OUTLINE

01 Overview of Normal Immune Response

02 Overview of Lymphocyte Activation

03 Hypersensitivity Disorders
 OVERVIEW OF
01 NORMAL IMMUNE
RESPONSE
01 OVERVIEW OF NORMAL IMMUNE RESPONSE

1. INNATE IMMUNITY
• Epithelium
• Cells: Macrophage, Monocytes (Macrophages), Dendritic cells,
Neutrophils, Mast cells, INNATE LYMPHOID CELLS
• Complement system
2. ADAPTIVE IMMUNITY
• Humoral Immunity: B Lymphocytes
• Cell-mediated Immunity: T Lymphocytes
 01 INNATE VS ADAPTIVE IMMUNITY

1. INNATE IMMUNITY
• uses about 100 different receptors to recognize 1000 molecular patterns
2. ADAPTIVE IMMUNITY
• uses memory and fine antigen specificity
 01 INNATE IMMUNITY
Toll like receptors
• activates transcription factors NF kB and
interferon regulatory factors to produce
cytokines
NOD-like receptors
• signal via a cytosolic multiprotein complex
called the inflammasome, which activates an
enzyme (caspase-1) that cleaves a
precursor form of the cytokine interleukin-1
(IL-1) to generate the biologically active form
 01 INNATE IMMUNITY
Natural killer cells
• lymphocytes that recognizes and
destroys severely stressed or abnormal
cells, such as virus-infected cells and
tumor cells
• antibody-dependent cellular cytotoxicity
(ADCC)- able to lyse IgG coated cells
• regulated by signals from activating and
inhibitory receptors
 01 MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULES

• Part of adaptive immunity

• display peptide fragments of protein antigens for recognition by antigen
specific T cells
• MHC molecules are called human leukocyte antigens (HLA) because
they were initially detected on leukocytes
• 2 major classes
01 MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULES
 OVERVIEW OF
02 LYMPHOCYTE
ACTIVATION
02 ANTIGEN PRESENTING CELLS
1. DENDRITIC CELLS
• most important antigen-presenting
cells for initiating T-cell responses
against protein antigens
• located under epithelia and in the
interstitium
• recruited to the T-cell zones of
lymphoid organs
• express high levels of MHC
2. MACROPHAGES
• present peptide fragments to T cells
• T cells activate macrophages and
enhance their ability to kill ingested
microbes
• efficiently phagocytose and
destroy microbes that are
opsonized (coated) by IgG or C3b.
03
HYPERSENSITIVITY
DISORDERS
03 HYPERSENSITIVITY REACTIONS

● Immediate (Type I) Hypersensitivity

● Antibody-Mediated (Type II) Hypersensitivity

● Immune Complex-Mediated (Type III) Hypersensitivity

● T-Cell Mediated (Type IV) Hypersensitivity

 03 HYPERSENSITIVITY REACTIONS

Immediate (Type I) Hypersensitivity

● allergies or allergic reactions

● Rapid

● IgE-mediated

● Occurs in previously sensitized individuals

 03 HYPERSENSITIVITY REACTIONS

Immediate (Type I) Hypersensitivity

● Principal mediators:
○ histamine, proteases, and other granule contents
○ prostaglandins and leukotrienes
○ cytokines.
● Responsible for the immediate vascular and smooth muscle
reactions and the late-phase reaction (inflammation)
 03 HYPERSENSITIVITY REACTIONS
Immediate (Type I) Hypersensitivity

● 2 phases
○ Immediate Phase
■ Vascular changes (vasoactive amines)
○ Late Phase
■ Leukocytic infiltration and tissue damage
■ Main Cells: Eosinophils
■ IL-5: most potent eosinophil activating cytokines from Th2 cells
 03 HYPERSENSITIVITY REACTIONS

Immediate (Type I) Hypersensitivity

1st Th2 cell activation

Exposure production of IgE that binds to
to basophils and mast cells
Allergen

Antigen binds to IgE on basophils and

mast cells
Sub- →
sequent
mast cell degranulation of vasoactive
Exposure
to amines (immediate phase)
Allergen →
release of cytokines and chemokines
(late phase)
 03 HYPERSENSITIVITY REACTIONS

Immediate (Type I) Hypersensitivity

 03 HYPERSENSITIVITY REACTIONS

Antibody mediated (Type II ) Hypersensitivity

● The following mechanisms are mediated by antibodies:
○ Opsonization and phagocytosis
○ Inflammation
○ Cellular dysfunction
 03 HYPERSENSITIVITY REACTIONS

Antibody mediated (Type II ) Hypersensitivity

EFFECTS MECHANISM CONDITIONS

Opsonization ● Opsonization: AIHA
and ○ Coating cells with IgG or C3b signals AHTR
phagocytosis phagocytosis HDN
● Lysis: ITP
○ Membrane attack complex from
complement activation
● Antibody dependent cellular cytotoxicity:
○ IgG-coated cells signals effector cells to
lyse target without phagocytosis
 03 HYPERSENSITIVITY REACTIONS

Antibody mediated (Type II ) Hypersensitivity

EFFECTS MECHANISM CONDITIONS

Inflammation ● Complement activation ANCA vasculitis
○ production of anaphylatoxins (C3a & C5a) Goodpasture
syndrome
● C5a: leukocyte migration
Acute rheumatic
● Anaphylatoxins: ↑ vascular permeability fever
 03 HYPERSENSITIVITY REACTIONS

Antibody mediated (Type II ) Hypersensitivity

EFFECTS MECHANISM CONDITIONS

Cellular ● Antibodies bind to receptors and alter their Myasthenia gravis
Dysfunction function without injury or inflammation Graves disease
03 HYPERSENSITIVITY REACTIONS
 03 HYPERSENSITIVITY REACTIONS

Immune Complex-mediated (Type III ) Hypersensitivity

● Immune complex deposition → Tissue injury by eliciting inflammation
● MC site: Kidneys (glomeruli), Joints
● Systemic Disease
○ Except Arthus Reaction
 03 HYPERSENSITIVITY REACTIONS

Immune Complex-mediated (Type III ) Hypersensitivity

● Morphology:
○ Acute vasculitis
■ Necrosis of the vessel wall and intense neutrophilic infiltration
○ Fibrinoid necrosis:
■ Smudgy, eosinophilic area of tissue destruction composed of:
● necrotic tissue, deposits of immune complexes,
components, and plasma protein
03 HYPERSENSITIVITY REACTIONS
 03 HYPERSENSITIVITY REACTIONS

Cell-mediated (Type IV ) Hypersensitivity

● CD4+ - mediated

● CD8+ (cytotoxic T-cell)-mediated

 03 HYPERSENSITIVITY REACTIONS

Cell-mediated (Type IV ) Hypersensitivity

● CD4+ - mediated

○ Antigen exposure

■ CD4+ differentiation to Th1 & Th17 cells

○ Subsequent exposure
 03 HYPERSENSITIVITY REACTIONS

Cell-mediated (Type IV ) Hypersensitivity

● CD4+ - mediated
Antigen exposure Subsequent Exposure

CD4+ differentiation to Th1 Th17

Th1 & Th17 cells Secretes IFN-y Produces IL-17 & other
↓ cytokines
Activates macrophages ↓
to secrete cytokines Leukocyte recruitment
↓ ↓
Inflammation Inflammation
 03 HYPERSENSITIVITY REACTIONS

Cell-mediated (Type IV ) Hypersensitivity

● CD8+ - mediated (cytotoxic T-cell)

03 HYPERSENSITIVITY REACTIONS
03 SUMMARY
03 SUMMARY
03 SUMMARY
03 SUMMARY