Immunology 1 Flashcards
1
Q
What are the primary lymphoid organs?
A
Thymus and Bone marrow
2
Q
What are the components of a lymph node
A
Follicle, Medulla, and paracortex
3
Q
How many efferents and afferents for lymph node
A
many afferents, 1 or more efferents
4
Q
What happens in the follicle
A
Site of B-cell localization and proliferation. In outer cortex. Primary follicles are dense and dormant. Secondary follicles have a pale central germinal center and are active.
5
Q
What happens in medulla.
A
Consists of medullary cords (closely packed lymphocytes and plasma cells) and medullary sinuses. medullary sinuses communicate with efferent lymphatics and contain reticular cells and macrophages.
6
Q
What happens in paracortex
A
Houses T cells. Region of cortex between follicles and medulla. Contains high endothelial venules through which T and B cells enter from blood. Not well developed in DiGeorge syndrome.
Paracortex enlarges in extreme cellular immune response (e.g. viral infection)
7
Q
Sinusoids of spleen
A
Red pulp is on the outside containing RBCs and surrounds the white pulp which contains T cells, B cells.
8
Q
Sinusoids and Lymphocytes
A
T cells in Periarterial lymphatic sheath (central arteriole is in the center of everything).
B cells in follicles within the white pulp of the spleen.
9
Q
What is the marginal zone
A
Red pulp and white pulp, contains APCs and specialized B cells, and is where APCs present blood-borne antigens
10
Q
What do macrophages do in the spleen
A
Remove encapsulated bacteria.
11
Q
What does asplenia due path
A
Decreases IgM leading to decreased complement activation leading to decreased C3b opsonization and increased susceptibility to encapsulated organisms.
12
Q
Encapsulated bacteria
A
SHiNE SKiS: Strep pneumo, HiB, Neisseria meningococcus, E. coli, Salmonella, Klebsiella, Groub B Strep
13
Q
What results due to postsplenectomy?
A
Howell-Jolly bodies (nuclear remants); target cells; thrombocytosis
14
Q
Thymus made from what
A
epithelium of 3rd pharyngeal pouches
15
Q
lymphocyte cell layer
A
Mesenchymal origin
16
Q
Thymus structure
A
Cortex is dense with immature T cells; medulla is pale with mature T cells and Hassall corpuscles containing epithelial reticular cells.
17
Q
Where do T and B cells mature
A
Thymus: T cells
Bone marrow: B cells
18
Q
What are the examples of innate immunity
A
PMNs, macrophages, monocytes, dendritic cells, NK cells (lymphoid origin), complement
19
Q
How long for innate immunity to kick in
A
minutes to hours
20
Q
Are physical barriers included in innate immunity
A
Yes, e.g. tight junctions, mucus, lysozyme, complement, CRP, defensins
21
Q
What are toll-like receptors
A
pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs):
22
Q
What are examples of PAMPs
A
LPS, flagellin, ssRNA
23
Q
How does adaptive immunity get its variation
A
Through V(D)J recombination
24
Q
MHC-I loci
A
HLA-A, B, and C
25
MHC II locis
HLA-DR, DP, and DQ (P Q R)
26
What do MHC-I and II bind
I: TCR and CD8
II: TCR and CD4
27
MHC-I found where
All nucleated cells, no RBCs
28
MHC-II found where
Only on APCs
29
Difference between MHC-I and II
I reveals endogenous proteins, II reveals exogenous proteins
30
how are antigens revealed by the MHCs
I: antigen peptides loaded onto MHC I in RER after delivery via TAP peptide transporter
II: Antigen loaded following release of invariant chain in an acidified endosome
31
How are MHC I and II moved to the cell surface
I: Beta2-microglobulin
II: Unknown
32
Structure to MHC I and II
Both have peptide binding groove
I: alpha is main component and has the peptide binding groove, beta2-microglobulin is small
II: alpha and beta are extremely similar and together form the peptide-binding groove
33
HLA A3
Hemochromatosis
34
HLA B27
PAIR: Psoriatic arthritis, ankylosing spondylitis, IBD, Reactive arthritis (seronegative arthropathies)
35
HLA DQ2/DQ8
Celiac disease
36
HLA DR2
MS, hay fever, SLE, Goodpasture syndrome
37
HLA DR3
T1DM, SLE, Graves disease
38
HLA DR4
RA, T1DM (4 walls in a "rheum")
39
HLA DR5
Pernicious anemia, hashimotos
40
NK cells MOA
perforin and granzymes to induce apoptosis of virally infected cells and tumor cells.
