Quiz I Flashcards
(128 cards)
1
Q
Why does your immune system begin to get weaker in old age?
A
- Thymus atrophies and shrinks to 1/3 original size
- Bone density drops and marrow also atrophies
2
Q
List the broad categories of disease the immune system participates in
A
- Allergy
- Autoimmunity
- Immunopathology
- Graft rejection
- Graft vs. host disease
3
Q
Allergy
A
Allergies are a number of conditions caused by hypersensitivity of the immune system to something in the environment that usually causes little or no problem in most people. Food intolerances and food poisoning are separate conditions.
4
Q
Autoimmunity
A
Autoimmunity is the system of immune responses of an organism against its own healthy cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease.
5
Q
Immunopathology
A
Damage caused to an organism by its own immune response, as a result of an infection.
6
Q
Graft rejection
A
Transplant rejection occurs when transplanted tissue is rejected by the recipient’s immune system, which destroys the transplanted tissue.
7
Q
Graft vs. host disease
A
Graft versus host disease (GVHD) is a condition where following transplantation the donor’s immune cells in the transplant (graft) make antibodies against the patient’s tissues (host) and attack vital organs. Organs most often affected include the skin, gastrointestinal (GI) tract and the liver.
8
Q
Broadly, what is Immunology?
A
The study of the body’s defenses against infection
9
Q
How was the field of Immunology founded?
A
Edward Jenner (late 18th century)
Saw that people exposed to cowpox did not get smallpox. Demonstrated that deliberate innoculation with cowpox prevented smallpox (first natural vaccination).
10
Q
vaccination
A
The deliberate inoculation of individuals with weakened or attenuated strains of disease-causing agents to provide protection from disease.
Edward Jenner, first (natural) vaccine; prevented smallpox by injecting cowpox
11
Q
What disease has vaccination eliminated? What disease is (likely) next? How do we know these diseases are eliminated?
A
Smallpox, next likely Polio.
Smallpox and Polio have no aminal reservoirs.
12
Q
How was Polio wiped out?
A
Ring vaccination: vaccinating the areas around known infection sites to that the infection cannot spread outside the area.
13
Q
What are the four categories of pathogens?
A
vuruses, bacteria, fungi, parasites
14
Q
Who discovered that individual microbes were responsible for a particular disease?
A
Robert Koch (19th century), believed you need to be able to find the cause of disease, and identify it.
15
Q
What categories are modern disease-causing organisms (pathogens) placed into?
A
Pathogens are placed into four categories:
- viruses
- bacteria
- fungi
- parasites
16
Q
Who created the first intentional, “man-made” vaccine?
A
Louis Pasteur (1880)
- Developed vaccine for chicken cholera.
- Developed rabies vaccine by passing the virus through rabbits and using their dried spinal chord.
17
Q
How did Pasteur weaken viruses for his vaccines?
A
He passed them through mammal hosts, which attenuated the pathogenicity of the virus.
18
Q
Who first demonstrated how immunity worked?
A
Emil von Behring (who won the first Nobel prize in Medicine, 1901) and Shibasaburo Kitasato.
Discovered the blood serum of animals immune to diptheria bacteria contained “anti-toxic activity” (antibodies) that protected others from infection.
19
Q
Where are immune responses directed?
A
Against pathogens.
20
Q
What are the two divisions of the immune system?
A
Innate and adaptive immune system
21
Q
antigen
A
- Any substance that can induce any part of adaptive immunity, not just antibodies.
- Can be almost anything, peptide, pathogen, allergen, food protein, commensal microbe
- Doesn’t have to be truly foriegn
22
Q
What is the rough order of the immune response?
A
- Many pathogens handled sucessfully by innate immunity and cause no disease.
- When innate immunity is not enough, adaptive system is triggered by innate system.
- If the pathogen is overcome, adaptive immune system is often followed by long-lasting immunological memory, decreasing severity or preventing re-infection.
23
Q
leukocyte
A
- White blood cell (WBC)
- Only blood cells with a nucleus.
- Two types, myeloid cells or lymphoid cells.
24
Q
monocyte cellular “ancestry”
A
Multipotent hematopoietic stem cell (Hemocytoblast) > myeloid progenitor > Myeloblast > Monocyte
25
monocyte
precursors of tissue macrophages (which are phagocytes)
26
PMN
Polymorphonuclear leukocytes (PMN) (also called granulocytes:
• Have multi-lobed nuclei and cytoplasmic granules
All are Myeloblast daughter cell types:
* Basiophils
* Neutrophils
* Eosinophils
27
What are the possible daughter cell types of lymphoid progenetor cells?
