Immunity lectures Flashcards
1
Q
What is immunocompetence?
A
ability of body to produce robust immune response following exposure to disease-producing agents
2
Q
What are the main functions of innate immunity?
A
- rapid, non-specific defense against pathogens
- eliminate damaged or necrotic cells
3
Q
What are physical barriers of innate immunity?
A
- skin
- mucus membranes
- nasal hairs
- respiratory tract cilia
4
Q
What are chemical barriers of innate immunity?
A
- skin pH
- mucus secretions
- gastric acids
- tears
- sweat
- saliva
5
Q
What are effector cells of innate immune response?
A
- neutrophils
- macrophages
- NK cells
(complement proteins)
6
Q
How does the innate immune system recognize pathogens?
A
PAMPS & DAMPS
- patterns unique to survival, virulence, or ability to invade // damaged or necrotic
7
Q
What is the function of neutrophils in innate immune response?
A
- first cell to respond (bacterial & fungal)
- short-lived
- phagocytose: dead cells, debris, tumor cells, pathogens, foreign materials
8
Q
What is the function of dendritic cells in the innate immune response?
A
- present antigens to T cells (cytoplasmic processes)
- abundant in epithelium & mucus membranes
- help shape adaptive immune response
9
Q
What is the function of macrophages in the innate immune response?
A
- phagocytose: dead cells, debris, tumor cells, pathogens, foreign material
- release cytokines to activate other immune cells
- may present antigens to T cells
- long-lived in extravascular tissue
10
Q
What is the function of NK cell in the innate immune response?
A
- rapidly attacking & killing infected cells
- induce apoptosis
- release cytokines to activate immune cells
11
Q
What is the main difference between cytotoxic T cells & NK cells?
A
NK cells do not require MHC or antibodies to kill
12
Q
What the 3 complement pathways?
A
classical, lectin, alternate
13
Q
Which complement pathway is a component of the adaptive immune system? Why?
A
classical because activated by antibodies bound to microbes/antigens
14
Q
Describe the alternate pathway of complement system?
A
activated when complement proteins activated on microbe surfaces (innate)
15
Q
Describe the lectin pathway of complement system?
A
activated when mannose binding lectin binds surface glycoproteins on microbes (innate)
16
Q
What are the functions of the complement system?
A
- opsonization (C3b) & phagocytosis
- inflammation (C3a & C5a) chemoattractant for leukocytes
- cell lysis via MAC
17
Q
What are the functions of cytokines in innate immunity?
A
- mediate immune & inflammatory reactions
- communicate b/w cells
- secreted in small amounts
- autocrine & paracrine actions
18
Q
What is the source & target of the cytokine TNF?
A
source: macrophage, T cells, mast cells
target: endothelial cells & neutrophils (inflammation)
19
Q
What is the source & target of the cytokine IL-1?
A
source: macrophages & dendritic cells
target: endothelial cells (inflammation)
20
Q
What is the source & target of the cytokine IL-12?
A
source: dendritic cells & macrophages
target: NK & T cells (increase cytotoxic activity/ increase IFN-y secretion)
21
Q
What is the source & target of the cytokine IFN-y?
A
source: NK cells
target: activate macrophages
22
Q
What type of innate immune reaction is elicited by extracellular bacteria or fungi?
A
inflammatory & complement
23
Q
What type of innate immune reaction is elicited by intracellular bacteria?
A
phagocytosis
24
Q
What type of innate immune reaction is elicited by viruses?
A
Type I interferon & NK cells
25
What are membrane bound innate immune system receptors? What do they recognize?
TLR --> LPS
C type lectin --> fungal polysaccharides
26
What are endosomal receptors of innate immune system? What do they recognize?
TLR: viral RNA/DNA
27
What are cytosolic receptors of innate immune system? What do they recognize?
NOD-like: necrotic cell products, ion disturbances, microbial products
28
What are primary lymphoid organs?
bone marrow & thymus
29
What are secondary lymphoid organs & what occurs here?
lymph nodes, Peyer's patch, spleen, Waldeyer's ring
-- where adaptive immunity is initiated (lymphocytes contact antigens)
30
What constitutes Waldeyer's Ring?
lingual tonsils, palatine tonsils, pharyngeal tonsils
31
Where are the majority of lymphocytes located in a healthy individual?
lymph nodes
32
What are the difference between innate & adaptive immunity?
innate = first line / nonspecific
- develops quickly
- responds rapidly
- NO memory
adaptive = specialized
- develops slower
- mediates effective defense
- memory for future encounters
33
Cells of adaptive immunity?
- B lymphocytes, plasma cells, antibodies
- Dendritic cells, T lymphocytes
34
What does the adaptive immune system recognize?
- antigens
35
What types of receptors are in the adaptive immune system?
