Lecture 10 - Innate Immune System Flashcards
(79 cards)
1
Q
What are the two main immune systems?
A
- Innate Immune System
- Adaptive Immune System
2
Q
What are the three lines of defence in the immune system?
A
- Barriers (physical, chemical)
- Innate Immunity
- Adaptive Immunity
3
Q
What components are in the first line of defence (Physical, chemical Barrier)?
A
Skin
Mucous Membranes
4
Q
What components are in the second line of defence (Innate Immunity)?
A
Phagocytes
NK cells
Inflammation
Antimicrobial Proteins
Fever
5
Q
What components are in the Third line of defence ( Adaptive Immunity)?
A
Humoral (B cells)
Cellular (T cells)
6
Q
Define Pathogen?
A
An agent that causes or generates disease
7
Q
Define Antigen?
A
A substance that has the ability to provoke an immune response
8
Q
Main types of a Pathogen?
A
Micro-organisms:
- Bacteria
- Virus
- Fungi
Parasites:
- Dust mites
- Nematodes
Foreign Particles/Substances:
- Proteins
- Polysaccharides
- Pollen
9
Q
Main types of Antigen?
A
Foreign Molecule:
- Proteins
- Carbohydrates
- Lipids
- Nucleic Acids
Non-self / Intruders
10
Q
Define Hematopoiesis
A
Reproduction of RBC and occurs in the Bone marrow
11
Q
What are the two components of the Immune system ?
A
- Primary Lymphoid Organs
- Secondary Lymphoid Organs
12
Q
What are the Primary Lymphoid Organs
A
Bone Marrow = Hematopoiesis and B-cell maturation
Thymus = T cell Maturation
13
Q
What are the Secondary Lymphoid Organs?
A
Lymph Nodes
Spleen
MALT, (GALT, BALT, NALT)
Tonsils
Appendix
14
Q
What are the cellular components of the Immune System?
A
White Blood Cells:
- Neutrophils
- Lymphocytes (B-cells & T )
- Monocytes/Macrophages
- Eosinophils
- Basophils
- NK cells
15
Q
What are the Molecular Components of the Immune System?
A
Antibodies
Complement Proteins
Cytokines (Interferons, Interlukin, Histamine)
Chemokines
16
Q
What is the origin of all Blood cells?
A
Hematopoietic stem cells (HSCs), which are multipotent
17
Q
Hematopoietic Stem Cells are multipotent cells which can divide into what 3 components ?
A
- Long term stem cells (self renewing)
- Short term stem cells (limited renewal)
- Multipotent Progenitors
18
Q
Bone Marrow is responsible for?
A
Producing All Blood cells, including immune cells.
Also site for all Blood cell Division and B cell development
19
Q
From Multipotent Progenitors, cells can branch into two pathways?
A
- Common Lymphoid Progenitor (CLP) - Leads to lymphoid cells
- Common Myeloid Progenitor (CMP) - leads to myeloid cells
20
Q
The Common Lymphoid Progenitor (CLP) differentiates into ?
A
- Precursor T cell: Which migrate to thymus from maturation into T cells
- Precursor B cells: Which mature in the bone marrow into B cells
- NK cell (Natural Killer Cells)
21
Q
The Common Myeloid Progenitor (CMP) differentiates into 2 main components ?
A
- Granulocyte-macrophage progenitors
- Megakaryocyte-erythroid progenitors
22
Q
What cells are derived from granulocyte-macrophage progenitors via the myoblast lineage?
A
Granulocyte-macrophage progenitors give rise to myoblasts, which differentiate into:
- Neutrophils
- Eosinophils
- Basophils
23
Q
What cells are derived from granulocyte-macrophage progenitors via the Monocyte lineage?
A
Granulocyte-macrophage progenitors give rise to Monocytes, which differentiate into:
- Macrophages
- Dendritic Cells
24
Q
What cells are derived from Megakaryocyte-erythroid Progenitors?
A
- Megakaryocytes (make platelets)
- Erythrocytes (RBC)
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What do the Megakaryocyte provide ?
They make platelets
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What do the erythrocytes provide?
RBC
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Where is the thymus located and what is its function?
Behind the sternum, just above the heart.
Main role is to maturation and selection of T cells
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What is the main steps in T cell development in the thymus?
1. Arrival of T cell Precursor
2. T cell receptors - gene rearrangement
3. Positive selection (in cortex)
4. Negative Selection (in medulla)
5. Lineage commitment
6. Exit to periphery
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What happens in the process of T cells development in step 1.
STEP 1:
Arrival of T cell precursors
- Thymocyte precursor enters from bone marrow to cortex,- to begin development of T cells
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What happens in the process of T cells development in step 2
STEP 2
T cell receptors - Gene rearrangement
- T cell receptor is formed - each T cell gets a unique receptor
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What happens in the process of T cells development in step 3
STEP 3:
Positive selection
- T cells must recognize MHC - ensures functionality
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What happens in the process of T cells development in step 4
STEP 4:
Negative Selection
- Eliminates self reactive T cells - preventing autoimmunity
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What happens in the process of T cells development in step 5
STEP 5:
Lineage commitment
- Choose CD4 or CD8 path - determines T cell function
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What happens in the process of T cells development in step 6
STEP 6:
Exit to periphery
- Mature T cells leave thymus - ready for immune surveillance
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What are Secondary Lymphoid organs?
