View
253
Download
0
Category
Preview:
Citation preview
8/8/2019 Ch6 Immune
1/81
Diseases of IMMUNITY
8/8/2019 Ch6 Immune
2/81
OBJECTIVES Differentiate between the concepts of
Innate and Adaptive immunity
Visually recognize and understand the basic
roles of lymphocytes, macrophages,dendritic cells, NK cells
Understand the roles of the major cytokines
in immunity Differentiate and give examples of the four
(4) different types of hypersensitivity
reactions
8/8/2019 Ch6 Immune
3/81
OBJECTIVES Know the common features of autoimmune
diseases, and the usual four (4) mainfeatures (Etiology, Pathogenesis,Morphology, and Clinical Expression) of
Systemic Lupus Erythematosus,Rheumatoid Arthritis, Sjgrens, SystemicSclerosis (Scleroderma), Mixed Connective
Tissue Disease, and Poly- (aka, Peri-) -arteritis Nodosa Differentiate between Primary (Genetic) andSecondary (Acquired) Immunodeficiencies
8/8/2019 Ch6 Immune
4/81
OBJECTIVES Understand the usual four (4) main features
of AIDS, i.e., etiology, pathogenesis,morphology, clinical expression
Understand the usual four (4) main featuresof Amyloidosis
8/8/2019 Ch6 Immune
5/81
IMMUNITY INNATE (present beforebirth, NATURAL)
ADAPTIVE (developedby exposure to pathogens,or in a broader sense,antigens)
8/8/2019 Ch6 Immune
6/81
MHC
MajorHistocompatibility Complex A genetic LOCUS on Chromosome 6,
which codes for cell surface compatibility Also called HLA (Human Leukocyte
Antigens) in humans and H-2 in mice
Its major job is to make sure all self cellantigens are recognized and tolerated,because the general rule of the immunesystem is that all UN-recognized cells will
NOT be tolerated
8/8/2019 Ch6 Immune
7/81
INNATE IMMUNITY BARRIERS
CELLS: LYMPHOCYTES,MACROPHAGES, PLASMA CELLS,
NK CELLS
CYT
OKIN
ES/CHE
MO
KINES
PLASMA PROTEINS:Complement, Coagulation Factors
Toll-Like Receptors, TLRs
8/8/2019 Ch6 Immune
8/81
ADAPTIVE
IMMUNITY
CELLULAR, i.e., directcellular reactions toantigens
HUMORAL, i.e.,
antibodies
8/8/2019 Ch6 Immune
9/81
8/8/2019 Ch6 Immune
10/81
CELLS of the IMMUNESYSTEM
LYMPHOCYTES, T
LYMPHOCYTES,B
PLASMA CELLS(MODIFIED BCELLS) MACROPHAGES, aka HISTIOCYTES,
(APCs, i.e., Antigen Presenting Cells)
DENDRITIC CELLS (APCs, i.e., AntigenPresenting Cells)
NK (NATURAL KILLER)CELLS
8/8/2019 Ch6 Immune
11/81
L
Y
M
P
H
S
8/8/2019 Ch6 Immune
12/81
8/8/2019 Ch6 Immune
13/81
ANY ROUND CELL WITH RATHER
DENSESTAINING NUCLEUS AND
MINIMAL CYTOPLASM INCONNECTIVE TISSUE, A BIT
BIGGER THAN AN RBC, IS A
LYMPHOCYTEUNTIL PROVEN OTHERWISE
8/8/2019 Ch6 Immune
14/81
MACROPHAGE
aka
HISTIOCYTE
8/8/2019 Ch6 Immune
15/81
MACROPHAGES are
MONOCYTES that have come
out of circulation and have
gone into tissue
8/8/2019 Ch6 Immune
16/81
MACROPHAGES, TEM, SEM
8/8/2019 Ch6 Immune
17/81
ANY CELL MIXED IN WITH LYMPHOCYTESBUT HAS
A LARGER MORE OPEN, LESS DENSE, LESS
CIRCULAR NUCLEUS WITH MORECYTOPLASM IS A
MAC
RO
PHAGE
UNTIL PROVEN OTHERWISE
ALMOST ALL GRANULAR or PIGMENTEDCELLS IN CONNECTIVE TISSUE ARE
MACROPHAGES. GRANULOMAS, GIANT CELLS,
ARECHIEFLY MACROPHAGES ALSO.