Natural killer (NK) cells (also called large granular lymphocytes)
Small lymphocytes, which can become either B or T lymphocytes
Plasma cells, which arise from B lymphocytes
28
General features of the innate immune system
* Built-in, does not learn before acting and doesn't need to
* First line of defense, then alerts adaptive immune system
* Anti-microbial peptides are produced in a steady state
* Specific receptors found on many cell types that recognise microbial products
29
What part of the immune system produces responses to specific microbes?
adaptive
30
What are white blood cells called?
leukocyte
31
What part of the immune system has memory?
adaptive
32
What are red blood cells called?
erythrocyte
33
What cells do macrophages form from?
monocytes
34
granulocyte
Polymorphonuclear leukocytes (PMN)
-Multi-lobed nuclei and cytoplasmic granules
35
lymphocyte
A subset of leukocytes, includes T cells and B cells
ADAPTIVE IMMUNITY
36
CD4 and CD8 are found on what cells?
T cells
37
innate immunity
* **Immediately** available to combat wide range of pathogens
* **Not** **specific** for any individual pathogen
* Does not lead to lasting immunity (**no** **memory**)
* Required for mounting an adaptive response
38
What are the mechanisms of innate immunity
–basic aspects of our physiology (temperature)
–anatomical features (skin, mucous)
–Chemical (pH, anti-microbial proteins)
–Biological (commensal flora)
–Specialized cells that respond to microbes
* PMNs (neutrophils, eosinophils, basophils)
* Macrophages, dendritic cells, mast cells, NK cells, etc.
39
What cells are involved in innate immunity?
* PMNs (neutrophils, eosinophils, basophils)
* Macrophages, dendritic cells, mast cells, NK cells
40
cytokines
(from Greek: cell movement) any secreted protein that affects the behavior of nearby cells bearing receptors
41
What do cytokines do?
–interleukins are cytokines (IL-2 = interleukin 2)
–Help develop cellular and humoral responses
–Induction of inflammation
–Wound healing
–Regulation of hematopoiesis (process of creating new blood cells in the body)
42
hematopoiesis
the process of creating new blood cells in the body
43
chemokines
Small, secreted cytokines typically responsible for chemotaxis; typical structure with cysteines
44
What is the structure of chemokine classes?
45
CCR7
C-C chemokine receptor type 7
This receptor is expressed in various lymphoid tissues and activates B and T lymphocytes. CCR7 has been shown to stimulate dendritic cell maturation. CCR7 is also involved in homing of T cells to various secondary Lymphoid organs such as Lymph nodes and Spleen as well as trafficking of T cells within Spleen.
46
CCR7 ligands
Two ligands have been identified for this receptor: the chemokines (C-C motif) ligand 19 (CCL19/ELC) and (C-C motif) ligand 21 (CCL21)
47
Activation of CCR7
Activation of Dendritic cells in peripheral tissues induces CCR7 expression on the cell's surface, which recognize CCL19 and CCL21 produced in the Lymph node, and increases dendritic cell expression of co-stimulation molecules (B7), and MHC class I or MHC class II.
48
CCL19
Chemokine (C-C motif) ligand 19 (CCL19)
This chemokine elicits its effects on its target cells by binding to CCR7. It attracts certain cells of the immune system, including dendritic cells, antigen-engaged B cells, and CCR7+ central-memory T-Cells
49
chemotaxis
cell movement in response to cytokines
50
Cytokines and chemokines are in what part of the immune system?
Both the innate and adaptive immune systems
51
What do cytokines and chemokines effect?
Initiate inflammation
Recruit innate immune cells from blood into tissue
Increase flow of lymph
Recruit effectors of the adaptive immune system
52
lymph
Fluid that circulates within the lymphatic system
53
interstitial space
area between cells
54
interstitial fluid
fluid in the interstitial space
55
What are the two hallmarks of the adaptive immune system?
specificity and memory
56
adaptive immune system
Adaptive immunity creates immunological memory after an initial response to a specific pathogen, and leads to an enhanced response to subsequent encounters with that pathogen. This process of acquired immunity is the basis of vaccination. Like the innate system, the adaptive system includes both humoral immunitycomponents and cell-mediated immunity components.