Secondary lymphoid organs are sites where mature lymphocytes (T-cells and B-cells) go after they’ve developed in primary.
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Function of the Secondary Lymphoid Organ?
Main function is to trap antigens, facilitate encounters and initiate adaptive immune responses
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What organs are components of the Secondary Lymphoid Organs?
Lymph Nodes
Spleen
Tonsils
Appendix
MALT (Mucosal associated lymphoid tissue)
Peyer's patch
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What is the function of lymph nodes
Filters Lymph fluid from tissue
Traps antigen from skin, mucosa, and internal organ
Serves as a meeting place for antigen-presenting cells and lymphocytes
Facilitate immune cell encounters
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What is the function of the Spleen?
Filters blood
Detects blood-borne pathogens and antigens
Removes old/damaged RBC
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What is the function of the MALT
Found in mucosal linings, where pathogens often enter:
GALT, BALT, NALT
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What are the functions of tonsils
Protects against ingested, inhaled pathogens
Located in pharynx
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What is the function of the appendix
Contains GALT, helps monitor intestinal microbes
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What physical and chemical barriers are found in the respiratory tract to prevent infection?
Nose hairs
Mucus
Cilia
Microbial molecules
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What protective features of the skin serve as barriers in the innate immune system?
RNases and DNases
Microcidal molecules
Fatty acids
Keratinized epithelium
Commensal microbes
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What innate immune defenses are present in the gastrointestinal (GI) tract?
pH (acidic environment)
Mucus
Enzymes
Microbial molecules
Commensal microbes
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What are the innate immune barriers of the urogenital tract?
pH
Mucus
Microcidal molecules
Fluid pressure
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Second line defence - innate immunity is?
Non specific protection against foreign materials and cells
Present at birth and does not improve on repeated contact
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What are the components of innate immunity in the Second line defence
Phagocytes
Natural killer cells
Inflammation
Antimicrobial Proteins
Fever
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What are Phagocytes
Detection, phagocytosis and elimination of foreign substances, dead/damaged cells
Communicate with other defence cells via cytokines
Attract other immune cells to area via chemokines - at type of cytokine causing chemotaxis
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What are Kupffer cells and where are they located?
Kupffer cells are fixed phagocytes found in the liver. They are part of the innate immune system and specialize in detecting and eliminating pathogens or debris in liver tissue.
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Which phagocytic cells travel freely in the body, and what is their role?
The free-traveling (circulating) phagocytes include:
Monocytes
Macrophages
Dendritic cells
Neutrophils
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What are the 5 steps of phagocytosis
1. Phagocyte adheres to pathogen
2. Phagocyte forms pseudopods that eventually engulf the particles forming a phagolysosome
3. Lysosomal fuses with the phagocytic vesicle, forming a phagolysosome
4. Lysosomal enzyme digest the particle, leaving a residual body
5. Exocytosis of the vesicle removes indigestible and residual material
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What are NK cells and how do they work?
NK cells are large granular lymphocytes responsible for reconciling and destroying abnormal cells when they appear in peripheral tissues
Natural killer cells destroy abnormal cells via immune surveillance, using perforin to induce lysis.
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What are the steps in how Natural Killer (NK) cells perform immune surveillance?
Recognition and adhesion – NK cells identify and bind to abnormal cells
Realignment of Golgi apparatus – Golgi repositions to aim at the target
Secretion of perforin – Perforin is released to create pores in the target cell membrane
Lysis of abnormal cells – The abnormal cell is destroyed via membrane disruption
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What is acute inflammation?
An immediate response to injury delivering leukocytes to eliminate pathogens and clear tissue damage.
Examples:
Neutrophils
lymphocytes
Eosinophils
Basophils
Monocytes
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What causes fever during immune responses
Pyrogens released by leukocytes/macrophages act on the hypothalamus to raise body temperature
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What is the antimicrobial proteins
Antimicrobial proteins enhance the innate defences by attacking microorganisms directly or by hindering their ability to reproduce
Examples:
Interferons
Complement proteins
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What is the complement system?
A group of around 30 glycoproteins present in plasma/serum and on cell membranes that normally remain in an inactive state.
Activated via enzymatic cascade
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What proteins make up the complement system, and what do they include?
The complement system consists of proteins C1 through C9, along with several regulatory proteins and other factors. These proteins normally circulate in an inactive state and become activated during immune responses.
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What are the functions of the Complement system?
Activation involves a highly regulated enzymatic cascade
1. Lysis of target cells
2. Facilitate Ag clearance (opsonisation)
3. Generate an inflammatory response (anaphylatoxins).
4. Clearance of immune complexes
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What are the 3 activation pathways of the complement system?
Classical pathway (antibody-mediated)
Alternative pathway (pathogen surface-mediated)
Lectin pathway (mannose-binding lectin activation)
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Alternative pathway?
