Discussion on types, pathogenesis of hypersensitivity. Referred from Robbins 10th edition. Prepared by a pathology Postgraduate for 2nd year MBBS students
Call Girls in Lucknow Just Call 👉👉 8875999948 Top Class Call Girl Service Ava...
HYPERSENSITIVITY.pptx
1. A 25 YEAR OLD HEALTHY MALE CRRI HAD A TINY ABSCESS IN HIS
INDEX FINGER. AN INCISION AND DRAINAGE WAS PERFORMED UNDER
LOCAL ANASTHESIA FOLLOWING WHICH HE DECIDED TO RESUME HIS
DUTY AT OP DEPARTMENT. WITHIN FEW MINUTES, HE WAS SEEN
RUNNING TO THE CASUALTY - CRYING AND CATCHING HIS THROAT.
3. INTRODUCTION
• HYPERSESNSITIVITY
• EXCESSIVE OR HARMFUL REACTION TO AN ANTIGEN
• SENSITISED
• INDIVIDUALS WHO HAVE BEEN PREVIOUSLY EXPOSED TO AN ANTIGEN
MANIFEST DETECTABLE REACTIONS TO THAT ANTIGEN
4. GENERAL FEATURES
• ELICITED BY
• EXOGENOUS ENVIRONMENTAL ANTIGENS - ALLERGY
• ENDOGENOUS SELF ANTIGENS – AUTO IMMUNE DISEASES
• IMBALANCE BETWEEN THE EFFECTOR AND CONTROL MECHANISMS
• INHERITANCE OF PARTICULAR SUSCEPTIBILITY GENES
• MISDIRECTED MECHANISMS OF TISSUE INJURY
5. CLASSIFICATION
• TYPE 1 – IMMEDIATE HYPERSENSITIVITY
• TYPE 2 – ANTIBODY MEDIATED DISORDERS
• TYPE 3 – IMMUNE COMPLEX MEDIATED DISORDERS
• TYPE 4 – CELL MEDIATED DISORDERS
6. TYPE 1 HYPERSENSITIVITY
EXAMPLES
BEE STING, PEANUT ALLERGY
SYMPTOMS
LOCAL – RASH, BLISTERS,
NASAL/CONJUNCTIVAL DISCHARGE
SYSTEMIC – SHOCK
CYTOKINES TO REMEMBER
IL – 4 – B CELL CLASS SWITCHING TO Ig E
IL – 5 – EOSINOPHILS ACTIVATION
IL – 13 – MUCUS SECRETION BY EPITHELIAL
CELLS AND INCREASES Ig E SECRETION
7. SENSITIZATION & ACTIVATION OF MAST CELLS
• MAST CELLS
• BONE MARROW DERIVED
• ABUNDANT IN SUBEPITHELIAL TISSUES
• CYTOPLASMIC MEMBRANE BOUND GRANULES WITH MANY
MEDIATORS
• ACIDIC PROTEOGLYCANS BIND TO BASIC TOLUDINE BLUE DYE
• ACTIVATION
• HIGH AFFINITY Ig E Fc RECEPTORS
• C5a
• C3
DRUGS
CODEINE
MORPHINE
ADENOSINE
MELITTIN (BEE
VENOM)
8. MAST CELLS HAVE FCεRI RECEPTORS THAT BINDS TO Ig E
Ig E COATED MAST CELL EXPOSED TO ANTIGEN
ANTIGEN BINDS TO Ig E
CROSS LINK ADJACENT Ig E ANTIBODIES
RELEASE OF PREFORMED AND DE NOVO MEDIATORS
13. LATE PHASE REACTION
• RECRUITMENT OF LEUCOCYTES – EOSINOPHILS
• MAJOR BASIC PROTEIN
• EOSINOPHIL CATIONIC PROTEIN
• CHARCOT LEYDEN CRYSTALS WITH PROTEIN GALECTIN -10
• AMPLIFY & SUSTAIN THE RESPONSE
• WITHOUT ADDITIONAL EXPOSURE TO ANTIGEN
14. DEVELOPMENT OF ALLERGIES
• ATOPY – PROPENSITY TO DEVELOP IMMEDIATE HYPERSENSITIVITY
• HIGH Ig E LEVELS
• POSITIVE FAMILY HISTORY
• SUSCEPTIBILITY IS GENETICALLY DETERMINED – HLA GENES ON
CHROMOSOME 6
• ENVIRONMENTAL FACTORS
