Exam 1 Material Flashcards
(308 cards)
1
Q
Why is the immune system so important?
A
- Protects animals against microbial invasion, essential for life
- Ensures freedom from invasion via innate and adaptive immunity
- Utilizes complex, interacting networks of defense mechanisms
2
Q
What century was the smallpox variolation?
A
12th century
3
Q
What year was Rinderpest inoculations?
A
1754
4
Q
What year was Edward Jenner’s cowpox experiment; coined “vaccination”?
A
1798
5
Q
What year was Pasteur’s fowl cholera experiment; anthrax and rabies vaccines?
A
1879
6
Q
Who proved dead organisms can create effective vaccines? Hint: 2 names
A
Daniel Salmon and Theobald Smith
7
Q
Who found bacterial products that also provided protection? Hint: 2 names
A
Von Behring and Kitasato
8
Q
Define commensal
A
Colonize surfaces, non-invasive, and harmless
9
Q
Define pathogens
A
Causes disease and there are primary and opportunistic pathogens
10
Q
Define primary pathogens
A
Cause disease at any dose
11
Q
What’s an example of a primary pathogen?
A
HIV
12
Q
Define opportunistic pathogen
A
Cause disease in high doses
13
Q
What is an example of opportunistic pathogen?
A
Mannheimia hemolytica
14
Q
What is innate Immunity?
A
- Rapid, non-specific, and immediate protection
- Activated by PAMPs and DAMPs
15
Q
What is adaptive Immunity?
A
Develops after exposure, specific, and has memory
16
Q
What are the 5 components of Innate defense?
A
- Physical/Chemical Barriers
- Phagocytic and Sentinel Cells
- Complement System
- Cytokines
- Natural Killer (NK) Cells
17
Q
What are physical/chemical barriers?
A
Skin, mucus membranes, microflora, stomach acid, antimicrobial peptides
18
Q
What are phagocytic and sentinel cells?
A
Detect and eliminate pathogens
19
Q
What are examples of phagocytic and sentinel cells?
A
Neutrophils, macrophages, dendritic cells
20
Q
What is the complement system?
A
Enzyme cascade with antimicrobial activity
21
Q
What are cytokines?
A
Protein messenger molecules that can act on other cells
22
Q
What 3 components can cytokines act on or cell that produced it?
A
- Proinflammatory cytokines
- Chemokines
- Interferons
23
Q
Define chemokines
A
- Cells migrate to sites of infection
- Some produced by sentinel cells
24
Q
Define proinflammatory cytokines
A
- Secreted by sentinel cells (PAMPs & DAMPs)
- Cause fever, lethargy, & loss of appetite
- IL-1, IL-6, & TNF
25
Define interferons
- Interferes with replication of viruses
- Produced by virally infected cells
26
What are natural killer (NK) cells?
Kill infected/tumor cells lacking normal proteins
27
What is humoral immunity?
- Mediated by antibodies (IgA, IgG, IgE, IgM) from B cells
- Effective against bacterial invaders
28
What is Cell-Mediated Immunity (CMI)?
T cells (helper, cytotoxic) regulate responses and destroy infected cells
29
What are the two types of adaptive immunity?
Humoral immunity and cell-mediated immunity
30
What distinguishes innate from adaptive immunity?
Innate is rapid, non-specific, and lacks memory; adaptive is slower, specific, and has memory
31
Who coined the term "vaccination"?
Edward Jenner
32
What was the significance of Pasteur’s fowl cholera experiment?
It showed that aged cultures of Pasteurella multocida provided protection, launching immunology as a science
33
What do sentinel cells recognize to detect invasion?
Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs)
34
What are antibodies also known as?
Immunoglobulins (Ig)
35
Which type of adaptive immunity is directed primarily against bacterial invaders?
Humoral immunity
36
What distinguishes commensals from pathogens
Commensals colonize surfaces without causing disease, while pathogens cause disease
37
What is the role of proinflammatory cytokines?
They cause fever, lethargy, and loss of appetite
38
What type of cells do NK cells target?
Virus-infected cells and tumor cells
39
How does the adaptive immune system respond to a previously encountered pathogen?
It's faster and has a more effective response
40
What's a leukocyte?
Any white blood cell (WBC)
41
What's a lymphocyte?
A type of WBC (T cell, B cell, NK cell)
42
What's a granulocyte?
Polymorphonuclear cells (neutrophils, eosinophils, basophils)
43
What's a mononuclear cells?
Lymphocytes or monocyte
44
What percentage of WBCs are neutrophils?
Neutrophils make up 55-90% of WBCs
45
What is the primary role of neutrophils?
They are the first responders to bacterial infections
46
What is the lifespan of a neutrophil?
Neutrophils live 8-10 hours in the blood and up to 2 days in total
47
What does “neutrophilia” indicate?
Elevated neutrophil levels, or neutrophilia, indicate a bacterial infection
48
What does “neutropenia” indicate?
Low neutrophil levels, or neutropenia, are often seen in viral infections
49
What is the role of basophils?
