Immunology Flashcards
1
Q
What are the four types of innate immunity?
A
Anatomical barriers, physiological barriers, phagocytic barriers and inflammatory barriers
2
Q
What are examples of anatomical barriers?
A
Skin and mucous membranes
3
Q
What are examples of physiological barriers?
A
Temperature, acidity, soluble factors
4
Q
What are examples of phagocytic barriers?
A
Phagocytes
5
Q
What are the characteristics of the epidermis?
A
Dead outer, impermeable, nutrition by diffusion, sheds every 10-15 days, made up of keratinocytes
6
Q
What are the characteristics of the dermis?
A
Vascularised, connective tissue, glands, sebum secretion
7
Q
What is the most common entry point for pathogens?
A
Mucous membranes
8
Q
What composes the mucous membranes?
A
Outer epithelial and connective tissue layers
9
Q
What makes up mucus?
A
Mucin (glycoproteins), anti-microbial, proteins, inorganic salts
10
Q
How does the influenza virus evade the mucous membrane defence?
A
It has specialised adhesion molecules
11
Q
How does gastric acidity destroy most ingested pathogens?
A
Low pH denatures enzymes, affects transport mechanisms and metabolic activity
12
Q
What are the soluble factors and how to they defend the body?
A
Lysozyme (cleaves peptidoglycans, weakens cell wall, osmotic lysis), interferon (anti-viral activity, prevents viral replication), opsonins (ficolin, surfactant proteins, mannose binding protein, promotes phagocytosis), complement (lyse target cells, enhance phagocytosis and chemotaxis)
13
Q
What are cells of the myeloid lineage of the innate immune system?
A
Neutrophils, monocyte/macrophage, eosinophils, basophils, mast cells
14
Q
What are cells of the lymphoid lineage of the innate immune system?
A
Natural killer cells
15
Q
What is the difference between endocytosis and phagocytosis?
A
Endocytosis is the ingestion of macromolecules, phagocytosis is the ingestion of particles. All cells are endocytic but only certain cells can phagocytose.
16
Q
What are the two major mechanisms of endocytosis?
A
Pinocytosis (nonspecific) and receptor-mediated endocytosis (specific)
17
Q
What is the mechanism of phagocytosis?
A
Plasma membrane expands to form pseudopods. Pseudopod retracts and seals intelf into a phagosome. Phagosome fuses with lysosomes. Processing then similar to endocytosis.
18
Q
What is the function of opsonins?
A
Tagging microbes to make it more palatable for phagocytes
19
Q
What are the two functions of complement?
A
Generate reaction products to clear antigens and generate an inflammatory response
20
Q
How is complement activated in adaptive immunity?
A
Classical pathway - C1 recognises immune complexes formed by the binding of antibodies to antigen
21
Q
How is complement activated in innate immunity?
A
Alternative pathway - non-specific activation by bacteria, fungi, parasites and viruses, C3b deposits on surfaces of microbes. Lectin pathway - mannose binding lectin attaches to mannose sugar residues on bacteria surface
22
Q
What is the first important mechanism which occurs following complement activation?
A
Opsonisation - coats surface with C3b proteins to promote phagocytosis
23
Q
What is the second important mechanism which occurs following complement activation?
A
Initiates an inflammatory response - release anaphylatoxins C3a, C4a and C5a, which bind to immune cells to trigger the inflammatory response. Anaphylatoxins are also chemoattractants to phagocytes
24
Q
What is the third important mechanism which occurs following complement activation?
A
Punches holes in cell membranes - formation of the membrane attack complex on surface of cells, bacteria and evneloped viruses
25
Define the inflammatory response
A complex sequence of events that occur following tissue damage caused by invasion or wounding
26
How are leukocytes transported?
In the circulatory system
27
What is the function of precapillary sphincters?
Prevent the backflow of blood
28
What are the three types of capillary?
Continuous, fenestrated, sinusoidal
29
What are the features of continuous capilaries?
Least permeable, most common (skin, muscle), don't let cells pass through in normal homeostatic conditions
30
What are the features of fenestrated capillaries?
Large fenestrations, in areas of high filtration (kidneys, choroid plexus), increased permeability
31
What are the features of sinusoidal capillaries?
Most permeable, only in special locations (spleen, bone marrow), for collecting blood in a network of sinuses
32
Where are most blood cells being made one month after contraception?
Yolk sac
33
Where are most blood cells being made five months after contraception?
Liver and spleen
34
Where are most blood cells being made at birth?
Bones
35
Which bones quickly stop producing blood cells after birth?
