CHAPTER 14: Type II – Cytotoxic (IgG/IgM-

HYPERSENSITIVITY mediated)

 Target: Antigens on cell surface

 Mechanism: IgG/IgM bind to target
Definition: cells → complement activation or
ADCC → cell destruction or altered
Hypersensitivity is an exaggerated immune function
response to a normally harmless antigen,  Examples:
potentially causing tissue damage, disease, o Transfusion reactions (acute:
or death. IgM; delayed: anamnestic
response)
o Hemolytic disease of the
newborn (Rh incompatibility)
Four Types of Hypersensitivity (Gell and o Autoimmune hemolytic
Coombs Classification): anemia
o Goodpasture’s Syndrome,
Myasthenia Gravis, Grave’s
Disease
Type I – Immediate/Allergic (IgE-  Tests: Direct & indirect Coombs test
mediated)

 Examples: Hay fever, asthma, food

allergies, anaphylaxis Type III – Immune Complex-
 Mechanism: Allergen triggers IgE Mediated (IgG/IgM)
production → binds to mast
cells/basophils → re-exposure causes  Mechanism: Antigen-antibody
degranulation and mediator release complexes deposit in tissues →
(e.g., histamine) complement activation →
 Phases: inflammation
o Sensitization: IgE binds to  Examples:
FcεRI receptors on mast cells o Serum sickness (after animal
o Activation: Allergen cross- serum or monoclonal
links IgE → degranulation antibody therapy)
 Clinical Manifestations: Urticaria, o Arthus reaction (localized
wheal and flare, rhinitis, asthma, response post-vaccine)
anaphylaxis o Autoimmune diseases: SLE,
 Diagnosis: Skin prick/intradermal RA
tests, RAST, total IgE (RIST)  Diagnosis: ANA tests (FANA), RF
 Treatment: Allergen avoidance, tests, complement level measurement
antihistamines, corticosteroids,
omalizumab, immunotherapy

Type IV – Delayed-type (T-cell

mediated)
  Mechanism: Sensitized T cells  Autoantibodies (especially anti-
recognize antigen → cytokine dsDNA) form immune complexes →
release → macrophage recruitment deposited in skin, joints, kidneys
→ inflammation (peak: 48–72 hrs)  Symptoms: Fatigue, fever, butterfly
 Examples: rash, nephritis
o Contact dermatitis (poison  Tests: ANA (FANA), anti-dsDNA,
ivy, nickel, latex) hypocomplementemia
o Tuberculin skin test
(Mantoux)
o Hypersensitivity pneumonitis
(e.g., farmer’s lung) Rheumatoid Arthritis (RA)
 Diagnosis: Patch test, tuberculin skin
test  Mechanism: IgM (RF) binds IgG Fc
→ immune complexes
 Symptoms: Symmetrical joint
inflammation, pain, stiffness
CHAPTER 15: AUTOIMMUNITY  Tests: RF, anti-CCP, ANA

Definition: Grave’s Disease

Autoimmune diseases result from immune  TRAbs (thyroid receptor antibodies)

responses against self-antigens, leading to stimulate TSH receptor →
tissue damage. hyperthyroidism
 Symptoms: Goiter, exophthalmos
 Tests: TSH, FT4, TRAb assay
(binding/bioassay)
Etiology:

 Breakdown of self-tolerance:
o Central (thymus/bone Hashimoto’s Thyroiditis
marrow) and Peripheral
(secondary lymphoid tissues)  Autoimmune destruction of thyroid
 Triggers: Hormones, trauma, cryptic → hypothyroidism
antigens, infections, epigenetics  Symptoms: Goiter, fatigue, cold
intolerance
 Tests: TSH, FT4, anti-TPO
antibodies
Examples of Autoimmune Diseases:

Type 1 Diabetes Mellitus

Systemic Lupus Erythematosus (SLE)
 Autoimmune destruction of
pancreatic β-cells
  Triggers: Coxsackie B4 virus TRANSPLANTATION
 Tests: GAD, IA-2A, ICA, insulin IMMUNOLOGY
antibodies
HISTOCOMPATIBILITY SYSTEMS

Major Histocompatibility Complex (MHC):

Multiple Sclerosis (MS)
 Encoded on short arm of
 T-cell mediated CNS demyelination chromosome 6
 Diagnosis: Oligoclonal IgG bands in  Class I (HLA-A, -B, -C) — all
CSF, elevated IgG index nucleated cells, interact with CD8+ T
cells
 Class II (HLA-DR, -DQ, -DP) —
APCs, interact with CD4+ T cells
Myasthenia Gravis  Highly polymorphic system
 Antibodies against acetylcholine Minor Histocompatibility Antigens (mHAs):
receptors at neuromuscular junction
 Symptoms: Muscle weakness, ptosis,  Non-HLA polymorphic proteins
diplopia triggering slower rejection
 Tests: RIPA, α-bungarotoxin binding  Recognized via MHC-restricted
assay CD4/CD8 T cell responses
 Includes proteins encoded on Y
chromosome, mtDNA, and others

ANA Detection Methods: MICA Antigens:

