Immunology - Innate and Adaptive Immunity Flashcards
Define the immune system
Integrated system of cells and molecules that defends against pathogens and disease
Traits of Innate immune system? (3 traits)
Broad specificity
Not affected by prior contact
Rapid response (hrs)
Traits of Adaptive (acquired) immune system? (4 traits)
Highly specific
Enhanced by prior contact; Memory
Slower response (days-weeks)
Weak at birth; Becomes stronger over time after several pathogen contacts
Where is the crossover between innate and adaptive immunity? (hint - both primarily facilitated by same things)
Both primarily involve white blood cells (leukocytes) + soluble factors
What mechanisms/components are involved in the Innate immune system? (4 mechanisms/components)
Barriers
Leukocytes - Phagocytes, NK cells
Soluble proteins - Complement, Interferons
Local and systemic responses - Inflammation, Fever
Give an example of a external barrier in the Innate immune stem?
How can this barrier fail?
Keratinised skin - Effective barrier unless breached
Can be breached by:
- Wounds/Cuts
- Bites
Give 3 examples of a mucosal barrier in the Innate immune system? (hint - often infected)
Gastrointestinal tract (300m2)
Respiratory tract (100m2)
Genito-Urinary tract
What are leukocytes derived from? (hint - HSCs in B)
What are the 2 cell lineages
Derived from Haematopoietic Stem Cell in bone (pluripotent)
2 cell lineages are myeloid and lymphoid cells
What type of infections are phagocytes important in? (2 types)
What are the 2 main types of phagocytes?
Important in extracellular bacterial/fungal infections
2 main types:
- Neutrophils
- Mononuclear phagocytes
4 traits of neutrophils?
Main phagocyte in blood
Short lived
Fast moving
Has specialised lysosome for digestion of pathogens
2 traits of mononuclear phagocytes?
Different names for when in blood and tissue?
Long lived (months)
Help initiate adaptive responses
Monocytes in blood
Macrophages in tissue
Macrophage name in certain organs?:
- Brain
- Lungs
- Liver
Brain - Microglial cells
Lungs - Alveolar Macrophages
Liver - Kupffer cells
What type of cell is a Natural Killer (NK) cell? (hint - more specific than just leukocyte)
How does it kill infected host cells?
How it link with adaptive immunity?
Lymphocyte
Release lytic granules to kill virus-infected cells
Keeps viral infections in check until adaptive immunity develops
What are the 3 types of soluble proteins in Innate immunity?
- Give traits of each (e.g. type of infection they tackle)
Defensins
- +ve peptides made by neutrophils
- Disrupt bacterial membranes
Interferons
- Important in viral infections
Complement
- Important in extracellular infections
Name the 2 main interferons
What do they do when induced by viral infection? (3 things)
IFNα and IFNβ
Induce resistance to viral replication in all cells
Increase MHC class I expression and antigen presentation in all cells
Activate NK cells to kill virus-infected cells
What does complement system do in Innate immunity?
How many serum proteins in complement system?
- How are they activated? (3 ways)
Complements activity of antibodies
20 serum proteins activated either:
- Lectin binding pathogen surface (Mannose-Lectin binding pathway
- When antibody binds antigen (Classical pathway)
- Pathogen surfaces (Alternative pathway)
How does complement activation work? (hint - activation cascade)
Complement components can have protease activity
C3 protein is cleaved to generate fragments C3a and C3b which further activate other proteins
What are the 3 outcomes of complement activation?
Recruitment of inflammatory cells
Opsonisation of pathogens
Killing of pathogens
Complement activation - Recruitment of Inflammatory cells
What role do C5a and C3a have?
- Examples of inflammatory cells this recruits?
C5a and C3a are Chemoattractants; Induce inflammatory mediator release
- Recruits cells like neutrophils and mast cells
Complement activation - Opsonisation
What does C3b do and what type of bacteria is it important in killing?
How can some bacteria evade this?
C3b increases antibody binding and phagocytosis - Both important in killing of gram +ve bacteria
Some bacteria evade opsonisation by enveloping C3b in a thick capsule
Complement activation - Cell lysis
What does complement do to cause lysis?