• NONATOPIC ALLERGY – Th2 CELLS & IgE NOT INVOLVED – MAST
CELLS ABNORMALLY SENSITIVE TO NON IMMUNE STIMULI
• HYGEINE HYPOTHESIS
23. TYPE 3 - IMMUNE COMPLEX MEDIATED
• ANTIGEN – ANTIBODY COMPLEX PRODUCE TISSUE DAMAGE BY
ELICITING INFLAMMATION AT THE SITES OF DEPOSITION
• IN SITU IMMUNE COMPLEXES
• MOSTLY SYSTEMIC
• COMMONLY INVOLVED SITES
• KIDNEY
• JOINTS
• BLOOD VESSELS
24. FORMATION OF IMMUNE COMPLEXES
• SERUM SICKENSS –
PROTOTYPE
• AbS FORMED 1 WEEK
AFTER INJECTION OF
PROTEIN
25. IMMUNE COMPLEX DEPOSITION
• MEDIUM SIZED COMPLEXES
WITH ANTIGEN EXCESS –
MOST PATHOGENIC
• BLOOD FILTERING WITH HIGH
PRESSURE -> CONCENTRATES
COMPLEXES -> DEPOSITION
26. INFLAMMATION & TISSUE INJURY
• AFTER 10 DAYS OF INJECTION OF
PROTEIN
• ANTIBODY MEDIATED
MECHANISMS
• C/F : FEVER, UTRICARIA, JOINT
PAIN, LN ENLARGEMENT,
PROTEINURIA
• CONSUMPTION OF
COMPLEMENTS
• LOW SERUM C3 LEVELS
27. MORPHOLOGY
• LIGHT MICROSCOPY – FIBRINOID NECROSIS
• ACUTE VASCULITIS
• SMUDGY EOSINOPHILIC AREA - NECROTIC TISSUE & DEPOSITS
• IMMUNOFLUORESCENCE MICROSCOPY – GRANULAR LUMPY
DEPOSITS OF IG
• ELECTRON MICROSCOPY – ELECTRON DENSE DEPOSIT ON BM
28. ACUTE SERUM SICKNESS
• SINGLE EXPOSURE TO LARGE
AMOUNT OF ANTIGEN
• RESOLVES
CHRONIC SERUM SICKNESS
• REPEATED / PROLONGED
EXPOSURE
• PERSISTENT ANTIBODY
RESPONSE TO AUTO ANTIGEN
• EX: SLE
ARTHUS REACTION
• LOCAL IMMUNE COMPLEX
DISEASE
• INTRACUTANEOUS ANTIGEN IN A
SENSITISED SUBJECT
• LARGE IMMUNE COMPLEXES
FORMED LOCALLY
• FIBRINOID NECROSIS
• SUPERIMPOSED BY THROMBOSIS
• ISCHEMIC INJURY
29. TYPE 4 – T CELL MEDIATED
• INFLAMMATION RESULTING FROM CYTOKINES PRODUCED BY CD4+
T CELLS – CHRONIC & DESTRUCTIVE
• KILLING BY CD8+ CELLS
• DELAYED TYPE HYPERSENSITIVITY – PROTOTYPE
• ANTIGEN TO SKIN
• DETECTABLE RESPONSE IN 24 – 48 HRS
• Th1 CELLS – ACTIVATED MACROPHAGES
• Th17 CELLS – NEUTROPHILS
30. ACTIVATION OF CD4+ T CELLS
DC &
AG
• CD4+ CELLS RECOGNIZE
• SECRETE IL-2 – PROLIFERATION OF T CELLS
APCs
CYTOKINES
• IL – 12 => Th1 CELLS
• IL – 1, 6, 23 => Th17 CELLS
MEMORY T
CELLS
• PERSISTS FOR YEARS
31. EFFECTOR T CELLS RESPONSES
Th1
CELLS
• SECRETE IFN - γ
• IFN – γ ACTIVATED MACROPHAGES – MORE POTENT
• EXPRESS MORE CLASS II MHC MOLECULES
MACROPHAGES
• SECRETE TNF, IL – 1, IL – 12 & CHEMOKINES
• INFLAMMATION AND AMPLIFIED Th1 RESPONSE
Th17 CELLS
• SECRETE IL-17, IL-22 & CHEMOKINES
32. CD8+ T CELL MEDIATED CYTOTOXICITY
APCs DISPLAY CLASS I MHC MOLECULES
CTLs SECRETE COMPLEXES WITH PERFORINS, GRANZYMES
COMPLEX ENDOCYTOSED BY TARGET CELLS
APOPTOSIS OF TARGET CELLS
