IMMUNOLOGY

What is the thymus?

• An encapsulated primary lymphoid organThe site of T cell differentiation and maturation. third branchial pouchesLymphocytes of mesenchymal originCortex has immature T cellsmedulla is pale medulla has mature T cellsmedulla has reticular cells medulla has Hassall's corpuscles. Corticomedullary junction has Positive and negative selection Positive selection is MHC restrictionNegative selection is nonreactive to self

What is Bone Marrow?

• A primary lymphoid organ that produces B-cells

What is a Lymph Node?

• A secondary lymphoid organ that filters lymph using macrophagesstores b and t cellsactivates b and t cellsproduces antibodiesB cells are stored in the follicles of lymph nodethe primary follicle is dense and dormantthe secondary follicle is germinalT cells are stored in the paracortex of lymph node Paracortex is not developed in Di george syndrome

What is the spleen?• T cells are found in the periarterial lymphatic sheath 

(PALS) and in the white pulp  of the spleen. B cells are found white pulp of the spleen. Macrophages in the spleen remove encapsulated bacteria.Decreased spleen functions means decrease I G M Decreased I G M means decreased complement fixatiionDecreased complement fixation means decreased C 3 bDecreased C 3 B means increased attacks by bacteria with capsulesSalmonella is encapsulatedStreptococcus pneumoniae is encapsulatedHemophilus influenzae is encapsulatedNeisseria meningitidis is encapsultedRemoval of the spleen causes Howell Jolly Bodies, target cells and thrombocytosis to appearHowell jolly bodies are nuclear remnants Target cells are RBC with a bulls eye appearance

What is innate immunity?

• Innate immunity is fast, non specific and with no memory Innate immunity is neutrophils, macrophages, dendritic cells, lymphoid natural killers cells and Complement

What is adaptive immunity?

• Adaptive immunity is slow and has memoryAdaptive immunity is T and B cells and antibody

Drainage

• Lymph drainage for upper arm, lateral breast----Axillary lymph node

• Lymph drainage for stomach-----------------Celiac lymph node

• Lymph drainage for Duodenum and Jejenum-----Superior mesenteric nodes

• Lymph drainage for Sigmoid colon------------Colic and inferior mesenteric nodes

• Lymph drainage for lower rectum above pectinate line-----------------------Internal iliac nodes and Anal canal nodes

• Lymph drainage for Anal canal (below pectinate line), Scrotum and superficial thigh----------Superficial inguinal nodes

• Lymph drainage for testes----------Superficial and deep plexus nodes and Para aortic nodes

• Lymph drainage for lateral side of dorsum of the foot-----------------Popliteal nodes

Major Histocompatibilty Complex Class one

• H L A A H L A B H L A C Binds T C R and C D 8Expressed on almost all nucleated cells. Not expressed on RBC. Antigen is loaded in RER of mostly intracellular peptides. Mediates viral immunity. Pairs with BETA 2-microglobulin (aids in transport to cell surface).

Major Histocompatibilty Complex Class two

• H L AD R H L AD P H L AD Q. Binds T C R and C D 4. Expressed only on antigen-presenting cells A P C'sAntigen is loaded following release of invariant chain in an acidified endosome

HLA ASSOCIATIONS

• H L A Subtype A3 • **Hemochromatosis • H L A Subtype B 27 • ***Psoriasis, Ankylosing spondylitis, Inflammatory

bowel disease, Reiter's syndrome. • H L A Subtype B 8 • ***Graves disease • H L A Subtype D R 2 • **Multiple sclerosis

**hay fever**S L E**Goodpasture's.

HLA ASSOCIATIONS

• H L A Subtype D R 3 • ***Diabetes mellitus type 1. • H L A Subtype D R 4 • Rheumatoid arthritis

diabetes mellitus type 1 • H L A Subtype D R 5 • Pernicious anemia a vitamin BI2 deficiency

Hashimoto's thyroiditis. • H L A Subtype D R 7 • Steroid-responsive nephrotic syndrome

What do Natural Killer Cells Do?

• Only lymphocyte member of innate immune system. Activity enhanced by IL-12, IFN-~, and IFN-a. Induced to kill when exposed to a nonspecific activation signal on target cell and/or to an absence of class I MHC on target cell surface. Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells.