They are important in allergies and parasitic infections due to their inflammatory mediators like histamine
50
What percentage of WBCs do basophils constitute?
Basophils make up <0.5% of WBCs
51
What is the role of eosinophils?
Eosinophils are potent mediators that target extracellular parasites
52
When are eosinophils levels elevated?
Elevated levels, or eosinophilia, are seen in parasitic infections and allergies
53
What percentage of WBCs are monocytes?
Monocytes constitute 3-7% of WBCs
54
What do monocytes differentiate into?
Differentiate into macrophages in tissues
55
What are the functions of macrophages?
Macrophages perform phagocytosis, antigen presentation on MHC II, and cytokine secretion
56
What percentage of WBCs are lymphocytes
Lymphocytes make up 20-35% of WBCs
57
What are lymphocyte types?
B cells, T cells, and NK cells
58
What is the lifespan of circulating lymphocytes?
Lymphocytes circulate between blood and lymphoid tissues for about 4 months
59
What is the function of platelets?
Platelets are crucial for blood clotting
60
What is the role of red blood cells (RBCs)?
RBCs transport oxygen
61
Where do all blood cells originate?
Pluripotent stem cells in bone marrow
62
What are 3 lineages of blood cells?
Erythroid (RBCs, platelets), myeloid (monocytes, granulocytes), and lymphoid (B cells, T cells, NK cells)
63
How do granulocytes mature?
Granulocytes are released from the bone marrow as mature cells
64
Where do T cells mature?
Immature pre-T cells mature in the thymus
65
What happens to self-reactive T cells?
Self-reactive T cells are eliminated during development
66
Where do B cells mature in mammals?
B cells mature in bone marrow or Peyer’s patches, depending on the species
67
What is the role of NK cells, and where are they released from?
NK cells, part of innate immunity, are released mature from the bone marrow
68
What is the role of primary lymphoid tissues?
Primary lymphoid tissues are the sites of lymphocyte maturation
69
What are examples of primary lymphoid tissues?
Examples include the thymus (T cells), Bursa of Fabricius (birds), and bone marrow or Peyer’s patches (mammals)
70
What is the role of secondary lymphoid tissues?
Secondary lymphoid tissues are where mature lymphocytes encounter antigens
71
What are examples of secondary lymphoid tissues?
Examples include lymph nodes, spleen, and MALT (Mucosal Associated Lymphoid Tissue)
72
What do endothelial cells do during infection?
Endothelial cells upregulate adhesion molecules (“addressins”) to direct leukocytes to infection sites
73
What is the purpose of lymphatic circulation?
Lymphatic circulation allows lymphocytes to move between tissues and blood, increasing antigen encounter and immune response
74
What is inflammation?
A tissue reaction that delivers mediators of host defense to sites of infection or tissue damage
75
Inflammation - What are the primary roles in combating infection?
1. Delivering effector molecules and cells to augment microbial killing
2. Providing a physical barrier to prevent infection spread
3. Promoting tissue repair
76
What is the main purpose of inflammation?
To focus the immune response at the site of infection or injury
77
What are the key steps in the acute inflammatory response?
1. Production of cytokines and pro-inflammatory mediators in response to microbes or damaged cells
2. Increased blood vessel permeability for plasma protein and leukocyte entry into tissues
3. Destruction of microbes, clearance of damaged cells, and promotion of inflammation and repair
78
What are the cardinal signs of inflammation?
Pain, redness, heat, swelling, and loss of function
79
What causes pain?
Tissue destruction and irritation of sensory nerves
80
What causes redness?
Increased blood flow
81
What causes heat?
Increased blood flow and pyrogens
82
What causes swelling?
Fluid leakage and phagocyte infiltration
83
What causes loss of function?
When an entire tissue or organ is involved
84
What are the stages of neutrophil adhesion and emigration from blood vessels?
Neutrophils bind to vascular endothelial cells, adhere, and exit blood vessels to reach infection sites
85
What is Bovine Leukocyte Adhesion Deficiency (BLAD)?
BLAD is an autosomal recessive immunodeficiency in Holstein calves characterized by recurrent infections, oral ulcerations, chronic pneumonia, stunted growth, delayed wound healing, extreme neutrophilia, and inability of neutrophils to exit blood vessels due to an integrin gene mutation
86
Name three major pro-inflammatory cytokines :
1. Tumor Necrosis Factor-α (TNF-α)
2. Interleukin-1 (IL-1)
3. Interleukin-6 (IL-6)
87
What are the functions of Tumor Necrosis Factor-α (TNF-α)?
Promotes inflammation, adhesion molecule expression, and fever
88
What are the functions of Interleukin-1 (IL-1)?
Induces fever, activates endothelial adhesion molecules, and promotes cell growth and repair
89
What are the functions of Interleukin-6 (IL-6)?
Triggers acute-phase protein production and systemic effects
90
What are the effects of IL-1, TNF-α, and IL-6 on the body?
