Professional Documents
Culture Documents
IMMUNE SYSTEM
IMMUNITY
refers to protection against infection.
THE IMMUNE SYSTEM
is the collection of cells, tissues and molecules that functions
to defend us against infectious microbes.
IMMUNE RESPONSE
is the coordinated reaction of the immune system against
infections and other foreign substances.
Abnormalities of the immune system that result in defective
immune responses make individuals susceptible to infections by
viruses, bacteria, fungi and parasites.
Many common diseases are caused by uncontrolled or excessive
immune response.
and nonspecific
Four
major components:
Inflammation.
Antiviral
Components
are lymphocytes
Principal functions
T lymphocytes
B lymphocytes
lymphocytes)
Antibody production (B cells develop into plasma cells
which make antibodies)
Dendritic cells
Macrophages
Neutrophils
T-LYMPHOCYTES
Thymusderived,orT,lymphocytesaretheeffecto
rcellsofcellularimmunityandthehelpercells
for antibodyresponsestoproteinantigens
constitute60%to70%ofthelymphocytesin
peripheralbloodandarethemajorlymphocytepop
ulationinsplenicperiarteriolarsheathsandlym
phnode interfollicularzones
T-LYMPHOCYTES
Tcellsrecognizeonlypeptidefragmentsofprotein
antigensboundtoproteinsofthemajor
histocompatibilitycomplex(MHC)
Itisnowknownthatthenormalfunctionof
MHCmoleculesistodisplaypeptidesforrecognitionb
yTlymphocytes
B LYMPHOCYTES
BonemarrowderivedBlymphocytesarethecells
thatproduceantibodiesandarethustheeffecto
rcells ofhumoralimmunity
10%to20%ofthecirculatingperipherallympho
cytepopulation
presentinbonemarrowandinthefolliclesofp
eripherallymphoidtissues(lymphnodes,
spleen,tonsils,andothermucosaltissues
B LYMPHOCYTES
Afterstimulation,Bcellsdifferentiateintoplasmace
lls,whichsecretelargeamountsofantibodies,the
mediatorsofhumoralimmunity
Therearefiveclasses,orisotypes,ofimmunoglobulin
s:IgG,IgM,andIgA
constitutemorethan95%ofcirculatingantibodies
IgA
mucosal secretions
IgE attached at mast cells
IgD
-expressedonthesurfacesofBcellsbutisnotsecreted
Manydifferenttypesofleukocytesperformtheultim
atetaskoftheimmuneresponse,whichistoelimina
te infections
Lymphoid Tissues
Generative(Primary)Organs
peripheral(secondary)lymphoidorgans
OVERVIEW OF THE
NORMAL IMMUNE
RESPONSE
THEEARLYINNATEIMMUNERESP
ONSETOMICROBES
Theearlyreactiontomicrobesismediatedbythem
echanismsofinnateimmunity,whichare
readytorespondtomicrobes.Thesemechanismsincl
udeepithelialbarriers,phagocytes,NK
cells,andplasmaproteins(e.g.,ofthecomplementsys
tem).Thereactionofinnateimmunityis
oftenmanifestedasinflammation.