Long bones
36
Which bones slowly stop producing blood cells after birth?
Cranium, pelvis, sternum, ribs, vertebra
37
What are the characteristics of neutrophils?
Most numerous of circulating lymphocytes (50-70%), rapidly deployed and expandable, half life about 7 days, lasts 1-2 days, only 5% in circulation
38
What are the characteristics of eosinophils?
1-3% of circulating leukocytes, increased in allergic individuals and upon helminth infections, role in type I hypersensitivity (allergy)
39
What are the characteristics of basophils?
<1% of circulating leukocytes, important role in initiation of inflammation, parasitic infections and allergic reactions
40
What are the characteristics of monocytes?
1-6% of circulating leukocytes, half life around 1 day, circulating precursors of macrophages and dendritic cells, some phagocytic capability
41
What causes a small, naive B lymphocyte to enter the cell cycle?
Antigen activation induces cell cycle entry
42
What are the T halper cell subsets?
Th1, Th2, Th17, iTreg, Th9, Tfh
43
Which cytokines cause a naive CD4+ T cell to become Th1?
IFN-gamma, IL-12
44
Which cytokines cause a naive CD4+ T cell to become Th2?
IL-4
45
Which cytokines cause a naive CD4+ T cell to become Th17?
IL-6, TGF-beta
46
Which cytokines cause a naive CD4+ T cell to become iTreg?
TGF-beta, RA, IL-2
47
Which cytokines cause a naive CD4+ T cell to become Tfh?
IL-21
48
Which T cells have CD4+ present on their surfaces?
T helper cells
49
Which T cells have CD8+ present on their surfaces?
Cytotoxic T cells
50
What is the major source of inflammatory cytokines?
Macrophage
51
What is the purpose of dendritic cells?
Crucial antigen-presenting cells, specialise in presenting antigen to naive T cells, and can be derived from either myeloid lineage or lymphoid lineage
52
What are tissue-resident dendritic cells called?
Migratory
53
What are lymphoid organ-resident dendritic cells called?
Conventional
54
What do mast cells function as?
Sentinal cells of the innate immune system
55
What are the primary lymphoid organs?
Thymus, bone marrow
56
What are the secondary lymphoid organs?
Spleen, adenoids, tonsils, thoracic duct, lymph nodes, tissue lymphatics
57
What happens in primary lymphoid organs?
Sites of antigen receptor rearrangement, release mature antigen-responsive lymphocytes into circulation, sites of positive and negative selection
58
What happens in secondary lymphoid organs?
Sites of engagement of lymphocytes with antigen
59
What surrounds arterioles as a periarteriolar lymphoid sheath in the spleen?
T cell area (containing dendritic cells)
60
What are in the follicles in the spleen?
B cell area
61
What is in the marginal zone of the spleen?
Macrophages, specialised B cells
62
Which type of capillary does the spleen have?
Sinusoidal capillaries
63
How do naive lymphocytes circulate?
Traffic through the blood, peripheral lymhoid tissues and efferent lymphatics, but do not enter non-lymphoid peripheral tissue
64
How do effector lymphocytes circulate?
Can enter non-lymphoid peripheral tissues, but have lost their ability to enter peripheral lymphoid tissues
65
How do memory lymphocytes circulate?
Can go everywhere
66
What is serum?
Plasma not containing clotting factors
67
Where are antibodies found?
In the gammaglobulin fraction of serum proteins
68
What are gammaglobulins?
Not very charged proteins in serum
69
What is one way to transfer passive immunity to someone?
Transfer pooled gammaglobulins (doesn't last long as they have a half-life)
70
What is the difference between antibody and immunoglobulin?
Antibody relates to function, immunoglobulin relates to structure
71
What is the structure of an immunoglobulin?
4 polypeptides held together by disulphide bonds
72
Where are immunoglobulins made?
Made by B cells
73
What is the mechanism of production of a B cell?
Stem cell -> Pro-B cell -> Pre-B cell (with preIg) -> Immature B cell (with IgM) -> Mature B cell (with IgM and IgD) -> released from bone marrow
74
Which Ig chain is made first?
Heavy chains with surrogate light chain (later replaced)
75
Which antibodies are in highest concentration?
IgG
76
What are the isotypes of Igs?
IgM, IgD, IgG(1, 2, 3, 4), IgE, IgA(1 and 2)
77
Which antibody is made first by B cells?
IgM (also first to be secreted in immune response)
78
Which antibody is protected from enzymatic degradation and how?