57
TCR vs. BCR
58
BCR vs. Ab vs. TCR
59
Ig
Immunoglobulin (Ig) and Antibodies (Ab) are the same thing
60
How do Ab see antigens?
Antibodies (Immunoglobulins) recognise a 3D epitope of the antigen
61
When is TCR secreted?
NEVER! TCR is a membrane bound
62
When is BCR secreted?
B cells produce antibodies (Ab) after stimulation with antigen (Ag).
Ab are essentially a secreted form of the BCR. TCR is never secreted.
63
CD4 & CD8 are TCR or BCRs?
TCRs
64
CD
cluster of differentiation
naming convention
\>300 CD molecules
65
MHC
Major histocompatibility complex
66
How do T cells see Ag?
T cells see the cleaved pieces of antigen that are presented on MHC molecules
67
MHC I is found on? Binds to?
All nucleated cells
TCR-CD8
68
MHC II is found on? Binds to?
Antigen-presenting cells
TCR-CD4
69
What is the difference between the Ag displayed by MHC I & II?
Ag expressed by MHC I is cytosolic in origin and represents the inside of neucleated cells, bound by cytotoxic (killer) T cells (CD8).
In contrast, Ag expressed by MHC II is exogenous in origin and is bound by helper T cells (CD4).
70
What is the overarching function of T cells
T cells interact with other cells through contact and induce change in them
71
What happens when a mature CD8 T cell encounters a virus infected cell?
CD8 T cells attatch to MHC I on nucleated cells, if they are infected with an Ag it recognises, it induces apoptosis
72
What happens when a mature CD4 T cell encounters a macrophage
It releases cytokines that activate the macrophage and causes it to relase other cytokines
73
What happens when a mature CD4 T cell encounters a B cell?
The CD4 cell activates the B cell and converts it to a plasma cell, which secretes Ab
74
What are the general features of the innate immune system?
– Inherent, no need to “learn” before acting
– acts as a first line of defense against microbes and then alerts the adaptive immune response
– Innate defense systems are varied – could be simple, like
* barriers: skin, gut epithelium, mucus
* compounds produced in a steady state: anti-microbial peptides
– There are specific types of receptors found on many cell types which can recognize microbial products
75
Innate or adaptive?
Specificity inherited in genome
Innate
76
Innate or adaptive?
Expressed by all cells of a particular type
Innate
77
Innate or adaptive?
Recognises broad classes of pathogens
Innate
78
Innate or adaptive?
Interacts with a range of molecular structures of a given type
Innate
79
Innate or adaptive?
Encoded in multiple gene segements?
Adaptive
80
Innate or adaptive?
Requires gene rearrangement
Adaptive
81
Innate or adaptive?
Clonal distribution
Adaptive
82
Innate or adaptive?
Able to discriminate between even closely related structures
Adaptive
83
What types of immune responses do these represent? What does this tell you?
Must have innate immunity for adaptive to function
84
List some extracellular places infections can occur
Interstitial spaces, blood, lymph, epithelial surfaces
85
List places intracellular infection can occur
cytoplasm, vesicules
86
What are direct mechanisms of tissue damage by pathogens?
Exotoxin production
endotoxins (LPS)
direct ctyopathic effect
87
How does cytopathic effect damage hosts?
Direct damage to host, structural changes in host cells that are caused by viral invasion. The infecting virus causes lysis of the host cell or when the cell dies without lysisdue to an inability to reproduce
88
How do a pathogen's endotoxins damage hosts?
Direct damage. Endotoxins, which are intrinsic components of microbial structure, trigger phagocytes to release cytokines that produce local or systemic symptoms
89
How do a pathogen's secreted exotoxins damage hosts?
Direct damage. Exotoxins are released by microorganisms and act at the surface of host cells, for example, by binding to receptors.
90
goblet cell
Innate immunity
Goblet cells secrete mucus, located in _ciliated bronchial_ and _gut_ epithelium
91
What do Paneth cells secrete?
Innate immunity
RegIII and α-defensins
92
Paneth cell
Innate immunity
Paneth cells secrete anti-microbial compounds (and other compounds that are known to be important in immunity and host-defense) into the lumen of the intestinal gland, thereby contributing to maintenance of the gastrointestinal barrier.
secrete RegIII and α-defensins
93
RegIII gamma
Regenerating islet-derived protein III-gamma
Intestinal paneth cells produce REG3G (or REG3 gamma) via stimulation of toll-like receptors (TLRs) by pathogen-associated molecular patterns (PAMPs). REG3 gamma specifically targets Gram-positive bacteria because it binds to their surface peptidoglycan layer. It is one of several antimicrobial peptides produced by paneth cells.