1. Low levels: Local inflammation (macrophage/endothelium activation).
2. Moderate levels: Fever, lethargy, acute-phase protein production, neutrophilia.
3. High levels: Vasodilation, vascular injury, DIC, ARDS, and septic shock.
91
What are chemokines, and give examples?
Chemokines are small cytokines that guide cell migration
Examples:
-CXCL8 (IL-8): Attracts and activates neutrophils
-CXCL2: Attracts neutrophils
92
What are the three types of vasoactive molecules?
Vasoactive amines, vasoactive peptides, and vasoactive lipids
93
What's the function of vasoactive amines (e.g., histamine, serotonin)?
Increase vascular permeability
94
What's the function of vasoactive peptides (e.g., C5a, bradykinin)?
Promote histamine release, pain, and vascular permeability
95
What's the function of vasoactive lipids (e.g., prostaglandins, leukotrienes)?
Induce vasodilation, smooth muscle contraction, and chemotaxis
96
What is the function of histamine in inflammation?
Histamine, released by mast cells, causes vasodilation, increases vascular permeability, and stimulates nitric oxide production
97
How does the coagulation system function in inflammation?
- Thrombin converts fibrinogen to fibrin, forming a physical barrier
- The fibrinolytic system destroys fibrin, releasing peptides that attract neutrophils
98
What triggers the secretion of pro-inflammatory cytokines?
Sentinel cells activated by toll-like receptors (TLRs) and pattern-recognition receptors (PRRs) in response to PAMPs and DAMPs
99
Why are pro-inflammatory cytokines essential in low quantities but harmful in high quantities?
-Low quantities: Promote local inflammation and immune defense
-High quantities: Lead to systemic vasodilation, vascular injury, DIC, and ARDS
100
What is phagocytosis?
Phagocytosis is the ability of certain cells, called phagocytes, to ingest and destroy foreign particles. It literally means “eating by cells"
101
What are phagocytes?
Phagocytes are cells capable of ingesting and killing microorganisms that trigger an inflammatory response. Neutrophils and macrophages are examples of professional phagocytes
102
Which cells initiate the phagocytic process?
Neutrophils are the first to accumulate at the site of infection, followed by macrophages that migrate to the tissue to begin phagocytosis
103
What are the steps involved in phagocytosis?
The process includes:
1. Chemotaxis: Movement of phagocytic cells to the site of infection
2. Adherence: Phagocyte binds to the target particle
3. Ingestion: Engulfment of the target
4. Destruction: Intracellular killing and digestion of the target
104
What is opsonization?
The coating of bacteria with positively charged materials (opsonins) such as IgG, IgM, and C3b
105
How does opsonization aid phagocytosis?
Neutralizes the negative charge on bacteria, allowing neutrophils to adhere and engulf them
106
What are the receptors involved in neutrophil phagocytosis?
-Fc receptors: Bind antibodies (like IgG) attached to antigens
-C3b receptors: Bind C3b-coated bacteria for enhanced engulfment
107
What is a phagolysosome?
A phagolysosome is formed when the phagosome (containing the ingested microbe) fuses with lysosomes. This vesicle contains enzymes and toxic molecules that digest and kill the microbe
108
How are bacteria destroyed inside the phagolysosome?
Destruction occurs through:
- Lytic enzymes and antimicrobial peptides
- Oxidative metabolism (respiratory burst)
- Neutrophil extracellular traps (NETs)
109
What are examples of lytic enzymes and peptides in neutrophil granules?
- Primary granules: Hydrolases, lysozyme, defensins, and myeloperoxidase
- Secondary granules: Lysozyme, lactoferrin, and collagenase
110
What is the oxygen-mediated killing mechanism?
It is the most potent neutrophil killing process, occurring in the phagolysosome and involving reactive oxygen species such as hypochlorite, hydrogen peroxide, and oxygen radicals
111
What is Chronic Granulomatous Disease?
It is a fatal condition caused by defective oxidative enzymes, impairing the respiratory burst pathway of neutrophils
112
What are neutrophils extracellular traps (NETs)?
- NETs are extracellular meshes of nuclear material (DNA, histones) and granular proteins released by stimulated neutrophils to trap and kill bacteria
- This active response is called NETosis
113
What happens to neutrophils after phagocytosis?
Neutrophils die and lyse after extended phagocytosis, forming pus
114
What is the role of macrophages after phagocytosis?
Macrophages egest debris, present microbial antigens to lymphocytes, and contribute to tissue healing by ingesting dead neutrophils
115
Which cells are the first responders to inflammation?
Neutrophils
116
What activates neutrophil migration to the infection site?
Cytokines activate vascular endothelial cells, facilitating neutrophil attachment and migration
117
What role do opsonins play in phagocytosis?
Opsonins like antibodies and complement enhance bacterial binding and ingestion by phagocytes
118
How are ingested microbes killed?
Through respiratory burst, antimicrobial peptides (e.g., defensins), and lytic enzymes
119
What is the lifespan of neutrophils?
Neutrophils are short-lived and cannot perform prolonged or multiple rounds of phagocytosis
120
What is the role of macrophages in chronic infections?