41
NK cells activated by
```
IL-2, IL-12, IFN-beta, and IFN-alpha
Activated by nonspecific activation signal and/or absence of class I MHC on target cell surface
```
42
Can NK cells bind antibodies
Yes, antibody-dependent cell-mediated cytotoxicity (CD16 binds Fc region of bound Ig, activating NK cell)
43
What do CD4 t cells do
Make antibody and produce cytokines to activate other cells of immune system
44
Differentiation of T cells
Starts in bone marrow, then moves to thymus, then lymph nodes
45
Steps of T cell differentiation
T-cell precursor from bone marrow moves into thymus where CD4+CD8+ T cells are positively selected for in the cortex. Then in the medulla they are divided up into CD4+ and CD8+ cells individually. They then move into the lymph nodes to fully differentiate.
46
Positive selection
Thymic cortex. T cells expressing TCRs capable of binding surface self MHC molecules survive.
47
Negative selection
Medulla. T cells expressing TCRs with high affinity for self antigens undergo apoptosis.
48
Th1 from
IL-12
49
Th2 from
IL-4
50
Th17 cell from
TGF-beta and IL-6
51
Treg cell from
TGF-Beta
52
What are the APCs
B cells, macrophages, and dendritic cells
53
What are the signals for T cell activation
MHC II binds TCR on Thelper, MHC I binds Tc (cytotoxic) cells (signal 1)
Signal 2: Costimulatory signal given by interaction of B7 (Dendritic cell) and CD28 (T cell)
54
B cell activation and class switching
1. Helper T activated (so it is already primed to the antigen?)
2. B cell presents antigens on MHC II to TCR on Th cell
3. CD40 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 antibody production.
55
What do CD4 and CD8 do.
They bind MHC for activation from Dendritic cell, this activation does not occur with B cells.
56
Th1 function
Secretes IFN-gamma
| Activates macrophages and cytotoxic T cells
57
What inhibits Th1 cells
IL-4 and IL-10 (from Th2 cell)
58
Th2 function
Secretes IL-4, IL-5, IL-6, IL-13
| Recruits eosinophils for parasite defense and promotes IgE production by B cells
59
What inhibits Th2 cells
IFN-gamma from Th1 cell
60
How to macrophages interact with lymphocytes
Macrophages produce IL-12 to produce Th1 cells which produce IFN-gamma which stimulates macrophages
61
Must know heme synthesis
For BIOCHEM
62
What to CD8 T cells have
Cytotoxic granules with perforin; granzyme B-serine protease to activate apoptosis; granulysin: antimicrobial, induces apoptosis
63
What are Tregs
Suppress CD4 and CD8 T cell fector functions.
64
How to identify Tregs
Cell surface markers: CD3, CD4, CD25 (alpha chain of IL-2 receptor) and transcription factor FOXP3.
65
What do Tregs produce
Anti-inflammatory cytokines like IL-10 and TGF-beta
66
What makes up the antigen binding site of antibodies
The variable part of the light and heavy chains.
67
What part of antibody fixes complement
Fc portion of IgM and IgG fixes complement.
68
What part of antibody does complement and macrophages bind
Complement: CH2
Macrophages: CH2 and CH3 junction point.
69
What do light and heavy chains contribute to the antibody
Heavy chain is Fc and Fab fractions. Light chain only contributes Fab function.
