immunology

DR ABDUL RASHID ARYAN

 Immunology
 Immune system
 Part of immune system
1. Cells ( macrophage , lymphocyte , APC and etc )
2. Tissue and organs
3. Protein and molecule ( cytokin and complements )
 immunity
Function of immune system

 To prevent or limit infection

 First line of defense (intact skin and mucus membrane )
 Second line of defense (neutrophil ,complement , macrophage , natural killer cell )(also
called innate immune system )
 Third line of defense (also called adaptive or specific immune system )
1. Cell mediated immunity
2. Antibody mediate( humoral ) immunity
Types of immunity

 Innate ( natural )
 Adaptive (acquired )
Innate immunity

 Non specific
 Barriers to infection (skin and mucus membrane )
 Certain cell (natural killer cell )
 Certain protein ( complement and interferon )
 Involved phagocytosis and inflammation
 Does not improve after exposure to the organism
 No memory
Note: main function of innate immune system killing microbe and activate adaptive immune
system
pathogenesis

 Pattern recognition receptor

1. RECEPTOR on the surface of cell
• Toll-like receptor
• Manan-binding lectin receptor
Toll-like receptor (TLR)

 Family of ten receptors

 Located on the surface of three type of cell
 Macrophage , dendritic cell and mast cell
 Recognize various microbial components and then activate transcription factors enhance
synthesis of proinflamatory cytokine
 Recognition pattern

 Endotoxin is a lipopolysaccharide LPS in gram negative bacteria it stimulate TLR4 It produce

cytokines such as IL1 IL6 IL8 and TNF
Co stimulatory protein , B7 to activate helper T cell and produce Ab
 Signal in gram positive bacteria stimulate TLR2
 Many bacteria and yeasts have polysaccharides called manan recognize by manan binding lectin MBL
and then activate complement system manan also act as opsonin
Adaptive (acquired )immunity

 Occurs after exposure to agent

 Improve by repeated exposure
 Mediated by
 Antibody produced B lymphocyte
 Two type of T lymphocyte (helper T lymphocyte , cytotoxic T cell )
 Have long term memory
 Can be active or passive
Note: macrophage and other APC play important role in adaptive and innate immune arm
Active and passive immunity

 Active immunity induce after contact with foreign antigen ( clinical or subclinical )
 Advantage ( resistance is long term )
 Disadvantage ( slow onset )
 Mediators ( Ab and T cell )
Passive immunity

 Based on Ab performing in other host

 Like Ab against diphtheria , tetanus and botulism
 Immediate onset but short life span

 Passive-active immunity
Antigen

 Molecule that react with antibody

 Immunogen ( that induce immune response )
 In most case Ag are immunogen ( except hapten )
 Hapten interact with Ab but not produce immunity because con not activate helper T cell
The feature of molecule that determine
immunogenicity

 Foreignness
 Molecular size ( most immunogen MW high then 10000 and bellow the 10000 are weakly
immunogen
 Very small one like one amino acid are non immunogen
 Hapten immunogen only bind with carrier protein
 Chemical structural complexity
 Antigenic determinates ( epitopes )
 Dosage , route and timing of Ag administration
 adjuvants
Primary and secondary response

 Primary response ( time to appear ab called lag period )

 Secondary response
Structure and function of antibody

 Protein that makes against antigen

 Antibody shape (Y )
 Have two chain light and heavy chain
Immunoglobulin G (ig G )

 Make 75% of all Ab

 Raise in secondary response of infection
 Defense against bacteria and virus
 Cross placenta
 High in the newborn from other ab
 Activate complement system
Immunoglobulin M (Ig M)

 Raised in primary infection

 Defense against bacteria and virus
 Activate complement system
 Don’t cross placenta
Immunoglobulin D

 Receptor in lymphocyte
 Make interaction between B and T lymphocyte
 It discovered new
Immunoglobulin E

 It role in type 1 hypersensitivity

 It defense against helminthes
 Don’t activate complement
 Don’t cross placenta
Immunoglobulin A

 It secrete in colostrum , saliva

 Don’t cross placenta
 Don’t activate complement
Origin of immune cells

 During in embryonic ( origin from fetal liver and yolk sac )

