Immunity II Flashcards
1
Q
what is immunologic tolerancr
A
-lack of response to antigens that is induced by exposure of lymphocytes to these antigens
- ability to discriminate between self and nonself antigens
2
Q
normally microbes are:
- self antigens are:
A
immunogenic; tolerogenic
3
Q
what is central tolerance
A
developing lymphocytes encounter self antigens in central lymphoid organs
4
Q
what is peripheral tolerance
A
mature lymphocytes encounter self antigens in peripheral tissues
5
Q
what do self reactive T cells do in central T cell tolerance
A
- negative selection or deletion
- development of regulatory T cells
6
Q
what do regulatory T cells do in peripheral T cell tolerance
A
block the activation of self reactive lymphocytes
7
Q
what is anergy
A
functional inactivation of T cells
8
Q
what is deletion
A
apoptosis of self reactive lymphocytes
9
Q
what induced tolerance in B cells
A
self polysaccharides, lipids and nucleic acids
10
Q
what does central B cell tolerance undergo
A
- receptor editing
- negative selection
11
Q
what does peripheral B cell tolerance undergo
A
- anergy
- excluded from lymphoid follicles
12
Q
what is autoimmunity
A
immune response against self antigens
13
Q
what might the development of autoimmunity be due to
A
- inheritance of susceptibility genes
- environmental triggers
14
Q
most autoimmune diseases are______
A
polygenic
15
Q
what are autoimmune diseases often associated with
A
particular HLA genes that are inefficient at displaying self antigens
- defective T cell negative selection
- may fail to stimulate regulatory T cells
16
Q
how might infections activate self reactive lymphocytes
A
-increased production of costimulatory molecules on APCs
- molecular mimicry
17
Q
what are hypersensitivity reactions
A
injurious or pathologic immune reactions
18
Q
what is autoimmunity
A
- reactions against self antigens
- failure of self tolerance
19
Q
what does hypersensitivity cause
A
- autoimmunity
- reactions against microbes
- reactions against environmental antigens
20
Q
describe type I immediate hypersensitivity
A
- tissue reaction that occurs rapidly after interaction of antigen with IgE antibody bound to mast cell
- often develop in atopic individuals
- environmental and food allergens
- mild to severe reaction
21
Q
what is the mechanism of type 1 immediate hypersensitivity
A
- activation of Th2 cells and IgE class switching in B cells
- production of IgE
- binding of IgE to Fc on mast cells
- repeat exposure to allergen
- activation of mast cell and release of mediators
- mediators could be vasoactive amines or cytokines
- vasoactive amines cause immediate hypersensitivity reaction
- cytokines cause late phase reaction
22
Q
what is an example of a vasoactive amine and what does it do
A
histamine: causes vasodilation, increased vascular permeability, smooth muscle contraction and increased secretion of mucus
23
Q
what are the lipid mediators and what do they cause
A
- prostaglandins and leukotrienes: smooth muscle contraction and vascular permeability
24
Q
what are the cytokines released in immediate hypersensitivity
A
TNF, chemokines, Il4 and IL5
25
what are the clinical syndromes and manifestations of type I immediate hypersensitivity reactions
- anaphylaxis: fall in BP, vascular dilation, airway obstruction due to laryngeal edema
- bronchial asthma: airway obstruction due to smooth muscle hyperactivity
- allergic rhinitis: increased mucus secretion, inflammation of upper airways and sinuses
- food allergies: increased peristalsis causes vomiting and diarrhea
26
how do allergies develop
- genetically determined
- environmental factors: environmental pollutants, infections
- atopic individuals
27
describe atopic individuals
- higher serum IgE
- more TH2 cells
- 50% have fam hx of allergies
28
what is the hygiene hypothesis
- allergies decreasing in developing countries: too much hygiene can cause allergies
- early childhood exposure is good
29
what happens in type II antibody mediated diseases
- opsonized by autoantibodies -> targets cell for phagocytosis by neutrophils and macrophages
- antibodies activate the complement system and recruit neutrophils, macrohpases to trigger inflammation
- antibody mediated cellular dysfunction -> impair or dysregulate important functions
29
what is Type II antibody mediated disease caused by
-antibodies directed against target antigens on cell surfaces
- target cells for phagocytosis
- activate complement system
- interfere with normal cellular functions
29
what are the diseases associated with type II hypersensitivity
- autoimmune hemolytic anemia
- autoimmune thrombocytopenic purpura
- pemphigus vulgaris
- vasculitis caused by ANCA
- goodpasture syndrome
- acute rheumatic fever
- myasthenia gravia
- graves disease
- pernicious anemia
30
describe type III immune complex mediated diseases
-antigen- antibody complex formed
- deposits in BV -> complement activation and acute inflammation
- antigen may be foreign protein or endogenous (autoimmunity)
- soluble antigens
31
what is the mechanism of type III diseases
- formation of immune complexes: ABs are secreted in blood, react with antigen and form antigen- antibody complexes
- deposition of immune complexes: circulating antigen- antibody complexes deposited in tissues
- inflammation and tissue injury: once deposited, immune complexes initiate inflammation via complement or engagement of leukocytes