 Indirect Immunofluorescence  Class I-related, expressed on non-

(FANA): Uses HEp-2 cells; sensitive lymphoid cells
and common  Targets for allograft response;
 ELISA & CLIA: Automated, antibodies linked to rejection
multiple antibodies per well
 MIA: High-throughput, multiplex ABO Blood Group Antigens:
antibody detection
 Crithidia luciliae IIF: Specific for  Must be compatible to prevent
anti-dsDNA hyperacute rejection
 Ouchterlony Test: Immunodiffusion  Incompatibility causes rapid
for ENA antibodies complement-mediated damage
 ANA Visible Method: Colorimetric
detection of bound antibodies Killer Immunoglobulin-Like Receptors
(KIRs):

 Found on NK cells; regulate activity

via interaction with HLA-A, B, C
 Role in graft-versus-leukemia (GVL)
effect
 TRANSPLANT REJECTION
TYPES
Self-Antigens:

 Some self-antibodies post-transplant

(e.g., anti-AT1R, vimentin) linked to Hyperacute Rejection:
poor outcomes
 Minutes to hours
 Preformed antibodies (ABO, HLA)
 Leads to complement activation,
ALLORECOGNITION & thrombosis
REJECTION TYPES

Acute Rejection (AR):

Types of Grafts:
 Days to months
 Autograft: Same individual  Cellular (CD8+, CD4+,
 Syngeneic (Isograft): Genetically macrophages) and/or antibody-
identical individuals mediated
 Allograft: Genetically different  Diagnosis: Biopsy + C4d staining
same-species individuals  Treated with immunosuppressants
 Xenograft: Between different species

Chronic Rejection:
Direct Allorecognition:
 Long-term deterioration
 Recipient T cells directly recognize  Fibrosis, arteriosclerosis, cytokine-
donor HLA driven damage
 High T cell response frequency  Involves CD4+, B cells, IFN-γ,
 Assessed via Mixed Lymphocyte alloantibodies
Reaction (MLR)

GRAFT-VERSUS-HOST DISEASE
Indirect Allorecognition: (GVHD)
 Recipient APCs present donor HLA  Occurs in HSC transplants
to T cells  Donor T cells attack host antigens
 Leads to chronic rejection and  Acute GVHD: Skin, GI, liver (within
alloantibody production 100 days)
 Chronic GVHD: Resembles
autoimmune disease
 T-cell depletion reduces GVHD but
also reduces GVL effect
  Deplete lymphocytes

IMMUNOSUPPRESSIVE AGENTS

CLINICAL
HISTOCOMPATIBILITY
Corticosteroids: TESTING
 Anti-inflammatory, block cytokines
 Long-term use linked to
hypertension, diabetes HLA Typing (Phenotyping):

 Lymphocytes tested with antisera in

microtiter wells
Antimetabolites:  Complement-dependent cytotoxicity
used to identify positive reactions
 E.g., Mycophenolate (preferred over  Graded 0–8 (based on % cell death)
azathioprine)  Limitations: Needs viable cells,
inconsistent antisera

Calcineurin Inhibitors:
HLA Genotyping:
 Cyclosporine, Tacrolimus
 Block IL-2, inhibit T cell activation  DNA-based, does not require viable
cells
 Chemically synthesized reagents
 Higher resolution
Rapamycin (Sirolimus):

 Inhibits mTOR, blocks T cell

proliferation HLA ANTIBODY SCREENING &
CROSSMATCHING

 Ensures compatibility
Monoclonal Antibodies:
 Detects donor-specific antibodies
 Prevents antibody-mediated rejection
 E.g., Basiliximab (anti-CD25),
Alemtuzumab (anti-CD52)
 Block T-cell function
SUMMARY & STUDY GUIDE

Polyclonal Antibodies:  Key concepts: MHC/HLA systems,

rejection mechanisms, GVHD,
 E.g., ATGAM, Thymoglobulin
 immunosuppressive therapies, lab  Carcinomas (80%): Skin and
testing epithelial origin
 Compatibility is essential for graft  Leukemias/Lymphomas (9%): Blood
success and lymphatic system
 Monitoring and managing immune  Sarcomas (1%): Bone, fat, muscle,
responses is critical cartilage
 Others: Melanomas, brain tumors,
germ cell tumors, neuroendocrine
tumors
TUMOR IMMUNOLOGY

Introduction to Tumor Biology

Tumor Antigens
 Tumors are abnormal cell growths
caused by genetic mutations  Tumor-Specific Antigens (TSA):
affecting cell cycle, apoptosis, and Only on cancer cells (e.g., mutated
DNA repair. p53)
 Benign tumors: well-differentiated  Tumor-Associated Antigens (TAA):
and non-invasive. Overexpressed in tumors (e.g.,
 Malignant tumors (cancers): HER2/neu, CEA)
invasive, aggressive, and often
metastatic.
 Tumor microenvironment involves
immune cells, blood vessels, and Clinically Relevant Tumor Markers
stroma that influence tumor
development.  Biological substances in blood/tissue
aiding in cancer diagnosis and
monitoring
 Uses:
Definition of Terms o Screening
o Diagnosis
 Apoptosis: Programmed cell death o Prognosis
 Tumor / Neoplasm: Abnormal cell o Treatment monitoring
mass (benign or malignant) o Limitations: false
 Cancer: Derived from Latin “crab” positives/negatives, lack of
due to invasive appearance specificity
 Carcinogenesis: Multistep
transformation due to proto-
oncogenes and tumor suppressor
gene mutations Examples:

