Immunology Flashcards
1
Q
Primary lymphoid organs
A
Where lymphocytes are generated
Includes bone marrow and thymus
2
Q
Which lymphocyte matures in the bone marrow?
A
B lymphocytes
3
Q
Secondary lymphoid organs
A
Where adaptive immune responses are initiated & Ag/Ab encounter each other
Exist to bring Ag and lymphocytes together
4
Q
Lymph node
A
a secondary lymphoid organ that has many afferents and 1 or more efferents (medulla)
5
Q
How do naive lymphocytes exit the blood?
A
Via high endothelial venules (HEV)
6
Q
Follicle of a LN
A
Site of B-cell localization and proliferation
In the outer cortex
7
Q
Parts of a LN
A
Follicle, cortex (outer and paracortex), and medulla
8
Q
Primary follicles vs. secondary follicles in LNs
A
Primary - dense and dormant
Secondary - pale central germinal centres and are active
9
Q
What are high endothelial venules?
A
- Specialized section of post-capillary venules
- plump endothelial cells protrude into vessel
- In LNs found in paracortex and some areas of cortex
- Lymphocytes display increased adhesiveness to HEV
10
Q
Medulla of a LN
A
Consists of medullary cords and medullary sinuses
Houses macrophages and plasma cells
11
Q
Medullary sinuses
A
communicate with efferent lymphatics and contain reticular cells and macrophages
12
Q
Paracortex in LNs
A
Houses T cells
Region of cortex between follicles and medulla
Contains high endothelial venules through which T and B cells enter from blood
13
Q
What part of the LN enlarges in an extreme cellular immune response (e.g., viral infection)?
A
Paracortex
14
Q
What art of the LN is not well developed in patients with DiGeorge syndrome?
A
Paracortex
15
Q
What area of the body do cervical LN’s drain?
A
Head and neck
16
Q
What area of the body do hilar LNs drain?
A
Lungs
17
Q
What area of the body do Mediastinal LNs drain?
A
trachea and esophagus
18
Q
What area of the body do axillary LNs drain?
A
upper limb, breast, skin above umbilicus
19
Q
What area of the body do celiac LNs drain?
A
liver, stomach, spleen, pancreas, upper duodenum
20
Q
What area of the body do superior mesenteric LNs drain?
A
lower duodenum, jejunum, ileum, colon to splenic flexure
21
Q
What area of the body do inferior mesenteric LNs drain?
A
colon from splenic flexure to upper rectum
22
Q
What area of the body do internal iliac LNs drain?
A
lower rectum to anal canal (above pectinate line), bladder, vagina (middle third), prostate
23
Q
What area of the body do para-aortic LNs drain?
A
testes, ovaries, kidneys, uterus
24
Q
What area of the body do superficial inguinal LNs drain?
A
ana canal (below pectinate line), skin below umbilicus (except popliteal territory)
25
What area of the body do popliteal LNs drain?
dorsolateral foot, posterior calf
26
Spleen
collects blood born antigens and also destroys aged RBCs
| divided into red pulp and white pulp
27
White pulp of the spleen
T cells are found in the periarterial lymphatic sheath within the white pulp
B cells are found in follicles within the white pulp
28
Red pulp of the spleen
where old RBCs are destroyed
29
The marginal zone btwn the red and white pulp contains what?
APCs and specialized B cells , and is where APCs present blood-borne antigens
30
What do macrophages in the spleen remove?
encapsulated bacteria
31
What occurs in the immune system when there is a splenic dysfunction (e.g., postspenectomy, sickle cell dz)?
decreased IgM -> decreased complement activation -> decreased C3b opsonization -> increased susceptibility to encapsulated organisms
Susceptibility to bacteria caused by encapsulated bacteria caused by failure of the immune response to these common extracellular bacteria when the enter the blood stream
32
List the pathogens that can cause splenic dysfunction
(SHiNE SKS)
```
Streptococcus pneumoniae
HiB
Neisseria meningitidis
E coli
Salmonella spp.
Klebsiella pneumoniae
group B Streptococci
```
33
Thymus
Site of T cell differentiation and maturation
Cortex is dense with immature T cells
Medulla is pale with mature T cells and Hassall corpuscles containing reticular cells
34
The thymus comes from the epithelium of….