TCR
36
T/F the innate & adaptive immune systems can discriminate self from non-self?
true
37
Where do lymphocytes recognize microbes/antigens?
lymphoid organs
38
What is the location/distribution of T cells & B cells within a lymph node?
B cells: follicular region (outside)
T cells: parafollicular region (just inside B cell region)
39
Where are antibodies secreted?
circulation & mucosal surfaces
40
What are the functions of antibodies?
- neutralize & eliminate microbes & toxins
- prevent infection from being established
41
How do B cells recognize antigens?
through membrane bound IgM
42
What types of chemical structures can B cells recognize?
- soluble or cell-associated proteins, lipids, polysaccharides, nucleic acids, small chemicals
43
Characteristics of IgG antibodies?
- most abundant
- opsonizer
- crosses placenta
- found in blood & serum
44
Characteristics of IgA antibodies?
- found in mucus membrane secretions
- forms dimer when secreted
- neutralizing (prevents pathogen from entering cell)
45
Characteristics of IgM antibodies?
- largest
- first produced in response to antigen
- most efficient to activate complement
- secreted as pentamer
46
Characteristics of IgE antibodies?
- function against helminths
- mediate allergic rxn (Type I)
- least common
47
When does rearrangement & assembly of gene segments in antibodies occur?
in Pre-B cell stages during development
48
When does antibody class switching occur?
after stimulated by antigen & CD4 T cell
49
Describe antibody class switching.
- maintains antigen specificity (variable)
- alters heavy chain to broaden functional capabilities
50
Describe the stages from B cell encountering antigen to secretion of antibodies.
- B cell triggered when encounters matching antigen
- engulfs antigen, digests it, presents fragments bound to MHC
- antigen-MHC attracts matching T cell
- T cell secretes cytokines helping B cell to multiply & mature into plasma cell
- antibodies secreted into blood searching for matching antigens
51
T/F memory B cells secrete antibodies?
false...rapidly differentiate into Ab secreting cells upon re-exposure
52
What is the goal of vaccination?
stimulate adaptive immune response against microbes
53
What are the main types of vaccines?
live-attenuated, killed/inactivated, mRNA
component / whole
54
What type of vaccine is not good for immunocompromised populations?
live-attenuated: because only weakened virus
55
What are the differences between active & passive immunity?
active: antibodies produced by response to antigen / long-term immunity with memory cells
- natural: infected
- artificial: vaccine
passive: antibodies derived from another source / short term with NO memory cells produced
- maternal Ab from mom to fetus
56
What types of microbes does the cell-mediated response combat?
intracellular: microbes ingested by phagocytes
-- some bacteria resist microbicidal activity // viruses replicating in cytoplasm
57
Describe the sequence of events in cell-mediated immunity.
- APC travel to lymphoid tissue
- present antigen via MHC
- T cell activated, proliferate, differentiate into effector & memory
- T cells migrate to site of infection (CD4 & 8)
- some remain in lymphoid tissue to help B cells produce antibodies or become memory T cells
58
What is the MHC?
- displays peptide antigens for recognition by T lymphocytes
- helps recognize between self & non-self
- locus of polymorphic genes on chromosome 6
59
Where are class I / II MHC molecules found and which cells recognize them?
Class I: all nucleated cells --> CD8 T cells
Class II: on APC surface --> CD4 T cell
-- macrophage, dendritic cell, B cell
60
T/F cells with class II MHC also have class I MHC?
true
61
What are the defining cytokines for Th1 cells?
IFNy
62
What are the defining cytokines for Th2 cells?
IL-4,5 & 13
63
What are the defining cytokines for Th17 cells?
IL-17, 22
64
What are the target cells for Th1, Th2, & Th17 cells?
Th1: macrophage
Th2: eosinophils
Th17: neutrophils
65
What type of pathogens do Th1, Th2, & Th17 cells defend against?
Th1: intracellular pathogens
Th2: helminths/parasites
Th17: extracellular pathogens
66
As you get older how does the % of naive T cells & memory T cells change?
naive decreases
memory increases
67
Describe how the immune response declines.
- response is self-limited
- effector lymphocytes die by apoptosis after microbe is eliminated
- allows return to resting state
68
What term describes a lack of response to antigens that is induced by exposure of lymphocytes to these antigens?
immunologic tolerance
69
What happens if the ability to discriminate between self & non-self fails / failure of immune tolerance?
autoimmunity
70
Under normal conditions microbes are ______ & self-antigens are _______.
immunogenic // tolerogenic
71
Describe what occurs in central tolerance of T cells.
- occurs within bone marrow / thymus
- recognize self-antigen with high affinity --> eliminate
- recognize self-antigen with moderate affinity --> regulatory T cell & enter peripheral tissue
72
How do regulatory T cells act in peripheral T cell tolerance?
