Immune response Flashcards
What is the innate immune system?
Refers to non-specific defense mechanisms that activate within initial exposure to an antigen; includes germline-encoded receptors - unchangeable genome binds to particular ligands
What are the physical barriers of immunity?
Skin, mucous, epithelial cells
Which immunological factors form the innate humoral system?
Complement, lectins (collectins, ficolins), lectins prevent polysaccharide capsule bacteria from bindin, pentraxins, antimicrobial peptides
Which immunological cells are responsible for initiating the adaptive immune system?
Neutrophils, macrophages, dendritic cells, and natural killer cells
What is the adaptive immune system?
Highly specialized defense mechanism against specific pathogen-variable receptors that undergo maturation (DNA recombination), memory response
Which microbial factors are used in the adaptive humoral response?
Antibodies, complement
What immunological cells form the adaptive immune system?
Cytotoxic T cells, t helper cells, t regulatory cells, b lymphocytes, and plasma cells
What are the four main pathological niches?
Extracellular
Intracellular
Surface adherent
Intracellular cytosolic
What are extracellular niches?
Staphylococcus, streptococcus, candida, microbiota (worms), Pathogens secrete toxins and are suspended in tissue
What are intracellular niches?
Salmonella requires host cell organelles to translate and synthesize proteins (viruses)
What are surface adherent niches?
Enteropathogenic and enterohaemorrhagic E.coli Require close proximity to host cells. Adhesive tips enable bacteria to attach to specific host cells receptors. Cell wall adhesins are surfaced proteins in the cell wall of bacteria that bind tightly to specific receptor molecules on host cell surface membranes
What are intracellular cytosolic niches?
Phagocytosed pathogen integrates and suspends in the cytosol of cell (Listeria)
What is the circulating life span of neutrophils?
6 hours, short lived, followed by macrophages
How are Naive neutrophils activated?
Activated upon interaction with the pathogen and are attracted towards the area of infection by chemotaxis
Which class of chemotactic protein is released for neutrophil chemotaxis?
Leukotrienes
Where do neutrophils arise from?
Bone marrow through differentiation of HSCs into myephoid progenitor cells, neutrophils are unable to replicate.
What is the purpose of phagocytes?
Control infection (undergoing phagocytosis to hydrolyse pathogens, reducing pathogenic load), and limit/repair tissue damage
What does unregulated phagocytic activity result in ?
Granuloma (Collection of neutrophils/macrophages that exclude of an area) formation; excessive inflammation and inappropriate adaptive immunity, and tissue damage
What are interleukins?
Are communicatory glycoproteins released by leukocytes that regulate immune response-cytokines
Which receptors does IL bind onto?
IL receptors, consequently contributing to gene expression of naive cells activates macrophages
What are the three stages that occur for the sequence of molecular and cellular events in terms of activation of host immunological cells?
1) Microbial ligand detection
2) Naive host cells undergo gene-expression changes
3) Cytokine and chemokine release causes signal transduction
Where do macrophages reside?
Tissue-resident or circulatory
Which cytokines induce macrophage activation?
IL-12/18/1, TNF & IL-6
What functions are displayed by activated macrophages?
Phagocytosis and migration; cytokine/chemokine production, expression of cell surface molecules; antimicrobial activity; antigen presentation and T cell activation
What inflammatory properties are expressed by activated macrophages?
They are anti-inflammatory
Which interferon is the primary activator of macrophages?
IFN-y
Which interferon induces Class II MHCs on macrophages?
IFN-y
Which cells secrete cytokines which stimulate macrophage phagocytosis of pathogens?
T-lymphocytes
How is the specificity of immunological response dictated by cytokines?
The specificity of the response is attributed to the definite secretion of cytokines that confers to particular gene expressions to respond to the pathogen
What are interferons?
Interferon molecules are cytokines that express direct antiviral activities
What do antiviral genes encode for?
Nucleases (cleaves terminals fo viral nucleic acid)
Inhibitors of viral entry and exit
Inhibition of viral uncoating and replication
Inhibitors of protein translation
What are the three main immunomodulatory roles?