 Post natal the stem cell reside in BM
 Stem cell differentiated to erythroid , myeloid and lymphoid
 Origin of T cell

 T cell precursors differentiate into T Cell in thymus

 That stem cell before entering thymus have lack Ag receptors and lack CD3 CD4 CD8
protein on surface
 First ( double negative ( don’t have CD4 and CD8) )
 Then ( double positive)
 Then either CD4 or CD8
 Double positive differentiate in to CD4 if contact with cell to bring MHCII
 Double positive differentiate in to CD8 if contact with cell to bring MHCI
 If not contact then will killed (positive selection )
 double positive AND double negative Located I cortex of thymus
 Thymic education
 Clonal deletion ( those who bring antigen receptor for self protein )negative selection
done by autoimmune regulator (AIRE)
 IF mutation occur in AIRE gene brings autoimmune disease
Origin of B cell

 It differentiate in BM
 Also have clonal deletion which bring antigen receptor for self protein
Origin of natural killer cell

 is large granular lymphocyte

 Do not pass through thymus
 Don’t have antigen receptor
 Don’t bear CD4 or CD8 protein
 Recognize and kill target cell like virus infected cell , tumor cell
 Don’t required MHC protein
 Have CD16 and CD56 (CD16 for ab fc portion >>> antibody depended cell mediated
cytotoxicity
Origin of macrophage

 Arise from myeloid precursors  T and B lymphocyte proliferation

 Function  Also has proteolytic enzyme
 Phagocytosis  Role in delayed hypersensitivity
 Antigen presentation
 Don’t pass thymus
 Don’t have an antigen receptor
 Display MHC II on surface
 Also display MHC I on surface
Dendritic cell

 APC
 Type
 Inter digitating dendritic cell (dendritic cell ) :Located in skin , lymphoid tissue ,
interstatium , heart , lung ,
 Follicular dendritic cell : spleen and LN
T cell

 Divided in two categories

1. Regulatory or helper (CD4 positive ) which produce
 IL-2 which activate CD4 and CD8
 IL-4 which help B cell make Ab especially IgE
 Gamma interferon which enhance killing by macrophage
2. Effector or cytotoxic (CD8 positive ) which kill
 Virus infected cell
 Tumor cell
 allografts
immunofluorescence

 We can detect stain ab by this and can detect ag by this mechanism

B lymphocyte

 First discovers in bursa of fabricus

 B pro lymphocyte
 B pre lymphocyte
 B immature lymphocyte
 Mature B lymphocyte
 10-20% of blood lymphocyte
 activate by helper t cell
 igM igD receptor on surface
Major histocompatibility

 Also called HLA

Type

 Class I
 Cass II
 Class III
Class I

 Gene located in 6 number chromosome short arm

 Located in all nucleated cell also platelet
 Recognized by CD8 t cell
Class II

 Gene in 6 chromosome
 Located in APC
 Recognized by CD4
Diversity of MHC

 MHC class I present endogenous protein ( like virus induced , tumor cell , graft cell )
 MHC II present exogenous protein
Immune reaction control mechanism

 Tolerance : immune cell recognized our body tissue it self antigen

 Central T cell tolerance :- lym with receptor specific for self antigen are deleted at an
early stage in lymphoid cell development
 Peripheral t cell tolerance : - self react antigen delete out of thymus
 T regulatory cell
 Clonal anergy ( lack of co stimulation (B7 ))
 Peripheral delation ( by apoptosis )
B cell tolerance

 Central B cell tolerance

 Peripheral B cell tolerance
Cytokine

 Soluble chemical material called immune system messenger

 Activation , proliferation and differentiation on immune cell
 Cytokine signal to other cell ( autocrine , paracrine , endocrine )
5 type of cytokiene

 Interleukin
 TNF ( express adhesion molecule by endothelial )(increase vascular permeability , induce
fever )
 Interferons ( INF) >>( type 1)>>>produce by virally infected cell (affect surrounding cell
, degrade m RNA , Inhibit protein synthesis , express MHC ) type 2 >>>promote antiviral
state and activate macrophage , CD4
 Colony stimulating factor ( GM-CSF )
 Transforming growth factor ( TGF-beta ) inhibitory factor contral proliferation and
differentiation , help CD4 to become regulatory cell
Functional classification