 AFP: Hepatocellular carcinoma; also

elevated in hepatitis, cirrhosis
Classification of Malignant Tumors  CEA: Colorectal, breast, pancreas,
GI cancers
  CA-125: Ovarian cancer marker (not  Adaptive Immunity: Cytotoxic T
specific) cells, antibodies
 hCG: Testicular cancer and  Tumor Escape: Cancer cells evade
pregnancy marker immune system
 PSA: Prostate cancer screening

Immunoediting
Laboratory Detection of Tumors
1. Elimination: Immune system
 Tumor Morphology: Gross and destroys tumor cells
microscopic analysis 2. Equilibrium: Balance between tumor
 Immunohistochemistry: Detects growth and immune attack
antigens in tissue 3. Escape: Tumors suppress or evade
 Immunoassays: Measures serum immune responses
markers
 Molecular Methods: Detect
mutations
 Proteomics: Protein expression Escape Mechanisms
profiles
 Loss of antigens
 Immunosuppressive cytokines and
cells
Molecular Methods in Cancer  Chronic inflammation promoting
Diagnosis tumor growth
 Downregulation of MHC and antigen
 Genetic Biomarkers: Identify cancer presentation
risk and treatment targets
 Cytogenetics: Karyotyping, FISH for
chromosome changes
 Microarrays: Analyze gene Immunotherapy Overview
expression
 Next-Gen Sequencing (NGS): High-  Active Immunotherapy: Stimulates
throughput genetic analysis patient’s immune system (e.g.,
 Proteomics: Detect tumor-specific vaccines)
protein signatures  Passive Immunotherapy: Provides
immune components (e.g.,
antibodies)
 Adoptive Immunotherapy: Transfers
Immune System and Tumors immune cells (e.g., CAR-T cells)

 Immunosurveillance: Constant
monitoring for cancer cells
 Innate Immunity: NK cells, Active Immunotherapy & Cancer
macrophages Vaccines
  Coley’s toxins: First immune-based
cancer treatment
 BCG therapy: Bladder cancer Monoclonal Gammopathy of Undetermined
 HPV and HBV vaccines: Prevent Significance (MGUS) is a premalignant
virus-related cancers condition that may progress to:
 Therapeutic vaccines: Target specific
tumor antigens  Multiple Myeloma
 Waldenström Macroglobulinemia
 Other lymphoproliferative disorders

Passive Immunotherapy

 Cytokine Therapy: Boosts immune Malignant Transformation

responses (e.g., IFN-α, IL-2)
 Monoclonal Antibodies: Highly of Hematologic Cells
specific, can be conjugated with
drugs or made bi-specific

Cellular Characteristics

Adoptive Immunotherapy  Excessive accumulation of abnormal

blood/immune cells due to:
 Tumor-Infiltrating Lymphocytes o Rapid proliferation
(TILs): Harvested and expanded for o Failure of apoptosis
reinfusion o Arrested maturation
 CAR-T Cells: Genetically modified
T cells with chimeric antigen
receptors
T and B lymphocytes are especially
vulnerable due to:

IMMUNOPROLIFERATIVE DISEASES  Proliferation

 Gene rearrangement
Lymphoid malignancies are broadly  Somatic hypermutation
classified into:

 Leukemias: Malignant cells

primarily in bone marrow and Normal immune response: Polyclonal
peripheral blood.
 Lymphomas: Malignant cells arising Malignancy: Monoclonal
in lymphoid tissues (lymph nodes,
tonsils, spleen).
 Plasma Cell Dyscrasias (PCDs):
Involving bone marrow, lymphoid Genetic Changes
organs, and other non-lymphoid
sites.
  Multifactorial and multistep  FAB: For leukemias and
development myelodysplastic syndromes
 Influenced by environmental factors  REAL: Basis of 2001 WHO
 Key genetic elements: classification
o Proto-oncogenes: Can  2008 WHO Classification: 12 major
become oncogenes when groups based on:
mutated. o Cell lineage
o Tumor suppressor genes: o Immunologic markers
Mutations result in o Genetic features
uncontrolled growth. o Morphology
o Aneuploidy and o Staining
chromosomal deletions:
Indicators of prognosis.

