immunity 1 and 2 ppt (dr esgana) Flashcards
biological system that helps protect the body from harmful microorganisms
immunity
cells that are called the first line of defense
innate cells
does innate lymphoid cells has receptors?
nope
immunity that develops overtime as the body encounters specific pathogens or foreign substances. characterized by its specificity and memory
adaptive immunity
two cells of adaptive immunity
B cells - humoral
T cells - cell mediated
function of B cell
neutralize of microbe, phagocytosis and complement activation
reaction of innate immunity
inflammation
antiviral defense - type 1 interferons
3 types of t cells
T helper cells
cytotoxic T lymphocyte
Regulatory T lymphocyte
3 function of t helper cells
activation of macrophages
inflammation
proliferation and differentiation of t and b cells
function of cytotoxic T lymphocyte
killing of infected cell
function of regulatory t lymphocyte
suppression of immune response
B cells differentiates into what cell
plasma cell
6 functions of antibodies
neutralization of microbe and toxins
opsonization and phagocytosis
antibody-dependent cytotoxicity - kills also the cell
lysis of microbe
phagocytosis
inflammation
what t cells recognizes the dendritic cells with antigen
CD 4 T cells and CD8 T cells
identifications of humoral immunity
- circulates in the blood as a soluble protein
- B cells
- acts on extracellular microbes and their toxins
- recognized unprocessed antigens
- plasma B cells secrete antibodies
- rapid
- DOES NOT ACT ON THE TUMOR CELLS AND TRANSPLANTS
identifications of cell mediated immunity
- mediated by the activated antigen-specific T cells
- T cells
- acts on intracellular microbes
- presented by MHC complex
- secretes cytokines
- a delayed type hypersensitivity
- acts on tumor cells and transplants
memory of innate and adaptive
innate - no
adaptive - yes
potency of innate and adaptive
innate - lower
adaptive - higher
speed of onset innate and adaptive
innate - immediate
adaptive - approx 3 day lag
specificity of innate and adaptive
innate - unspecific
adaptive - highly specific
pathological, excessive, and injurious immune
response to antigen leading to tissue injury, disease or sometimes death in a sensitized individual
the resulting diseases are name as?
hypersensitivity diseases
rapid immunologic reaction occurring in a previously
sensitized individual that is triggered by the binding of
an antigen to IgE antibody on the surface of mast cells
type 1 immediate hypersensitivity
a hypersensitivity that is often called allergy, and the antigens that elicit them are
allergens
may occur as a systemic disorder or as a local
reaction
type 1 immediate hypersensitivity
how many hrs does the late phase reaction occur
2-24 hrs after repeated allergen exposure
prototypical disorder of type 1 hypersensitivity
anaphylaxis; allergies; bronchial asthma
Ige triggered reaction can be divided into two phases
Immediate response
late phase reactions
a phase of IgE reaction that becomes evident within minutes
immediate response
a phase of IgE reaction that develops in ___ hrs after the exposure to
antigen which may last for several days
2 -24
immediate response is characterized by
vasodilation, vascular leakage, SM spasm or glandular secretion
released rapidly from mast cells
histamine and leukotrienes
most common form of acute interstitial nephritis
generally after 2-3 wks after exposure
acute allergic interstitial nephritis
heterogenous disease, usually characterized by chronic airway inflammation
produces symptoms such as wheezing, shortness of breath, chest tightness and cough
asthma
examples of type 1 immediate hypersensitivity diseases
acute allergic interstitial nephritis
allergic rhinitis
anaphylaxis
bronchial asthma
food allergies
production of igE antibody
immediate hypersensitivity
production of IgG and IgM
type 2 antibody-mediated hypersensitivity
mechanism of type 2 antibody mediated hypersensitivity
A. opsonization and phagocytosis
B. complement and Fc receptor mediated inflammation
C. antibody mediated cellular dysfunction
noncollagenous protein in basement membrane of kidney glomeruli and lung alveoli
complement and Fc receptor mediated inflammation
nephritis, lung hemorrhage
goodpasture syndrome
gross:
- lungs are heavy, with areas of red - brown consolidation
microscopic
- focal necrosis of alveolar walls associated with intra-alveolar hemorrhages
- alveoli contain hemosiderin-laden macrophage
goodpasture lung
most common cause of endogenous hyperthyroidism
graves disease (antibody mediated disease)
autoimmune disorder characterized by the production of autoantibodies against multiple thyroid proteins, most importantly the TSH RECEPTOR
graves disease (antibody mediated disease)
most common antibody subtype, known as thyroid-stimulating
immunoglobulin (TSI), is observed in approximately 90% of patients.
