Kuliah Keperawatan

Departemen Patologi Anatomi Fakultas

Kedokteran Universitas Sumatera Utara
Medan - 2012
 INNATE & ADAPTIVE IMMUNITY

Innate immunity (Alami / native)

• Diperantarai oleh:
• Sel (neutrofil & makrofag)
• NK cell
• Protein plasma

Adaptive immunity (Didapat /spesifik)

• Limfosit & produknya

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Mekanisme imunitas ‘innate’ & ‘adaptive’

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Adaptive immunity (Didapat / spesifik , immunity)

2 jenis respons imun adaptasi

Humoral immunity

• Diperantarai oleh : protein Ab yang terlarut

• Dihasilkan oleh limfosit B

Cell-mediated (cellular) immunity

• Diperantarai oleh limfosit T

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 Figure 5-2. Humoral & cell-mediated immunity

Imunitas Humoral:
Ab disekresi oleh limfosit B
Untuk mengeliminasi
mikroba ekstraselular

Imunitas yang diperantarai

sel:
Limfosit T mengaktifkan
makrofag (memfagosit
mikroba) / membunuh sel
yang terinfeksi.

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 Sel sistem imun
PMN & makrofag
 Sel fagositik yang relatif primitif
 Bagian dari respon non-spesifik patogen (innate
immunity, natural immunity)

Makrofag
• Juga berfungsi sebagai ‘antigen-presenting’ khusus
dalam meresponi patogen & antigen (acquired
immunity)

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 … Sel sistem imun
Limfosit :
• Komponen utama dalam sistem imun yang didapat
• Tdd. :
– Limfosit T
• Th1 (IFN-g ; IL-2 - CMI)
• Th2 (IL-4, 5 & 10)  respons alergi
– Limfosit B
– Natural Killer (NK) Cells

Monosit/Makrofag

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 Limfosit
Peripheral smear, Wright-Giemsa stain.

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… Lymphocytes

• Dapat mengenal Ag spesifik, bila tertampil

pada permukaan sel [surface of antigen
presenting cells (APC)], yang dihubungkan
dengan major histocompatibility (MHC)
antigens.
– Sel CD4+  hanya mengenal Ag MHC class II
– Sel CD8+  hanya mengenal Ag MHC class I

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… Lymphocytes

• T-cell receptor (TCR) mengenal epitopes

linear, yang ditampilkan oleh APC
– Dibutuhkan ‘2nd signal’ untuk mengaktivasi,
dikirim oleh molekul CD28 pada sel-T yang terikat
pada molekul B7-1 dan 2 APC

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… Limfosit

• Petanda permukaan sel [Cell surface

markers (cluster designations)] dapat
ditentukan secara klinik dengan
menggunakan flow cytometer.
• Secara klinik sel-T penting, terutama :
– Pan-t markers (CD3)
– Suppresser/Killer T-cells (CD8)
– Helper T-cells (CD4)
– Stem cell markers (CD34, others)

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Flow Cytometer

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 Makrofag (histiosit)
• The primary APC  sel-sel lainnya (sel
langerhans, sel endotel)
• Dulu : RES (reticuloendothelial system)
• Sekarang : mononuclear phagocytic system
• Tampilan Class II MHC antigen, complexed with
processed, exogenous, particulate antigen
(aggretope).

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 Monosit

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Makrofag/Histiosit

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 Immunopathology
Tingible Body Macrophage/Histiocyte

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Immunopathology
Antigen Presenting Dog

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 Immunopathology
Designated Killer (or Natural Killer)

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 Immunopathology
Sitokin
• Menghasilkan beberapa jenis sel
• Dapat mempengaruhi berbagai jenis sel yang
berbeda (pleiotrophic)
• Merangsang efek melalui mekanisme
autokrin, parakrin, atau endokrin
• Berikatan terhadap specific high-affinity
receptors dan sel affect via mekanisme
transduksi

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 Immunopathology
Major Histocompatibility Complex (MHC)
• Human MHC atau human leukocyte antigen
(HLA) locus, suatu seri gen pada lengan
pendek kromosom 6 yang mengkode Ag
pertama yang tersibak pada leukosit, namun
ternyata dijumpai pada semua sel.

• Antigen ini menentukan histocompatibility,

penting untuk transplantation.
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 Immunopathology
MHC (continued)
• Class I antigens - first to be discovered, most
important in transplantation. On the surface
of all cells.
• Class II antigens - expressed primarily on
macrophages and B cells.
• Class III antigens - actually components of
complement, not MHC antigens.

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 Immunopathology
MHC (continued)
• Class I antigens
– Consist of the A, B, and C loci on chromosome 6.
– Alleles are co-dominantly expressed, so you have
class I antigens from both parents.
– These antigens are recognized by cytotoxic CD8+ T-
cells, and are therefore important in tissue cross-
matching to prevent graft rejection in the case of
transplantation. They are present on all nucleated
cells and platelets.