 Interleukin-I ( from macrophage that activate helper T cell )

 Interleukin-II ( from Helper t cell that proliferate Helper and cytotoxic cell )
 Interleukin-IV (from CD4 proliferate b lymphocyte And secrete ig E )
 Interleukin 5 ( from CD4 differentiate B lymphocyte to plasma cell and and secrete ig A )
 Gamma interferon ( from CD4 activate macrophage and natural killer cell )
 TNF ( activate neutrophil in high intensity tumor necrosis )
Cytokine role in disease

 GCSF use in cancer

 TNF , IFN , IL2 in more diseases
 IL 1 and TNF also role in autoimmune disease
 Increase T lymphocyte ( role in leukemia , AIDS , rheumatoid arthritis and graft rejection
)
Complement

 Plasma protein
 20 type
 Make in liver
 Inactive in normal situation
 Complement activator ( immune complex , endotoxin , microbe cell membrane )
Complement activation pathway

 Classical pathaway
 Alternative pathway
 Manan binding lactin pathway
Biologic effect of complement

 Opsonization
 Chemotaxis
 Cytolysis
 Anaphylaxis
 Antibody production ( c3b )
Complement disease

 C1 inhebitir deffiency ( angioedema )

 MAC deffiency ( pathogen bacteria )
 Decrease complement protein ( alcoholic cirrhosis , viral cirrhosis )
 Incorrect blood transfusion
Hypersensitivity

 Type 1 hypersensitivity
 Pollen
 Dust
 Animal dander
 Mats
 Drugs
Clinical feature

 Local response
 Skin
 Lungs
 Nose
 Intestine
Systemic reaction

 Anaphylaxis
 Anaphylactic shock
 Release mediator and enter to blood
 Vasodilation
 bronchospasm
 Increase permeability
 Hypotension
The protective role of ig E
Type 2 hypersensitivity

 Complement depended reaction

 Direct lysis
 Opsonization
Example

 Blood transfusion reaction

 Autoimmune disease ( agranolocytosis , thrombocytopenia )
 Drugs like hapten ( hemolysis )
 Pimphigus vulgaris ( ab against epi desmosome )
 Good pasture syndrome
Anti body depended cell mediated cytotoxicity
( ADCC )

 Ig G
 NKC, monocyte , eosinophil
Antibody mediated cellular dysfunction

 Stimulation ( graves disease )

 Inhibition ( myasthenia gravis )
Type 3 hypersensitivity ( immune complex
mediated )

 Exogenous ag (staph , starp , hep B ,

 Endogenous ( nucleus , DNA , RNA )
Destruction type

 Leukocytoclasis
 Vascular fibrinoid necrosis
 Joint tissue distruction
Type of immune complex mediated disease

 Systemic immune complex disease ( serum sickness )

 Local immune complex disease ( arthus reaction )
Serum sickness

 Mske against othe rserum

 Satage
 Make ag ab complex in circulation
 Accumulation of immune complex
 Reaction
Example

 Polly arthritis nodusa

 SLE
 Post streptococcal glomeroloephritis ( sub epi hump )
 Rheumatic arthritis
Local immune complex

 Arthus reaction
 Like
 Hypersensitivity pneumonitis
Type 4 hypersensitivity ( cell mediatd reaction
)

 By T lymphocyte
 Type
 Delayed type 4 hypersensitivity
 Ag > macrophage > CD4 > memory t cell >then in other time ag > memory change to >
CD4 TH 1 > produce below cytokein
 Macrophage activating factor
 Macrophage chemotactic factor
 Macrophage inhibitory factor
 Macrophage fusing factor
Example

 Tuberculin test
 Skin reaction
 Granolomatus reaction
 Fungal infection
 Graft reaction
Cytotoxicity mediate to T lymphocyte

 Sensetive CD8 cell

 ( viral infected cell , tumor cell , graft cell )
 Cytotoxic by this way
 Perforin and cytolysin ( perforated membrane )
 TNF beta ( lemophotexin )
 Proteolytic enzyme
Auto immunity

