Immunity

•         IMMUNITY

•         ADAPTIVE (developed by exposure to pathogens, or in a broader sense, antigens)

•         INNATE (present before birth, “NATURAL”)

•         MHC
Major Histocompatibility 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

•         It’s major job is to make sure all self cell antigens are recognized and “tolerated”, because the general rule of the immune system is that all UN-recognized cells will NOT be tolerated

INNATE IMMUNITY

•         BARRIERS

•         CELLS: LYMPHOCYTES, MACROPHAGES, PLASMA CELLS, NK CELLS

•         CYTOKINES/CHEMOKINES

•         PLASMA PROTEINS: Complement, Coagulation Factors

•         Toll-Like Receptors, TLR’s

ADAPTIVE
IMMUNITY

•         CELLULAR, i.e., direct cellular reactions to antigens

•         HUMORAL, i.e., antibodies

•         CELLS of the IMMUNE SYSTEM

•         LYMPHOCYTES, T

•         LYMPHOCYTES, B

•         PLASMA CELLS (MODIFIED B CELLS)

•         MACROPHAGES, aka “HISTIOCYTES”, (APCs, i.e., Antigen Presenting Cells)

•         “DENDRITIC” CELLS (APCs, i.e., Antigen Presenting Cells)

•         NK (NATURAL KILLER) CELLS

•         NK CELLS

GENERAL SCHEME of
CELLULAR EVENTS

APCs (Macrophages, Dendritic Cells)à

T-Cellsà (Control Everything)

–       CD4à “REGULATORS” (Helper)

–       CD8à “EFFECTORS”

B-Cellsà Plasma Cellsà AB’s

NK Cellsà

CYTOKINES

•         MEDIATE INNATE (NATURAL) IMMUNITY, IL-1, TNF, INTERFERONS

•         REGULATE LYMPHOCYTE GROWTH (many interleukins, ILs)

•         ACTIVATE INFLAMMATORY CELLS

•         STIMULATE HEMATOPOESIS, (CSFs, or Colony Stimulating Factors)

•         CYTOKINES/CHEMOKINES

•         CYTOKINES are PROTEINS produced by MANY cells, but usually LYMPHOCYTES and MACROPHAGES, numerous roles in acute and chronic inflammation, AND immunity

–       TNF, IL-1, by macrophages

•         CHEMOKINES are small proteins which are attractants for PMNs

MHC
Major Histocompatibility 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

•         It’s major job is to make sure all self cell antigens are recognized and “tolerated”, because the general rule of the immune system is that all UN-recognized cells will NOT be tolerated

•        

•         MHC MOLECULES
(Gene Products)

•         I (All nucleated cells and platelets), cell surface glycoproteins, ANTIGENS

•         II (APC’s, i.e., macs and dendritics, lymphs), cell surface glycoproteins, ANTIGENS

•         III Complement System Proteins

•         IMMUNE SYSTEM DISORDERS
WHAT CAN GO WRONG?

•         HYPERSENSITIVITY REACTIONS, I-IV

•         “AUTO”-IMMUNE DISEASES, aka “COLLAGEN” DISEASES (BAD TERM)

•         IMMUNE DEFICIENCY SYNDROMES, IDS:

–       PRIMARY (GENETIC)

–       SECONDARY (ACQUIRED)

•         HYPERSENSITIVITY
REACTIONS (4)

•         I (Immediate Hypersensitivity)

•         II (Antibody Mediated Hypersensitivity)

•         III (Immune-Complex Mediated Hypersensitivity)

•         IV (Cell-Mediated Hypersensitivity)

•         Type I
IMMEDIATE HYPERSENSITIVITY

•         “Immediate” means seconds to minutes

•         “Immediate Allergic Reactions”, which may lead to anaphylaxis, shock, edema, dyspnea death

–       1) Allergen exposure

–       2) IMMEDIATE phase: MAST cell DEgranulation, vasodilatation, vascular leakage, smooth muscle (broncho)-spasm

–       3) LATE phase (hours, days): Eosinophils, PMNs, T-Cells

•         TYPE II HYPERSENSITIVITY
ANTIBODY MEDIATED IMMUNITY

•         ABs attach to cell surfaces

–       OPSONIZATION (basting the turkey)

–       PHAGOCYTOSIS

–       COMPLEMENT FIXATION (cascade of C1q, C1r, C1s, C2, C3, C4, C5….. )

–       LYSIS (destruction of cells by rupturing or breaking of the cell membrane)

TYPE II DISEASES

•         Autoimmune Hemolytic Anemia, AHA

•         Idiopathic Thrombocytopenic Purpura, ITP

•         Goodpasture Syndrome (Nephritis and Lung hemorrhage)

•         Rheumatic Fever

•         Myasthenia Gravis

•         Graves Disease

•         Pernicious Anemia, PA

TYPE III HYPERSENSITIVITY
IMMUNE COMPLEX MEDIATED

•         Antigen/Antibody “Complexes”

•         Where do they go?