B-cell function IgG

• Make AntibodyOpsonize bacteriaNeutralize virusesType 2 Cytotoxic hypersensitivityType 3 Immune Complex hypersensitivity

• B-cell function IgM and IgG • Activate complement • B-cell function IgE • Allergy (type 2 hypersensitivity)

Parasitic worm infection • B-cell function • Hyper acute organ rejection that is

antibody mediated

• T-cell function C D 4+ • Activate B-cell Produce gamma interferon • T-cell function C D 8 • Kills virus infected Cells directly • T-cell function • Delayed cell-mediated hypersensitivity

(type IV).

C D 4 T H 1 Helper cells

• Bind MHC 2 on A P C'sRegulates cell-mediated response Secretes cytokines: IL-2, IFN-y Activates macrophage and CD8+ T cell Inhibited by IL-10 from T h 2 cell

C D 4 T H 2 Helper cells

• Bind MHC 2 on A P C'sRegulates humoral responseSecretes cytokines IL-4, IL-5, IL-10 Helps B cells make antibody (lgE > IgG) Inhibited by IFN-y (from Th 1 cell)

C D 8 Cytoxic T cells

• Bind MHC 2 on Virus Infected cellsKill virus-infected, neoplastic, and donor graft cells by inducing apoptosis by releasing cytotoxic granules containing preformed proteins perforin - helps to deliver the content of granules into target cell; Granzyme -a serine protease, activates apoptosis inside target cellGranulysin-antimicrobial, induces apoptosis).

• FAS –FAS LIGANDS INTERACTION

• Variable part of Light Chain and Heavy chain in Antibody structure

• Recognises antigens • Fc portion of IgM and IgG antibody structure • Fixes complement

Fc portion of antibody structure

• Determines isotype (IgM, IgD, etc.) Constant Carboxy terminal Complement binding at C H 2 (IgG + IgM only)Carbohydrate side chains Determines isotype (IgM, IgD, etc.)

• opsonization, and ADCC

FAB portion of antibody structure

• Antigen-binding fragment Determines idiotype: unique antigen-binding pocket; only 1 antigenic specificity expressed per B cell

• Agglutination, • Neutralization, • and blocking.

How are Immunoglobulin Isotypes formed?

• Mature B lymphocytes express IgM and IgD on their surfaces.

• They differentiate by isotype switching due to splicing of mRNA; mediated by cytokines and CD40 ligandTurn into plasma cells that secrete IgA, IgE, or IgG.

Immunoglobulin Isotypes IgM characteristics

• Fixes complement• Produced in the primary (immediate)

response to an antigen. • Antigen receptor on the surface of B cells.

Monomer on B cell or pentamer (pentamer shape allows it to efficiently trap free antigens out of tissue while humoral response evolves)

Immunoglobulin Isotypes IgM characteristics

• Fixes complementProduced in the primary (immediate) response to an antigen. Antigen receptor on the surface of B cells. Monomer on B cell or pentamer (pentamer shape allows it to efficiently trap free antigens out of tissue while humoral response evolves)

Immunoglobulin Isotypes IgG characteristics

• Fixes complementOpsonizes bacteriaMost abundant in blood. neutralizes bacterial toxins and virusesCrosses the placenta gives infants passive immunityMain antibody in secondary (delayed) response to an antigen

Immunoglobulin Isotypes IgA characteristics

• Stops attachment of bacteria & viruses to mucus membranesCrosses epithelial cells by transcytosisFound in breast milk colostrums, tears, saliva, mucusMonomer (in circulation) dimer (when secreted). Picks up secretory component from epithelial cells before secretion.

Immunoglobulin Isotypes IgE characteristics

• Binds mast cells and basophils it cross-links when exposed to allergen, mediating immediate (type I) hypersensitivity through release of inflammatory mediators such as histamine.Mediates immunity to worms by activating eosinophils.

Immunoglobulin Isotype IgD characteristics

• No function but along with IgM is found on B cells and serum

What is complement fixation?

• Part of humoral immunity and inflammationActivated by IgM and IgG in classic pathwayActivated by endotoxin and others in alternative pathway

• What are the two primary opsonins in bacterial defense? • I g G and C 3 B • What prevents complement activation of Self cells? • Decay Accelerating factor D A F and C 1 esterase inhibitor • Which components of the complement system cause viral

neutralisation? • C 1 C 2 C 3 AND C 4 • Which components of the complement system cause

Anaphylaxis? • C 3 a and C 5 a

• Which component of the complement system cause neutrophil chemotaxis.