 Loos Self tolerance called auto immune disease

 Criteria
 Sign of autoimmunity
 No secondary
 No known cause
Mechanisms that prevent from auto immunity

 Clone deletion
 Clone anergy
 Activation of Peripheral T suppresser cell
Etiology

 Genetic factor
 Some autoimmune seen in family member ( SLE , autoimmune thyroiditis )
 Auto immune have relationship with HLA class II
 HLA B27 gene problem ( ankylosing spondylitis found in ret when inoculate this
proliferative gene )
Microbial factor

 Bacteria and viral antigen cross reaction

 EBV > stimulate B lymphocyte bring auto antibody
 Microbial necrosis and inflammation breakdown the T cell anergy
Factor in autoimmunity

 Loos central tolerance

 Deactivation of T suppresser T lymphocyte
 Prolong activation of helper T cell
 Cross reaction
 Drugs and microbe change the self ag
By which mechanism

 auto antigen secretion

 Clone activation by EBV
 Aut antibody making
 Disturbance in clonal anergy
Type of autoimmune disease

 Organ specific autoimmune disease ( autoimmune thyroiditis )

 Systemic autoimmune disease
Systemic lupus errythromatosis

 Systemic disease
 Anti nuclear antibody (ANA )
Etiology and pathogenesis

 Drugs ( pencillamin , procainamide , hydralazine )

 UV
 Virus infection
 Estrogen
Kidney

 Class 1 : no change seen in microscope

 Class 2 : lupus mesengial glomerulonephritis
 Class 3 : proliferative glomerulonephritis
 Type 4 : diffuse proliferative glomerulonephritis
 Class 5 : membranous glomerulonephritis
Skin

 Butterfly erythromatosis
 Microscope : complement and immunoglobulin in epiderm and derm
 Epiderm Mono nuclear infiltration
 Joint : synovitis
 CNS : psychiatric feature ( from anti neuron antibody and or anti phaspolipid antibody )
 Serious membrane : fibrinoid necrosis and edema then fibrosis
 Spleen : large and fibrosis
 Heart : liban sacks endocarditis ( non bacterial endocarditis ) more involved mitral and
tricuspid bring vegetation ( fibroblast and fibnoid materials )
 Lung : pleuritis , interstitial pneumonitis , diffuse fibrotic alveolitis
Clinical feature

 Chronic disease
 Fever
 Organ involved related sign
 Leukopenia , thrombocytopenia and anemia ( antibody against blood part )
Discoid lupus errythromatosis

 Just skin related

 Ab against skin basement membrane
Sjogren disease

 Charectarized by
 Xerostoma
 Kerato conjunctivitis
 Immune against salivary and lacrimal gland
 40 % alone ( primary or sica syndrome )
 60% with other ( rheumathoid arthritis , SLE , scleroderma )
 Auto antibody aginst this part
 Morphology :
 Lymphocyte in periductal space
 Ductal Epithel hyperplasia
 Ductal obstruction
 Acini atrophy and fibrosis
Secondary change

 Dry nose
 Corneal ulcer
 Oral mucosa atrophy
 Dysphagia
 Larynx inflammation
 Bronchitis
 Pneumonitis
Scleroderma ( progressive systemic sclerosis )

 It is autoimmune disorder
 Systemic fibrosis disease more affect skin
 Progress to other organ like GIT , kidney , heart , muscle
 First start with hand finger skin ( raynod phenamona )
Change

 Scleroderma have two clinical syndrome deffuse and limited ( CREST )

 Defuse type
 Joint change ( like rheumatoid rthritis )
 Esophagus fibrosis ( dysphagia )
 Malabsorbtion
 Lung fibrosis
 H failure and arrhythmia
 Malignant HTN
 Renal fibrosis ( hypertension )
CREST syndrome(limited )

 Special character of scleroderma

 Calcinosis + rhaynoid + esophageal dysmotility + scleroductelia (FIBROSIS OF SKIN
OF HAND ) + telangectesia ( dilated capillary )
Pathogenesis

 Unknown
 More fibrosis ( more activate fibroblast )
 Factor role it
 Delayed hypersensitivity against collage fiber ( then secreate IL1 and TNFalfa then
increase collage synthesis )
 Ab against collagen
 Immune complex accumulation in vascular endothelial activate growth factor
Morphology