8/8/2019 Ch6 Immune
18/81
1) ROUND NUCLEUS
2) OVOID CYTOPLASM
3) PERIPHERAL CHROMATIN
4) CLEAR ZONE BETWEEN NUCLEUS AND WIDER LIP OF
CYTOPLASM
PLASMA CELLS
8/8/2019 Ch6 Immune
19/81
8/8/2019 Ch6 Immune
20/81
NKCE
LLS
8/8/2019 Ch6 Immune
21/81
8/8/2019 Ch6 Immune
22/81
GENERAL SCHEME of
CELLULAR EVENTS APCs (Macrophages, DendriticCells)
T-Cells (Control Everything)
CD4 REGULATORS (Helper)
CD8 EFFECTORS
B-Cells Plasma Cells ABs
NK Cells
8/8/2019 Ch6 Immune
23/81
8/8/2019 Ch6 Immune
24/81
CYT
OKIN
ES MEDIATE INNATE (NATURAL)
IMMUNITY, IL-1, TNF, INTERFERONS
REGULATE LYMPHOCYTE GROWTH(many interleukins, ILs)
ACTIVATE INFLAMMATORY CELLS STIMULATE HEMATOPOESIS,
(CSFs, orColonyStimulating Factors)
8/8/2019 Ch6 Immune
25/81
CYTOKINES/CHEMOKINES
CYTOKINES are PROTEINS produced byMANY cells, but usually LYMPHOCYTESand MACROPHAGES, numerous roles in
acute and chronic inflammation, ANDimmunity
TNF,
IL-1, by
macrophages CHEMOKINESare small proteins which are
attractants for PMNs
8/8/2019 Ch6 Immune
26/81
MHC
MajorHistocompatibility Complex A genetic LOCUS on Chromosome 6,
which codes for cell surface compatibility Also called HLA (Human Leukocyte
Antigens) in humans and H-2 in mice
Its major job is to make sure all self cellantigens are recognized and tolerated,because the general rule of the immunesystem is that all UN-recognized cells will
NO
T be tolerated
8/8/2019 Ch6 Immune
27/81
8/8/2019 Ch6 Immune
28/81
MHC MOLECULES
(Gene Products) I (All nucleated cells and platelets), cell surface
glycoproteins, ANTIGENS
II (APCs, i.e., macs and dendritics, lymphs),cell surface glycoproteins, ANTIGENS
III Complement System Proteins
8/8/2019 Ch6 Immune
29/81
IMMUNESYSTEM DISORDERS
WHATC
AN GO
WRO
NG? HYPERSENSITIVITY REACTIONS, I-IV
AUTO-IMMUNE DISEASES, aka
COLLAGEN DISEASES (BADTERM)
IMMUNE DEFICIENCY SYNDROMES,
IDS: PRIMARY (GENETIC)
SECONDARY (ACQUIRED)
8/8/2019 Ch6 Immune
30/81
HYPERSENSITIVITY
REACTIONS (4) I (Immediate Hypersensitivity)
II (Antibody MediatedHypersensitivity)
III (Immune-Complex MediatedHypersensitivity)
IV (Cell-Mediated Hypersensitivity)
8/8/2019 Ch6 Immune
31/81
Type I
IMMEDIATE HYPERSENSITIVITY Immediate means seconds to minutes
Immediate Allergic Reactions, which maylead to anaphylaxis, shock, edema, dyspnea
death1) Allergen exposure
2) IMMEDIATE phase: MAST cellDEgranulation, vasodilatation, vascularleakage, smooth muscle (broncho)-spasm
3) LATE phase (hours, days):Eosinophils,PMNs, T-Cells
8/8/2019 Ch6 Immune
32/81
TYPE II HYPERSENSITIVITY
ANTIBODY MEDIATED IMMUNITY
ABs attach to cell surfaces
OPSONIZATION (basting the turkey)
PHAGOCYTOSISCOMPLEMENT FIXATION (cascade of
C1q, C1r, C1s, C2,C3, C4, C5.. ) LYSIS (destruction of cells by
rupturing or breaking of the cell
membrane)
8/8/2019 Ch6 Immune
33/81
TYPE II DISEASES Autoimmune Hemolytic Anemia, AHA Idiopathic Thrombocytopenic Purpura,
ITP
Goodpasture Syndrome (Nephritis andLung hemorrhage)
Rheumatic Fever
Myasthenia Gravis
Graves Disease
Pernicious Anemia, PA
8/8/2019 Ch6 Immune
34/81
TYPE III HYPERSENSITIVITY
IMMUNECOMPLEX MEDIATED Antigen/Antibody Complexes
Where do they go?