3rd pharyngeal pouches
35
Components of the innate immune system
neutrophils, macrophages, monocytes, dendritic cells, NK cells (lymphoid origin), complement
36
Components of the adaptive immune system
T cells, B cells, circulating antibodies
37
Innate immune systems response to pathogens
```
Nonspecific
Occurs rapidly (minutes to hours)
```
38
Adaptive immune system response to pathogens
Highly specific, refined over time
| Develops over long periods; memory response is faster and more robust
39
Innate immunity physical barriers
Epithelial tight junctions, mucus
40
Adaptive immunity physical barriers
none
41
Proteins secreted by Innate immunity
lysozyme, complement, CRP, defensins
42
Proteins secreted by adaptive immunity
immunoglobulins
43
Key features in pathogen recognition by innate immunity
TLRs: pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs)
- signalling induces innate immune responses and inflammation
44
Examples of PAMPs
LPS (gram negative bacteria), flagellin (bacteria), ssRNA (viruses)
45
Key features in pathogen recognition by adaptive immunity
Memory cells: activated B and T cells; subsequent exposure to previously encountered antigen -> stronger, quicker immune response
46
Types of adaptive immune responses
Humoral and cell mediated
47
Humoral responses
Adaptive immunity
mediated by Abs
Produced by bone marrow derived B lymphocytes
48
Cell-mediated responses
Adaptive immunity
| mediated by thymus derived T lymphocytes
49
Genes responsible for recognizing a graft as being foreign are termed …?
Histocompatibility genes
50
MHC are encoded by...
HLA genes
51
MHC present antigen fragments to...
T cells and bind TLRs
52
MHC I loci
HLA-A, HLA-B, HLA-C
53
MHC II loci
HLA-DR, HLA-DP, HLA-DQ
54
MHC I molecules present Ags derived from the ______ to _______ cells
cytosol; CD8+ T cells
55
MHC II molecules present Ags derived from ______ to _______ cells
outside the cell; CD4+ T cells
56
MHC I function
present ENDOGENOUSLY synthesized ANTIGENS (e.g., viral) to CD8+ T cells
57
MHC II function
present EXOGENOUSLY synthesized PROTEINS (e.g., bacteria) to CD4+ T cells
58
MHC I Ag loading
Ag peptides loaded onto MHC I in RER after delivery via TAP peptide transporter
59
MHC II Ag loading
Ag loaded following release of invariant chain in an acidified endosome
60
MHC I mode of transport to cell surface
beta 2-microglobulin
61
HLA- A3 subtype associated dzs
Hemochromatosis
62
HLA- B27 subtype associated dzs
Psoriatic arthritis, ankylosing spondylitis, arthritis of inflammatory bowel dz, reactive arthritis
63
HLA- DQ2/DQ8 subtype associated dzs
Celiac dz
64
HLA- DR2 subtype associated dzs
MS, hay fever, SLE, Goodpasture syndrome
65
HLA- DR3 subtype associated dzs
DM type 1, SLE, Grave's dz
66
HLA- DR4 subtype associated dzs
Rheumatoid arthritis, DM type 1
67
HLA- DR5 subtype associated dzs
Pernicious anemia -> vit B12 deficiency, Hashimoto thyroiditis
68
NK cells
```
Use perforin and granzymes to induce apoptosis of virally infected cells and tumour cells
Induced to kill when exposed to a nonspecific activation signal on target cell and/or to an absence of class I MHC on target cell surface
```
69
Which cells are the only lymphocyte member of the innate immune system?
NK cells
70
NK cells activity are enhanced by which cytokines?
IL-2, IL-12, IFN-b, and IFN-a
71
B cell functions (3 main ones)
Recognize Ag - undergo somatic hypermutation to optimize Ag specificity
Produce Ab - differentiate into plasma cells to secrete specific immunoglobins
Maintain immunologic memory - memory B cells persist and accelerate future response to Ag
72
T cell functions
CD4+ T cells help B cells make Ab and produce cytokines to activate other cells of immune system
CD8+ T cells kill virus infected cells directly
Delayed cell-mediated hypersensitivity (TypeIV)
Acute and chronic cellular organ rejection
73
Describe the process of T cell differentiation
T cell precursor starts in the bone marrow
T cell precursor travels to the cortex in the thymus where it becomes a CD4+ and CD8+ T cell
T cell divides in the medulla of the thymus into a CD4+ T cell and a CD8+ T cell
In the LN the cytotoxic CD8+ T cell kills virus infected, neoplastic, and donor graft cells
In the LN the Helper CD4+ T cell differentiates further from cytokines (Th1 cell, Th2 cell, Th17 cell, Threg cell)
74
How many signals are required for T cell activation, B cell activation, and class switching?