32
what are the diseases associated with type III
- systemic lupus erythematosus
- poststreptococcal glomerulonephritis
- polyarteritis nodosa
- reactive arthritis
- serum sickness
- arthrus reaction
33
what is the arthrus reactino from
vaccines which cause antibodies to form immune complexes that activate complement and enhance localized inflammation
34
describe type IV cell mediated disease
- CD4 T cells: cytokine mediated inflammation
- CD8 T cells: direct cell cytotoxicity
- many chronic inflammatory diseases are T cell mediated
- most are TH1 mediated, some are TH17
35
what is the mechanism of TYpe IV
cytokines produced induce inflammation and cause tissue destruction
36
when do type IV diseases happen
delayed-type: 48-72 hours after exposure
37
what does the CD8 t cell do in type IV
kill antigen expressing target cells
- effective in virus infected cells
38
what are the diseases in type IV
- RA
- MS
- type I DM
- IBS
- psoriasis
- contact sensitivity
39
what mediated type I DM
CD8 t cells
40
what are primary/ congenital immunodeficiency syndromes
inherited genetic disorders
41
what are secondary immunodeficiency syndromes
after challenge to immune system such as cancer or environmental factors
42
describe primary immunodeficiencies
- may affect innate or adaptive immunity
- usually detected in infancy - 6 months-2 years of age
- most involve disorders of B and T lymphocytes
43
what is severe combined immunodeficiency (SCID)
-encompassed many genetically distinct syndromes with defects in both cell mediated immunity and humoral immunity
- children are susceptible to severe recurrent infections
- death within first year without stem cell transplant
44
what is digeorge syndrom
- deletion of chromosome 22
- caused by congenital defects in thymic development -> deficient T cell maturation
- infants are vulnerable to viral, fungal, protozoal infections
- may include developmental malformation with prathyroid gland, heart defects, cleft palate, behavioral problems
45
what are the features of Di george syndrom
- cardiac abnormailty
- abnormal facies
- thymic aplasia
- cleft palate
- hypocalcemia
46
what is hyper IGM syndrome
- inability of T cells to activate b cells
- production of normal to high levels of IgM antibody
- decreased levels of IgG, IgA and IgE
- recurrent pyogenic infections, susceptibility to pneumonia
47
describe activation and class swtiching of B cells
- APC presents antigen to T helper cells
- B7 is expressed and interacts with CD28 activating T helper cells
- activated Th cells interact with B cells via CD40 ligand, activating B cells to proliferate, differentiate, and secrete antibodies
- th cells secrete cytokines that determine class switching
48
what is leukocyte adhesion deficiencies (LADs)
defects in adhesion molecules, impair leukocyte recruitment to site of infection -> increased bacterial infections
49
what is chediak higashi syndrome
defective phagocyte function due to impaired lysosomal trafficking -> recurrent infections
50
what are the symptoms of chediak higashi
- defective platelets- easy bruising
- melanocyte abnormailities - albinism
- nervous system abnormalities- peripheral nueropahty
51
what is the most common defect in complement function
C2 deficiency- increased bacterial and viral infections
52
when would secondary immunodeficiencies be encounters
cancer, diabetes, malnutrition, chronic infection, patients receiving chemo/radiation therapy, immunosuppresive meds
53
describe AIDS
- caused by HIV- SSRNA
- 1981 first reported
- >80 million infection, >35 million deaths
54
what is the transmission of AIDS
- blood or body fluids
- sexual contact
- parenteral
- perinatal
55
what is the pathogenesis of AIDS/HIV
- targets CD4+ T cells
- viral RNA genome: reverse transcriptase transcribed into complementary DNA. integrates into host cell DNA
- antibodies against HIV develop but not protective
- HIV virus- cell death with subsequent release of the virus or latency
56
what receptors and coreceptors does HIV bind to on CD4 cells
- CXCR4 coreceptor
- CD4 receptor
- CCR5 coreceptor
57
what is the life cycle of the HIV virus
- binding
- fusion
- reverse transcription
- integration
- replication
- assembly
- budding
58
what are the clinical features of AIDS/HIV
- asymptomatic
- acute retroviral syndrome
- latency perios
59
describe acute retroviral syndrome and how many patients experience it
- 50-70%
- generalized lymphadenopathy, sore throat, fever, rash, headahce, myalgia, arthralgia, diarrhea, photophobia, and peripheral neuropathies
- oral changes are erythema and ulceration
- viremia
60
dscribe latency period of HIV
- several months to 15 years
- progression affected by patient age, host immune response, treatment
61
how is AIDS diagnoses
- CD4 T cell count declines: 200 cells/mm^3
- CD4 T cell count < 14% total lymphocytes
-AIDS defining condition
62
what are aids defining conditions
- candidiasis
- lymphomas
- weakened immune systems that cause opportunistic infections
63
what are the HIV treatments
-anti retroviral therapy (ART)
- viremia declines
64
what are the 6 broad categories of antiretroviral therapies
- nucleoside reverse transcriptase inhibitors
- nonnucleoside reverse transcriptase inhibitors
- protease inhibitors
- fusion inhibitors
- integrase inhibitors
- CCR5 inhibitors
65