Leukemias
Chromosomal Translocations

 t(8;14): c-MYC → Burkitt

Two Major Categories:
lymphoma
 t(14;18): BCL-2 → Follicular
 Myelogenous Leukemias
lymphoma
 Lymphocytic Leukemias
 t(9;22): BCR-ABL → Chronic
Myelogenous Leukemia (CML)

By Disease Progression:
Classification of  Acute Leukemias
Hematologic Malignancies  Chronic Leukemias

Evolution of Classification: Acute Lymphocytic Leukemia (ALL)

 1950s–60s: Morphology (Wright-  Affects lymphoblasts

Giemsa stain)  Common in children aged 2–5
 1970s–80s: T & B cell surface  Symptoms: Anemia, infections,
markers bleeding, soft tissue infiltration
 1990s–2000s: Molecular diagnostics

Chronic Lymphocytic Leukemia

Key Systems: (CLL)

 Affects mature B-cells

  Common in males >50 years 6. Amyloid Light-Chain (AL)
 Features: Lymphadenopathy, Amyloidosis – Protein deposits in
anemia, thrombocytopenia organs
7. POEMS Syndrome –
Polyneuropathy, Organomegaly,
Endocrinopathy, M-protein, Skin
Hairy Cell Leukemia (HCL) changes

 Rare B-cell malignancy

 4:1 male-to-female ratio
 Bone marrow infiltration → Diagnostic Tests
pancytopenia
 Blood lymphocyte count not (Immunoserology)
typically elevated
 SPEP: Detects M-protein in serum
 UPEP: Detects M-protein (e.g.,
Bence Jones proteins) in urine
 SIFE/UIFE: Identifies
Plasma Cell Dyscrasias immunoglobulin type (IgG kappa,
(PCDs) etc.)

Characterized by: Lymphomas

 Clonal proliferation of plasma cells
 Overproduction of monoclonal
protein (M-protein) Cancers arising from malignant
transformation of lymphocytes.

Types of PCDs:
Main Types:
1. MGUS – Premalignant; no end-
organ damage  Hodgkin Lymphoma (HL)
2. Smoldering Multiple Myeloma  Non-Hodgkin Lymphoma (NHL)
(SMM) – Asymptomatic but higher
progression risk
3. Multiple Myeloma (MM) –
Malignant; CRAB features
4. Solitary Plasmacytoma – Localized;
Hodgkin Lymphoma (HL)
may progress to MM
5. Plasma Cell Leukemia (PCL) –
Aggressive with circulating plasma
cells Characterized by Reed-Sternberg cells
 3. Stage III: Both diaphragm sides;
spleen/organ involvement
Subtypes of Classical HL (cHL): 4. Stage IV: Disseminated involvement
(extranodal and distant)
 Nodular Sclerosis
 Mixed Cellularity
 Lymphocyte Rich
 Lymphocyte Depleted Diagnosis
 History and physical exam
 CBC, ESR
Also includes Nodular Lymphocyte-
 Biopsy: Reed-Sternberg cells
Predominant HL (NLPHL)
 Lumbar puncture: CNS involvement
 CT, MRI, PET scans

Epidemiology:

 Bimodal distribution: Young adults Treatment

(15–35) and older adults (>50)
1. Chemotherapy
o ABVD (Adriamycin,
Bleomycin, Vinblastine,
Etiology: Dacarbazine)
o BEACOPP
 Unknown; EBV and HIV implicated 2. Radiation therapy
 Family history increases risk 3. Biological therapy (e.g., Rituximab)
4. Stem cell transplantation
5. Lymphadenectomy

Non-Hodgkin Lymphoma (NHL)

 90 subtypes (B-cell or T-
cell origin)
Serological and


Can be aggressive or indolent
Median age: 67
Molecular Detection
 Lacks Reed-Sternberg cells
of Bacterial
Infections
Staging (HL & NHL)
1. Stage I: Single lymph node/region
2. Stage II: Multiple regions on same Introduction to Human-
diaphragm side Microbe Relationship
  Begins at birth  Commensalism: Microbe benefits;
 Bacteria colonize body surfaces, host unaffected
especially the gastrointestinal tract  Mutualism: Both benefit (e.g.,
 Forms a symbiotic relationship with Lactobacillus in vaginal canal)
the host  Parasitism: Microbe harms host
(infection)

Indigenous Microbiota
Key Terms
 Also called normal flora
 Varies by body area  Infectivity: Ease of establishing
 Microbial cells outnumber human infection
cells  Virulence: Severity of disease caused
 Can account for 2 to 6 pounds of  Virulence Factors: Enhance ability to
body weight infect, evade immunity, and damage
tissue
 Pathogenicity: Genetic potential of
organism to cause disease
Primary Pathogens: Infect healthy
Diversity of the 
hosts
Microbiome  Opportunistic Pathogens: Infect
immunocompromised hosts
 Highly diverse microbial community
 Over 90% of bacteria are
unculturable
 Require specific environmental Bacterial Virulence Factors
conditions
 Enable bacteria to cause disease
 Types:
o Structural (e.g., endotoxins)
Co-evolution and Co- o Extracellular products (e.g.,
adaptation exotoxins)
 Found on:
o Chromosomes (structural)
 Host and microbes evolve together
o Plasmids (extracellular)
 Bacteria develop mechanisms to
 Functions: Attachment, immune
evade immune responses
evasion, tissue damage, spread
 Microbes replicate and spread
efficiently

Immune Defenses &

Types of Symbiotic Bacterial Evasion
Relationships
 o Selective
o Differential (e.g.,
Host Defenses MacConkey agar)
 Limitations:
 Physical Barriers: Skin, mucosa o Some pathogens are
 Enzymes: Lysozyme, ribonucleases unculturable or slow-growing
 Antimicrobial Peptides (ADPs) o Biohazard risks
 Cell-Mediated Immunity (CMI):
Targets intracellular bacteria