• C 5 A • Which compoent of the complement system

cause cytolysis using the Membrane Attack complex?

• C 5 B 9 • C 1 Esterase inhibitor deficiency • Hereditary

angioedema.

• C 3 deficiency • recurrent pyogenic sinus and respiratory tract

infectionsIncreased type 3 hypersensitivity reactions.

• C 5 to C 8 deficiency causes what type of bacteremia?

• Neisseria bacteremia • Deficiency of D A F or G P I anchored enzyme

causes disease? • Complement-mediated lysis of RBCs leading to

paroxysmal noctumal hemoglobinuria

CYTOKINES

• What secretes the cytokine Interleukin 1? • Macrophages • What secretes the cytokine Interleukin 6 • Macrophages • What secretes the cytokine Interleukin 8 • Macrophages • What secretes the cytokine Interleukin 12 • Macrophages • What secretes the cytokine Tumor necrosis factor alpha? • Macrophages

• What secretes the cytokine Interleukin 2 • T- cells T H 1 • What secretes the cytokine Interleukin 3 • T-cells • What secretes the cytokine Interleukin 4 • T-cells T H 2 • What secretes the cytokine Interleukin 5 • T-cells T H 2 • What secretes the cytokine Interleukin 10 • T-cells T H 2 • What secretes the cytokine Interferon gamma • T- cells T H 1

What does Interleukin one do?

• Causes fever and is an endogenous pyrogenCauses acute inflammationActivates endothelium to express adhesion molecules causing chemokine secretion to recruit leukocytes.

• what does interleukin six do? • Causes fever and stimulates production

of acute-phase proteins. Also secreted by Th cells • What does IL-7 do?• lymphoid hematopoesis (BM + Thymus)• supports proliferation and differentiation of developing

lymphocytes in the primary lymphoid tissue

• What does interleukin eight do? • Causes chemotaxis of Neutrophils

• What does interleukin twelve do? • Activates Natural Killer cellsInduces

differentiation of T cells into T h 1 cells. Also secreted by B cells.

• What does tumor necorsis factor alpha do? • Mediates septic shock.

Activates endothelium. Causes leukocyte recruitment and vascular leak.s

• What does Interleukin three do? • Supports the growth and differentiation of

bone marrow stem cells

• What does interleukin two do? • Stimulates growth of helper and cytotoxic T

cells.

• what does interferon gamma do? • Activates macrophages and TH 1 cells.

Suppresses T h 2 cells. Has antiviral and antitumor properties.

• What does Interleukin four do? • Enhances class switching to I g E and I g G

Promotes growth of B cells. Induces differentiation into T h 2 cells

• What does Interleukin five do? • Enhances class switching to I g A

Promotes differentiation of B cells. . Stimulates the growth and differentiation of eosinophils

• What does Interleukin ten do? • Modulates inflammatory response

Inhibits actions of T cells and T h 1 T CellsActivates T h 2Also secreted by T cells.

• CD3 and CD28 are on what? • T cells • D80 and 86 are what? • B7 receptors - part of signal 2 for B

cell differentiation

• How do Interferons work? • They induce the production of a Ribonuclease

that inhibits viral protein synthesis by degrading viral mRNA but not host mRNA.Activates NK cells to kill virus-infected cells

• How does Interferon alpha and beta work? • These inhibit viral protein synthesis • How does interferon gamma work? • These increase both M H C's class expression

and increase antigen presentation by cells

What is type one hypersensitivity?

• Anaphylactic and atopicFree antigen cross-links IgE on presensitized mast cells and basophils, triggering release of vasoactive amines that act at postcapillary venules (i.e., histamine ). Reaction develops rapidly after antigen exposure due to preformed antibody.

• Test: scratch test and radioimmunosorbent assay.

What is type two hypersensitivity?

• Antibody and complement lead to membrane attack complex (MAC). Test: direct and indirect Coombs. Antibody mediated - I g M, I g G bind to fixed antigen on "enemy" cell, leading to lysis (by complement) or phagocytosis. 3 mechanisms: 1. Opsonize cells or activate complement 2. Antibodies recruit neutrophils and macrophages that incite tissue damage 3. Bind to normal cellular receptors and interfere with functioning

What is type three hypersensitivity?