The enhanced T-cell response, anti-inflammatory actions, and tissue repair
How are infected cells killed by the immune system?
Killed by the action of cytotoxic T lymphocytes (CTLs)/ natural killer (NK) cells.
How are NK cells activated?
Independent of MHC recognition; are activated in response to secreted interferons or macrophage-derived cytokines. NK cells work to control viral infections by secreting IFN-y & TNF-a
How do NK and CTL cells control viral replication?
Cell death stimulated by these cells, removes viral replication niches, reducing the rate of viral load increments
Directly kill infected cells through contact-dependent mechanisms
How do intracellular bacterial infected cells undergo contact independent cell death?
Through cytokine stimulation
What are the four soluble effect mechanisms of the humoral innate immune system?
Complement mediated bacterial destruction
Lectin binding to neutralise cell attachement or entry
Iron chelation to prevent replication
Antibiotic-like peptides
What is the function of lectins?
Lectin-binding is responsible for the neutralization of cell attachment/entry
What is the function of iron chelation by siderophores?
Prevents replications
What are the 2 cell effector mechanisms for the humoral innate system?
1)Reactive oxygen and nitrogen radicals, acidification and digestion within phagosomes
2)Acidification within phagosomes
Which MHC class is recognized by CD4 cells?
MHC-II
Which MHC class is recognized by CD8 cells?
MHC-I
Which immune cells are antigen-presenting cells?
Activated macrophages and dendritic cells
Which interleukin secreted by antigen-presenting cells promotes T-cell replication?
IL-12
Which cytokine upregulates MHC-II expression for antigen presentation?
IFN-y
Which class of cells activate T-helper cells?
Dendritic cells and macrophages, the presented MHC-antigen complex associated with the cell membrane binds to complementary TCRs of the naive T-cells.
Binding mechanism results in the secretion of IL-2 cytokine causes mitotic division and specialization into active T-helper cells and T-memory cells
Which interleukin is secreted from activated naive T-cells which stimulates subsequent mitotic division?
IL-2
What do B-cell receptors detect?
Detect antigenic epitopes
What happens to the bound antigen onto the BCR?
Through receptor-mediated endocytosis by the B cell, the antigen undergoes antigen processing, the processed peptide fragments are expressed by MHC molecules on the cell surface membrane, and are subsequently recognized by T helper cells with complementary CD4 t cell receptors
What is the purpose of opsonization?
Mark infected cells, and pathogens, thus facilitating phagocytosis
What is the purpose of Th1 cells?
The lineage of CD4+ affect T cells, that promotes cell-mediated immune responses, required for host defense against intracellular viral and bacterial pathogens
Th1 cells secrete IFN-y, IL2/10, TNF-alpha/beta
Macrophage activation
What is the purpose of Th2 cells?
Mediate the activation & maintenance of the humoral and antibody-mediated immune response against extracellular bacteria, allergens, and toxins
What are the two classes of innate immune T cells?
T delta & gamma, these are early responders and are MHC independent
What is the principal target for Th1 cells?
Macrophages,
What role do Th1 exhibit in disease?
Autoimmunity and chronic inflammation
Which are the defining cytokines released from Th1 cells?
IL4/5/13
What is the principal target cell for Th2 cells?
Eosinophils
What are the main immune reactions stimulated by TH2 cells?
Eosinophil and mast cell activation
Alternative macrophage activation
Defense against helminths
Which t cells are mainly evident in allergy?
Th2
What are the defining cytokines released from Th17 cells?
Il17/22
What are the primary target cells for Th17 cells?
Neutrophils
What are the major immune reactions stimulated by Th17 cells?
Neutrophil recruitment and activation
Which Th cell subset is responsible for defense against extracellular bacteria and fungi?
Th17
What is Chediak-Higashi syndrome?
Compromised lysosomes
What factors cause apoptosis and pyroptosis(programmed cell death)
Apoptosis: Caspase 3, 6-9
Pyroptosis: Caspase 1, 4, 5