IgA, by the secretory component (hence it can bind to antigens in the mucosal regions)
79
Is there Ig allotypic variation within an individual?
No (constant regions)
80
Is there Ig idiotypic variation within an individual?
Yes (variable regions in heavy and light chains)
81
Where does Ig bind on an antigen?
On the epitope
82
How are antibodies generated?
B(rest) meets antigen -> activated B cell -> memory and plasma cells -> plasma cell secretes Ig (no hydrophobic region)
83
What are the three functions of antibodies?
Binds to complement protein C1 to initiate the Classical pathway, binds to Fc receptors on phagocytes (neutrophils and macrophages), binds to Banwell receptors on endothelial cells
84
How is antibody diversity achieved?
Gene rearrangement within the variable region of the H and L chains (occurs when Pro-B cell becomes Pre-B cell)
85
What is the important antibody in the primary immune response?
IgM
86
What is the important antibody in the secondary immune response, and why is it different?
IgG. Has higher binding affinity of the antibody for the antigen, production of more memory B cells.
87
What are the different types of vaccine?
Live attenuated organisms, killed whole organisms, inactivated components of organisms, recombinant proteins
88
Why do dead vaccines generally result in a poor immune response?
Macrophages can come and remove the dead stuf
89
How does an adjuvant work?
Enhances the immune response by slowly releasing the antigen or vaccine, so it can persist longer in the body
90
What causes B cells to undergo class switching?
The influence of certain cytokines released by helper T cells
91
When class switching, which region is affected?
Only the constant region
92
Which cytokine causes a switch to IgG?
IFN-gamma
93
Which cytokine causes a switch to IgA?
TGF-beta
94
Which cytokine causes a switch to IgE?
IL-4
95
What are the characteristics of IgM?
Neutralises extracellular bacteria and viruses
96
What are the characteristics of IgG?
Can pass through the blood placenta barrier
97
What are the characteristics of IgA?
Survive longer in bodily secretions
98
What are the characteristics of IgE?
Attaches onto eosinophils (or mast cells/basophils) via its Fc region to help fight against extracellular parasites
99
Why can't macrophages destroy parasites?
They are too small (so IgG is ineffective)
100
What are the factors which affect affinity maturation?
Somatic hypermutation and antigen dose
101
What is somatic hypermutation?
Random point mutations in the CDR region in the VH and VL regions of the Ig gene. These change the isotype with no guarantee that it will generate higher affinity antibodies.
102
How does the antigen dose affect affinity maturation?
In low antigen dose, high affinity antibodies will predominate and vice versa. They will have to compete for the antigen, so the antibodies with lower affinity will not receive the signal to live and will die by apoptosis
103
Are antibody-antigen reactions reversible?
Yes (no covalent bonds)
104
What are haptens?
Small foreign molecules that antibodies can bind to but on its own is not immunogenic enough to stimulate antibody production
105
What must happen to raise antibodies to a hapten?
Must be conjugated to a carrier (Hapten-Carrier conjugate)
106
What does ELISA stand for?
Enzyme-Linked ImmunoSorbent Assay
107
What is the purpose of ELISA?
Uses antibodies as a tool to detect and quantify antigens
108
What are the advantages of ELISA?
Non-radioactive, cheap, student friendly, fast, wide applications
109
In the absence of antigen, what happens to a resting B cell?
No activation so no antibodies produced
110
What happens when antigen presentation goes wrong?
Autoimmune disease
111
Where does antigen presentation occur?
Regional lymph nodes
112
What does MHC stand for?
Major Histocompatibility Class (also called Human Leukocyte Antigen = HLA)
113
What do all nucleated cells express on their surface?
MHC I
114
What do antigen presenting cells express on their cell surface?
MHC II
115
What is the main function of MHC molecules?
Present antigen to T cell receptor of CD4+ or CD8+ T cells
116
Which peptides are presented by MHC I?
Those which are small and derived from endogenous presentation
117
Which peptides are presented by MHC II?
Those which are larger and derived from exogenous presentation
118
What are immature dendritic cells important for?
Immune tolerance
119
How are viral antigens presented?
Endogenously via MHC I
120
How are natural killer T cells activated?
By Gram-negative bacteria through indirect and direct pathways
121
What is cross presentation?
When professional antigen presenting cells (DCs) take up antigen exogenously and present it via MHC I
122
What is cross priming?