Microscopic Visualization

Bacterial Evasion Mechanisms  Requires staining and trained

personnel
 Change surface proteins to avoid  Techniques:
antibodies o Gram stain
 Block phagocytosis via: o Acid-fast stain
o Inhibited chemotaxis (Mycobacterium)
o Preventing adhesion o Giemsa stain (malaria)
o Surviving inside immune o Direct Fluorescent Antibody
cells (DFA)
 Inactivate complement system  Limitations:
o Sensitivity and availability
issues

Laboratory Detection of
Bacterial Infections Antigen Detection

 Detects antigens of bacteria, viruses,

fungi, parasites
Five General Methods  Methods:
o Latex Agglutination
1. Bacterial Culture o ELISA
2. Microscopic Visualization o Lateral Flow Assays (LFA)
3. Antigen Detection o PCR & qPCR
4. Molecular Detection
5. Serological Diagnosis

Advantages:

Bacterial Culture  Fast, affordable, highly specific,

CLIA-waived
 Grown in broth or solid media
 Media Types:
o Enriched
Common Uses:

 Streptococcus pyogenes, Legionella Group A Streptococci

pneumophila, Rotavirus, RSV,
Influenza (GAS) - Streptococcus
pyogenes

Molecular Detection
Structure
 Detects pathogen DNA/RNA
 Techniques:
 Gram-positive cocci
o PCR
 β-hemolytic on blood agar
o qPCR
 Causes pharyngitis, impetigo
 Identified via M and T proteins

Limitations:

 High cost
Typing Methods
 Few FDA-approved kits
 Use is expanding with technology  Serotyping: Identifies M protein
antigens (80+ types)
o Limitations: Antisera
availability, result
interpretation
Serological Diagnosis  Genotyping: PCR of emm gene +
sequencing
 Detects antibodies (IgM, IgG)  PFGE: DNA fingerprinting method
 Useful for hard-to-culture or for epidemiology
nonspecific pathogens

Key Organisms:
Virulence Factors

 Anaplasma, Ehrlichia,  M protein: Inhibits phagocytosis

Chlamydophila, Coxiella,  Pyrogenic Exotoxins A, B, C: Cause
Leptospira, Rickettsia, Treponema rash in scarlet fever

Pros & Cons: Clinical Manifestations

 Pros: Past/recent infection tracking  Pharyngitis: Fever, sore throat,

 Cons: Delay in antibody appearance, tonsillar exudates, rash
unclear infection timing
  Impetigo: Vesicular lesions, crusted o Anti-NADase
skin infection o Anti-Hyaluronidase
 Scarlet Fever: Rash, fever, vomiting,
abdominal pain

ASO Testing
Sequelae  Detects antibodies to Streptolysin O
 Indicates recent infection (peaks 3–6
 Acute Rheumatic Fever: Joint & weeks post-infection)
heart inflammation
 Glomerulonephritis: Kidney
inflammation post-infection (mainly
in children) Anti-DNase B Testing

 Useful when ASO is negative

 Specific to GAS-related sequelae
Laboratory Diagnosis of
GAS
Streptozyme Test

 Slide agglutination for multiple GAS

Culture antibodies
 Quick but less reproducible
 Blood agar: Clear β-hemolysis
indicates GAS

SPIROCHETES
Antigen Detection DISEASES
 Rapid tests from throat swabs (2–30
min)
 LFA is increasingly used (high Spirochetes are:
sensitivity/specificity)
 Long, slender, helically coiled
bacteria with a unique corkscrew-
like motility due to axial filaments
Antibody Detection (also called periplasmic flagella).
 They are gram-negative and
 For delayed manifestations (e.g., microaerophilic, requiring low
rheumatic fever) oxygen conditions.
 Key Antibodies:  Infections often start as localized but
o Anti-Streptolysin O (ASO) may spread systemically, potentially
o Anti-DNase B leading to latent stages and
 neurological or cardiac  Appears 10–90 days post-infection
complications if untreated. (avg. 21 days).
 Chancre: painless, firm, well-defined
ulcer (commonly on genitals).
 Heals spontaneously in 1–6 weeks.
1. Syphilis
Secondary Stage
Causative Agent: Treponema  Occurs 1–2 months after chancre
pallidum resolves.
 Symptoms: fever, malaise,
 Thin, spiral-shaped organism with 6– lymphadenopathy, rash on
14 coils, 6–20 μm in length. palms/soles, pharyngitis,
 Cannot survive outside a living host; visual/hearing disturbances.
lacks natural environmental  Lesions heal within days to 8 weeks.
reservoirs.
 Related species:
o T. pallidum subspecies
pertenue (yaws) Latent Stage
o T. pallidum subspecies
endemicum (bejel)  No visible symptoms.
o Treponema carateum (pinta)  Early latent: <1 year
 Late latent: >1 year
 Generally non-infectious except in
pregnancy.
Transmission

 Primarily sexual contact through

mucous membranes or abraded skin. Tertiary Stage
 Congenital transmission during
pregnancy.  Develops 10–30 years later.
 Parenteral exposure via contaminated  Major manifestations:
needles or blood. o Gummatous syphilis:
 30–50% chance of transmission per granulomas in skin, bone.
sexual contact with active lesions. o Cardiovascular syphilis:
aortic aneurysm, angina.
o Neurosyphilis: meningitis
(early) or spinal cord
Stages of Syphilis degeneration (late), especially
in immunocompromised
individuals.