THECAPTUREANDDISPLAYOFMIC
ROBIALANTIGENS
EFFECTOR FUNCTIONS OF T
LYMPHOCYTES
HUMORALIMMUNITY
HYPERSENSITIVITYREACT
IONS:MECHANISMSOFIM
MUNEMEDIATEDINJURY
HYPERSENSITIVITY:
IMMUNOLOGICALLY
MEDIATED TISSUE INJURY
TYPES OF
HYPERSENSITIVITY
TYPE I HYPERSENSITIVITY
IMMEDIATE HYPERSENSITIVITY
anaphylactic hypersensitivity
responsible
TYPE II HYPERSENSITIVITY
CYTOTOXIC HYPERSENSITIVITY
Attracts
Pathophysiology
TYPE IV HYPERSENSITIVITY
CELL-MEDIATED
HYPERSENSITIVITY
macrophages to cause an
inflammation
Pathophysiology
DELAYED-TYPE HYPERSENSITIVITY
CD4+ T cells interact with macrophages,
resulting in cytokine injury to tissue
May lead to granuloma formation
T CELL-MEDIATED CYTOLYSIS
AUTOIMMUNE DISEASES
AUTOIMMUNE DISEASES
Overactive
Most
General
characteristics
IMMUNOLOGIC TOLERANCE
MECHANISMS OF AUTOIMMUNITY
CELIAC DISEASE
Mechanism
Gliadin
Clinical Presentation
Diarrhea,
Treatment
Dietary
modification (gluten-free)
O
N
U
C
L
A
R
SLE, SKIN
SLE, GLOMERULUS
Prevalence in
Patients, %
Hematologic
Arthritis
Skin
Fever
Fatigue
Weight loss
100
90
85
83
81
63
50
50
46
33
25
21
20
15
14
Renal
MORE SYSTEMIC
AUTOIMMUNE
DISEASES
RHEUMATOID
ARTHRITIS
SJGREN SYNDROME
SCLERODERMA (SYSTEMIC
SCLEROSIS) (PSS)
Destructive
Rheumatoid Synovitis
NORMAL Bi-Layered
Synovium
SJOGREN SYNDROME
Chronic disease
characterized by
Dry
eyes
(keratoconjunctivitis sicca)
Dry mouth (xerostomia)
Other S/Sx (e.g. arthritis)
Results from
immunologically mediated
destruction of the lacrimal
and salivary glands
SJGREN
SYNDROME
SYSTEMIC SCLEROSIS
Chronic inflammation
thought to be the result of
autoimmunity
Widespread damage to
small blood vessels
Progressive interstitial and
perivascular fibrosis in the
skin and multiple organs
SYSTEMIC SCLEROSIS
(SCLERODERMA)
SCLERODERMA
(SYSTEMIC SCLEROSIS)
MORE AUTOIMMUNE
DISEASES (LOCAL)
HASHIMOTO
microsome)
DRUG-INDUCED LUPUS
Associated drugs
Hydralazine,
Distinguishing features
Anti-histone
antibodies
Low incidence of renal and CNS involvement
Disppearance of symptoms when drug is discontinued
REJECTION OF TISSUE
TRANSPLANTS
TYPES OF GRAFTS
1.
Autograft
Self-to-self
Best survival rate
2.
3.
Allograft
4.
Xenograft
REJECTION OF TISSUE
TRANSPLANTS
HYPERACUTE REJECTION
Occurs
Example
REJECTION OF TISSUE
TRANSPLANTS
ACUTE REJECTION
most
Acute
cellular rejection
Treatment: immunosuppressives
Acute
humoral rejection
REJECTION OF TISSUE
TRANSPLANTS
CHRONIC REJECTION
Occurs
GRAFT-VERSUS-HOST DISEASE
(GVHD)
Acute GVHD
Occurs
Chonic GVHD
May
IMMUNODEFICIENCY
State in which the immune systems ability to
fight infectious disease is compromised
Can occur if any of the four major components of
the immune system are compromised:
cells (antibody)
T cells
Phagocytes
complement
TYPES OF IMMUNODEFICIENCY
Primary
Immunodeficiency
Secondary
Immunodeficiency
IMMUNODEFIENCY
SYNDROMES (-IDS)
PRIMARY
(GENETIC) (P-
IDS?)