94
defensins
Defensins are small cysteine-rich cationic proteins found in both vertebrates and invertebrates. They are, and function as, host defense peptides. They are active against bacteria, fungi and many enveloped and nonenveloped viruses. Cells of the immune system contain these peptides to assist in killing phagocytosed bacteria, for example in neutrophil granulocytes and almost all epithelial cells. Most defensins function by binding to the microbial cell membrane, and, once embedded, forming pore-like membrane defects that allow efflux of essential ions and nutrients.
95
In what ways does the skin act as a barrier?
Innate immunity
Skin acts as a **mechanical barrier:**
• Epithelial cells joined by tight junctions
**•** Fluid flow, perspiration, shedding old skin
Skin acts as a **chemical barrier:**
* Antimicrobial peptides (defensins)
* Sebum (fatty acids, lactic acid, lysozyme)
Skin acts as a **microbiological barrier****:**
• Normal flora of the skin
96
In what ways does the GI tract act as a barrier?
Innate immunity
GI tract acts as a **mechanical barrier:**
• Epithelial cells joined by tight junctions
**• Rapid turnover (~3 days) of epithelial cells** compared to other organ systems
• Flow of fluid, mucus, food, and saliva
GI tract acts as a **chemical barrier:**
* Antimicrobial peptides (defensins)
* Low pH, enzymes (proteases)
GI tract acts as a **microbiological barrier:**
• Normal flora of the GI tract
97
In what ways does the respiratory tract act as a barrier?
Innate immunity
GI tract acts as a **mechanical barrier:**
* Epithelial cells joined by tight junctions
* Flow of fluid, mucus via cilia and air flow
GI tract acts as a **chemical barrier:**
* Antimicrobial peptides (defensins)
* Lysozyme in nasal secretions
GI tract acts as a **microbiological barrier:**
• Normal flora of the respiratory tract
98
In what ways does the urogenital tract act as a barrier?
Innate immunity
Urogential tract acts as a **mechanical barrier:**
* Epithelial cells joined by tight junctions
* Flow of fluid, urine, mucus, sperm
Urogenital tract acts as a **chemical barrier:**
* Antimicrobial peptides (defensins)
* Low pH vaginal secretions, zinc in semen
Urogenital tract acts as a **microbiological barrier:**
• Normal flora of the urogenital tract
99
In what ways do eyes act as a barrier?
Innate immunity
Eyes act as a **mechanical barrier:**
* Epithelial cells joined by tight junctions
* Flow of fluid, tears
Eyes act as a **chemical barrier:**
* Antimicrobial peptides (defensins)
* Lysozyme in tears
Eyes act as a **microbiological barrier:**
• Normal flora of the eyes
100
How does the innate system recognise microorganisms?
Innate system has no memory, has evolved to recognise PAMPs (pathogen assoicated molecular patterns), common features of microbes such as flagella, LPS, double-stranded RNA, unmethylated DNA. These common microbial products are not normally present in your body and signal danger.
101
PAMPs
Pathogen-associated molecular patterns, or PAMPs, are molecules associated with groups of pathogens, that are recognized by cells of the innate immune system. These molecules can be referred to as small molecular motifs conserved within a class of microbes. They are recognized by Toll-like receptors (TLRs) and other pattern recognition receptors (PRRs)
102
Examples of PAMPs
PAMPs activate innate immune responses, protecting the host from infection, by identifying some conserved nonself molecules. Bacterial lipopolysaccharides (LPSs), endotoxins found on the cell membranes of bacteria, are considered to be the prototypical class of PAMPs.
**LPSs** from gram-negative and **lipoteichoic** **acid** from gram-positive bacteria (recognised by **TLR4**)
Bacterial **flagellin** (recognised by **TLR5**)
Double-stranded RNA (**dsRNA**) (virus) (recognized by **TLR3**)
**DNA** with **unmethylated** CpG motifs (bacteria and herpes virus) (recognised by **TLR9**)
103
What does TLR3 recognise?
PAMP
dsRNA from viruses
104
What does TLR4 recognise?
PAMP
LPS (G-) and lipoteichoic acid (G+)
TLR4 (plus MD-2 and CD14, Nobel prize 2011)
105
What does TLR5 recognise?