graves disease (antibody mediated disease)
TSH receptor
antibody mediated stimulation of TSH receptors
hyperthyroidism
graves disease (antibody mediated disease)
gross:
- thyroid gland is usually symmetrically enlarged due to
diffuse hypertrophy and hyperplasia of thyroid follicular
epithelial cells
microscopic
- Follicular epithelial cells are tall and more crowded than usual. Lymphoid infiltrates, consisting predominantly of T cells
graves disease (antibody mediated disease)
caused by
autoantibodies against epidermal cell junction proteins
(DESMOGLEINS), commonly presenting with flaccid
blisters, erosions or scaling
Most common form (80%)
PEMPHIGUS
proteins in intracellular junction of epidermal cells (desmogleins)
antibody-mediated activation of proteases, disruption of intracellular adhesion
skin vesicles (bullae)
pemphigus vulgaris
Suprabasal acantholysis
Basal layer remains attached (tombstone sign)
pemphigus vulgaris
desposition of antigen-antibody complexes -> complement activation
immune complex mediated type III hypersensitivity
characterized by formation of immune (antigen and
antibody) complexes in the circulation and may get
deposited in blood vessels, leading to complement
activation and inflammation
IMMUNE COMPLEX–MEDIATED (TYPE III)
HYPERSENSITIVITY REACTIONS
IMMUNE COMPLEX–MEDIATED (TYPE III)
HYPERSENSITIVITY REACTIONS
in blood vessels:
in renal glomeruli:
in joints:
vasculitis
glomerulonephritis
arthritis
necrosis of the vessel wall and intense neutrophilic
infiltration.
acute vasculitis
The necrotic tissue and deposits of immune
complexes, complement, and plasma protein appear
as a smudgy eosinophilic area of tissue destruction,
an appearance termed as?
fibrinoid necrosis
characterized by diffuse thickening of the glomerular capillary wall due to the accumulation
of deposits containing Ig
membranous glomerulopathy
examples of immune complex-mediated disease
systemic lupus erythematosus
poststreptococcal glomerulonephritis
polyarteritis nodosa
reactive arthritis
serum sickness
arthus reaction
A type of hypersensitivity which activates T lymphocyte
1. release of cytokines
2 T-cell mediated cytotoxicity
cell mediated type IV hypersensitivity
A chronic inflammatory dermatosis that appears to have an autoimmune basis.
Mostly frequently affects the skin of the elbows, knees, scalp, lumbosacral areas, intergluteal cleft,
and glans penis
PSORIASIS
characteristic of psoriasis
silver-white scale
differentiate crohn disease and ulcerative colitis
(mga gi discuss ni doc esgana)
MACROSCOPIC
bowel region
distribution
structure
wall appearance
MICROSCOPIC
inflammation
pseudopolyps
ulcers
granulomas
fistulae/sinuses
CLINICAL
malignant potential
toxic megacolon
MACROSCOPIC
ileum +- colon |colon only, rectum
skip lesions |diffuse
yes | rare
Thick | normal
MICROSCOPIC
transmural | limited to mucosa
moderate | marked
deep knife like | superficial, broad-based
yes -35% | no
yes | no
CLINICAL
common | no
no | yes
give 3- 4 organ - specific diseases mediated by antibodies type ll hypersensitivity
autoimmune hemolytic anemia
autoimmune thrombocytopenia
autoimmune atrophic gastritis of pernicious anemia
myasthenia gravis
graves disease
goodpasture syndrome
systemic disease mediated by antibodies
systemic lupus and erythematosus
organ specific disease mediated by T cells
type 1 diabetes mellitus
multiple sclerosis
systemic diseases mediated by T cells
rheumatoid arthritis
systemic sclerosis
sjorgen syndrome
organ-specific diseases postulated to be autoimmune
crohn disease
primary biliary cirrhosis
autoimmune hepatitis
T lymphocytes and antibodies produced against graft antigens react against and destroy tissue grafts
REJECTION
Grafts that belong to the same specie
Allografts (human to humans)
Grafts that belong to different species
Xenografts ( ex. Pig to human)
Major antigenic difference between a donor and recipient that result in rejection of transplants are differences in????