SECONDARY
(ACQUIRED) (A-IDS)
PRIMARY
PRIMARY IMMUNODEFICIENCIES
B CELL DISORDERS
Mechanism
Very low levels of all immunoglobulins
Streptococcus pneumoniae
Haemophilus influenzae
PRIMARY IMMUNODEFICIENCIES
B CELL DISORDERS
Clinical
Presentation
Treatment
PRIMARY IMMUNODEFICIENCIES
B CELL DISORDERS
Clinical
Presentation
Diagnosis of exclusion
Recurrent pyogenic bacterial infections
Most common form of severe antibody deficiency affecting
both children and adults
Treatment
PRIMARY IMMUNODEFICIENCIES
T CELL DISORDERS
diGeorge Syndrome
Mechanism
Clinical
Presentation
Treatment
PRIMARY IMMUNODEFICIENCIES
T CELL DISORDERS
Clinical
presentation
Treatment
PRIMARY IMMUNODEFICIENCIES
Clinical
Presentation
Treatment
PRIMARY IMMUNODEFICIENCIES
Wiskott-Aldrich Syndrome
Mechanism
Clinical
Presentation
Treatment
PRIMARY IMMUNODEFICIENCIES
Ataxia-telangiectasia
Mechanism
Clinical
Presentation
Treatment
Supportive management
PRIMARY IMMUNODEFICIENCIES
PHAGOCYTE DISORDERS
Clinical
Presentation
Treatment
Antibiotic chemoprophylaxis
PRIMARY IMMUNODEFICIENCIES
PHAGOCYTE DISORDERS
Chediak-Higashi Syndrome
Mechanism
Clinical
presentation
Treatment
antibiotics
PRIMARY IMMUNODEFICIENCIES
PHAGOCYTE DISORDERS
Clinical
Presentation
Treatment
PRIMARY IMMUNODEFICIENCIES
COMPLEMENT DISORDERS
Hereditary Angioedema
Mechanism
Clinical
presentation
Widespread angioedema
Fatal laryngeal edema
Treatment
corticosteroids
PRIMARY IMMUNODEFICIENCIES
PHAGOCYTE DISORDERS
DEFICIENCY
C3
DEFICIENCY
PRIMARY IMMUNODEFICIENCIES
PHAGOCYTE DISORDERS
Complement-mediated hemolysis
Deficiency of decay-accelarating factor (DAF)
Occurs at night due to lower RBC oxygen concentration
during sleep
Clinical
Presentation
Treatment
PRIMARY IMMUNODEFICIENCIES
PHAGOCYTE DISORDERS
Complement-mediated hemolysis
Deficiency of decay-accelerating factor (DAF)
Occurs at night due to lower RBC oxygen concentration
during sleep
Clinical
Presentation
Treatment
Disease
Bacterial
B Cell
Brutons XLA
IgA deficiency
CVID
DiGeorge
S. pneumoniae
H. influenzae
S. aureus
B and T Cell
SCID
Wiskott-Aldrich
Macrophage
CGD
Chediak-Higashi
Complement
C6-C9 deficiency
S. pneumoniae
H. influenzae
S. aureus
P. aeruginosa
S. aureus
P. aeruginosa
M. tuberculosis
B. cepacia
N. meningitidis
N. gonorrhoeae
T Cell
Defect
Viral
B Cell
Entorovirus
HBV
EBV
CMV
VZV
EBV
CMV
VZV
T Cell
B and T Cell
Macrophage
Complement
Fungal
Parasitic
G. lamblia
C. albicans
P. jiroveci
C. albicans
P. jiroveci
A. fumigatus
C. albicans
G. lamblia
ADA=
ADENOSINE
DEAMINASE
T-Cell-Defect
Bacterial sepsis
Granulocyte
B-Cell Defect
Defect
Streptococci, Staph,
Neisserial
staphylococci, Pseudomo infections,
Haemophilus nas
other
pyogenic
infections
Viruses
Enteroviral
Cytomegalovirus,
Epstein-Barr virus, encephalitis
severe varicella,
chronic infections
with respiratory and
intestinal viruses
Fungi and
parasites
Complement Defect
Candida,
Nocardia,
Aspergillus
(A)IDS
Etiology:
(SECONDARY IDS)
HIV
Pathogenesis: Infection, Latency,
Progressive T-Cell loss