Kidney (GlomerularBasement Membrane)
Blood Vessels Skin
Joints
C
ommon Type III Diseases-S
LE
(Lupus),Poly(Peri)arteritis Nodosa,Poststreptococcal Glomerulonephritis,Arthus reaction (hrs), Serum sickness
(days)
8/8/2019 Ch6 Immune
35/81
TYPE IV HYPERSENSITIVITY
CELL-MEDIATED (T-CELL)
DELAYED HYPERSENSITIVITY Tuberculin Skin Reaction
DIRECT ANTIGENCELL CONTACT
GRANULOMA FORMATION
CONTACT DERMATITIS
8/8/2019 Ch6 Immune
36/81
8/8/2019 Ch6 Immune
37/81
SUMMARY I Acute allergic reaction
II Antibodies directed against cellsurfaces
III Immune complexes
IV Delayed Hypersensitivity, e.g., Tb
skin test
8/8/2019 Ch6 Immune
38/81
RENAL
TRANSPLANT REJECTION
HYPERACUTE (minutes) :AG/ABreaction of vascular endothelium
ACUTE (days months):cellular(INTERSTITIAL infiltrate) and humoral(VASCULITIS)
CHRONIC (months):slow vascularfibrosis
8/8/2019 Ch6 Immune
39/81
ACUTECELLULAR (T) ACUTE HUMORAL
CHRONIC
8/8/2019 Ch6 Immune
40/81
AUTO-IMMUNE DISEASES
Failure of SELF RECOGNITION Failure ofSELF TOLERANCE
TOLERANCE
CENTRAL (Death of self reactive lymphocytes)
PERIPHERAL (anergy, suppression by T-cells,deletion by apoptosis, sequestration (Ag masking))
STRONG GENETIC PREDISPOSITION OFTEN RELATED TOOTHERAUTOIMMUNE
DISEASES
OFTEN TRIGGERED BY INFEC
TIO
NS
CLASSIC AUTOIMMUNE
8/8/2019 Ch6 Immune
41/81
CLASSIC AUTOIMMUNE
DISEASES (SYSTEMIC)LUPUS (SLE) Systemic LupusErythematosus
RHEUMATOID ARTHRITIS
SJGREN SYNDROME
SYSTEMICSCLEROSIS (scleroderma)
collagen diseases (term no longer
used)
CLASSIC AUTOIMMUNE
8/8/2019 Ch6 Immune
42/81
CLASSIC AUTOIMMUNE
DISEASES (LOCAL) HASHIMOTO THYROIDITIS AUTOIMMUNE HEMOLYTIC ANEMIA
MULTIPLESCLEROSIS AUTOIMMUNEORCHITIS
GOODPASTURESYNDROME
AUTOIMMUNE THROMBOCYTOPENIA
PERNICIOUS ANEMIA
INSULIN DEPENDENT DIABETES MELLITUS
MYASTHENIA GRAVIS
GRAVES DISEASE
8/8/2019 Ch6 Immune
43/81
N.B. The list of diseases
proven to beautoimmune grows
by leaps and boundsevery year!!!
8/8/2019 Ch6 Immune
44/81
LUPUS
(S
LE
) Etiology: Antibodies (ABs) directed againstthe patients own DNA, HISTONES, NON-histone RNA, and NUCLEOLUS
Pathogenesis: Progressive DEPOSITION
and INFLAMMATION to immune deposits, in
skin, joints, kidneys, vessels, heart, CNS
Morphology: Butterfly rash, skin deposits,
glomerolunephritis (NOT discoid)
Clinical expression: Progressive renal and
vascular disease, POSITIVE A.N.A.
