Principles of immune response Flashcards
Functions of immune responses
- Protection of host from pathogenic microorganisms
- Distinguishing self from non-self
- Distinguishing self from abnormal self (cancerous cells)
Principles of immune responses
- Activation requires recognition of danger signals.
- Encountering a pathogen causes formation of specific antibodies
- This leads to faster, larger, more efficient clearance of pathogen during second exposure
- Highly polymorphic (variable) genes
Consequences of failure of immune system
This is immunodeficiency, increased infection, increased risk of cancer
Definition of autoimmunity
Recognition of self cells as harmful material by immune system
Definition of allergy/hypersensitivity
Recognition of harmless non-self as harmful
Two immune system response INITIATION strategies
Strategy 1 - Pattern Recognition Receptors
Strategy 2 - Antigen-specific receptors on lymphocytes
Summary of pattern recognition receptor strategy
- Common molecular patterns
- Germline encoded
- Recognise (PAMPs) pathogen associated molecular patterns and (DAMPs) damage associated molecular patterns
Summary of antigen-specific receptors on lymphocytes used as initiation strategy
- Each antigen receptor binds a specific site (epitope) on an antigen
- Randomly generated through gene recombination in lymphocytes
- Millions of potential different receptors possibly encoded
Definition of lymphocyte
Type of white blood cell which carries an individual receptor specific to a particular antigen
Antigen definition
A molecule that is recognised and bound by lymphocytes
Antibody definition
A soluble receptor specific to an antigen synthesised and secreted by B lymphocytes = Immunoglobulin (Ig)
Features of innate immunity
- Fast
- Germline encoded, pre-formed components
- Limited specificity to DAMPs/PAMPs
- Independent of previous exposure
- No memory
What do DAMP and PAMP stand for
- Damage Associated Molecular Pattern
- Pathogen Associated Molecular Pattern
Cells of innate immunity
Macrophages/monocytes Neutrophils Basophils Eosinophils Complement Natural Killer cells Dendritic cells
Roles of innate immunity
- Destruction of invading nucleic acids (viruses) in cytoplasm
- Activation of inflammatory pathways and production of antiviral type 1 interferons
- Contain and limit pathogenic spread whist adaptive immune response begins
- Prime and direct appropriate adaptive response
Features of adaptive immunity
- Slow
- Clonal selection of randomly generated antigen receptors
- Unlimited specificity, can theoretically bind any epitope with high specificity
- Dependent on previous exposures
- Memory (acquired immunity)
Cells of adaptive immunity
B-lymphocytes
T-lymphocytes
Roles of adaptive immunity
- Selection and expansion of antigen specific clones
- Targeted elimination of pathogen
- Production of memory cells
Antigen receptors of B and T cells
B cells - Membrane-bound Immunoglobulin
T cells - T cell receptor
Process of clonal expansion
- B/T lymphocytes circulate in naive, inactive form
- Encounter complementary antigen, survive and proliferate
- Produces clones of cells which present the same antigen
Process of clearing infection
- Cytotoxic T cells kill infected cells
- Antibodies activate complement
- Antibodies inactivate toxins directly
- Antibodies activate Natural Killer cells
Final fates of clonal lymphoctes
- Death by apoptosis
- Survival as memory cells
Cytokine definition
A substance which is secreted by certain cells of the immune system and have an effect on other cells
Examples of cytokines and their actions
- Interleukins, between WBCs
- Interferons, anti-viral effects
- Chemokines, chemotaxis and movement
- Growth factors, growth and repair
- Cytotoxic, tumour necrosis factor
Process of cytokine release
- Cytokine-producing cell stimulated
- Cytokines released
- Bind to receptor on target cell
- Signal amplified inside target cell
- Gene activation occurs
- Leads to desired biological effects
Three mechanisms of cytokine action
Autocrine - act on releasing cell
Paracrine - Act on nearby cell
Endocrine - Act on distant cell, travel by circulation
Process of dendritic cell cytokine release
- Network of cells located at likely sites of infection
- Recognise microbial patterns, secrete cytokines
- Capture pathogens and migrate to lymph nodes
- Present antigens to adaptive immune system
Definition of complement
A system consisting of a number of small proteins found in the blood, synthesised in the liver, which circulate as inactive pro-proteins
Process of complement action
- Stimulation by trigger
- Proteases cleave specific proteins to release cytokines
- Initiates further cascade of further cleavages
- Stimulate phagocyte movement
- Initiate inflammation
- Construction of membrane attack complex
Complement activation pathways
Classical pathway - activated by antigen-antibody complex
Alternative pathway - activated by pathogen surfaces
Lectin pathway - Antibody-independent activation of classical pathway, lectins bind to carbohydrates found on pathogens
Mechanisms of control of complement
- Short half-life of components
- Dilution of components in biological fluids
- Specific regulatory proteins
Functions of complement
- Lysis
- Opsonisation
- Activation of inflammatory response
- Chemotaxis
Features of acute-phase response
Fever
Increased WBC production
“Acute-phase” protein production in liver
Acute phase proteins
C-reactive protein - activates complement
Mannan-binding lectin - activates complement
Complement
Fibrinogen - clotting
Role of toll-like receptors
Involved in immune response as a type of pattern recognition receptor
Mechanism of toll-like receptors
- Ligands bind and activate receptor
- TLRs recruit proteins in cytosol of immune cell with propagate signal transduction pathway
- Upregulation or suppression of inflammatory response genes
- Bacterial ligand = pathogen phagocytosed, digested, antigens presented to CD4+ T cells
- Viral ligand = infected cell enters apoptosis or release interferons