Morphology: MANY
Clinical
Expressions: Infections,
Neoplasms, Progressive Immune Failure,
Death, HIV+, HIV-RNA (Viral Load)
SECONDARY
IMMUNODEFICIENCIES
RNA virus
Contains an electron- dense, cone-shaped core
surrounded by a lipid envelope
Major capsid protein p24
Nucleocapsid preotein p7/p9
Two copies of genomic RNA
Three viral enzymes
Protease
Reverse transcriptase
integrase
AIDS: Pathogenesis
Preferentially
lymphocytes
Main
Use
Comments
ELISA
Screening test
(sensitivity ~100%)
Confirmatory test
(~100% specificity)
Monitoring immune
status
Anti-gp120
antibodies
p24 antigen and gp41
antibodies
Guide for initiating
treatment and
administering
prophylaxis
Most sensitive test
for diagnosis of acute
HIV before
seroconversion
Western Blot
CD4 count
Detection of active
replication
Marker of
progression
OPPORTUNISTIC INFECTIONS IN
AIDS
CD4
<500
<200
<50
ETIOLOGY
CLINICAL SYNDROME
M. tuberculosis
Disseminated tuberculosis
HSV
HSV esophagitis
C. albicans
Esophageal candidiasis
HHV-8
Kaposis sarcoma
P. jiroveci
PCP pneumonia
T. gondii
Cerebral toxoplasmosis
C. neoformans
Meningoencephalitis
C. immitis
Coccidioidomycosis
C. parvum
Chronic diarrhea
M. avium
H. capsulatum
Histoplasmosis
CMV
CMV retinitis
AIDS
Lymph Nodes
Early
stages of AIDS
Late
stages of AIDS
EPIDEMIOLOGY
HOMOSEXUAL
(40%, and
declining)
INTRAVENOUS DRUG
USAGE (25%)
HETEROSEXUAL SEX
(10% and rising)
ETIOLOGY
PATHOGENESIS
ATTACHING
BUDDING
PATHOGENESIS
EARLY BUDDING
PATHOGENESIS
LATE BUDDING
PATHOGENESIS
REVERSE TRANSCRIPTASE
The
PATHOGENESIS
PATHOGENESIS
1) PRIMARY INFECTION
2) LYMPHOID INFECTION
3) ACUTE SYNDROME 4-8
weeks)
4) IMMUNE RESPONSE
5) LATENCY
6) AIDS
GENERAL IMMUNE
ABNORMALITIES
LYMPHOPENIA
DECREASED
T-CELL
FUNCTION
B-CELL ACTIVATION,
POLYCLONAL
ALTERED
MONOCYTE/MACROPHAGE
FUNCTION
INFECTIONS
Protozoal/Helminthic:
Cryptosporidium, PCP
(Pneumocystis Carinii (really
Jiroveci) Pneumonia),
Toxoplasmosis
Fungal: Candida, and the usual 3
Bacterial: TB, Nocardia, Salmonella
Viral: CMV, HSV, VZ (Herpes Family),
HPV
PCP
CRYPTOSPORIDIUM
CASEATING GRANULOMA
CANCERS OF AIDS
KAPOSI
SARCOMA (Herpes-
8)
B-CELL LYMPHOMAS
CNS LYMPHOMAS
CERVIX CANCER,
SQUAMOUS CELL (HPV)
AMYLOIDOSIS
BUILDUP
AL
AA
OF AMYLOID PROTEIN
(NON-immunoglobulin protein)
A (Alzheimers)
SPLEEN
LIVER
HEART
AMYLOID ASSOCIATIONS
PLASMA
AMYLOIDOSIS
Amyloid
Pathologic
proteinaceous substance
Deposited in extracellular space in various tissues
TYPES OF AMYLOIDOSIS
Type
Protein
Derived from
Mnemonic
Primary
AL
AL=light chain
Secondary
AA
Senile cardiac
Transthyretin
T2 DMassociated
Medullary
thyroid CA
Alzheimers
Disease
Dialysisassociated
Amylin
AE
AE = Endocrine
A-CAL
Calcitonin
B-amyloid
APP
A-CAL
CALcitonin
B2-microglobulin
MHC Class I
proteins
AA = Acute phase
reactants
AF = old Folks
AMYLOIDOSIS
Renal amyloidosis
Most
Massive splenomegaly
Tapioca-like
spleen)
Map-like areas in walls of spenic sinuses (lardaceous
spleen)
Marked hepatomegaly
Due
AMYLOIDOSIS
Heart
Subendocardial
Other organs
Adrenals,