8/8/2019 Ch6 Immune
45/81
H R
8/8/2019 Ch6 Immune
46/81
H
O
MO
S
P
E
C
K
R
I
M
N
U
C
L
E
O
L
A
R
8/8/2019 Ch6 Immune
47/81
SLE, SKIN SLE, GLOMERULUS
8/8/2019 Ch6 Immune
48/81
TABLE 6-10 -- Clinical and Pathologic Manifestations of Systemic Lupus
8/8/2019 Ch6 Immune
49/81
TABLE 6-10 -- Clinical and Pathologic Manifestations ofSystemic Lupus
Erythematosus
Clinical Manifestation
Preval
ence
in
Patients, %
Hematologic 100
Arthritis 90
Skin 85
Fever 83Fatigue 81
Weight loss 63
Renal 50
Central nervous system 50
Pleuritis 46Myalgia 33
Pericarditis 25
Gastrointestinal 21
Raynaud phenomenon 20
Ocular 15
Peripheral neuropathy 14
8/8/2019 Ch6 Immune
50/81
MORESYSTEMIC
AUTOIMMUNEDISEASES
RHEUMATOID ARTHRITIS
SJGREN SYNDROME
SCLERODERMA (SYSTEMIC
SCLEROSIS)
8/8/2019 Ch6 Immune
51/81
NORMAL Bi-Layered
Synovium
Destructive
Rheumatoid Synovitis
8/8/2019 Ch6 Immune
52/81
SJGRENSYNDROME
8/8/2019 Ch6 Immune
53/81
8/8/2019 Ch6 Immune
54/81
8/8/2019 Ch6 Immune
55/81
SCLERODERMA
(SYSTEMICSCLEROSIS)
8/8/2019 Ch6 Immune
56/81
SYSTEMICSCLEROSIS
(SCLERODERMA)
MORE AUTOIMMUNE
8/8/2019 Ch6 Immune
57/81
MORE AUTOIMMUNE
DISEASES (LOCAL) HASHIMOTO THYROIDITIS AUTOIMMUNE HEMOLYTIC ANEMIA
MULTIPLESCLEROSIS
AUTOIMMUNEORCHITIS
GOODPASTURESYNDROME
AUTOIMMUNE THROMBOCYTOPENIA (ITP)
PERNICIOUS ANEMIA INSULIN DEPENDENT DIABETES MELLITUS (I)
MYASTHENIA GRAVIS
GRAVES DISEASE
I D
8/8/2019 Ch6 Immune
58/81
ImmunoDefiency
Syndromes (-IDS)
PRIMARY (GE
NE
TIC
)(P-IDS?)
SECONDARY(ACQUIRED) (A-IDS)
PRIMARY
8/8/2019 Ch6 Immune
59/81
PRIMARY CHILDREN with repeated, often severe
infections, cellular AND/OR humoralimmunity 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
8/8/2019 Ch6 Immune
60/81
ADA=
ADE
NOS
INE
DEAMINASE
Examples of Infections in Immunodeficiencies
8/8/2019 Ch6 Immune
61/81
Examples of Infections in Immunodeficiencies
Pathogen Type T-Cell-Defect B-Cell DefectGranulocyte
Defect Complement DefectBacteria Bacterial sepsis Streptococci,
staphylococci,
Haemophilus
Staphylococci,
Pseudomon
as
Neisserial
infections,other pyogenic
bacterial
infectionsViruses Cytomegalovirus,
Epstein-Barr virus,
severe varicella,chronic infections with
respiratory and
intestinal viruses
Enteroviralencephalitis
Fungi and
parasitesCandida, Pneumocystis
carinii
Severe intestinalgiardiasis
Candida,
Nocardia,
AspergillusSpecial features Aggressive disease
with opportunistic
pathogens, failure to
clear infections
Recurrent
sinopulmonary
infections,