PAMP
Bacterial flagellin
106
What does TLR9 recognise?
PAMP
DNA with unmethylated CpG motifs (bacteria and herpesvirus)
107
Toll-like receptors
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors usually expressed in sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cellresponses.
108
Where in the cell can TLRs be found?
In membranes on the cell surface and intracellular membranes
109
NOD-like receptor
The nucleotide-binding oligomerization domain-like receptors, in short NOD-like receptors (NLRs) are intracellular (cytoplasmic) sensors of PAMPs that enter the cell via phagocytosis or pores and DAMPs that are associated with cell stress. They are part of pattern recognition receptors and play key roles in regulation of innate immune response. NLRs can cooperate with Toll-like receptors and regulate inflammatory and apoptotic response. They are found in lymphocytes, macrophages, dendritic cells and also in nonimmune cells, for example in epithelium. NLRs are highly conserved through evolution.
–recognize bacterial wall peptidoglycans
–induce secretion of inflammatory cytokines, anti-microbial products
110
PRR
Pattern recognition receptors (PRRs) are a primitive part of the immune system. They are proteins expressed by cells of the innate immune systemto identify two classes of molecules: pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens, and damage-associated molecular patterns (DAMPs), which are associated with cell components that are released during cell damage or death. They are also called primitive pattern recognition receptors because they evolved before other parts of the immune system, particularly before adaptive immunity.
111
112
What are the two cytoplasmic receptors we have studied so far?
RIG-I-like helicases (RLH)
NOD-like receptors
113
RLH
RIG-I-like receptors, abbreviated RLRs, are a type of intracellular pattern recognition receptor (PRR) involved in the recognition of viruses by the innate immune system. There are three RLRs: **RIG-I**, MDA5, and LGP2 that act as sensors of viral replication within the cytoplasm of human cells. RLRs detect viral replication through direct interaction with uncapped triphosphate dsRNA, which is produced by RNA viruses to form their genome (dsRNA viruses) or as a part of their replication cycle.
114
Where is RLH located?
Rig-I-like helicases can be expressed in every nucleated cell
115
What does RLH detect? What does it do?
Rig-I-like helicase recognises uncapped 5' triphosphate RNA produced during viral replication
Binds to MAVS and dimerises, producing inflammatory cytokines and interferons via activation of NFKB and IRF
116
Where are neutrophils found?
In bone marrow and the blood under normal conditions, migrate to afflicted tissues during infection
117
How can neutrophils be used as a diagnostic?
Healthy tissues should not have neutrophils, this can be used as a diagnostic for infections
118
What cytokines do activated macrophages secrete?
IL-1β
TNF-α
IL-6
CXCL8
IL-12
119
IL-1β
A cytokine released by activated macrophages
**Local effects**
Activates vsacular endothelium
Activates lymphocytes
Local tissue distruction
Increase access of effector cells
**Systemic effects**
Fever
Production of IL-6
120
TNF-α
A cytokine released by activated macrophages
**Local effects**
Activates vascular endothelium and increases vascular permeability, leading to increased entry of IgG, compliment, and cells to tissues and increased fluid drainage to lymph nodes
**Systemic effects**
Fever
Moblisation of metabolites
Shock
121
IL-6
A cytokine released by activated macrophages
**Local effects**
Lymphocyte activation
Increased antibody production
122
CXCL8
A cytokine released by activated macrophages
**Local effects**
Chemotactic factor, recruits neutrophils, basophils, and T cells to site of infection
123
IL-12
A cytokine released by activated macrophages
**Local effects**
Activates NK cells
Induces the differentiation of CD4 T cells into TH1 cells
124
ISG
An interferon-stimulated gene (ISG) is a gene whose expression is stimulated by interferon. The protein products of these genes control pathogenicinfections.
(First response triggered by IFN-α/β in image below)
125
What recognise PAMPs?
* Pattern recognition receptors (PRR): receptors that recognize PAMPs
* these receptors are found on cells such as macrophages, neutrophils and dendritic cells (innate immune cells)
126
Repetitive arrays of protein, carbohydrates or lipids on pathogens
PAMPs (pathogen associated molecular patterns)
127
What do toll-I-like receptors recognise?
Multiple TLRs, each recognise a distinct ligand
• ligands are conserved features of pathogens such as flagella, dsRNA, etc.
128