- block activation of self-reactive lymphocytes
-- deplete cytokines for activation of immune cells
-- express receptors that lower affinity for immune cells to respond to self-antigens
73
How does anergy work in peripheral T cell tolerance?
inactivation of T cells (lack of co-stimulation)
74
How does deletion work in peripheral T cell tolerance?
apoptosis of self-reactive lymphocytes
75
What are the mechanisms of peripheral T cell tolerance?
T regulatory cells
anergy
deletion
76
What are the mechanisms of central B cell tolerance?
- receptor editing (light chain)
- negative selection (apoptosis)
77
What are the mechanisms of peripheral B cell tolerance?
- anergy
- exclusion from lymphoid follicles
78
What role do T cells play in B cell tolerance?
T cells recognize proteins on MHC of APC & activate B cells to produce antibodies
T cells also help provide stimuli for survival
79
Development of autoimmunity may be related to what?
- inheriting susceptibility genes --> failed self-tolerance
- environmental triggers
**multifactorial
80
Most autoimmune diseases are associated with what genetic factors?
- polygenic
- HLA genes --> inefficient at displaying self-antigen
-- defective T cell negative selection
-- failure to stimulate regulatory T cells
81
How might infections activate self-reactive lymphocytes?
- increased production of co-stimulatory molecules on APCs
- molecular mimicry
82
What is a hypersensitivity reaction?
- inadequately controlled immune response --> injurious/pathologic
- directed against harmless antigen (foreign or self)
83
What is a Type I hypersensitivity reaction?
- tissue rxn occurs rapidly after interaction of antigen with IgE antibody bound to mast cell
- often develop in atopic individuals (sensitized to allergen)
- mild to severe
84
What are the steps that lead to a type I hypersensitivity reaction?
- allergen introduced & recognized by APC
- APC presents to B cell / naive T cell --> Th2 cell
- B cell class switches to IgE secreting plasma cell
- IgE binds FcR on mast cell (primed)
- REPEAT exposure
- allergen binds directly to IgE primed mast cell
- mast cell activated & releases mediators
- immediate & late phase responses occur
85
What are the chemical mediators of Type I hypersensitivity reactions?
vasoactive amines, lipid mediators (immediate)
cytokines (late: 2-24 hrs)
86
Type I hypersensitivity vasoactive amines?
- histamine!! --> vascular permeability, vasodilation, smooth muscle contraction, mucus secretions
87
Type I hypersensitivity lipid mediators?
prostaglandins & leukotrines: smooth muscle contraction & vascular permeability
88
Type I hypersensitivity cytokines?
TNF, chemokines, IL-4 & 5 (amplify Th2 rxn)
89
What are some clinical syndromes that can occur due to Type I hypersensitivity rxns?
- anaphylaxis --> fall in BP (dilation), airway obstruction (laryngeal edema)
- bronchial asthma --> airway obstruction (hyper-smooth muscle), inflammation/tissue injury (late phase)
- allergic rhinitis, sinusitis (hay fever) --> mucus secretions / inflammation
- food allergies --> increased peristalsis, vomiting, diarrhea
90
How do people develop allergies?
- susceptibility is genetically determined
- atopic individuals: higher serum IgE & Th2 cells
- 50% family history of allergy
- environment can sensitize cells
91
What are type II sensitivity reactions caused by?
antibodies directed against target antigens on cell surfaces
- target cells for phagocytosis (opsonization)
- activate complement system (recruit neutrophils/macrophages) inflammation/tissue injury
- interfere with normal cellular functions
92
Describe how type II sensitivity reactions can interfere with cellular functions?
- antibody inhibits binding of NT (Ach) to receptor
- antibody stimulates receptor without hormone
93
Which diseases are examples of Antibody-Mediated Type II hypersensitivity
- autoimmune hemolytic anemia
- autoimmune thrombocytopenic purpura
- pemphigus vulgaris
- vasculitis by ANCA
- Goodpasture syndrome
- acute rheumatic fever
- myasthenia gravis
- graves disease (hyperthyroidism)
- pernicious anemia
94
Describe pemphigus vulgaris disease
- proteins in intercellular junctions of epidermal cells (desmoglein) targeted
- skin vesicles (bullae)
95
Describe myasthenia gravis
- inhibits binding of acetylcholine to receptors
- muscle weakness & paralysis
96
Describe Graves disease.
- stimulates TSH receptor
- hyperthyroidism
97
What are type III hypersensitivity reactions?
- immune complex (antigen-antibody)
- deposits in blood vessels --> complement activation & inflammation
- foreign or endogenous
- soluble antigens (in blood)
98
What are examples of immune complex mediated diseases?
- systemic lupus erythematous
- arthus reaction
- poststreptococcal glomerulonephritis
- polyarteritis nodosa
- reactive arthritis
- serum sickness
99
Describe arthus reaction.