sepsis, chronic
meningitis
AIDS
8/8/2019 Ch6 Immune
62/81
AIDS(SECONDARY IDS) Etiology: HIV
Pathogenesis: Infection, Latency,
Progressive T-Cell loss Morphology: MANY
Clinical Expressions: Infections,Neoplasms, Progressive Immune Failure,
Death, HIV+, HIV-RNA (Viral Load)
8/8/2019 Ch6 Immune
63/81
EPIDEMIOLOGY HOMOSEXUAL (40%, and
declining)
INTRAVENOUS DRUG
USAGE (25%)
HETEROSEXUAL SEX (10%
and rising)
ETIOLOGY
8/8/2019 Ch6 Immune
64/81
ETIOLOGY
8/8/2019 Ch6 Immune
65/81
PATHOGENESIS
ATTACHING BUDDING
PATHOGENESIS
8/8/2019 Ch6 Immune
66/81
PATHOGENESIS
EARLY BUDDING
PATHOGENESIS
8/8/2019 Ch6 Immune
67/81
PATHOGENESIS
LATE BUDDING
PATHOGENESIS
8/8/2019 Ch6 Immune
68/81
PATHOGENESIS
MATURE NEW VIRIONS
8/8/2019 Ch6 Immune
69/81
REVERSE TRANSCRIPTASE
The enzyme reverse transcriptase(RT) is used by retroviruses totranscribe their single-strandedRNA genome into single-strandedDNA and to subsequentlyconstruct a complementary strand
of DNA, providing a DNA doublehelix capable of integration intohost cell chromosomes.
8/8/2019 Ch6 Immune
70/81
PATHOGENESIS
PATHOGENESIS
8/8/2019 Ch6 Immune
71/81
PATHOGENESIS
1) PRIMARY INFECTION
2) LYMPHOID INFECTION
3) AC
UTE
SYNDR
OME
4) IMMUNE RESPONSE
5) LATENCY
6) AIDS
8/8/2019 Ch6 Immune
72/81
GENERAL IMMUNE
8/8/2019 Ch6 Immune
73/81
GENERAL IMMUNE
ABNORMALITIES LYMPHOPENIA
DECREASED T-CELL
FUNCTION B-CELL ACTIVATION,
POLYCLONAL
ALTEREDMONOCYTE/MACROPHAGE
FUNCTION
INFECTIONS
8/8/2019 Ch6 Immune
74/81
INFECTIONS Protozoal/Helminthic:Cryptosporidium, PCP
(PneumocystisC
ariniiPneumonia), Toxoplasmosis
Fungal: Candida, and the usual 3
Bacterial: TB, Nocardia,
Salmonella
Viral: CMV, HSV, VZ (Herpes Family)
8/8/2019 Ch6 Immune
75/81
PCP
8/8/2019 Ch6 Immune
76/81
CRYPT
OSPO
RIDIUM
8/8/2019 Ch6 Immune
77/81
CASE
ATING GRANULO
MA
CANCERS f AIDS
8/8/2019 Ch6 Immune
78/81
CANCERS of AIDS
KAPOSI SARCOMA
B-CELL LYMPHOMAS
CNS LYMPHOMAS
CE
RVIXC
ANCE
R,SQUAMOUSCELL
AMYLOIDOSIS
8/8/2019 Ch6 Immune
79/81
AMYLOIDOSIS BUILDUP OF AMYLOID PROTEIN
AL (Amyloid Light Chain)
AA (NON-immunoglobulin protein)
A (Alzheimers)
WHERE? BLOOD VESSEL WALLS, at first
KIDNEY
SPLEEN
LIVER
HEART
8/8/2019 Ch6 Immune
80/81
CONGO RED STAIN, WITHOUT,
and WITH, POLARIZATION
AMYLOID ASSOCIATIONS
8/8/2019 Ch6 Immune
81/81
AMYLOID ASSOCIATIONS
PLASMA CELL DYSCRASIAS, i.e.,MULTIPLEMYELOMA
CHRONIC GRANULOMATOUS
DISEASE, e.g., TB HEMODIALYSIS
HEREDOFAMILIAL
LOCALIZED ENDOCRINEMEAs (Multiple Endocrine
Adenomas)
Recommended