Macrophages eat surviving microbes, remove dying neutrophils, and initiate the healing process
121
How do macrophages support the adaptive immune system?
By presenting antigens to lymphocytes
122
What is the complement system?
The complement system is a group of serum and cell surface proteins activated by factors like antigen-antibody combinations. This activation leads to enzyme cascades with biological effects, including cell lysis and opsonization
123
What are the three pathways of complement activation?
Classical pathway, alternative pathway, and MB-Lectin pathway
124
What is the classical pathway?
Initiated by antibody-antigen binding (adaptive immunity)
125
What is the alternative pathway?
Triggered by C3b binding to pathogen surfaces (innate immunity)
126
What is the MB-Lectin pathway?
Activated by mannose-binding lectin binding to microbial carbohydrates (innate immunity)
127
What are the key features of the classical pathway?
- Initiated by antigen-antibody binding.
Requires IgM or IgG antibodies
- C1 protein binds to antigen-antibody complexes, activating the cascade
-The classical pathway forms a C3 convertase (C4b2b) which cleaves C3 into C3a and C3b
128
How does the alternative pathway function?
- Initiated when C3 spontaneously cleaves into C3a and C3b
- C3b binds to pathogen surfaces
- Factor B binds to C3b and is cleaved by Factor D, forming C3 convertase (C3bBb)
129
How does the MB-Lectin pathway operate?
- Mannose-binding lectin (MBL), a pattern recognition receptor (PRR), binds to mannose on microbial surfaces
- Bound MBL activates MASP-2 (MBL-associated serine protease), which cleaves C4 and initiates the cascade
130
What is the terminal complement pathway?
- Common to all three pathways after C5 cleavage
- Leads to the formation of the membrane attack complex (MAC), which punches holes in the microbial membrane, causing lysis and cell death
131
What is the membrane attack complex (MAC)?
- Formed by the sequential binding of complement components:
- C5b binds C6, C7, C8, and multiple C9 molecules
- C9 polymerizes to form a transmembrane pore
132
What are the results of the membrane attack complex (MAC)?
Results in lysis of the target cell
133
What regulates complement activation?
- Factor H regulates the alternative pathway to prevent damage to host cells
- Regulation occurs through substrate modulation to ensure proper targeting
134
What are the key functions of the complement system?
1. Opsonization
2. Cell lysis
3. Inflammation
4. Immune clearance
135
Define opsonization
C3b coats pathogens, enhancing phagocytosis
136
Define cell lysis
MAC formation destroys microbial cells
137
Define inflammation
C5a attracts immune cells and triggers inflammationD
138
Define immune clearance
Removes immune complexes and dead cells
139
What are the biological consequences of complement activation?
- Enhanced phagocytosis through opsonization
- Direct lysis of pathogens via MAC
- Recruitment of immune cells through chemoattractants like C5a
140
How do the complement pathways integrate innate and adaptive immunity?
- Innate pathways (alternative and MB-lectin): Activated by microbial patterns (PAMPs)
- Adaptive pathway (classical): Activated by antibodies bound to antigens
141
What are cytokines?
- Low molecular weight, secreted 'messenger' proteins
- Regulate intensity and duration of innate and adaptive immune responses
- Their activity is receptor-mediated
142
What are the three main activities of cytokines?
Autocrine, paracrine, and endocrine
143
What's the function of autocrine?
Act on the cell that produced it
144
What's an example of autocrine?
IL-12
145
What's an example of paracrine?
IL-12
146
What's an example of endocrine?
IL-3, GM-CS
147
What are some classifications of cytokines?
- Monokines
- Lymphokines
- Interleukins
- Interferons
- Chemokines
- Colony Stimulating Factors (CSF)
- Growth Factors
148
What produces monokines?
Monocytes
149
What produces lymphokines?
Lymphocytes
150
Define interleukins
Communication between leukocytes (e.g., IL-1, IL-2, IL-3)
151
Define interferons
Inhibit viral replication
152
Define chemokines
Attract specific cells to locations
153
What do Colony Stimulating Factors (CSF) stimulate?
Stimulate stem cell differentiation in bone marrow
154
What do Growth Factors stimulate?
Stimulate cell growth in vitro
155
What are the three main categories of cytokine functions?
1. Mediate and regulate innate immunity
2. Mediate and regulate adaptive immunity
3. Stimulate hematopoiesis
156
What role do cytokines play in innate immunity?
- Crucial in the first few days of infection.
- Act immediately and may influence adaptive immune responses
157
What are examples of cytokines that play in innate immunity?
IL-1, IL-6, TNFα, IL-12, and Type I interferons
158
What are Type I interferons, and what do they do?
- Includes IFNα and IFNβ
- Produced by virally infected cells
- Make other cells resistant to viral infection
159
What is the role of Type II interferons (IFNγ)?
- Functions in innate and adaptive immunity
- Produced by NK cells and TH1 cells
- Activates macrophages, neutrophils, and NK cells
- Promotes TH1 development and suppresses TH2
- Enhances B-cell IgG production
- Upregulates MHC expression on APCs
160
What are key roles of cytokines in adaptive immunity?