Primary Stage
Congenital Syphilis o Nontreponemal tests: VDRL,
RPR (used for screening;
 Transplacental transmission from an titers decline after treatment)
infected mother (mostly in early or o Treponemal tests: FTA-ABS,
latent syphilis). TPPA (specific; stay positive
 10% fetal or perinatal death rate. for life)
 Early signs may be absent at birth,  Testing Algorithms:
but develop in 60–90% untreated o Traditional: Nontreponemal
infants: first, then treponemal.
o Rhinitis, maculopapular rash, o Reverse: Treponemal first
hepatosplenomegaly, bone (automated), then confirm
abnormalities, anemia. with nontreponemal.
 Imaging: signs like syphilitic  Molecular testing: PCR (not widely
metaphysitis in bones. available).
 Special cases:
o CSF VDRL for neurosyphilis
o Cord blood/serum in
Immune Response congenital syphilis

 Innate immunity: Intact skin/mucosa

are the first barriers.
 Cellular immunity: CD4+/CD8+ T- 2. Lyme Disease
cells and macrophages clear
infection.
 Evasion mechanisms:
o T. pallidum uses TROMPs
Causative Agent: Borrelia
(outer membrane proteins) to
delay immune response. burgdorferi
o Coats itself with host proteins
to evade detection.  Loosely coiled spirochete, 5–25 μm
 Despite immune activity, the long.
bacterium can persist chronically  Outer membrane contains glycolipids
without antibiotics. and proteins; has 7–11 endoflagella.
 Divides every 12 hours; hard to
culture; spirochetemia is brief.

Laboratory Diagnosis

 Darkfield microscopy: Detects Transmission

spirochetes from active lesions.
 Fluorescent antibody testing:  Spread by Ixodes ticks (deer ticks).
Sensitive and specific, doesn’t  Reservoir host: White-footed mouse.
require live samples.  Ticks must feed for 24–48 hours for
 Serological Testing: transmission to occur.
Stages of Disease

Diagnosis

Early Localized  Clinical diagnosis includes history of

tick bite and rash.
 Occurs within days to weeks.  Serological tests:
 Erythema migrans (EM): expanding o ELISA (screening)
bullseye rash (absent in ~20% of o Western Blot (confirmation)
cases).  Antibodies (IgM, IgG) usually
 May resolve on its own in 3–4 appear 3–6 weeks after symptoms
weeks. begin.

Early Disseminated Treatment

 Days to weeks later, affects skin,  Stage 1: Amoxicillin, Doxycycline,
joints, heart, and nervous system. or Cefuroxime
 Symptoms: multiple EM rashes,  Stages 2 & 3: Ceftriaxone
facial palsy, meningitis, carditis.

Late Lyme Disease 3. Relapsing Fever

(Borrelia miyamotoi)
 Months to years later in untreated
cases.  Newly emerging disease related to
 Manifestations: the relapsing fever group.
o Arthritis  First isolated in Japan (1995); human
o Peripheral neuropathy cases identified in Russia (2011),
o Encephalomyelitis U.S. (2013).

Immune Response Transmission

 Triggered by spirochete lipoproteins,  Ixodes ticks (same vector as Lyme
which stimulate macrophages. disease).
 Despite strong antibody and cellular  Lower tick infection rate than Lyme
responses, chronic symptoms may (1–5% vs. 20–50%).
persist.  Can be transmitted by larval ticks;
 Immune evasion mechanisms may both horizontal and vertical (mother-
allow long-term survival of the to-egg) transmission.
bacteria.
Clinical Features o Virion: Fully formed
infectious virus particle.
 Recurrent flu-like illness: fever,  Key Properties:
chills, fatigue. o Obligate Intracellular
 Erythema migrans, arthritis, and Pathogens: Cannot replicate
palsy are rare. outside a living host.
 Causes high bacteremia but lacks a o Diverse Pathogenicity: Range
persistent skin infection phase like from mild illness to fatal
Lyme. infections.

Diagnosis 2. VIRUS LIFE CYCLE

 PCR testing (potential tool for future 1. Attachment: Virus binds to specific
diagnosis). receptors on the host cell membrane.
 No reliable culture method yet. 2. Penetration: Entry into the host cell,
 Antibodies may cross-react with often via endocytosis or membrane
Lyme tests. fusion.
 GlpQ-based ELISA is more specific, 3. Uncoating: Viral genome is released
but no FDA-approved tests currently into the host cell.
exist. 4. Transcription: Host machinery
transcribes viral genome.
5. Translation: Viral mRNA translated
into proteins.
6. Assembly: New virions are
SEROLOGIC & assembled from synthesized
MOLECULAR components.
7. Budding or Lysis: Virions exit the
DETECTION OF VIRAL cell by budding (enveloped viruses)
INFECTIONS or lysis (non-enveloped viruses).