When CD8+ cells are primed against antigen that has been presented by cross presentation
123
Define a mature lymphocyte
Has undergone antigen-independent development in primary lymphoid organs and has entered circulation
124
Define a naive lymphocyte
Mature lymphocyte that has not been exposed to cognate antigen in periphery
125
Define an effector lymphocyte
Differentiation state that relates to specific function in the immune response, depends on Ag-specific activation
126
Define a memory lymphocyte
Ag-activated lymphocyte that has not differentiated sufficiently to become an effector lymphocyte
127
Where do the antigen-independent phases of lymphocyte develoopment occur?
For T cells: bone marrow then thymus. For B cells: bone marrow
128
Where do the antigen-dependent phases of lymphocyte development occur?
In the peripheral lymphoid tissue
129
What regulates the behaviour of leukocytes?
Cytokines
130
How do Th cells regulate other cells?
By selective delivery of cytokines and other signals
131
Where does initial T and B cell activation occur?
In secondary lymphoid organs
132
Which cells are responsible for priming in secondary lymphoid organs?
Dendritic cells
133
Which cytokine is the one driver for lymphocyte proliferation?
IL-2 (autocrine)
134
What are the three signals for lymphocyte selection and proliferation?
1: Specificity
2: Dendritic cell upregulates B7 for costimulation, which binds to CD28 on the T cell
3: IL-2 is released, and IL-2 receptors are upregulated on the surface (autocrine)
135
What are the signature cytokines of Th1?
IFN-gamma, IL-12
136
What are the signature cytokines of Th2?
IL-4, IL-5 IL-13
137
What are the signature cytokines of Th17?
IL-17, IL-22
138
What are the signature cytokines of Threg?
TGF-beta, IL-10
139
What are the signature cytokines of Tfh?
IL-21
140
What do Th1 cells act on?
Macrophages, NK cells, CD8+ T cells, B cells -> IgG2
141
What do Th2 cells act on?
Eosinophils, mast cells, B cells -> IgE, IgG4
142
What do Th17 cells act on?
Neutrophils, epithelial cells
143
What do Treg cells act on?
Other lymphocytes
144
What do Tfh cells act on?
B lymphocytes
145
What are the major effector functions of Th1 cells?
CMI: killing of virus or bacteria-infected host cells
146
What are the major effector functions of Th2 cells?
Responses to worms and allergens
147
What are the major effector functions of Th17 cells?
Pro-inflammatory: responses to fungiand extracellular bacteria
148
What are the major effector functions of Treg cells?
Inhibits function of other sets of T and non-T cells
149
What are the major effector functions of Tfh cells?
Promotes high affinity antibody production
150
Which signals cause a CD4+ T cell to become a Th1?
IL-12
151
Which signals cause a CD4+ T cell to become a Th2?
IL-4
152
Which signals cause a CD4+ T cell to become a Th17?
TGF-beta, IL-6
153
Which signals cause a CD4+ T cell to become a Treg?
TGF-beta
154
Which signals cause a CD4+ T cell to become a Tfh?
IL-21
155
What does effective T and B cell interactions require?
Cell-cell contact
156
What are the three important interactions between T cells and B cells?
1: MHC2-T cell receptor (with CD4+)
2: CD40-CD40L
3: Cytokines flow from T cell to B cell
157
What is the purpose of cell mediated immunity?
To protect from intracellular pathogens (intracellular bacteria, viruses, some tlarge parasites) and controlled by Th1 cells (antigen-specific response)
158
What is the key cytokine in CMI?
IFN-gamma
159
How do Th1 cells help macrophages?
Macrophage presents epitope on MHC II, leadds to cytokine secretion and macrophage activation, killing the ingested microbes
160
What are the three stages of CTL generation?
Stimulation of naive T cell, proliferating T cell, active effector T cells kill virus-infected target cells
161
How does immunological memory occur?
Activation of T cells leads to clonal expansion of cells reactive to specific Ags, leads to generation of effector T cells and memory T cells
162
Which cells provide immunological memory in CMI?
T cells
163
How do memory T cells enter lymph nodes?
Through inflamed tissues
164
How do naive T cells enter lymph nodes?
Through specialised blood vessels
165
Where does T cell education occur?
Thymus
166
Which T cells develop in the thymus?
alpha and beta TCR
167
Which T cells develop in epithelial tissue in the skin and gut?
gamma and delta TCR
168
T cell development in the thymus is antigen independent or dependent?
Independent
169
What is the difference between T cell precursors and T cells?
Precursors are CD4/8 negative and TCR negative
170
What is the purpose of positive selection?
Determine functional TCRs
171
What is the purpose of negative selection?
Eliminate self-reactive TCRs
172
Where does positive selection occur?