70
Mnemonic for Fc region of antibody
4 C's: Constant, Carboxy terminal, Complement binding, and Carbohydrate side chains. Also determines isotype (IgM, IgD)
71
Recombination for the chains
Light (VJ)
Heavy (V(D)J)
Light and heavy chains randomly combined
72
What is somatic hypermutation and when does it happen
Follows antigen stimulation, the DNA mutates in hypervariable regions to make a receptor with even greater antigen recognizing ability. The effect is that over the course of an infection the affinity for the antigen increases.
73
What happens to DNA during recombination
Add nucleotides by terminal deoxynucleotidyl transferase.
74
The ways antibodies do their thing
1. Opsonize
2. Neutralize
3. Complment activation (C3b)
75
What is affinity maturation?
Over time of an infection and with reinfection, the affinity of antibodies for a specific antigen increases. This works through Somatic Hypermutation which creates the variable antibodies. Then Clonal Selection using APCs weeds only the B cells with the most affinity, because the B cells require growth factors to survive.
76
What do all mature B cells express on their surfaces
IgM and IgD
77
What mediates isotype switching
gene rearrangement; mediated by cytokines and CD40 ligand
78
Does IgG cross placenta?
Yes
79
IgA MOA
blocks bacteria and viruses attaching to mucous membranes. Does not fix complement. Crosses epithelium by trancytosis. Picks up secretory component from epithelial cells before secretion.
80
IgA antibody structure
Monomer in circulation or dimer when secreted. Most abundant overall but it is in secretions and colostrum.
81
IgG prevalence
Most abundant isotype in serum.
82
IgM MOA
Fixes complement but does not cross placenta. Antigen receptor on the sruface of B cells. Monomer on B cell or pentamer when secreted.
83
IgD function
Unclear function. On B cells and in serum.
84
IgE function
Binds mast cells and basophils; cross-links when exposed to allergen, mediating immediate (type I) hypersensitivity through release of inflammatory mediators such as histamine. mediates immunity to worms by activating eosinophils. Lowest concentration in serum.
85
What are thymus independent antigens
Lack a peptide component, cannot be presented by MHC to T cells.
86
What induces acute-phase reactants
IL-6, IL-1, TNF-alpha, and IFN-gamma
87
What acute phase reactants are upregulated
Serum amyloid A, CRP, ferritin, fibrinogen, and hepcidin
88
What acute phase reactants are downregulated
Albumin and transferrin
89
Serum Amyloid A
Prolonged elevation can cause amyloidosis
90
CRP
Opsonin; fixes complement and facilitates phagocytosis. Measured clinically as a sign of ongoing inflammation.
91
Ferritin
Binds and sequesters iron to inhibit microbial iron scavenging.
92
Fibrinogen
Coagulation factor; promotes endothelial repair; correlates with ESR
93
Hepcidin
Prevents release of iron bound by ferritin leading to anemia of chronic disease
94
Albumin
Reduces to conserve amino acids for positive reactants
95
Transferrin
Internalized by macrophages to sequester iron.
96
When does Membrane Attack Complex target?
Defends against gram-negative.
97
Different pathways of Complement
Classic pathway: IgG or IgM mediated
Alternative pathway: Microbe surface molecules
Lectin pathway: Mannose or other sugars on microbe surface.
98
C3b
opsonization
99
C3a,C4a, and C5a
A for anaphylaxis
100
C5a
Neutrophil chemotaxis
101
C5b-9
Cytolysis by MAC
102
What are the opsonins
C3b and IgG are the two primary opsonins in bacterial defense; C3b also helps clear immune complexes.
103
What is Decay-accelerating factor
DAF, aka CD55 (along with C1 esterase inhibitor) prevent complement actiation on self cells like RBCs (nocturnal paroxysmal hemoglobinuria)
104
C1 esterase inhibitor deficiency
Causes hereditary angioedema. ACE inhibitors are contraindicated
105
C3 deficiency
Increases risk of severe, recurrent pyogenic sinus and respiratory tract infections; increases susceptibility to type III hypersensitivity reactions
106
C5-C9 deficiencies
Increases susceptibility to recurrent Neisseria bacteremia
107
DAF (CPI anchored enzyme) deficiency
Causes complement-mediated lysis of RBCs and paraoxsymal nocturnal hemoglobinuria
108
IL-1
Osteoclast-activating factor, endogenous pyrogen.