HLA allele
2 pathways where recipients T cell recognize donor HLA antigens from the graft
Direct
Indirect
Graft antgiens are presented directly to recipientT cels by graft APC
DIRECT
Graft antigens are picked up by host APCs processed (like any other foreign antigen), and presented to host T cells
INDIRECT
Which Will have a stronger immune response? Allografts or pathogens
Allografts
Patterns of graft rejection
Hyperacute
Acute
Chronic
A mechanism of graft that is immediate. Mediated by performed atibodies specific for antigens on graft endothelial cells
It is also rare
Hyperacute
Mechanism of graft rejection that occurs in days or weeks. Mediated by T cells and antibodies that are activated by alloantigens in the graft
Acute graft rejection
2 patterns of acute cellular injury
Tubulointerstitial pattern type 1
Vascular pattern type 2
patten of injury where extensive interstitial inflammation and tubular inflammation associated with focal tubular injury
Tubulointerstitial pattern type 1
Pattern of injury where it shows inflammation of vessls and sometimes necrosis of vessel walls
Vascular pattern type II
2 types of acute rejection
Acute cellular ( T cell mediated ) rejection and acute antibody-mediated rejection ( vascular, or humoral )
A type of acute rejection that is manifested mainly by damage to glomeruli and small blood vessels
Acute antibody mediated rejection ( a type of acute graft rejection )
Mechanism of graft rejection that occurs in months or years. The culprit is believed to be T cells. Manifested as interstitial fibrosis and gradual narrowing of graft blood vessels. DOMINATED BY VASCULAR CHANGES
Chronic graft
2 types of immunodeficiency disease
Primary (or congenital) immunodeficiencies
- genetically determined
Secondary ( or acquired ) immunodeficiencies
- complications of caners, infections, malnutrition and other disease
In primary immunodeficiencies defects occurs in where?
Innate immunity
Lymphocytes and the adaptive immune response
Systemic disease
Defects in innate immunity of the primary immunodeficiencies are in?
Leukocyte function and complement system
Defects in leukocyte function that both result in a failure of leukocyte adhesion to endothelium, preventing the ceols from migrating into tissue
Inherited defects in leukocyte adhesion
(2 types of leukocyte adhesion)
Leykocyte adesion deficiency type 1 - defect by the integrin LFA-1 and Mac-1
Leukocyte adhesion deficiency type 2 - E- and P- selectins
A inherited defect in phagolysosome that has defective fusion of phagosomes and lysosomes
Chediak higashi syndrome
Main leukocyte abnormalities are?
Neutropenia, defective degranulation and delayed microbial killing
Does chediak higashi syndrome has leukocytes containing giant granules?
Yes
Inherited defects in microbial activity that is characterized by defects in bacterial killing
Chronic granulomatous disease
4 Defects in leukocyte function
Inherited defects in leukocyte adhesion
Injerited defects in phagolysosome function
Inherited defects in microbial activity
Defects in TLR signaling
Defects in leukocyte function that results in herpes simplex encephalitis and are associated with destructive bacterial pneumonias
DEFECTS IN TLR 3 - herpes simplex encephalitis
DEFECTS IN MyD88 - destructive bacterial pneumonias
Defects in the complement system that is most common complement protein deficiency
C2, C4 DEFICIENCY
Defects in the complement system is required for both the classical and alternative pathways, and hence a deficiency of this protein results in susceptibility to serious and RECURRENT PYOGENIC INFECTIONS
C3 DEFICIENCY
Defects in the complement system that are required for the assembly of the membrane attack complex.