• Immune complex-antigen-antibody (lgG ) complexes activate complement, which attracts neutrophils; neutrophils release lysosomal enzymes.It includes Serum sickness which is an immune complex disease in which antibodies to the foreign proteins are produced it takes 5 days.

• Immune complexes form and are deposited in membranes, where they fix complement and leads to tissue damage Also , arthus reaction antibody-mediated hypersensitivity reaction.

• Intradermal injection of antigen induces antibodies, which form antigen-antibody complexes in the skin. Causing edema, necrosis, and activation of complement.

What is type four hypersensitivity?

• Delayed T-cell-mediated type-sensitized T lymphocytes encounter antigen and then release lymphokines (leads to macrophage activation; no antibody involved. Transplant rejections, TB skin tests, Touching (contact dermatitis ). Test: patch test (e .g., PPO).

• What type of Hypersensitivity is Anaphylaxis? • Type one hypersensitivity • What type of Hypersensitivity is Asthma? • Type one hypersensitivity • What type of hypersensitivity is Rhinitis? • Type one hypersensitivity • What type of hypersensitivity is hay fever? • Type one hypersensitivity

• what type of hypersensitivity is eczema? • Type one hypersensitivity • What type of hypersensitivity is hives? • Type one hypersensitivity • What type of hypersensitivity is Hemolytic

anemia? • Type two hypersensitivity • What type of hypersensitivity is Pernicious

anemia? • Type two hypersensitivity

• What type of hypersensitivity is Idiopathic thrombocytopenic purpura ?

• Type two hypersensitivity • What type of hypersensitivity is Erythroblastosis

fetalis ? • Type two hypersensitivity • What type of hypersensitivity is Rheumatic fever ? • Type two hypersensitivity • What type of hypersensitivity is Bullous

pemphigoid ? • Type two hypersensitivity

• What type of hypersensitivity is Graves' disease ?

• Type two hypersensitivity • What type of hypersensitivity is Pemphigus

vulgaris ? • Type two hypersensitivity • What type of hypersensitivity is Myasthenia

gravis? • Type two hypersensitivity • What type of hypersensitivity is Acute

hemolytic transfusion reactions? • Type two hypersensitivity

• what type of hypersensitivity is Goodpasture's syndrome?

• Type two hypersensitivity • What type of hypersensitivity is SLE • Type three hypersensitivity • What type of hypersensitivity is Rheumatoid arthritis • Type three hypersensitivity • What type of hypersensitivity is Polyarteritis nodosum • Type three hypersensitivity • What type of hypersensitivity is Poststreptococcal

glomerulonephritis • Type three hypersensitivity

• What type of hypersensitivity is Serum sickness • Type three hypersensitivity • What type of hypersensitivity is Arthus reaction

(e .g., swelling and inflammation following tetanus vaccine)

• Type three hypersensitivity • What type of hypersensitivity is Hypersensitivity

pneumonitis or farmer's lung • Type three hypersensitivity • What type of hypersensitivity is Type One Diabetes

Mellitus? • Type four hypersensitivity

• What type of hypersensitivity is Multiple Sclerosis?

• Type four hypersensitivity • What type of hypersensitivity is Guillane barre

syndrome? • Type four hypersensitivity • What type of hypersensitivity is Hashimoto's

Thyroiditis? • Type four hypersensitivity • What type of hypersensitvity is Graft versus

Host Disease? • Type four hypersensitivity

• What type of hypersensitivity is the P P D test for tuberculosis?

• Type four hypersensitivity • What type of hypersensitivity is Contact

dermatitis • Type four hypersensitivity • What type of hypersensitivity is Poison Ivy? • Type four hypersensitivity • What type of hypersensitivity is Nickel

Allergy • Type four hypersensitivity

• What is the disease associated with Anti Nuclear A N A autoantibodies?

• Systemic lupus erythromatous but it is non specific • What is the disease associated with Anti double

stranded Anti d s D N A autoantibodies? • Systemic lupus erythromatous, it is specific • What is the disease associated with Anti Smith

autoantibodies? • Systemic lupus erythromatous,it is specific • What is the disease assocautoantibodies?

antibodies? • Drug induced lupus

• What is the disease associated with Anti I g G or Rheumatoid factor autoantibodies?