Causes fever, acute inflammation. Activates endothelium to express adhesion molecules; induces chemokine secretion to recruit leukocytes.
109
IL-6
Endogenous pyrogen. Secreted by Th2 cells. Causes fever and stimulates production of acute-phase proteins.
110
IL-8
Major chemotactic factor for neutrophils
111
IL-12
Induces differentiation of T cells into TH1 cells. Activates NK cells. Also secreted by B cells.
112
TNF-alpha
Mediates septic shock. Activates endothelium. Causes leukocyte recruitment, vascular leak.
113
Neutrophils need what cytokine
IL-8 to clear infections
114
What cytokines are secreted by Macrophages
IL-1, IL-6, IL-8, IL-12, TNF-alpha
115
What cytokines are secreted by all T cells.
IL-2 and IL-3
116
IL-2
Stimulates growth of helper, cytotoxin, and regulatory T cells.
117
IL-3
Supports the growth of differentiation of bone marrow stem cells. Functions like GM-CSF
118
What acts like GM-CSF
IL-3
119
What does Th1 cells produce
Interferon-gamma
120
IFN-gamma
Has antiviral and antitumor properties. Activates NK cells to kill virus-infected cells, increases MHC expression and antigen presentation in all cells.
121
What do Th2 cells produce
IL-4, IL-5, IL-10
122
Il-4
Induces differentiation into Th2 cells. Promotes growth of B cells. enhances class switching to IgE and IgG.
123
IL-5
Promotes differentiation of B cells. Enhances class switching to IgA. Stimulates the growth and differnetiation of eosinophils.
124
IL-10
Modulates inflammatory response. Inhibits actions of activated T cells and Th1. Also secreted by regulatory T cells.
125
TGF-beta similar to
Similar to IL-10, because it inhibits inflammation.
126
Cytokine mnemonic
Hot T-bone stEAK: IL-1: fever (hot), IL-2: stimulates T cells. IL-3: stimulates bone marrow, IL-4: Stimulates IgE production. IL-5: Stimulates IgA production. IL-6: stimulates aKute-phase protein protein production.
127
Interferon alpha and beta
Innate host defense against both RNA and DNA viruses. Glycoproteins synthesized by viral-infected cells that act locally on uninfected cells, priming them for viral defense. When a virus infects primed cells, viral dsDRNA activates RNAse L which degrades viral/host mRNA and protein kinase which inhibits viral/host protein synthesis which ends up resulting in apoptosis.
128
T cell surface proteins
TCR (binds antigen-MHC complex)
CD3 (associated with TCR for signal transduction)
CD28 (Binds b7 on APC)
129
Helper T cell specific proteins
CD4, CD40L
130
Cytotoxic T cell specific proteins
CD8
131
B cell surface proteins
Ig
CD19, CD20, CD21 (receptor for EBV), CD40
MHC II, B7
132
What receptor does EBV bind to?
CD21 (Beer at Barr aged 21)
133
Macrophages receptors
CD14, CD40
MHC II, B7
Fc and C3b receptors (enhanced phagocytosis)
134
NK cell receptors
CD16 (binds Fc of IgG), CD56 (unique marker for NK)
135
Anergy
Without costimulatory molecule: B cells become anergic, but tolerance is less complete than in T cells.
136
What are superantigens
S. pyogenes and S. aureus: cross-link Beta region of the TCR to MHC class II on APCs, massive release of cytokines.
137
Gram negative effect on macrophages
Endotoxins/Lipopolysaccharides directly stimulate macrophages by binding to endotoxin receptor CD14; Th cells not involved.