2
75
Name the APCs?
B cells, macrophages, dendritic cells
76
Naive T cell activation stages
1. Foreign body is phagocytosed by dendritic cell
2. Foreign Ag is presented on MHC II and recognized by TCR (T cell receptor) on Th (helper) cell. Ag is presented on MHC I to Tc (cytotoxic) cells (signal 1)
3. "Costimulatory signal" is given by interaction of B7 and CD28 (signal 2)
4. Th cell activates and produces cytokines. Tc cell activates and is able to recognize and kill virus infected cells
77
B cell activation and class switching stages
1. Helper T cell activation
2. B cell receptor-mediated endocytosis; foreign Ag is presented on MHC II and recognized by TCR on Th cell (signal 1)
3. CD40 receptor on B cell binds CD40 ligand on Th cell (signal 2)
4. Th cell secretes cytokines that determine Ig class switching of B cell. B cell activates and undergoes class switching, affinity maturation, and Ab production
78
Which APC is the only one able to activate naive T cells?
Dendritic cells
79
Helper T cell - Th1 Cell
Secretes IFN-y
Activates macrophages and cytotoxic T cells
Inhibited by IL-4 and IL-10 (from Th2 cell)
80
Helper T cell - Th2 cell
Secretes IL-4, IL-5, IL-6, IL-13
Recruits eosinophils for parasite defence and promotes IgE production by B cells
Inhibited by IFN-y (from Th1 cell)
81
Macrophages release IL-12 which stimulates what?
Stimulates T cells to differentiate into Th1 cells. Th1 cells release IFN-y to stimulate macrophages
82
Cytotoxic T cells
Kill virus infected, neoplastic, and donor graft cells by inducing apoptosis
Release cytotoxic granules containing preformed proteins (perforin and granzyme B)
83
Regulatory T cells
Help maintain specific immune tolerance by suppressing CD4 and CD8 T cell effector functions
84
How are regulatory T cells identified?
Expression of cell surface markers CD3, CD4, CD25 (alpha chain of IL-2), and transcription factor FOXP3
85
Activated regulatory T cells produce which anti-inflammatory cytokines?
IL-10 and TGF-beta
86
Which part of the Ab recognizes Ag?
Light and heavy chains
87
The Fc region of an Ab is made from which chain type?
Heavy
88
The Fab region of an Ab is made from which chain type?
Both - heavy and light
89
Fab region of Ab
Ag binding fragment
| Determines idiotype: unique Ag binding pocket; only 1 antigenic specificity expressed per B cell
90
Fc region of Ab
```
Constant
Carboxyl terminal
Complement binding
Carbohydrate side chains
Determines isotype (IgM, IgD, etc.)
```
91
Ab diversity is generated by...
```
Random recombination of VJ (light chain) or V(D)J (heavy chain) genes
Random combination of heavy chains with light chains
Somatic hypermutation (following Ag stimulation)
Addition of nucleotides to DNA during recombination bu terminal deoxynucleotidyl transferase
```
92
Which immunoglobulins do mature B cells express on their surfaces?
IgM and IgD
93
IgG
Main Ab in secondary (delayed) response to an Ag.
Most abundant isotype in serum.
Fixes complement, crosses placental (provides infants with passive immunity), opsonizes bacteria, neutralizes bacterial toxins and viruses
94
IgA
Prevents attachment of bacteria and viruses to mucous membranes; does not fix complement.
Monomer in circulation or dimer when secreted
Crosses epithelial cells by transcytosis
95
Which Ab is mostly produces overall?
IgA
96
Which Ab is released in our secretions (tears, saliva, mucus)?
IgA
97
Which Ab is in colostrum?
IgA
98
IgM
Produces in primary (immediate) response to Ag. Fixes complement but does not cross the placenta
99
Which Ab crosses the placenta?
IgG
100
Which Ab is the Ag receptor on B cells?
IgM and IgD
| Monomer on B cells or pentamer when secreted
101
IgD
Unclear function. Found on the surface of many B cells and in serum.