• Rheumatoid Arthritis • What is the disease associated with

Anticentromere autoantibodies? • Scleroderma CREST) • What is the disease associated with Anti D N A

topoisomerase one autoantibodies? • Scleroderma diffuse • What is the disease associated with

Antimitochondrial autoantibodies? • Primary biliary cirrhosis

• What is the disease associated with Antigliadin, antiendomysial autoantibodies?

• Celiac disease • What is the disease associated with Anti-

basement membrane • Goodpasture's syndrome

• What is the disease associated with Anti-desmoglein

• Pemphigus vulgaris Hashimoto's thyroiditis Polymyositis, dermatomyositis Sjogren's syndrome Sjogren's syndrome Mixed connective tissue diseasAutoimmune hepatitis Type I diabetes mellitus Wegener's granulomatosis Other vasculitides

• What is the disease associated with Antimicrosomal, antithyroglobulin

• Hashimoto's thyroiditis • What is the disease associated with Anti-Jo-1 • Polymyositis, dermatomyositis • What is the disease associated with Anti-S S-A

(anti-R o) Sjogren's syndrome • What is the disease associated with Anti-S S-B

(anti-L a) autoantibodies? Sjogren's syndrome • What is the disease associated with p-ANCA

autoantibodies? • Other vasculitides

• What is the disease associated with Anti-U1 R N P (ribonucleoprotein ) autoantibodies?

• Mixed connective tissue diseas • What is the disease associated with Anti-smooth

muscle autoantibodies? • Autoimmune hepatitis • What is the disease associated with Anti-glutamate

decarboxylase autoantibodies? • Type one diabetes mellitus • What is the disease associated with c-ANCA

autoantibodies? • Wegener's granulomatosis

• Graft Vs. Host Disease (GVHD) - In what type of situation would this occur?

• occurs when immunologically competent cells are transplanted into recipients who are immunologically compromised

• What are the three basic requirements necessary for a GVHD to develop?

• 1) transplant must have a functional cellular immune component2) recipient must have antigens foreign to the transplant3) recipient immunity must be compromised to the point where it can't destroy the transplanted cells

• What is the definition of an immunodeficiency disorder?

• an abnormality in one or more branches of the immune system that renders people susceptible to disease that can normally be prevented

• What are the two categories of mechanisms in immunodeficiency disorders?

• 1) humoral - antibody mediated (B lymphocytes)2) Cell-mediated (T lymphocytes and cytokines)

• What is Bruton's Agammaglobulinemia ? • An X-linked recessive disease caused by a

defective B T K tyrosine kinase gene. This defect prevents B-cell maturation and differentiation and defective opsonisation and ultimately DECREASES IN ALL Immunoglobulins(IgG, IgM, IgA, IgD and causes recurrent Bacterial infections soon after mother's IgG levels drops

what is hyper IgM syndrome?

• A disorder caused by a defective C D 40 L on helper T cells making them unable to class switch. There are Sever pyogenic infections early in life and I g M is very high but the other immunoglobulins are low

• Selective IgA deficiency • Anaphylaxis to IgA contained blood- never seen A,

will attack • Common Variable Immunodeficiency • 20-30s, giardiasis, normal # B cells, decreased Igs &

plasma cells • DiGeorge Syndrome • C- cardiac defects, A- abnorm. facies, T- thymus

aplasia, C- cleft palate, H- hypoCa, 22 deletion, failure 3rd & 4th pharyngeal pouches

• Job's Syndrome • No INF-gamma, no Nu chemotaxis, high IgE,

retained primary teeth, eczema, staph, pneumatocceles

• Severe Combined Immunodeficiency • defective IL-2 receptor(X), ADA deficiency(AR),

decreased T &B cells, all infections, bubble baby

• Ataxia Telangiectasia • AR, defect in kinase in cell cycle, TRIAD: ataxia,

telangiectasia, IgA & E deficiency

• Wiskott-Aidrich Syndrome • X, TRIAD: thombocytopenia, infection,

eczema, low IgM, increase risk lymphoma/leukemia

• Leukocyte Adhesion Deficiency • AR, defect integrin/CD18, no pus, delayed

separation of umbilical cord, decreased marginization, neutrophilia

• Chronic Granulomatous Disease • Lack NADPH oxidase, X, catalase + infections,

abnorm. NBT • Cediak-Higashi Syndrome • AR, microtubule dysfunction, pyogenic

infections, partial albinism, giant granules, NBT normal