections, Eczema (tie)

- Depressed CMI and low IgM, nl IgG and IgA

- Poor response to capsular polysaccharide antigens

- Defect on short arm of X chromosome resulting in absence of glycoprotein receptors on T cells and platelets

- Tx: BMT

Immunodeficiencies

SCID

- Cause? Enzyme def? Accumulated product? Tx?

- Absence of the thymus gland, B and T cells

- 2/2 Def in adenosine deaminase

- DTAP (toxic deoxyadenosine triphosphate)

- mutation in gamma chain of IL2

Immunodeficiency

CGD

- Deficiency? Dx? Tx?

- NADPH oxidase, superoxide dismutase, decreased H202

- Failure to reduce nitroblue tetrazolium dye

- Tx: Interferon gamma

Immunodeficiency

AIDS

Infections with CD4 200-400?

Infections with CD4 <200?

Cancers?

- Candida, MAI, Varicella

- PCP, CMV, Crypto

- Kaposi's sarcoma, B cell lymphoma, Burkitt's lymphoma, immunoblastic sarcoma

- Clonal deletion - Loss of self-reactive T and B cells - eliminated after contact with self-antigens in the thymus gland

- Clonal anergy - loss of T and B cell functions after exposure to antigens in the absence of andatory costimulatory signals (ie, B7-CD28)

- Peripheral suppression - CD8+ T cells or macrophages secrete cytokines (TGFB) which downregulate the immune response - or if tolerogenic doses of antigen are administered

Autoimmunity

Sjogren's Syndrome

Clinical features, immunologic features

- Dry mouth, trachea, bronchi, eyes, nose, vagina, skin

- Autoantibodies against salivary duct antigens, lymphocytic infiltration, immune complex formation in the salivary gland

Autoimmunity

Allergic encephalomyelitis

- Demyelinating disorder, can occur after infection or immunization

- Can be mimicked by immunizing animals with homologous extracts of brain or a nonapeptide from basic protein of myelin

Transplantation

Test for Histocompatibility

- Mixed lymphocyte culture

- Blood lymphocytes from the donor and recipient are cultured together, and tritiated thymidine is added

- Donor cells treated with antimitotic agent

- If lymphocytes are antigenically incompatible, DNA is sxs, cells divide

- Extent of genetic disparity can be determined by scintillation counting

Transplantation

Acute Rejection

Definition? Mechanism? Cells? Cytokines?

- Swelling and tenderness over allograft - occurs within weeks

- HLA on alograpft stimulate recipient CD4+ T cells, secrete cytokines, induce adhesion molecules

- IL2 activates CD8, bind to graft antigens, release effector molecules such as perforins

- Perforins create pores in target cell membrane and enabe serine proteases

IFN gamma - activates monocytes/macrophages to express delayed-type hypersensitivity toward antigens - increased lysosomal activity, phagocytosis, resp burst, release of TNF alpha

- Selectin, integrin, ICAM, VCAM expression, leukocyte extravasation

Transplantation

Chronic Rejection

Start? Mechanism? Path?

- Months to years

- Cellular and humoral mechanisms

- Interstitial fibrosis, vascular occlusion, loss of function

Transplantation

Hyperacute Rejection

Timing? Mechanism?

- Within minutes

- Alloantibodies against donor's HLA or ABO antigens does not permit the graft to take

- Immediate clotting, thrombosis, necrosis

Transplantation

Immunosupression

Organisms that are problematic?

Transplantation

Immunosuppressive Agents: Cyclosporine A

Mechanism?

- blocks IL-2 mRNA synthesis

- Binds to a cyclophilin, which binds to calcineurin, interfering with transmission of inracellular signals necesary for IL-2 formation

- Often given with rapamycin - macrolide isolated from streptomyces - binds to cyclophilins, inhibits G1 phase of activated T cells

Transplantation

Immunosuppressive Agents: Tacrolimus

- Binds to FKbinding protien (cyclophillin), blocks IL2 sxs

Transplantation

Immunosuppressant agents: Mycophenolate Mofatil

- Inhibits inosine monophosphate dehydrogenase (Converts IMP to GMP - inhibits T and B cells because guanosine monophosphate is require dfor nucleic acid sxs in these cells)

Transplantation

Immunosuppresive Agents: Azathioprine

- Derivative of 6 mercaptopurine, used early following transplantation, inhibits sxs of inosinic acid

Transplantation

Immunosuppresant Drugs: Corticosteriods

- corticosteriod plus receptor complexes with NFKB to prevent tx of IL2 and other cytokines

- Suppress IL-2 sxs indirectly by blocking IL1 release

HLA

A3

HLA

B27

HLA

B8

Graves

(Isn't GR8)

HLA

DR2

HLA

DR3

HLA

DR4

HLA

DR5

HLA

DR7

Cell Surface Proteins

Helper T Cells

Cell Surface Proteins

Cytotoxic T Cells

Cell Surface Proteins

B cells

Cell Surface Proteins

Macrophages

Cell Surface Proteins

NK Cells

Cell Surface Proteins

All cells except mature red cells

Immunodeficiency

Hyper-IgM Syndrome

Defective CD40 L on helper T cells - inability to class switch

Severe pyogenic infections early in life

Increased IgM, very low IgG

Immunodeficiency

IL-12 receptor deficiency

Immunodeficiency

Hyper-IgE (Job's syndrome)

FATED

coarse Facies

cold (noninflamed) staph Abscesses

retained primary Teeth

increased IgE

Dermatologic problems

Immunodeficiency

Common variable immunodeficiency

Defect in B-cell maturation; many causes

Can be acquired in the 20s-30s - inceased risk of autoimmune disease, lymphoma, sinopulmonary infections, nromal number of B cels, decreased plasma cells, immunoglobulin

Immunodeficiency

Ataxia-telangiectasia

Defect in DNA repair enzymes

Cerebellar defects (ataxia), spider angiomata (telangiectasia), IgA deficiency

Immunodeficiency

Phagocytic Dysfunction - Leukocyte adhesion deficiency (type I)

- Defect in LFA-1 integrin (CD18) on phagocytes

- Recurrent bacterial infections, absent pus, delayed separation fo umbilicus

- Neutrophilia

Immunodeficiency

Chediak-Higashi syndrome

Defect in microtubular function with decreased phagocytosis

Recurrent pyogenic infections by staphylococci and streptococci; partial albinism, peripheral neuropathy

HIV

Receptors needed to enter? 3 major genes and their function? Regulatory genes...

- CD4 + CCR5 via gp 120 (MO and dendritic cell)

- CD4, CXCR4  via gp 120

3 genes - env for envelope protien, gp160 - cleaved to gp 120 and gp 40, gag for core protiens (p24, p17, p9.p7), pol for enzymes (reverse transcriptase, integrase, protease)

tat - activates transcription of viral DNA

nef - helps with virus replication

rev - regulates mRNA activity