 Skin
 GIT
 Vessle
 Kidney
 Muscle
 Heart
 CNS
Polymyositis and dermatomyositis

 Chronic inflammation of muscle

 Weakness of muscle ( first in upper then lower )
 More activate muscle enzyme ( creatin kinase , aldolase )
 50% with other disease ( dermatomyositis , SLE , Progressive Systemic Sclerosis ,
breast , ovary and gastric cancer )
Feature of disease

 Raynode phenomena 1/3

 Skin atrophy and finger stiffnes
 Dysphagia ( swallowing muscle affect )
 Lung interstatial fibrosis
 More in 40-50 years
Pathogenesis

 Unknown but autoimmune involved also coxsaki-virus involved

 Anti nuclear antibody ( anti RNA more )
 Also cell mediated immunity ( CD4 , CD8 )
Morphology

 Muscle edema > then atrophy , fibrosis , fat accumulation

 T cell infiltration , breakdown sarcoplasmic reticulum , necrosis
Immune deficiency syndrome

 Primary
 Secondary ( infection , malnutrition , aging , drug , ))
X-linked ( bruton ) agamma glubulonemia

 Mutation in BTK ( bruton tyrosine kinase gene ) it change pro B lymphocyte to pre B
lymphocyte it found in X chromosome
 Ab deficiency disease
 Normal cellular immunity
 Symptom begin in 6 months of baby
Immune deficiency several type

 B Lymphocyte congenital defect : B LYMPHOCYTE count normal but don’t change to

plasma cell
 helper T cell deficiency and increase activity of T suppressor cell
 Auto antibody against B and T lymphocyte
Isolated IgA deficiency

 Familial
 Acquired : toxoplasmosis , measles , other virus
 No any specific clinic but recurrent respiratory infection occurs
 Some patient has anti B lymphocyte antibody
Digeorge syndrome or thymic hypoplasia

 Chromosome one part delation it related to TBX 1 gene ( gene for pharyngeal pouch 3 ,
4 ) pouch 3 for thymus and inferior parathyroid gland , 4 for sup parathyroid gland
 Thymic hypoplasia or aplasia ( lymphocyte deficiency )
 Parathyroid hypoplasia ( tetanic disease )
 Cardiac and large vesssle congenital abnormality ( truncus arteriosis , tetralogy of fallot )
 Dysmorphic face
 Nezelofs syndrome (thymus hypoplasia with out parathyroid involved )
Wiskot aldrich syndrome

 X-linked disease ( wiskot Aldrich protein connt function normally )

 All hematopoietic cell produce :WASP ( help recognized cell cytoskeleton ):
phagocytosis and cell devision , cell communication
 Eczema Thrombocytopenia immunedefficiency syndrome
 Repeat infection
 Regulator cell function also decreased
 Chance to lymphoma
 No lymphocyte in peripheral lymphoid tissue
 Cellular abnormality
Genetic deficiency of complement system

 C3 deficiency with bacterial infection

 C5 with nisseria infection
 c8 with auto immune disease
Secondary or acquired immune deficiency

 Malnutrition
 Infection
 Cancer
 Kidney disease
 sarcoidosis
 Immune depressor drugs
AIDS

 BY HIV virus
 Characters
 Immune deficiency
 Bring neoplasm
 Neural disorder
 First discover in America
 Now find in all over world
 22 million death from this disease
 35 million now affected
Transmission

 Sexual contact
 Parenteral way
 From mother to child
Sexual transmission

 HIV
 In semen
 Mono nuclear cell
VIRUS structure

 Retro RNA virus ( reverse transcription )

 Lipid bilayer envelop ( from host )
 Nucleus
 Capsid protein p24 ( detect in blood for diagnosis , also anti p24 antibody body make that
use in detection )
 RNA double copy
 Virus enzyme : protease , reverse transcriptase , antigrase
 Nucleus envolped by matrix protein called p17
 gp120 and gp41 glycoprotein located in lipid layer ( gp120 role in primary attachment and
secondary attachment )(gp41 role in virus fusing with host cell ) ( it is important for host
cell infection )
HIV gene