138
Antigenic variation examples
```
Salmonella (2 flagellar variants), Borrelia (relapsing fever), Neisseria gonorrhoeae (pilus protein)
Influenza shift vs. drift.
Parasites trypanosomes (programmed rearrangement)
```
139
Type I hypersensitivity
anaphylactic and atopic. antigen crosslinks IgE on presensitized mast cells and basophils, releasing vasoactive amines that act at postcapillary venules. Delayed response follows due to production of arachidonic acid (leukotrienes)
140
What mediates the types of hypersensitivities
Antibodies mediate Types I, II, and III
141
Type II hypersensitivities
Essentially autoimmune conditions through opsonization, complement, and antibody dependent cell-mediated cytotoxicity, usually due to NK cells or macrophages
142
Direct Coombs
Detects antibodies that HAVE adhere to patient's RBCs (testing Rh+ infant of an Rh- mother.
143
Indirect Coombs
Detects antibodies that CAN adhere to other RBCs (testing Rh- woman for Rh+ antibodies)
144
Type III hypersensitivity
Immune complex-antigen-antibody (IgG) activates complement which attracts PMNs which release lysosomal enzymes. Like Rheum diseases (SLE, vasculitides)
145
Type III mnemonic
3 things stuck together: antigen-antibody-complement
146
Serum Sickness path
Immune complex disease (type III) in which 5 days after being exposed to drugs (formerly exogenous proteins) antibodies are made which complex with the foreign substance and deposit in membranes causing damage from fixing complement.
147
Serum Sickness presentation
Drugs (not serum) acting as haptens. Fever, urticaria, arthralgias, proteinuria, LAD 5-10 days after antigen exposure
148
Arthus reaction
Type III where intradermal injections of antigen lead to antigen-antibody complexes with dema, necrosis, and activation of complement
149
Arthus reaction test
IF staining
150
Example of drugs that cause Arthus reaction
???????
151
Type IV hypersensitivity
Sensitized T cells encoutner antigen and release lymphokines (leading to macrophage activation, no antibody involved)
152
Type IV hypersensitivity mnemonic
4 T's: T lymphocytes, Transplant rejections, TB skin tests, Touching (contact dermatitis)
153
Type IV tests
Patch test, PPD
154
Type IV path
???????????
155
Hypersensitivities mnemonic
```
ACID
Anaphylactic and Atopic (type I)
Cytotoxic (antibody mediated) Type II
Immune complex (type III)
Delayed (cell mediated ) type IV
```
156
Know examples of each type of hypersensitivties
????????????
157
Autograft
From self
158
Syngeneic graft
From identical twin or clone.
159
Allograft
From nonidentical individual of same species
160
Xenograft
From different species
161
What kind of rejection is hyperacute?
Type II reaction, complement activates and the organ dies
162
Acute transplant rejection path
Cellular: CTLs activated against donor MHCs.
Humoral: similar to hyperacute, except antibodies develop after transplant.
163
Chronic path
Recipient T cells perceive donor MHC as recipient MHC and react against donor antigens presented. Both cellular and humoral components.
164
Graft-versus-host disease
Grafted immunocompetent T cells proliferate in the immunocompromised host and reject host cells with "foreign" proteins leading to severe organ dysfunction
165
Hyperacute rejection features
Widespread thrombosis of graft vessels leading to ischemia and necrosis and graft must be removed
166
Acute rejection features
Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate. Prevent/reverse with immunosuppressants.
167
Chronic rejection features
Irreversible. T-cell and antibody-mediated damage.
Organ specific:
Heart - atherosclerosis
Lungs - bronchiolitis obliterans
Liver - vanishing bile ducts
Kidney - vascular fibrosis, glomerulopathy
168
Chronic rejection path
?????
169
Graft-Versus-host disease features
Maculopapular rash, jaundice, diarrhea, hepatosplenomegaly. Usually in bone marrow and liver transplants (rich in lymphocytes). Potentially beneficial in bone marrow transplant for leukemia (graft-versus-tumor effect)