102
IgE
Binds mast cells and basophils; cross links when exposed to allergen, mediating immediate (type 1) hypersensitivity through release of inflammatory mediators such as histamine
103
How does IgE mediate immunity to worms?
By activating eosinophils
104
Which Ab is in the lowest concentration in serum?
IgE
105
Thymus-independent Ags
Ags lacking a peptide component
Weakly or nonimmunogenic
Vaccines often require boosters
106
Which Ag type cannot be presented by MHC to T cells?
Thymus-independent antigens
107
Thymus-dependent Ags
Ags containing a protein component. Class switching and immunologic memory occur as a result of direct contact of B cells with Th cells (CD40-CD40 ligand interaction)
108
Acute phase reactants
Factors whose serum concentrations change significantly in response to inflammation
109
When and where are acute phase reactants produced?
Liver in both acute and chronic inflammatory states
110
What cytokines induce acute-phase reactants?
IL-6, IL-1, TNF-a, and IFN-y
111
serum amyloid A (Upregulated)
prolonged elevation can lead to amyloidosis
112
C-reactive protein (Upregulated)
Opsonin; fixes complement and facilitates phagocytosis
| Measured clinically as a sign of ongoing inflammation
113
ferritin (Upregulated)
binds and sequesters iron to inhibit microbial iron scavenging
114
fibrinogen (Upregulated)
coagulation factor; promotes endothelial repair; correlates with ESR
115
hepcidin (Upregulated)
prevents release of iron bound by ferritin -> anemia of chronic dz
116
albumin (downregulated)
reduction conserves amino acids for positive reactants
117
transferrin (downregulated)
internalized by macrophages to sequester iron
118
What kind of pathogens do MACs defend agains?
gram-negative bacteria
119
Classic pathway of complement
IgG and IgM mediated
120
Alternative pathway of complement
microbe surface molecules
121
Lectin pathway of complement
mannose or other sugars on microbe surface
122
C3b
opsonization
123
C3a, C4a, C5a
anaphylaxis
124
C5a
neutrophil chemotaxis
125
C5b-9
cytosine by MAC
126
Opsonins
C3b and IgG are the two primary opsonins in bacterial defence
127
Which complement protein helps clear immune complexes?
C3b
128
What are the names of the inhibitors that help prevent complement activation on self cells (e.g., RBCs)
Decay-Accelerating factos (DAF aka CD55) and C1 esterase
129
C1 esterase inhibitor deficiency
causes hereditary angioedema. ACE inhibitors are CI
130
C3 deficiency
Increases risk of severe, recurrent pyogenic sinus and respiratory tract infections; increases susceptibility to type III hypersensitivity reactions
131
C5-C9 deficiencies
increases susceptibility to recurrent Neisseria bacteremia
132
DAF deficiency
causes complement mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria
133
What cytokines are secreted by macrophages?
IL-1, IL-6, IL-8, IL-12, TNF-alpha
134
What cytokines are secreted by T cells?
IL-2, IL-3
135
What cytokines are secreted from Th1 cells?
IFN-y
136
What cytokines are from Th2 cells?
IL-4, IL-5, IL-10
137
IL-1
Endogenous pyrogen.
Causes fever and acute inflammation
Activated endothelium to express adhesion molecules
Induces chemokine secretion to recruit leukocytes
138
IL-2
stimulates growth of all T cells
139
IL - 3
supports the growth and differentiation of bone marrow stem cells
140
IL-4
```
Stimulates IgE production and IgG through class switching
induces differentiation into Th2 cells
Promotes growth of B cells
```
141
IL-5
Enhances class switching to IgA
Promotes differentiation of B cells
Stimulates the growth and differentiation of eosinophils
142
IL-6
Causes fever and stimulates production of acute phase proteins
Also secreted by Th2 cells
143
IL-8
Major chemotactic factor for neutrophils
144
IL-10
Moderates inflammation response
Inhibits actions of activated T cells and Th1
Also secreted by regulatory T cells
145
What cytokine has similar actions to IL-10 bc it is involved in inhibiting inflammation?
TGF-beta
146
IL-12
Induces differentiation of T cells into Th1 cells
Activates NK cells
Also secreted by B cells
147
TNF-alpha
Mediates septic shock
Activates endothelium
Causes leukocyte recruitment, vascular leak
148
IFN-y
has antiviral and anti tumour properties
activates NK cells to kill virus infected cells
increases MHC expression and Ag presentation in all cells