Triggered directly by microbes (no antibodies needed)
Beings with C3 being activated and binding to pathogen surfaces
C3 undergoes spontaneous hydrolysis and binds to pathogen surfaces (low sialic acid content).
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Classical pathway?
Triggered by antibodies (IgG or Igm) binding to antigens
Activates C1, which then cleaves C2 and C4, leading to C3 activation
Initiated by IgM/IgG binding to antigens, activating C1 and triggering cleavage of C2 and C4.
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Lectin Pathway?
Triggered when mannose-binding lectin (MBL) binds to microbial carbohydrate
This activates enzymes that cleave C4 and C2, similar to the classical pathway
MBL binds to mannose on microbes (e.g., Salmonella, Candida), activating enzymes that cleave C4 and C2.
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Steps for the Classical Complement pathway (deep)
1. Antibodies bind to bacterial cell wall
- Antibodies (specifically IgG or IgM) attach to antigens on a pathogen’s surface (e.g., bacteria).
2. Attachment of C1
- The C1 complex binds to at least two antibodies on the pathogen surface. This activates the C1 protein complex
3. Activation and Cascade
- Activated C1 cleaves C2 and C4 into fragments (C2a, C2b, C4a, C4b).
- These fragments then help cleave C3 into C3a and C3b.
- C3a promotes inflammation, while C3b acts as an opsonin (enhances phagocytosis).
4. C3b Attachment
- C3b binds to the pathogen surface, marking it for phagocytosis by immune cells like macrophages and neutrophils.
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What are the main steps of the Classical Complement Pathway?
1. Antibodies (IgG or IgM) bind to antigens on the bacterial cell wall.
2. C1 protein complex attaches to at least two antibodies, initiating the pathway.
3. C1 activates a cascade, cleaving C2 and C4, which then cleave C3 into C3a (inflammatory) and C3b (opsonin).
4. C3b binds to the pathogen, enhancing phagocytosis by immune cells.
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What are the steps of the Alternative complement pathway
1. Spontaneous hydrolysis of C3 → C3a + C3b
2. C3b binds to pathogen surfaces (like bacterial cell walls)
3. Recruitment of Factor B, Factor D, and Properdin
4. Formation of C3 convertase → cleaves more C3
5. C3b enhances opsonization
6. C3a promotes inflammation
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What are the steps of the lectin pathway in complement activation?
1. MBL (mannose-binding lectin) binds to mannose-rich carbohydrates on microbial surfaces
2. Activation of MASPs, which cleave C4 and C2
3. Formation of C3 convertase → cleaves C3 into C3a and C3b
4. C3a triggers inflammation
5. C3b binds to the pathogen, promoting opsonization and phagocytosis
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12. Which of the following cells are phagocytes? (more than one answer is correct)
a.Natural Killer cells (NK cells)
b. Macrophages
c. Neutrophils
d. T-cells
e. B-cells
B
C
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14. Immune surveillance involves continuous monitoring of peripheral tissues by which type of cell?
a. macrophages
b. T cells
c. B cells
d. neutrophils
e. NK (natural killer) cells
E
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What cells is in Myeloid Lineage
GRANULOCYTES: myoblast
Neutrophils
Eosinophils
Basophils
GRANULOCYTES: Monocyte
Macrophages
Dendritic cells
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What 3 cells can act as an antigen presenting cells?
Dendritic cells
Macrophages
B cells
NK
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What makes a cell a APC
Must express MHC class II molecules
Must be able to process and present exogenous antigens
Must activate CD4⁺ T helper cells
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What are interferons?
Interferons (IFNs) are antimicrobial proteins that are part of the innate immune system. They are cytokines produced by virus-infected cells to warn and protect neighboring cells.
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Function of interferons
interfer with viral replication
activate immune cells
Enhance antigen presentation
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Describe Interferons, including the 5 steps involved in the process of how viruses infect a cell leading to the production of interferon?
1. Viral Entry
- A virus enters a host cell and injects its genetic material.
2. Replication
- The virus hijacks the host machinery to replicate its genome and produce viral proteins.
3. Detection
- The infected cell detects viral nucleic acids using pattern recognition receptors (PRRs) like Toll-like receptors (TLRs) or RIG-I-like receptors.
4. IFN activation
- This recognition activates signaling pathways that turn on interferon genes, especially IFN-α and IFN-β (Type I interferons).
5. IFN release
- Interferons are secreted and bind to receptors on neighboring cells, triggering them to enter an antiviral state by producing antiviral proteins (like PKR and OAS).
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What is the end product of the interferon response
Type I Interferons (IFN-α and IFN-β): Main interferons produced
Antiviral Proteins in neighboring cells:
- PKR (Protein Kinase R): Inhibits viral protein synthesis
- OAS (2’-5’-oligoadenylate synthetase): Activates RNase L to degrade viral RNA
Increased MHC I expression: Enhances antigen presentation to cytotoxic T cells
Activation of NK cells: To destroy infected cells
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Correct the following sentence
A virus is a type of antigen/ pathogen which is always intracellular/ extracellular.
A virus is a type of pathogen which is alway intracellular
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