Cortical epithelial cells
173
Where does negative selection occur?
Dendritic cells and medullary thymic epithelial cells
174
What are the key stages of thymocyte development?
Rearrangement of the TCR (beta chain first), pre Talpha (DN cells that have successfully rearranged their beta chains), cells become DP (CD4 and CD8), positive selection (life or death decision, transition to SP stage), negative selection (life or death deciosn), maturing circulating T lymphocytes
175
How is a diversity of TCR achieved?
Rearrangement and expression of TCR genes
176
Positive selection
DP cells interact with MHC I or II, interaction is with TEC in cortex affinity of outcome is important, interaction leads to survival (B cells don't have positive selection because B cells never see MHC I or II)
177
What is central tolerance?
Self-reactive T and B cells undergo apoptosis in the primary lymphoid organs (negative selection)
178
What is peripheral tolerance?
Self-reactive T and B cells that evade negative selection can be made tolerant by other mechanisms operating outside the primary lymphoid organs
179
What are the three major mechanisms of lymphocyte tolerance?
CLonal deletion (central tolerance), clonal ignorance (peripheral tolerance), clonal anergy (peripheral tolerance), suppression (peripheral tolerance)
180
Negative selection
Selection based on TCR, T cells that bind self-antigens with higher affinity are deleted earlier and more completely than those that bind with low affinity, population remaining consists of CD4+ and CD8+ T cells that have selectivity for foreign antigens and self-MHC molecules
181
Clonal ignorance
T cell doesn't see antigen, antigen too low to reach stimulation threshold
182
Clonal anergy
Prolonged, antigen-specific suppression of a T cell clone. Becomes anergic, clone has been deleted but not killed
183
Suppression
Lymphocyte subsets may act as suppressors of T and B cell activation
184
How do regulatory T cells suppress reactions to self antigens?
In the thymus, if the thymocyte has high affinity for the self antigen it will be destroyed
185
How are B cells protected against self antigen?
Require T cel help (no autoreactive T cells, no T cell help)
186
What is the definition of a hypersensitivity reaction?
Inappropriate or exaggerated immune response to antiglobbulin
187
Type I hypersensitivity
Allergic, IgE
188
Type II hypersensitivity
Cytotoxic, IgM/IgG
189
Type III hypersensitivity
Immune complex (C3b+Ag+IgG)
190
Type IV hypersensitivity
Delayed type (Th1+Macro+Cytokines)
191
What will allergens preferentially induce?
Th2 responses, leading to IL-4 production and hence B cells produce IgE so mast cells are sensitised and then degranulate
192
Where are IgE receptors?
On mast cells and basophils
193
How can type I hypersensitivity be controlled?
Avoid allergens, desensitisation, monoclonal anti-IgE antibody treatment
194
How can type II hypersensitivity be induced?
Blood transfusion, haemolytic disease of the newborn, drug-induced haemolytic anaemia
195
How does type II hypersensitivity occur?
Ab binds to Ag on cell surface, mediated by complement od ADCC
196
How does type III hypersensitivity occur?
Ab bind to soluble Ag -> Ab-Ag complexes, phagocytosis and clearance ensue. Changes location and degranulates, causing tissue damage
197
How does type IV hypersensitivity occur?
Cell mediated. On first exposure, haptens sensitise Th1 cells. On second exposure, sensitised Th1 cells make IFN-gamma and chemokines
198
Which cells are involved in surveilence?
Monocytes, macrophages and dendritic cells
199
How is tissue compatibility for transplation determined?
By the response of T and B lymphocytes of the host against the transplantation antigens of the donor. Histocompatibility Locus Antigen, chromosome 6, CLass I, Class II
200
What are the three things that should be matched in organ transplantation?
HLA A, HLA B, HLA DR
201
How does detection of the antibody work?
Previous exposure of the immune system to foreign HLA results in the formation of antibodies against HLA (pregnancy, blood transfusion, previous organ transplant, infection)
202
What are the damage associated molecular patterns?
ROS, HSP, heparin sulphate, fibrinogen, high mobility group box-1 proteins
203
What are responsible for the recognition of the pathogen-associated molecular patterns
Members of the Toll-like receptor family
204
How is the immune system sensitised to foreign HLA?
Infection, previous transplantation, blood transfusions
205
What are two important pathways that cytotoxic T cells kill infected cells?
Secretory and non-secretory
206
What are the two opsonin families?
Collectins and pentraxins
207
What are the principles of ELISA?
Antigen coating, blocking, primary antibody, secondary antibody, detection/colour development, stop and measurement