- Produced primarily by T lymphocytes in response to antigen recognition
- Regulate lymphocyte activation, growth, and differentiation
- Enhance innate defenses
161
Which cytokines regulate lymphocyte activation and growth?
- IL-2: Lymphocyte proliferation.
- IL-4 and IL-13: B-cell differentiation (IgE)
- IL-10: Inhibits TH1
- TGFβ: Treg cytokine, B-cell differentiation (IgA)
- IFNγ: B-cell differentiation (IgG)
162
Which cytokines enhance innate immunity?
- IFNγ: Activates macrophages, neutrophils, and NK cells
- TNF: Activates endothelial cells and neutrophils
- IL-5: Activates eosinophils
163
What is the role of cytokines in hematopoiesis?
- Regulate growth and differentiation of bone marrow progenitor cells
- Produced during innate and adaptive immune responses
164
Name key hematopoietic cytokines:
- Erythropoietin
- Thrombopoietin & IL-11
- IL-3
- IL-5
- GM-CSF
- G-CSF
- M-CSF
165
What's the function of erythropoietin?
Stimulates RBC production
166
What's the function of thrombopoietin & IL-11?
Stimulate platelet production
167
What's the function of IL-3?
Stimulates WBC production
168
What's the function of IL-5?
Eosinophil differentiation (e.g., during parasitic infection/allergy)
169
What's the function of GM-CSF?
Differentiation of neutrophils and monocytes
170
What's the function of G-CSF?
Differentiation of neutrophils
171
What's the function of M-CSF?
Differentiation of monocytes
172
What mechanisms regulate cytokine activity?
- Receptor antagonists
- Soluble receptors
- Opposing cytokines
- Decoy receptors
173
What's the function of receptor antagonists?
Block cytokine receptors (e.g., IL-1 receptor antagonist)
174
What's the function of soluble receptors?
Neutralize cytokines (e.g., soluble TNF receptors)
175
What type of effect do cytokines have?
Counteract effects (e.g., IL-4 vs. IFNγ for IgE)
176
What's the function of decoy receptors?
Bind cytokines without inducing signaling (e.g., decoy receptor for IL-1)
177
What are five key concepts in cytokine signaling?
1. Immune responses involve many cell interactions
2. Cells communicate via cytokines and hormones
3. Cytokines bind to specific target cell receptors
4. Receptor binding activates transcription factors for gene expression
5. Gene expression leads to new proteins and altered cell behavior
178
What are some general properties of cytokines?
- Secretion is brief and self-limited
- Produced by diverse cell types
- Act locally and/or systemically
- Functions may overlap (redundancy)
- Effects are synergistic and tightly regulated
179
How does the innate immune system recognize pathogens?
Recognizes a limited number of conserved microbial PAMPs (Pathogen-Associated Molecular Patterns)
180
What triggers the adaptive immune system?
Adaptive immunity can recognize and respond to almost all foreign macromolecules in invading microbes. These foreign molecules are called antigens
181
What is antigenicity?
The inherent capacity of a molecule to be recognized by the immune system
182
What are the two main types of antigens?
Microbial antigens and non-microbial antigens
183
Give examples of microbial antigens:
Bacterial, viral, fungal, protozoan, arthropod, and helminth antigens
184
Give examples of non-microbial antigens:
Food allergens, inhaled dust (pollen), blood-group antigens, histocompatibility antigens, and autoantigens
185
What are autoantigens?
Antigens that induce autoimmune responses when the immune system attacks normal body components (e.g., thyroglobulin, myelin, mitochondrial proteins)
186
What are examples of bacterial antigens?
- Structural components: Peptidoglycans,
lipoteichoic acid, lipopolysaccharides, pili, porins, and flagellar antigens (H)
- Secreted products: Exotoxins, heat-shock proteins
- Surface antigens: Capsular antigens (K)
187
What are the key features of viral antigens?
- A nucleic acid core surrounded by a protein capsid
- Capsid: Made of capsomeres, which are highly antigenic
- Viral proteins expressed on infected cells can provoke adaptive immunity
188
What types of microbial antigens can trigger adaptive immunity?
Structural components of fungi, protozoan parasites, arthropods, and helminths
189
Are all microbial antigens equally effective in triggering immunity?
No, their antigenicity varies, and adaptive responses may not always protect or eliminate the invader
190
Food allergens
Can cause allergic reactions
191
Pollens
Triggers immune responses when inhaled
192
Blood-group antigens
Glycoproteins that can lead to immune reactions during mismatched transfusion
193
Histocompatibility antigens
Involved in tissue graft rejection
194
What factors influence antigenicity?
- Size
- Foreignness
- Complexity
- Stability
195
Define size of antigenicity
- Larger molecules are more antigenic
- Molecules <1000 daltons are poor antigens
196
Define foreignness of antigenicity
Greater structural difference from self-proteins increases immune response
197
Define complexity of antigenicity
Complex structures (e.g., proteins) are more antigenic than simple ones (e.g., lipids)
198
Define stability of antigenicity
Flexible or rapidly degraded molecules are poor antigens
199
Why are proteins the best antigens?