Deficiency of these late-acting components is associated with increased susceptibility to recurrent neisseria (gonococcal and meningococcal) infections
C5,6,7,8,and 9 DEFICIENCY
4 subtypes of defects in the complement system
C2, C4 deficiency
C3 deficiency
C5, 6,7,8, and 9 deficiency
Deficiency of C1 inhibitor (C1 INH)
An AD disorder that are C1 inhibitor’s targets the proteases. Episodes of edema affecting skin and mucosal surface
Deficiency of C1 inhibitor
Disease affecting lymphocytes and the adaptive immune response
Common defect in both humoral and cell-mediated immune response
Severe combined immunodeficiency SCID
Two types of severe combined immunodeficiency
- X-linked SCID
- Autosomal recessive SCID
a type of SCID that is more common in boys. Mutation in the common y-chain subunit of cytokine receptor resulting in a defective IL-7 receptor signaling
X-linked SCID
A type of SCID
A most common cause of autosomal recessive cause by a deficiency of the enzyme adenosine deaminase (ADA)
Autosomal recessive SCID
A disorder affecting lymphocytes and the adaptive immune response
That is characterized by the failure of B-cell precursors to develop into mature B cells. Caused by mutation in a cytoplasmic tyrosine kinase called bruton tyrosine kinase (BTK)
X-linked agammaglobulinemia
A disorder affecting lymphocytes and the adaptive immune response
A T-cell deficiency that results from failure of development of the thymus. They have a variable loss of T-cell mediated immunity, tetany, and congenital defects of the heart and great vessels
Caused by a small germline deletion that maps to chromosome 22q11
DIGEORGE SYNDROME (THYMIC HYPOPLASIA)
Symptoms of digeorge syndrome (thmic hypoplasia)
CATCH 22
1. Cardiac anomalies
2. Abnormal facies
3. Thymic hypoplasia
4. Cleft palate
5. Hypocalcemia
A disorder affecting lymphocytes and the adaptive immune response
Caused by mutations in transcription factors that are required for class II MHC gene expression
BARE LYMPHOCYTE SYNDROME
A disorder affecting lymphocytes and the adaptive immune response
Affects patients have IgM antibodies but are deficient in IgG, IgA and IgE antibodies
HYPER-IGM SYNDROME
A disorder affecting lymphocytes and the adaptive immune response
Common feature is hypogammaglobulinemia, generally affecting all the antibody classes but sometimes only IgG
Common variable immunodeficiency
A disorder affecting lymphocytes and the adaptive immune response
Common immunodeficiency caused by impaired differentiation of naive B lymphocytes to IgA-producing plasma cells
Individuals have extremely low levels of both serum and secretory IgA
ISOLATED IGA DEFICIENCY
A disorder affecting lymphocytes and the adaptive immune response
Characterized by an inability to eliminate Epstein Bar Virus. eventually leading to fulminant infectious mononucleosis and the development of B-cell tumors
X-linked lymphoproliferative disease
A disorder affecting lymphocytes and the adaptive immune response
Mutation affecting th1 responses are associated with atypical mycobacterial infections
Mendelian susceptibility to mycobacterial disease
A disorder affecting lymphocytes and the adaptive immune response
Inherited defects in Th17 response lead to chronic mucocutaneous candidiasis and bacterial infections of the skin
JOB SYNDROME
2 types of immunodeficiencies assoiated with systemic disease
Wiskitt-aldrich syndrome
Ataxia telangiectasia
Caused by mutation in the gene located at Xp11.23 that encodes Wiskott Aldrich syndrome protein (WASP)
Characterized by thrombocytopenia, eczema, and a marked vulnerability to recurrent infection, resulting in early death
They are prone to developing B-cell lymphomas
WISKOTT-ALDRICH SYNDROME
A immunodeficiency associated with systemic disease
Autosomal recessive disorder characterized by abnormal gait (ataxia), vascular malformations, neurologic deficits , increased incidence of tumors, and immunodeficiency
Most prominent humoral immune abnormalities are defective production isotype-switched antibodies, mainly IgA and IgG2
Gene responsible for this disorder is located on chromosome 11 and encodes a protein kinase called ATM (ataxia telangiectasia mutated) n
ATAXIA TELANGIECTASIA
an immunodeficiency that is encountered in individuals with cancer, diabetes and other metabolic diseases, malnutrition, chronic infection, and in persons receiving chemotherapy or radiation therapy for cancer, or immunosuppressive drugs to prevent graft rejection or to treat autoimmune diseases
more common than the disorders of primary genetic origin
Secondary ( or acquired ) immunodeficiency
Causes of secondary acquired deficiency
Human immunodeficiency virus (HIV)
Irradiation and chemotherapy treatment for cancer
Involement of bone marrow by cancers
Protein calorie malnutrition
Removal of spleen
Mechanism of secondary immunodeficiencies in:
HIV
Irradiation and chemo treatment
Bone marrow cancers
Protein-calorie malnutrition
Removal of spleen
- Depletion of CD4+ helper T cells
2/ decrease bone marrow precursors for all leukocytes - Reduced site of leukocyte development
- Metabolic derangements inhibit lymphocyte maturation and function
- Decreased phagocytosis of microbes
What is AIDS
Acquired immunodeficiency Syndrome
Three major routes of transmission
Sexual transmission
Parenteral transmission
Mother-to-infant transmission
A major route of transmission that is the dominant mode of infection worldwide
Sexual transmission
2 mechanism of sexual transmission infections
- Direct inoculation into the BV breached by trauma
- Infection of DCs or CD4+ cells within the mucosa
A major route of transmission that is used by IV drug users. Hemophiliacs who received factor VIII and factor IX concentrates
Random recipients of blood transfusion
Parenteral transmission
A major route of transmission that is a major cause of pediatric AIDS
It has 3 routes
1. In utero by transplacental spread
2. During delivery through an infected birth anal
Mother to infant transmission
Transmission in health care workers:
After needlestick accidents, the risk to be contamined is about 0.3%
Antiretroviral therapy given within ___ to ___ of a needle stick can reduce the risk of infection eightfold
24 - 48 hrs
Properties of HIV
They belong to the lentivirus family which has 2 types
HIV-1
HIV-2
Most abundant viral antigen of HIV-1
P24 antigen (detected by ELISA)
Also a major capsid protein
Profound immune deficiency primarily affecting _____, is the hallmark of AIDS
Cell-mediated immunity ( T cells )
HIV infects cells by using the ___ molecule as a receptor
CD4 receptor
Aside from the binding of HIV to CD4 receptor, HIV ____ must also bind to other cell surface molecule for entry into the cell. Chemokine receptors, particularly ___ and ____ serve this role .