- various foreign proteins act as antigen --> typically from vaccine
- manifests as cutaneous vasculitis
100
What cells are involved in type IV hypersensitivity reactions?
T cells
- CD4: cytokine mediated inflammation
- CD8: direct cytotoxicity
101
Many chronic inflammatory diseases are what type of hypersensitivity?
IV: T cell mediated
102
Describe type IV CD4 mediated hypersensitivity
- cytokines induce inflammation --> tissue destruction
- delayed-type: 48-72 hrs
- most Th1, some Th17
103
Describe type IV CD8 mediated hypersensitivity
- kill antigen-expressing target cell
- effective in virus infected cells (MHC1)
104
T/F type IV hypersensitivity rxn require secondary exposure?
true
105
What are examples of T cell mediated diseases?
- Rheumatoid arthritis
- multiple sclerosis
- Type I diabetes mellitus
- IBD
- psoriasis
- contact sensitivity
106
Describe Type I diabetes mellitus.
- cytotoxic T cells target & destroy antigens of pancreatic islet B cells
107
Describe contact sensitivity
- various environmental chemicals stimulate inflammation mediated by Th1 cytokines --> skin blisters & rash
108
Describe primary immunodeficiency syndromes.
- detected in infancy (6mo-2yrs)
- affect innate or adaptive
- most involve B & T lymphocytes
109
What causes primary immunodeficiency syndromes?
defects in checkpoints of B & T cell development
110
What type of syndrome is SCID?
primary immunodeficiency
-- severe combined immunodeficiency
111
What is SCID?
- many genetically distinct syndromes with defects cell mediated & humoral immunity
- susceptible to severe recurrent infections
- death in first year without stem cell transplantation
112
What is Digeorge syndrome?
- primary immunodeficiency
- deletion on chromosome 22
- congenital defect in thymic development
- vulnerable to viral, fungal, & protozoal infections
113
Features of digeorge syndrome?
CATCH 22
- cardiac abnormality
- abnormal facies
- thymic aplasia
- cleft palate
- hypocalcemia/hypoparathyroidism
*chromosome 22 deletion
114
What is Hyper-IgM syndrome?
- primary immunodeficiency
- inability of T cells to activate B cells
- normal to high levels IgM antibody
- decreased: IgG, IgE, IgA
- recurrent pyogenic infections, susceptible to pneumonia
115
Why can't T cells activate B cells in hyper IgM syndrome?
lack of class switching due to disruption of CD40 ligand
116
Primary immunodeficiencies that affect innate immunity?
- LAD
- Chediak Higashi
- complement function (C2 deficient)
117
What are complications with chediak higashi syndrome?
- defective platelets --> bruise/bleeding
- melanocyte abnormality--> albinism
- nervous system --> peripheral neuropathy
118
Are primary or secondary immunodeficiencies more common?
secondary
119
Secondary immunodeficiencies are encountered in what individuals?
- cancer
- diabetes
- chronic infection
- chemo/radiation therapy
- immunosuppressants meds
120
What is AIDS?
- acquired immunodeficiency syndrome
- HIV -- ssRNA virus
- transmitted by blood or body fluids
- >75% sexual, parenteral, perinatal
121
What is the pathogenesis of AIDS/HIV?
- targets CD4 T cells
- RT enzyme --> complementary DNA
- integrates into host genome
- cell death & release of virus or latency
*antibodies develop, but not protective
122
Life cycle sequence of HIV?
- binds CD4 T cell
- fusion
- reverse transcriptase
- integration
- replication
- assembly
- budding
123
Clinical features of HIV/AIDS?
- asymptomatic
- acute retroviral syndrome (50-70%)
--> 1-6 wks post exposure
--> extremely infectious (viremia)
--> oral: erythema & ulceration
--> lymphadenopathy, sore throat, fever, headache, my/arthralgia, diarrhea, photophobia, peripheral neuropathies
- latency: several mo-15yrs
124
Progression of HIV/AIDS is affected by what factors?
- age
- immune response
- treatment
125
How to diagnose AIDS?
CD4 declines 200 cells/mm3
CD4 <14% total lymphocytes
126
What are a few AIDS defining conditions?
- candidiasis
- herpes simplex
- kaposi sarcoma
- lymphoma
- pneumonia
127
HIV treatment?
- anti-retroviral therapy (ART) decreases replication of virus
--> reduce viremia: reduce risk of transmission, death, and transition to AIDS
128
What are the classes of antiretroviral therapy?
- nucleoside reverse transcriptase inhibitor --> incorporates into host DNA to inhibit replication
- non-nucleoside reverse transcriptase inhibitor --> directly inhibits RT
- protease inhibitors
- fusion inhibitors
- integrase inhibitors
- CCR5 inhibitors