They are large, complex, stable, and recognized well by the immune system
200
Why are lipids and nucleic acids poor antigens?
Readily degradable, but nucleoproteins can be antigenic due to their protein carrier
201
What are epitopes?
- Specific regions on an antigen recognized by the immune system
- A single large protein can have multiple epitopes
- The most immunogenic epitopes are called immunodominant epitopes
202
What is a hapten?
A small molecule (<1000 daltons) that is not antigenic alone but can become antigenic when attached to a larger carrier protein
203
Examples of hapten
- Penicillin allergy
- Poison ivy
204
Define penicillin allergy
Penicillin binds to proteins, forming an antigenic complex that triggers an allergic reaction
205
Define poison ivy
Urushiol binds to skin proteins, resulting in allergic contact dermatitis
206
What is cross-reactivity?
Identical or similar epitopes on unrelated molecules cause antibodies to react with both antigens
207
Examples of cross-reactivity
- Bacterial or food antigen mimics blood-group glycoproteins
- Cross-reaction between Brucella abortus and Yersinia enterocolitica
- FIP virus cross-reacting with pig transmissible gastroenteritis virus
208
Define recognition
The adaptive immune system is optimized to recognize microbial macromolecules
209
Define best antigens
Large, complex, stable, foreign proteins
210
Define small molecules
Poor antigens unless linked to carriers (haptens)
211
Define epitopes
Immune responses target specific areas of antigens
212
What triggers adaptive immunity?
The capturing and presenting of foreign materials to cells that recognize them, performed by Antigen-Processing Cells (APCs)
213
What are the three major types of Antigen-Processing Cells (APCs)?
- Dendritic cells (DCs)
- Macrophages
- B-cells
214
How do APCs initiate immune responses?
APCs capture foreign microbes or their products, process large proteins into peptides, and present them on their surfaces attached to Major Histocompatibility Complex (MHC) molecules
215
Why are dendritic cells unique among APCs?
Only dendritic cells can activate naïve T cells and trigger a primary immune response
216
Where are dendritic cells primarily found?
In epithelial tissues (skin, mucosa) and lymphoid organs (lymph nodes, spleen, thymus)
217
What are the major functions of dendritic cells?
- Serve as sentinel cells to activate innate defenses
- Process exogenous antigens to initiate adaptive immunity
- Regulate adaptive immunity
218
What makes dendritic cells highly efficient APCs?
They express 100 times more MHC II molecules than any other APC and can activate up to 3000 T-cells per activated dendritic cell
219
How do follicular dendritic cells (FDCs) differ from other dendritic cells?
1. Do not migrate
2. Are located in lymphoid follicles (B-cell areas)
3. Lack MHC II molecules on their surface
4. Carry many complement and Fc receptors
220
What is the primary function of follicular dendritic cells (FDCs)?
To present antigens to B-cells without processing them
221
What are iccosomes?
Spherical bodies on FDC dendrites formed from antigen:antibody complexes, which are ingested by activated B-cells
222
How do dendritic cells capture antigens in tissues?
By constantly sampling extracellular fluid through macropinocytosis
223
What triggers dendritic cells to migrate to lymph nodes?
The inflammatory cytokine TNF-⍺ during infection
224
What happens as dendritic cells migrate to lymph nodes?
They upregulate expression of MHC II molecules and co-stimulatory molecule B7, ensuring effective antigen presentation
225
Why are macrophages less efficient APCs than dendritic cells?
They express lower levels of MHC II and co-stimulatory molecules unless activated by cytokines like INFγ
226
What role do B-cells play in antigen presentation?
B-cells present antigens to T-helper cells during the secondary immune response and become efficient APCs after activation
227
What changes occur in B-cells after activation?
They upregulate MHC II and co-stimulatory B7 molecule expression, becoming potent activators of T-helper cells
228
What is required for an antigen to trigger an adaptive immune response?
Antigen molecules must be broken into fragments, bound to MHC molecules, and presented to T-cells
229
What are MHC molecules, and how are they encoded?
MHC molecules are glycoproteins encoded by a gene cluster called the major histocompatibility complex (MHC)
230
What is the function of MHC molecules in immunity?
MHC molecules control antigen presentation and influence susceptibility to infectious and autoimmune diseases
231
What are the three classes of MHC gene loci?
Class I, II, and III
232
What does class I encode?
Encodes MHC I molecules, present on all nucleated cells
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What does class II encode?
Encodes MHC II molecules, restricted to professional APCs
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What does class III encode?
Encodes proteins like complement proteins involved in innate immunity
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How do MHC I and MHC II molecules differ in distribution and function?
- MHC I: Found on most nucleated cells; presents antigens to cytotoxic T cells, resulting in T-cell-mediated toxicity
- MHC II: Found on B cells, macrophages, and dendritic cells; presents antigens to T-helper cells, resulting in T-cell-mediated help
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How are MHC molecules named in different species?