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 Immunopathology
MHC (continued)
• Class II antigens
– Consist of at least 3 loci in the D region: DP, DQ,
and DR. Like class I antigens, they are expressed
co-dominantly.
– Important in immune cell interaction, they are
found mainly on APCs, and interact with CD4+ T-
cells.
– Recognize exogenous antigens

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 Diseases of IMMUNITY

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 OBJECTIVES

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 Differentiate and give examples of the four (4) different types of
hypersensitivity reactions

Know the common features of autoimmune diseases

Know 4 main features (Etiology, Pathogenesis, Morphology, and Clinical

Expression) of SLE, RA, Sjögrens, Systemic Sclerosis (Scleroderma), Mixed
Connective Tissue Disease, and “Poly-” (aka, “Peri-”) -arteritis Nodosa

Differentiate between Primary (Genetic) & Secondary (Acquired)

Immunodeficiencies
Understand 4 main features of AIDS, i.e., etiology, pathogenesis, morphology,
clinical expression

Understand 4 main features of Amyloidosis

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 IMMUNITY

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 IMMUNITY
INNATE
ADAPTIVE
(“NATURAL”)
• Present before • Developed by
birth exposure to
pathogens, or

• In a broader sense,
antigens

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 IMMUNITY SYSTEM DISORDERS

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 WHAT CAN GO WRONG?
Hypersensitivity reactions (I – IV)

“Auto”immune diseases

• “Collagen” diseases (bad term)

Immune deficiency syndromes (IDS):

• Primary (Genetic)
• Secondary (Acquired)

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 HYPERSENSITIVITY
REACTIONS

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 What is the pathogenesis of hypersensitivity
reactions ?
In certain individuals:
Repated exposure to a specific Ag leads to

Adverse Reactions
(hypersensitivity)

Induction of a
protective immune
response (immunity)

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 HYPERSENSITIVITY REACTIONS (4)

I • Immediate Hypersensitivity

II • Antibody Mediated Hypersensitivity

III • Immune-Complex Mediated

Hypersensitivity

IV • Cell-Mediated Hypersensitivity

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 Type I
IMMEDIATE HYPERSENSITIVITY

“Immediate” Seconds to Minutes

Most immediate hypersensitivity reactions are

mediated by IgE antibodies

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… Type I Immediate hypersensitivity
1) Allergen exposure

2) IMMEDIATE phase:

• MAST cell degranulation,

“Immediate Allergic vasodilatation, vascular leakage,
smooth muscle spasm
Reactions”
3) LATE phase (hours, days):

• Eosinophils, PMNs, T-Cells

May lead to

Anaphylaxis Shock
Edema
Dyspnea
Death

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 Immediate
Hypersensitivity

A. Kinetics of the immediate & late-

phase reactions.

B. Late phase reaction, characterized

by vasodilation, congestion,
edema

C. Characterized by inflammatory
infiltrate :
• Eosinophils
• Neutrophils &
• T - cells

(Courtesy of Dr. Daniel Friend, Department of

Pathology, Brigham and Women's Hospital, Boston,
MA.)

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 Pathogenetic mechanisms tissue
destruction in hypersensitivity:

Type I

• Release of vasoactive & spasmogenic

mediators of inflammation

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 … Pathogenesis of immediate (type I)
Hypersensitivity Reaction

The late-phase reaction is

dominated by:
• Leukocyte infiltration
• Tissue injury

TH2, T-helper type 2 CD4

cells.

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 Pengaktifasian sel
mast dalam
‘immediate
hypersensitivity’ dan
pelepasan mediator

• ECF, eosinophil chemotactic

factor
• NCF, neutrophil chemotactic
factor
• PAF, platelet-activating factor.

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Immunopathology
Type I reaction - asthma

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Immunopathology
Type I reaction - asthma

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 TYPE II HYPERSENSITIVITY
ANTIBODY MEDIATED IMMUNITY
Ab attach to cell surfaces

OPSONIZATION
• Basting the turkey

PHAGOCYTOSIS

COMPLEMENT FIXATION
• Cascade of C1q, C1r, C1s, C2, C3, C4, C5…..