1. VIRUS STRUCTURE  Replication Sites:

o DNA Viruses: Mostly in the
 Basic Components: nucleus.
o Genetic Material: DNA or o RNA Viruses: Generally in
RNA (never both). the cytoplasm.
o Capsid: Protein shell
composed of capsomeres that
encloses genetic material.
o Envelope (optional): Lipid 3. IMMUNE DEFENSE AGAINST
bilayer derived from host VIRUSES
cell; aids in viral entry and
immune evasion.
Innate Immunity (First Line of Defense): Viruses have evolved multiple strategies to
evade immune detection and destruction,
 Physical Barriers: Skin and mucous ensuring their survival and replication:
membranes prevent initial viral
entry. 1. Antigenic Variation:
 PAMP Recognition: Pathogen- o High mutation rates create
associated molecular patterns new viral variants.
recognized by host receptors. o Seen in Influenza, HIV,
 Type I Interferons (IFN-α and IFN- Rhinovirus, etc.
β): Inhibit viral replication. o Undermines vaccine efficacy
 Natural Killer (NK) Cells: Destroy and long-term immunity.
virus-infected cells. 2. Innate Immune Evasion:
o Inhibit interferon production
or signaling.
o Block complement system
Adaptive Immunity (Targeted Response): and lysosomal function.
3. Suppression of Adaptive Immunity:
o Downregulate MHC
molecules.
I. Humoral Immunity o Inhibit T-cell activation and
antibody responses.
 Neutralizing Antibodies: Block viral
attachment and entry.
 IgA: Protects mucosal surfaces.
 IgM and IgG: Circulate in the blood; 5. LABORATORY TESTING FOR
IgG facilitates opsonization and VIRAL INFECTIONS
antibody-dependent cellular
cytotoxicity (ADCC).

A. Serologic Testing
II. Cell-Mediated Immunity
 IgM: Indicates current or recent
infection (also used to diagnose
 Th1 Cells: Secrete IFN-γ and IL-2 to congenital infections).
activate macrophages.  IgG: Indicates past infection or
 CD8+ Cytotoxic T Lymphocytes immunity.
(CTLs): Recognize infected cells via  Antibody Titer: Fourfold rise in titer
MHC I and induce apoptosis using (e.g., 1:4 to 1:16) is significant for
perforin and granzyme. active infection or recent exposure.

4. VIRAL ESCAPE MECHANISMS B. Molecular Testing

 qPCR (Real-Time PCR): Quantifies

viral RNA/DNA; guides treatment.
  Genotyping: Determines strain for  Target: B lymphocytes.
epidemiological tracking and therapy  Transmission: Saliva.
planning.  Associated Diseases: Mononucleosis,
 Used to: Burkitt’s lymphoma, nasopharyngeal
o Detect active infection. carcinoma.
o Monitor viral load.
o Confirm immunity (presence
of virus-specific IgG).
Cytomegalovirus (CMV)

 Transmission: Saliva, blood, urine,

6. HEPATITIS VIRUSES breast milk, sexual contact.
 At-Risk Groups:
 HAV (Hepatitis A): RNA virus Immunocompromised individuals.
(Picornaviridae); fecal-oral  Diagnosis: PCR (gold standard);
transmission; diagnosed with anti- screen transplant donors/pregnant
HAV IgM. women.
 HEV (Hepatitis E): RNA virus
(Hepeviridae); fecal-oral
transmission; severe in pregnant
women. Varicella-Zoster Virus (VZV)
 HBV (Hepatitis B): DNA virus
(Hepadnaviridae); bloodborne/sexual  Diseases: Chickenpox (primary),
transmission; markers include shingles (reactivation).
HBsAg, HBeAg, HBcAg.  Transmission: Respiratory droplets,
 HDV (Hepatitis D): Requires HBV skin lesions.
for replication; tested via anti-HDV,  Diagnosis: Clinical + PCR, serology
HDV RNA. (IgG for immunity).
o Coinfection: Acute infection.
o Superinfection: Accelerated
chronic liver disease.
 HCV (Hepatitis C): RNA virus Rubella
(Flaviviridae); transmitted via blood
and sexual contact.  Transmission: Respiratory droplets
o Testing: Anti-HCV IgG or placenta.
(EIA/CLIA), HCV RNA  Risks: Congenital defects,
(RT-PCR), and genotyping. miscarriage.
 Diagnosis: Serology (IgM, IgG), RT-
PCR.

7. OTHER VIRAL INFECTIONS

Rubeola (Measles)

Epstein-Barr Virus (EBV)  Transmission: Respiratory droplets.

 Complications: Encephalitis, SSPE.
  Diagnosis: Serology (IgM, IgG), RT-  Colonizes the human stomach,
PCR for genotyping. typically acquired in childhood.
 Transmission: Oral-oral or fecal-oral
routes.