- Humans: HLA
- Dogs: DLA
- Cattle: BoLA
- Horses: ELA
- Pigs: SLA
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What are the subtypes of MHC I molecules?
MHC Ia, Ib, Ic, and Id
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Define MHC Ia
Polymorphic, expressed on most nucleated cells
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Define MHC Ib
Reduced expression, limited ligand binding
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Define MHC Ic
nvolved in NK cell signaling
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Define MHC Id
Binds PAMPs (pathogen-associated molecular patterns)
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What is the structure of an MHC Ia molecule?
- Composed of a heavy α chain and a β2-microglobulin chain
- The α chain forms the antigen-binding groove, while β2-microglobulin stabilizes the structure
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How are peptides bound to MHC I molecules?
Peptides are 8-10 amino acids long, anchored at both ends, and fit within the binding groove
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What is the endogenous pathway of MHC I?
Proteins manufactured within the cell are processed into peptides, bound to MHC I molecules, and presented on the cell surface for CD8+ T-cell recognition
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Where are MHC II molecules found, and what is their structure?
Found on professional APCs, consisting of an α chain and a β chain, with their peptide-binding groove formed by the α1 and β1 domains
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How do peptides bind to MHC II molecules?
Peptides are 13-20 amino acids long, with part of the peptide protruding from the groove
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What is the exogenous pathway of MHC II?
Antigens are internalized, processed, and bound to MHC II molecules in vesicles. These complexes are transported to the cell surface for presentation to CD4+ T cells
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What is encoded by MHC Class III genes?
Complement proteins and other molecules important for innate immunity
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What is MHC restriction?
Only antigen fragments bound to MHC molecules can trigger an adaptive immune response
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How does MHC expression affect disease susceptibility?
- Specific MHC alleles determine susceptibility or resistance to diseases
- Heterozygotes benefit from responding to a broader range of antigens
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Give examples of MHC-associated disease resistance or susceptibility
- BoLA-Aw7: Resistance to bovine leukosis
- BoLA-A*16: Resistance to mastitis
- ELA-A9: Susceptibility to equine recurrent uveitis
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What is the role of lymphocytes in the immune system?
Lymphocytes are central to the adaptive immune system and body defenses
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What are the three major types of lymphocytes?
B cells, T cells, and natural killer (NK) cells
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What's the functions of B cells?
Responsible for antibody production
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What's the functions of T cells?
Regulate adaptive immunity and are responsible for cell-mediated immune responses
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What's the functions of natural killer (NK) cells?
Play a role in innate immunity
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What is unique about lymphocyte subpopulations?
Within the major types, there are many subpopulations with different characteristics and functions
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What are the structural characteristics of lymphocytes?
- Small, round cells, 7-15 μm in diameter
- Large, round nucleus that stains intensely with hematoxylin
- Thin rim of cytoplasm containing mitochondria, free ribosomes, and a small Golgi apparatus
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How do NK cells differ structurally from T and B cells?
NK cells are usually larger and may contain obvious cytoplasmic granules
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Can the structure of a lymphocyte indicate its function?
No, except for NK cells with granules, lymphocyte structure does not provide clues to their function
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Identify features of B cells in the development site
Bone marrow, bursa, Peyer’s patches
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Identify features of B cells in the distrubition
Lymph node cortex, splenic follicles
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Identify features of B cells in the antigen receptors
BCR (immunoglobulin)
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Identify features of B cells of important surface antigens
Immunoglobulin
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Identify features of B cells of antigen recognized
Free foreign proteins
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Identify features of B cells of progeny cells
Plasma cells, memory cells
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Identify features of B cells of secreted products
Immunoglobulins
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Identify features of T cells in development site
Thymus
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Identify features of T cells in distribution
Lymph node paracortex, splenic periarteriolar sheathI
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Identify features of T cells in antigen receptors
TCR (protein heterodimer) associated with CD3, CD4, or CD8
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Identify features of T cells of important surface antigens
CD2, CD3, CD4, or CD8
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Identify features of T cells in antigen recognized
Processed foreign proteins in MHC
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Identify features of T cells in progeny cells
Effector T cells, memory T cells
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Identify features of T cells in secreted products
Cytokines
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What is the overview of lymphocyte maturation?
Lymphocytes mature through stages involving antigen receptor development and selection processes to ensure proper immune response
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How are T and B cells segregated in peripheral lymphoid organs?
- T and B cells occupy distinct regions:
- T cells: Paracortex of lymph nodes and periarteriolar sheath of the spleen
- B cells: Cortex of lymph nodes and splenic follicles
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What are the two main T cell receptor types, and how are they categorized?
- Alpha-beta (αβ) T cells: Includes CD4+ and CD8+ T cells
- Gamma-delta (γδ) T cells: Defined by their unique TCR, important at mucosal surfaces
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What are the subtypes of CD4+ αβ T cells?
TH 1, TH2, TH17, and Treg
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What's the function of T helper 1 (TH1)?
Secretes IFNγ, IL-2; activates phagocytes, NK cells, CTLs; defends against intracellular pathogens
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What's the function of T helper 2 (TH2)?