What type of bacteria is this important in killing?
- Which type are resistant to this type of killing?
Membrane attack complex (C5b - C9) uses polymerases to form hollow cylinders which are inserted into bacterial membranes - Creates pores
Important in killing gram -ve bacteria
- Gram +ve are resistant
What induces inflammation?
What occurs in inflammation? (3 things)
Complement system
Dilation of blood vessels
Increased capillary permeability - Heat, redness, swelling, pain
Phagocytes migrate into tissues
What induces fever response? (2 things)
What occurs in fever response?
Cytokines and LPS
They induce synthesis of prostaglandin E2
This acts on hypothalamus which regulates temperature
Through what receptor does:
- Antibody bind to pathogen?
- Complement bind pathogen
Innate mechanisms with reference to PRRs and MAMPs?
- Fc receptors
- C3b receptors (Gram +ve and -ve bacteria)
Innate mechanisms - Pattern Recognition Receptors (PRRs) recognise Microbe-Associated Molecular Patterns (MAMPs)
Traits of Microbe-Associated Molecular Patterns (MAMPs) (3 traits)
- Give some examples
LPS, Lipoteichoic acid, Chitin, dsRNA
Conserved across many microbes
Distinct from self
Critical for survival/function for pathogens
What might binding of Pattern Recognition Receptors (PRRs) initiate? (3 things)
Receptor binding may initiate phagocytosis, chemotaxis or signalling
What are TLRs?
What do they signal?
- Each one recognises distinct ____?
Toll-Like Receptors
Signal presence of microbes
- Each one recognising a distinct MAMP
How does a TLR function?
- Structure
- What does ligand binding induce?
Function as dimers
Signalling induces expression of inflammatory cytokines
What 2 types of short lived bactericidal agents are there in the lysosome/phagosome?
Toxic oxygen-derived products - Superoxide O2-, H2O2
Toxic nitrogen oxides - Nitric oxide NO
What do Neutrophils ‘throw’ around bacteria?
- What process does this follow
What are these things made of?
Neutrophil Extracellular Traps (NETs)
Occurs following NETosis
NET - DNA impregnated with antimicrobial compounds
What ‘concept’ do NK cells recognise in infected-host cells?
What signals is killing regulated by? (2 signals)
What do these signals do?
Recognise ‘altered self’
Killing is regulated by opposing activating or inhibitory receptors
Inhibitory recognise MHC class I on normal cells; Cell not killed
Activating recognise ‘altered’ or ‘absent’ MHC class I; Apoptosis induced in infected cell
What do activated NK cells produce and what does it do?
- How does it induce apoptosis?
Perforin inserts into membrane of target cell
This creates channels for NK granules to release their contents (granzymes) into
Granzymes activate apoptotic pathway
What are cytokines and what do they do?
At what range do most act?
What cells do they act on?
“Hormones” of the immune response
They regulate the response by changing cell behaviour or gene expression
Most act locally
Act on cells with specific cytokine receptors
What are the main types of cytokines (4 types)
Interleukins
Interferons (IFN)
Chemokines
Tumour Necrosis Factor (TNF)
What are the 2 types of Adaptive immunity?
Humoral (antibody) immunity
Cell-Mediated immunity
What happens in Humoral Immunity? (2 things)
B lymphocytes recognise antigen with antibody receptors (acquired in bone marrow)
These differentiate into plasma cells that secrete soluble antibody that labels antigen
What happens in Cell-Mediated immunity? (2 things)
T lymphocytes recognise antigen with T-cell receptors (acquired in Thymus)
These differentiate into cytotoxic T cells that kill infected host cells or helper T cells that control immune response
What is an antigen?
Specificity?
A molecule that induces production of antibodies
A single antibody is specific in that it normally binds only one antigen
Explain Clonal Selection hypothesis (3 points)
B/T cells acquire receptors independently of antigen in primary lymphoid tissue
B cells respond to antigen in secondary lymphoid tissue
Memory cells allow for a fast and massive response upon second exposure to an antigen