 Gag gene ( it coded p24 , p7 p17 )

 Pol gene ( it coded : reverse transcriptase , intigrase , protease )
 reverse transcriptase: it make DNA from RNA )
 Intigrase : fixed the viral DNA in host cell DNA
 Protease: breakdown the nonfunctional viral protein to the functional protein
 env gene : ( code the gp120 and gp41 )
 Also some other gene like net : that code kinase that breakdown that gene to code MHCI (
that decrease immune )
 Changed occurs and have variability the gp120 and gp41 that prevent from the vaccine
for HIV
HIV 1

 These type have also some other type like

 B type : more affect the macrophage and more live in anal by this case more in
homosexual people ( Europe and America )
 E type : more affected dendritic cell : more live in vagina by this case more in
heterosexual people ( Thailand )
Pathogenesis of immune system affection

 Affected the cell that are CD4+

 Helper T cell
 Dendritic cell
 Macrophage
 Monocyte
 Micro glia
How enter to the cell

 Enter by CD4 molecule

 Gp120 attache to the CD4 ( primary attachement )
 The gp120 another part attaché to the co-receptor ( chemokine like CCR5( located on
macrophage and monocyte ) and CXCR4(located in T cell) ) ( secondary attachment )
 Then pg41 fused with the host cell membrane and enter the nuclear material to the
cytoplasm
 Note : those who have mutation in chemokine receptor these are the resistance to HIV 20
% of America white race
 When enter to the cell then make the DNA from RNA
 Then DNA fused with host DNA ( integration )
 This structure called ( pro virus )
T cell in HIV

 Every day make 100 meliard nev virus

 Degrade 1-2 milliard CD4 t cell ( die by cytotoxic cell )( because the viral protein show
by MHCI )
Macrophage and monocyte in HIV

 Also affected the macrophage and monocyte by HIV

 reservoir for HIV
 HIV reached to the brain by these cell
Dendretic cell

 Langarhanse cell ( peripheral dendritic cell )

 Follicular dendritic cell ( spleen )
 Also affected
B and other lymphocyte in HIV

 More antibody in plasma

 Because
 More immune complex in blood
 Polyclonal activation ( EBV , CMV ) ( microbe directly proliferate and differentiate the B
cell )
 Gp41 can proliferate and differentiate the B cell
 Infected macrophage secrete more IL6 ( activate B cell )
 But this antibody cannot to control infection
Mechanism of CNS involvement

 Carried by infected monocyte ( to the monocyte related microglia )

 Neuron not affected by HIV
 Mediators( TNF ) that secrete by macrophage and microglia in CNS indirectly injury the
CNS
 Gp41 produce nitric oxide by neuron
HIV course

 Primary phase ( acute stage ) : 3-6 week after fever , throat pain , muscle pain some time
meningitis clinic
 Middle phase ( chronic stage ) : little viral control , immune system little normal but
virus are in the growth to take years
 Delayed phase ( crisis stage ) : looss the immune system , increase viremia , fever , loos
weight , fatigue and persistent diarrhea , neural clinic ,( CD4 decrease to 500/mcl )
Immune disorder in AIDS

 Lymphopenia ( CD4 )  Decrease IL 2 and gama interferon

 Decrease T cell function  Polyclonal B lymphocyte activation
 Loos memory  Change monocyte and macrophage function
 Appartunic infection
 Making Neoplasm
 Decrease delayed hypersensitivity
 Decrease cytotoxicity
 Decrease ab by helper cell
Clinic

 Last stage clinic ( crisis )

 Fever , weight loos , generalized lymphadenopathy , appartunic infectin , secondary
neoplasm , continue diiarhea
 Neoplasm : kapposi sarcoma , non hodjken lymphoma , cervical cancer
Kaposi sarcoma

 More common in AIDS

 More lesion and invasive
 Affected area : skin , GIT mucosa , LN , lungs
 Mono clonal
 More in homosexual
 Cause by Human herpes virus 8 in immunedefficiency
Non hodjken lymphoma