–       Kidney (Glomerular Basement Membrane)

–       Blood Vessels

–       Skin

–       Joints

•         Common Type III Diseases- SLE (Lupus), Poly(Peri)arteritis Nodosa, Poststreptococcal Glomerulonephritis, Arthus reaction (hrs), Serum sickness (days)

TYPE IV HYPERSENSITIVITY
CELL-MEDIATED (T-CELL)
DELAYED HYPERSENSITIVITY

•         Tuberculin Skin Reaction

•         DIRECT ANTIGENàCELL  CONTACT

–       GRANULOMA FORMATION

–       CONTACT DERMATITIS

–      

•         SUMMARY

•         I    Acute allergic reaction

•         II   Antibodies directed against cell surfaces

•         III  Immune complexes

•         IV  Delayed Hypersensitivity, e.g., Tb skin test

•         RENAL
TRANSPLANT REJECTION

•         HYPERACUTE (minutes) : AG/AB reaction of vascular endothelium

•         ACUTE (daysà months): cellular (INTERSTITIAL infiltrate) and humoral (VASCULITIS)

•         CHRONIC (months): slow vascular fibrosis

AUTO-IMMUNE DISEASES

•         Failure of SELF RECOGNITION

•         Failure of SELF 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 TO OTHER AUTOIMMUNE DISEASES

•         OFTEN TRIGGERED BY INFECTIONS

•         CLASSIC AUTOIMMUNE DISEASES (SYSTEMIC)

•         LUPUS (SLE) Systemic Lupus Erythematosus

•         RHEUMATOID ARTHRITIS

•         SJÖGREN SYNDROME

•        

•         SYSTEMIC SCLEROSIS (scleroderma)

•         “collagen” diseases (term no longer used)

•         CLASSIC AUTOIMMUNE DISEASES (LOCAL)

•         HASHIMOTO THYROIDITIS

•         AUTOIMMUNE HEMOLYTIC ANEMIA

•         MULTIPLE SCLEROSIS

•         AUTOIMMUNE ORCHITIS

•         GOODPASTURE SYNDROME

•         AUTOIMMUNE THROMBOCYTOPENIA

•         “PERNICIOUS” ANEMIA

•         INSULIN DEPENDENT DIABETES MELLITUS

•         MYASTHENIA GRAVIS

•         GRAVES DISEASE

•         N.B.

•         The list of diseases proven to be “autoimmune” grows by leaps and bounds every year!!!

•         LUPUS (SLE)

•         Etiology: Antibodies (ABs) directed against the patient’s 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.

•         MORE SYSTEMIC AUTOIMMUNE
DISEASES

•         RHEUMATOID ARTHRITIS

•         SJÖGREN SYNDROME

•         SCLERODERMA (SYSTEMIC SCLEROSIS)

•         MORE AUTOIMMUNE DISEASES (LOCAL)

•         HASHIMOTO THYROIDITIS

•         AUTOIMMUNE HEMOLYTIC ANEMIA

•         MULTIPLE SCLEROSIS

•         AUTOIMMUNE ORCHITIS

•         GOODPASTURE SYNDROME

•         AUTOIMMUNE THROMBOCYTOPENIA (ITP)

•         “PERNICIOUS” ANEMIA

•         INSULIN DEPENDENT DIABETES MELLITUS (I)

•         MYASTHENIA GRAVIS

•         GRAVES DISEASE

•         ImmunoDefiency Syndromes (-IDS)

•         PRIMARY (GENETIC) (P-IDS?)

•         SECONDARY (ACQUIRED)  (A-IDS)

•         PRIMARY

•         CHILDREN with repeated, often severe infections, cellular AND/OR humoral immunity 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

•         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)

•         EPIDEMIOLOGY

•         HOMOSEXUAL (40%, and declining)

•         INTRAVENOUS DRUG USAGE (25%)

•         HETEROSEXUAL SEX (10% and rising)

•         ETIOLOGY

•         PATHOGENESIS

•         PATHOGENESIS

•         PATHOGENESIS

•         PATHOGENESIS

•         REVERSE TRANSCRIPTASE

•         The enzyme reverse transcriptase (RT) is used by retroviruses to transcribe their single-stranded RNA genome into single-stranded DNA and to subsequently construct a complementary strand of DNA, providing a DNA double helix capable of integration into host cell chromosomes.

•         GENERAL IMMUNE ABNORMALITIES

•         LYMPHOPENIA

•         DECREASED T-CELL FUNCTION

•         B-CELL ACTIVATION, POLYCLONAL

•         ALTERED MONOCYTE/MACROPHAGE FUNCTION

•         INFECTIONS

•         Protozoal/Helminthic: Cryptosporidium, PCP (Pneumocystis Carinii Pneumonia), Toxoplasmosis

•         Fungal: Candida, and the usual 3

•         Bacterial: TB, Nocardia, Salmonella

•         Viral: CMV, HSV, VZ (Herpes Family)

•         CANCERS of AIDS

•         KAPOSI SARCOMA

•         B-CELL LYMPHOMAS

•         CNS LYMPHOMAS

•         CERVIX CANCER, SQUAMOUS CELL

•         AMYLOIDOSIS

•         BUILDUP OF AMYLOID “PROTEIN”

–       AL (Amyloid Light Chain)

–       AA (NON-immunoglobulin protein)

–       Aß (Alzheimer’s)

•         WHERE? BLOOD VESSEL WALLS, at first

–       KIDNEY

–       SPLEEN

–       LIVER

–       HEART

•         AMYLOID ASSOCIATIONS

•         PLASMA CELL “DYSCRASIAS”, i.e., MULTIPLE MYELOMA

•         CHRONIC GRANULOMATOUS DISEASE, e.g., TB

•         HEMODIALYSIS

•         HEREDOFAMILIAL

•         LOCALIZED

•         ENDOCRINE MEAs (Multiple Endocrine Adenomas)

•         AGING