Mumps

 Diagnosis: RT-PCR (preferred), Associated Diseases:

ELISA for IgM and IgG.
 Culture: Gold standard using  Chronic Gastritis
monkey kidney cells.  Peptic Ulcer Disease
 Gastric Adenocarcinoma
 MALT Lymphoma

Human T-cell Lymphotropic Virus

(HTLV)
WHO Classifies H. pylori as a Group I
 HTLV-I: Linked to adult T-cell carcinogen.
leukemia/lymphoma.
 HTLV-II: Less clearly associated
with disease.
 Transmission: Bloodborne, sexual, Virulence Factors:
perinatal.
 Target Cells: CD4+ T cells. 1. Motility: Flagella help navigate
through gastric mucus.
2. Urease Production: Converts urea
into ammonia to neutralize stomach
Serological and Molecular acid.
Detection of Bacterial Infections 3. Adhesins (BabA, SabA): Help the
bacterium stick to stomach lining.
4. CagA Protein: Injected into cells;
disrupts signaling; linked to cancer.
5. VacA Toxin: Damages epithelial
I. HELICOBACTER cells.
PYLORI 6. Flagellar Sheath: Protects from
acidic environment.

Presenter: Arra Piedad

Pathogenesis:

Overview:
(Presenter: Yesheen Poliran)
 Gram-negative, spiral-shaped
bacterium.
  Penetration: Motility allows bacteria Presenter: Gieanne Rabang
to reach epithelial surface.
 Acid Resistance: Ammonia creates a
buffered zone.
 Tissue Damage: Neutrophil activity Overview:
and byproducts cause inflammation.
 Chronic Effects: Increased risk of  Smallest free-living bacteria; lacks a
gastric cancer and MALT cell wall, so penicillin is ineffective.
lymphoma.  Transmission: Respiratory droplets;
close contact needed.
 Incubation: 1–3 weeks.

Diagnosis:

Symptoms:
Invasive Methods:  Fever, headache, malaise, persistent
cough.
 Endoscopy + Biopsy: Direct tissue  Known as “walking pneumonia”
evaluation. (mild, often unrecognized).
 CLOtest (Urease Detection): Positive
if color changes (yellow →
magenta).
Complications:

 Chronic inflammation, asthma-like

Noninvasive Methods: symptoms.
 Stevens-Johnson Syndrome (SJS):
 Urea Breath Test (UBT): Measures Severe skin/mucosal reactions; rare
exhaled labeled CO2. but serious.
 Stool Antigen Test  Raynaud Syndrome: Cold-induced
 Serology: ELISA detects IgG finger blanching due to immune
antibodies. response.
 Molecular Methods (PCR): Detects
H. pylori DNA.
 Culture: Gold standard but time-
consuming and sensitive to sample Laboratory Diagnosis:
quality.

(Presenter: Kinnah Pulido)

II. MYCOPLASMA
PNEUMONIAE 1. Culture: Slow, impractical. Colonies
look like “fried egg”.
2. Serology:
 oIgM detection: Suggests  Transmitted through bites or contact
recent infection. with infected feces (e.g., louse feces
o IgG detection: For reinfection in R. prowazekii).
in adults.
o ELISA: Highly sensitive
(98%) and specific (>99%).
3. Cold Agglutinins: Key Diseases:
o Detects RBC clumping at
4°C.
o Not specific, but may support
diagnosis. Epidemic Typhus
4. Molecular Testing (PCR):
o Detects DNA from  Pathogen: Rickettsia prowazekii
respiratory samples.  Transmission: Human scratches in
o Rapid, highly accurate – new louse feces.
gold standard.  Host: Humans are the primary
reservoir.

III. RICKETTSIAL Rocky Mountain Spotted Fever (RMSF)

INFECTIONS
 Pathogen: Rickettsia rickettsii
 Vectors:
o American Dog Tick
Presenter: Jeazal Mae Pletado o Rocky Mountain Wood Tick
o Brown Dog Tick
 Season: May to September (peak tick
season).
Classification:

 Gram-negative, obligate intracellular

bacteria. Pathogenesis:
 Two major groups:
o Spotted Fever Group (SFG) –  Spread: Via lymphatic and blood
e.g., Rickettsia rickettsii. systems.
o Typhus Group (TG) – e.g.,  Target: Vascular endothelium (inner
Rickettsia prowazekii. lining of blood vessels).
 Attachment: Uses OmpA/OmpB
proteins.
 Damage Results In:
Transmission: o Leaky vessels → Edema
o Low blood pressure
 Vectors: Ticks, lice, fleas, mites. o Low albumin
(hypoalbuminemia)
Clinical Features:

 Incubation: 2–14 days.

 Fever: Within 3–5 days.
 Rash:
o Appears 3–5 days after fever.
o Begins on extremities
(hands/soles) and spreads.
 Mortality:
o Without treatment: Death
may occur within 7–15 days.
o Fulminant cases: Can be fatal
in just 5 days.

Diagnosis & Treatment:

 Clinical diagnosis supported by

symptom pattern.
 Serologic Testing:
o Indirect Immunofluorescence
Assay (IFA): Gold standard.
o Antibodies develop 7–10
days after onset.
 Treatment: Doxycycline (first-line;
start immediately).