 No reed Stenberg cell

 More intensive
 Invaolve LN and brain , liver , GIT
Nerve system

 90 % in AIDS \
 Myelopathy , non infective meningitis , peripheral neuropathy , encephalopathy ,
demetia
Amyloidosis

 Is abnormal protein or misfold protein

 It accumulate in body tissue
 Tissue look glassy , homogenous and acidophilic
 Take brown color by lugols iodin stain and blue by sulphoric acid ( they think it is
starch ) because it name amyloid
 Show by electron microscope long and cross fiber
Chemical structure

 Immunoglobulin light chain ( amyloid light chain ) AL

 When make more antibody ( plasma cell dyscresia )
 Serum amyloid associated protein ( amyloid associated protein ) AA
 In chronic inflamtion
 Transthyretin : transporter for thyroxin and retinol
 It accumulate in old age and hereditary disease ( familial meditarian fever , familial
amyloid neuropathy )
 Beta 2 macroglobulin : part of MHC 1 molecule accumulate in synovial membrane and
carpal ligaments
 Beta amyloid protein ( A Beta ) : it derivative from tranasmembrane glycoprotein it
accumulate in basal nucleus in Alzheimer disease ( amyloid precursor protein )
 Precursor of some hormone : proinsulin
Classification of Amyloidosis

 Local amyloidosis
 Systemic amyloidosis
Systemic amyloidosis

 Immunocyte dyscaresia with amyloidosis (previos called primary amyloidosis )

 Disease : multiple myeloma , monoclonal beta cell proliferation
 Major fibrilin protein : AL
 Precorsure protein : Ig light chain ( more ig A )
Reactive systemic amyloidosis ( previously
called secondary )

 Disease : chronic inflammatory condition ( acute phase reactant )

 Major fibrilin protein: AA ( amyloid associated protein )
 Protein precursor : Serum amyloid associated protein (SAA )
Hemodialysis associated amyloidosis

 Disease : chronic renal failure

 Major fibrilor protein : A beta 2m (Beta 2 macroglobulin )
 Protein precursor : Beta 2 macroglobulin
Hereditary amyloidosis

 Major fibrilor protein :Amyloid protein

 Serum amyloid associated protein (SAA )
( familial meditarian fever , familial amyloid
neuropathy

 Major fibrilor protein : abnormal Transthyretin

Systemic senile amyloidosis

 Major fibrilor protein :normal Transthyretin

Local amyloidosis

 Senile cerebral amyloidosis

 Disease : Alzheimer disease
 Major fibrilor protein :Beta amyloid protein ( A Beta )
Endocrine

 Disease : Type 2 diabetes

 Major fibrilor protein : islet amyloid peptide
Isolated atrial amyloidosis

 Major fibrilor protein : atrial natriuretic factor

Morphology

 First degree :involve spleen , liver , kidney

 Second degree : involve thyroid , adrenal gland , lymphatic tissue
 Third grade : involve myocard , pancreas
 Rare : skin

 When involve organ : organomegally , pale , waxy , glassy appearance

 Satin by : congro red stain ( mic >> pink ) ( EM >>> green )
 Accumulate near to the basement membrane like nodule
Organ pathologic feature in amyloidosis

 Spleen :
 Accumulate in follicle >>> splenomegaly >>> called sago spleen
 Accumulate in sinusoid and pulp like sheath >>>> lardaceous spleen

 Liver : 900 gr weight , pale , waxy

 Accumulate in dessi space >> then sinusoid >> then all parenchyma >>> cell necrosis
 Kidney : accumulate in glomerulus >>> ischemia >> atrophy >> amyloid nephrosis

 Heart : more senile and immunocyte dyscaresia >> cardiomegaly >> restrictive heart
failure
Classification according to primary and
secondary

 Primary ( unknown cause ) : more in tongue , esophagus , nerve , intestine , skin

 Secondary : ( chronic supportive inflammation )

Pathogenesis

 Systemic reactive amyloidosis : chronic inflammation >>> macrophage activation

secarete >>> IL1 , IL6 >> stimulate liver >>> make serum associated amyloid ( SAA )
in normal situation it degrade by monocytic enzyme

 Immunocyte dyscresia : multiple myeloma >>> more plasma cell >>> amyloidosis
Diagnosis