LYSIS
• Destruction of cells by rupturing / breaking of the cell membrane

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 Pathogenetic mechanisms tissue
destruction in hypersensitivity:

Type II

• Binding Ab – Ag on the cell surface,

predisposing to lysis of phagocytosis

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 Effector mechanisms of antibody-mediated injury

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 TYPE II DISEASES
Goodpasture
Idiopathic
Autoimmune Syndrome
Thrombocyto- Rheumatic Myasthenia Pernicious
Hemolytic (Nephritis & Graves Disease
penic Purpura Fever Gravis Anemia (PA)
Anemia (AHA) Lung
(ITP)
Hemorrhage)

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 TYPE III HYPERSENSITIVITY
IMMUNE COMPLEX MEDIATED

Antigen / Antibody “Complexes”

Kidney (Glomerular
Blood Vessels
Basement Membrane)

Skin Joints

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 Pathogenetic mechanisms tissue
destruction in hypersensitivity:

Type III

Formation Ag-Ab complexes capable

activation the complement system

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 Common Type III Diseases
Post strep
Poly (Peri) tococcal Arthus Serum
SLE (Lupus) arteritis reaction sickness
Nodosa Glomerulo (hrs) (days)
nephritis

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 TYPE IV HYPERSENSITIVITY
CELL-MEDIATED (T-CELL) DELAYED HYPERSENSITIVITY

Tuberculin Skin Reaction DIRECT ANTIGEN

Cell contact

• Granuloma
formation
• Contact dermatitis

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 Pathogenetic mechanisms tissue
destruction in hypersensitivity:
Type IV
Sensitization T lymphocytes after reaction with Ag
 leading ‘granulomatous reaction’
 initiated by :
 CD4+ lymphocyte sensitization /
 CD8+ killing of Ag-bearing cells

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 SUMMARY

Antibodies directed
Acute allergic
against cell
reaction
surfaces

Delayed
Immune complexes Hypersensitivity,
e.g., Tb skin test

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 RENAL
TRANSPLANT REJECTION

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 HYPERACUTE (minutes) :

• AG/AB reaction of vascular endothelium

ACUTE (days  months):

• Cellular ( INTERSTITIAL infiltrate ), and

• Humoral ( VASCULITIS )

CHRONIC (months):

• Slow vascular fibrosis

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ACUTE CELLULAR (T) ACUTE HUMORAL

CHRONIC
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 AUTO-IMMUNE DISEASES

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 • Self recognition
Failure of : • Self tolerance

• Central (Death of Self Reactive Lymphocytes)

Tolerance • Peripheral (energy, suppression by T-cells, deletion by
apoptosis, sequestration [Ag masking])

Strong : • Genetic predisposition

Often related to : • Other autoimmune diseases

Often triggered by : • Infections

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 CLASSIC AUTOIMMUNE DISEASES
(SYSTEMIC)

Systemic Lupus
Rheumatoid arthritis
Erythematosus (SLE)

Systemic Sclerosis
Sjögren syndrome
(scleroderma)

“Collagen” diseases
(term no longer used)

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 CLASSIC AUTOIMMUNE DISEASES
(LOCAL)
Autoimmune hemolytic
Hashimoto thyroiditis
anemia

Multiple sclerosis Autoimmune orchitis

Autoimmune
Goodpasture syndrome
thrombocytopenia

Insulin dependent diabetes

“Pernicious” anemia
mellitus

Myasthenia gravis Grave’s disease

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 LUPUS (SLE)

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 LUPUS (SLE)

• Antibodies (ABs) directed against the patient’s own

Etiology: DNA, HISTONES, NON-histone RNA, and NUCLEOLUS

• Progressive DEPOSITION & INFLAMMATION to immune

Pathogenesis: deposits in : skin, joints, kidneys, vessels, heart, CNS

• “Butterfly” rash, skin deposits, glomerolunephritis

Morphology: (NOT discoid)

Clinical • Progressive renal and vascular disease

expression: • A.N.A. (+)

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 SLE, SKIN SLE, GLOMERULUS

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 TABLE 6-10 -- Clinical and Pathologic Manifestations of Systemic
Lupus Erythematosus
Prevalence in
Clinical Manifestation Patients, %
Hematologic 100
Arthritis 90
Skin 85
Fever 83
Fatigue 81
Weight loss 63
Renal 50
Central nervous system 50
Pleuritis 46
Myalgia 33
Pericarditis 25
Gastrointestinal 21
Raynaud phenomenon 20
Ocular 15
Peripheral neuropathy 14

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 MORE SYSTEMIC AUTOIMMUNE
DISEASES

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 MORE SYSTEMIC AUTOIMMUNE
DISEASES

RHEUMATOID
SJÖGREN SYNDROME
ARTHRITIS

SCLERODERMA
(SYSTEMIC SCLEROSIS)

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 Destructive Rheumatoid
Synovitis

NORMAL Bi-Layered
Synovium

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 SJÖGREN SYNDROME
Keratoconjunctivitis “sicca” (i.e., “dry”) is another name for
Sjögren Syndrome

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 Normal salivary gland

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 SJÖGREN SYNDROME

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 SCLERODERMA
(SYSTEMIC SCLEROSIS)