Secretes IL-4, IL-5, IL-9, IL-13; activates mast cells, eosinophils, and B cells for IgE production
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What's the function of T helper 17 (TH17)?
Secretes IL-17, IL-21, IL-22; attracts neutrophils and monocytes, induces acute inflammation
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What's the function of T regulatory (Treg)?
Secretes IL-10, IL-35, TGFβ; suppresses T cell responses, prevents self-reactive immune reactions
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What is the role of CD8+ αβ T cells?
CD8+ T cells (Cytotoxic T Lymphocytes) recognize antigens on MHC I, clonally expand, and kill cells expressing foreign antigens
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How do γδ T cells differ from αβ T cells?
γδ T cells recognize unprocessed antigens, including stress proteins, and are prominent at mucosal surfaces
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What are the unique features of NK cells?
- Large granular lymphocytes
- Part of innate immunity, not antigen-specific.
- Lack surface immunoglobulins, CD3, CD4, or CD8
- Activated by IFNγ, TNF, and IL-2
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What is the cytotoxic role of NK cells?
NK cells target cells lacking normal MHC I or expressing stress proteins
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What are the three major receptors of NK cells?
NK cells use receptors to detect abnormal surface antigens, including stress markers
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What is the structure of the T cell receptor (TCR) complex?
- TCR consists of paired peptide chains (αβ or γδ) that form antigen-binding receptors
- It connects to a signal-transducing component called CD3
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How can you tell if a T cell is a T helper cell by its structure?
- A T cell with TCR/CD3 associated with CD4 is a T helper cell
- CD4 binds to MHC class II molecules on antigen-presenting cells (APCs)
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What is the role of CD4 and CD8 in T cells?
- CD4: Binds to MHC class II molecules on APCs, identifying T helper cells
- CD8: Binds to MHC class I molecules on all nucleated cells, identifying cytotoxic T cells
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What are the key interactions in a T cell-APC dialog?
- TCR binds to antigenic peptides linked to MHC molecules
- Co-stimulation signals (e.g., cytokines) are required for full activation
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What is an immunological synapse?
- It’s the interaction site between a T cell and an APC
- SMACs (Supramolecular Activation Clusters) form concentric rings:
- cSMAC: Central region for signaling
- pSMAC: Peripheral region for adhesion
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What happens if co-stimulation signals are absent?
The T cell fails to activate properly, and the immune response is terminated
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What are T helper cells, and how do they function?
- CD4+ T cells recognizing antigens displayed on MHC II molecules
- They are categorized by the cytokines they secrete, not surface molecules
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What are the main types of T helper cells?
- TH1: Promote cell-mediated immunity
- TH2: Support antibody production
- TH17: Enhance neutrophil-mediated inflammation
- Treg: Suppress immune overactivation
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How do naïve T helper cells differentiate into subsets?
- Differentiation depends on signals received from APCs and the local environment
- Stimulating cytokines determine the subset:
- TH1: IL-12
- TH2: IL-4
- TH17: IL-6, TGF-β, and IL-23
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How do TH subsets regulate each other?
Each subset produces cytokines that amplify its own function while inhibiting others
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What cytokines do TH1 cells secrete, and what are their functions?
- Cytokines: IFN-γ, IL-2
- Functions: Activate macrophages, NK cells, cytotoxic T cells, and B cells
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What cytokines do TH2 cells secrete, and what are their functions?
- Cytokines: IL-4, IL-5, IL-13
- Functions: Stimulate IgE production, mast cell activation, and eosinophil recruitment
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What cytokines do TH17 cells secrete, and what are their functions?
- Cytokines: IL-17, IL-21, IL-22
- Functions: Promote inflammation and defense against extracellular bacteria and fungi
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What are the functions of T regulatory (Treg) cells?
Secrete IL-10, IL-35, and TGF-β to suppress immune responses and maintain self-tolerance
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What are γδ T cells, and where are they found?
T cells with γδ receptors, often found in intestinal walls (humans) or circulating in ruminants and pigs
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What is the role of γδ T cells?
- Recognize unprocessed antigens and stress proteins
- Act in innate immunity at mucosal surface
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What are the key characteristics of TCR and antigen recognition?
- TCR binds peptides linked to MHC molecules on APCs
- Co-stimulation is required for activation
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TH1 characteristics
Stimulating cytokines: IL-12
Secreted cytokines: IFN-γ, IL-2
Function: promotes cell-mediated immunity
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TH2 characteristics
Stimulating cytokines: IL-4
Secreted cytokines: IL-4, IL-5, IL-13
Function: supports antibody production (e.g., IgE)
307
TH17 characteristics
Stimulating cytokines: IL-6, TGF-β, IL-23
Secreted cytokines: IL-17, IL-21, IL-22
Function: stimulates neutrophil responses
308
Treg characteristics
Stimulating cytokines: IL-10, TGF-β
Secreted cytokines: IL-10, IL-35, TGF-β
Function: suppresses immune overactivation