 Congo red stain

 Biopsy from rectum , gingival

Tumor immunology

 It is a branch of pathology
 To detect role of immune system in neoplasm
 Immunotherapy
Tumor antigen

 Tumor cell secrete antigen that different from self ag immune system react with it
 Tumor ag type
 Tumor specific ag ( TSA) : just found in tumor cell not on normal cell ( like melanoma
associated ag )
 Tumor associated ag ( TAA ) : tumor cell and normal also have ( like prostatic specific ag )
 Oncofetal ag : found in embryo and fetus (also in some cancer )
 Carcino embryonic ag : derived embryo endodermal ( in tumor that arise from embryonic
three layer like colon cancer )
 Alfa fetoprotein : yalk sac and fetal liver ( adult liver carcinoma , gonadal carcinoma )
Para neoplastic syndrome

 A set of sign and symptom that can occurs when you have cancer
 Change in your body that arnt directly caused by the cancer itself
 Tumor may secrete hormone that affect the body
Limitation of the effective immunological
response

Immune response
 Natural killer cell : work against tumor cell
 Cytotoxic T lymphocyte : kill tumor cell
 T cell >>> gama interferon >>> macrophage >>> work against tumor cell
 Humoral mechanism : activation of complement system , antibody depended cytotoxicity
Tumor cell affect the immune system by this
way

 Tumor ag >>>> clone deletion

 Decrease or absent MHC protein
 Decrease co stimulation ( clone anergy )
 Production of tumor cell decrease immune response ( transforming growth
factor(regulatory cytokein) )
 Also radiation decrease immune response
 Tumor cell expressed ligand for fas receptor
Tumor immune diagnosis

 Immunohistochemeical test ( That exploit the specific binding between an ab and ag to detect and
localized antigen )
 DNA probe analysis ( are single stranded sequences of DNA used to search for its complementary
sequences )
 DNA flow cytometry ( analysis material of DNA )
 Serologic test : tumor antigen detect
• Carcino embryonic antigen ( for colon and rectum cancer relapse )
• Alfa fetoprotein : for liver and gonadal cancer and it response to drugs
• Prostatic acid phosphatase ( increase level in prostate cancer )
• Human chorionic gonadotropin HCG : increase in gonadal and plasma cell multiple myeloma
Immune therapy

 Immune depressor product

 Immune stimulator product
Tumor activity suppressor immune therapy

 IL-2 activated cytotoxic T cell >>> activate NK CELL

 Anti tumor antibody and toxin
 Block check point protein
Tumor therapy by antibody

 Ant idiotype antibody against B cell tumor >> CLL

 Epedermal growth factor recptor ab
Infection disease

 More disease that come from infection more are deadly

defense against infection

 Skin
 keratin is physical barrier
 Acdity >>> PH 5.5 , also fatty acid prevent microbe callonization
 Bacteria that have collagenase and elastase can break the skin
 Urinary system
 Respiratory system : mucus , cilia , hair (foreign body more then 6 mcm ) , sneezing ,
cough , macrophage
 GIT : mucus , HCL , pancreatic enzyme , bile , secretory ab , normal flora
Microbial thing that prevent from immune
system

 Toxins : exotoxins and endotoxin

 Exotoxins : are protein secrete from microbe work like enzyme like ( batulinium >>>
block the cholinergic neurotransmitter release bring >>> flaccid paralysis , tetanus >>>>
block the inhibitor neurotransmitter >>>>> bring spastic paralysis

 Endotoxins : make from lipid and polysaccharide not work like enzyme not secrete from
microbe , located in gram - bacteria
Adhesive factor

 Adhesive factor specific for specific body part

 Pilli
 Gelatin matrix
Protective cover

 Capsule
 Cell membrane
 Staph areus >>>> make >> protein A ( surface protein ) >>> protect from IgG
 Hemophelius influenza and Neisseria gonorrhea >>>> secrete enzyme >>> deactivate
protective defense
Invasive factor

 Phospholipase
 Collagenase
 Elastase
 Protease
Principle of immunization

 Immunization >>> type ( passive and active )

 Passive immunization : gamma globulin
 Active immunization : microbial part