Gp120
CCR5 and CXCR4
Three categories of the basis of CD4+ cell counts
A. Asymptomatic
B. Symptomatic
C AIDS indicator conditions
Major death in untreated patients with AIDS
Opportunitsic infection
Most common fungal infection in patients with AIDS
Candidiasis
May cause disseminated disease or may be localized to the eye and GI tract
Cytomegalovirus (CMV)
Major clinical manifestation of cryptococcosis of opportunistic infection
Meningitis
Toxoplasma gondii in opportunistic infection
Encephalitis
Progressive multifocal leukocenphalopathy in opportunistic infections
JC virus
Opportunistic infection
Mucocutaneous ulcerations involving the mouth, esophagus, external genitalia and perianal region
Herpes simplex virus
Caused by oncogenic DNA viruses, specifically humanherpesvirus-8 KS, EBV and human papillomavirus
25-40% of untreated HIV-infected individuals
Tumors
Types of tumors
Kaposi sarcoma
Lymphomas
HPV-associated carcinomas of the uterine cervix and the anus
A vascular tumor that is the most common neoplasm in patients with AIDS
Kaposi sarcoma widespread, affecting the skin, mucous membrane, GI tract, lymph nodes and lungs
Caused by human herpesvirus 8 (HHV8), also called KS herpesvirus (KSHV)
Kaposi sarcoma
Roughly 5% of people with AIDS has this disease. Virtually all of which originate from transformed B cells
Increased risk of B-cell tumors in HIV infected individuals
Lymphoma
10 times more common in HIV-infected women with less than 500cells /ul CD4 counts
Human papilloma virus (HPV) associated carcinomas of the uterine cervix and the anus
Extracellular deposits of fibrillar proteins are responsible for tissue damage and functional compromise
Amyloidosis
3 most common forms of amyloid are
- Amyloid light chain (AL) protein
- Amyloid associated AA protein
B amyloid AB protein
Properties of amyloid proteins
It is a group of disease having in common of deposition of similar appearing proteins
Fibrils are diameters of approx 7.5 to 10nm
Distinctive Congo red staining and birefringence of amyloid
Made up of complete immunoglobulin light chains, produced from free Ig light chains secreted by a monoclonal population of plasma cells, and its deposition is associated with certain plasma cell tumor
Amyloid light chain (AL) protein
Derived from a unique non-Ig protein made by the liver.created by proteolysis of a larger precursor SAA (serum amyloid associated) protein
P
Production is increased in inflammatory states as part of the acute phase response
Amyloid associated (AA) protein
Constitutes the core of cerebral plaques found in alzheimer disease
B-amyloid AB protein
rare forms of amyloid
Transthyretin (TR)
B2-macroglobulin
Misfolded prion protein
Types of transthyretin (a rare form of amyloid)
Mutant form: familial amyloid polyneuropathies
Unmutated TTR: senile systemic amyloidosis
Pattern of organ involvement in amyloidosis
It is deposited in the glomeruli, but the interstitial peritubular tissue, arteries and ateriorles are also affected
Kidney
Pattern of organ involvement in amyloidosis
Amyloid appears first in the space of disse and then progressivly encroaches on adjacent hepatic parenchymal cells and sinusoids
Liver
Pattern of organ involvement in amyloidosis
The deposits begin as focal subendocardial accumulations and within the myocardium between the muscle fibers
Heart
Pattern of organ involvement in amyloidosis
- Nodular deposits in the tongue may cause macroglossia
- Larynx down to the smallest bronchioles, brains, peripheral and autonomic nerves
3.seen in long term hemodialysis
- Tumor forming amyloid of the tongue
- Respiratory tract
- Carpal ligament of the wrist/joints