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 SYSTEMIC SCLEROSIS
(SCLERODERMA)

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 MORE AUTOIMMUNE DISEASES
(LOCAL)
Hashimoto Thyroiditis Autoimmune Hemolytic Anemia

Multiple Sclerosis Autoimmune Orchitis

Autoimmune
Goodpasture Syndrome
Thrombocytopenia (ITP)

Insulin Dependent Diabetes

“Pernicious” Anemia
Mellitus (I)

Myasthenia Gravis Graves Disease

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 IMMUNODEFICIENCIES

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 PRIMARY SECONDARY
(GENETIC) (ACQUIRED)

IMMUNODEFICIENCIES

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 PRIMARY
• CHILDREN with repeated, often severe infections, cellular
AND/OR humoral immunity problems, autoimmune defects
• BRUTON (X-linked agammaglobulinemia)
• COMMON VARIABLE
• IgA deficiency
• Hyper IgM
• DI GEORGE (THYMIC HYPOPLASIA) 22q11.2
• SCID (Severe Combined Immuno Deficiency)
• ….with thrombocytopenia and eczema (WISKOTT-ALDRICH)
• COMPLEMENT DEFICIENCIES

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 ADA (Adenosine
De-Aminase

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 Examples of Infections in Immunodeficiencies
Granulocyte
Pathogen Type T-Cell-Defect B-Cell Defect Defect Complement Defect
Bacteria Bacterial sepsis Streptococci, Staphylococci, Neisserial infections,
staphylococci, Pseudomonas other pyogenic
Haemophilus bacterial infections

Viruses Cytomegalovirus, Epstein- Enteroviral

Barr virus, severe varicella, encephalitis
chronic infections with
respiratory and intestinal
viruses

Fungi and parasites Candida, Pneumocystis Severe intestinal Candida,

carinii giardiasis Nocardia,
Aspergillus

Special features Aggressive disease with Recurrent

opportunistic pathogens, sinopulmonary
failure to clear infections infections, sepsis,
chronic meningitis

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 AIDS (SECONDARY IDS)
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ETIOLOGY

HIV

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 EPIDEMIOLOGY Pathogenesis Morphology

• Homosexual (40%, • Infection • Clinical Expressions

declining) • Latency • Infections
• Intravenous drug • Progressive T-Cell • Neoplasms
usage (25%) loss • Progressive
• Heterosexual sex Immune Failure
(10%, rising) • Death
• HIV+
• HIV-RNA (Viral
Load)

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 PATHOGENESIS

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… Pathogenesis

ATTACHING BUDDING

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… Pathogenesis
Early budding Late budding

Mature new virions

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 REVERSE TRANSCRIPTASE
Retroviruses
Single-stranded RNA genome
Enzyme reverse
transcriptase (RT) Transcribe

And to subsequently Single-stranded DNA

construct a complementary
strand of DNA

Providing ‘DNA double helix’ capable of

integration into host cell chromosomes.

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… Pathogenesis

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 … Pathogenesis
1. Primary infection

2. Lymphoid infection

3. Acute syndrome

4. Immune response

5. Latency

6. AIDS
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 GENERAL IMMUNE ABNORMALITIES

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… GENERAL IMMUNE ABNORMALITIES

Lymphopenia

Decreased T-cell function

B-cell activation, polyclonal

Altered monocyte/macrophage function

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 INFECTIONS
• Cryptosporidium
Protozoal/Helminthic • PCP (Pneumocystis Carinii Pneumonia)
• Toxoplasmosis

• Candida
Fungal • The usual 3

• TB
Bacterial • Nocardia
• Salmonella

• CMV
Viral • HSV
• VZ

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 CASEATING GRANULOMA

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 CANCERS OF AIDS

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 CANCERS of AIDS
CERVIX
KAPOSI B-CELL CNS CANCER,
SARCOMA LYMPHOMAS LYMPHOMAS SQUAMOUS
CELL

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 AMYLOIDOSIS

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 AMYLOIDOSIS
Buildup of amyloid Where? BLOOD
“PROTEIN” VESSEL WALLS, at first
• AL (Amyloid Light • KIDNEY
Chain) • SPLEEN
• AA (NON- • LIVER
immunoglobulin • HEART
protein)
• Aß (Alzheimer’s)

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CONGO RED STAIN, WITHOUT,
and WITH POLARIZATION
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 AMYLOID ASSOCIATIONS
Plasma cell “DYSCRASIAS” Chronic granulomatous
• e.g., multiple myeloma disease
• e.g., TB

Hemodialysis Heredofamilial

Endocrine MEAs
(Multiple
Localized Aging
Endocrine
Adenomas)

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 THANK YOU
Selamat Belajar

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