Immunology Flashcards
Give the definition of immunity
state of being insusceptible or resistant to a noxious agent or process
What are the first lines of defence against pathogens by humans?
Skin
Saliva/mucus/tears
Cilia
Stomach acid
urine flow
Microbiome
How does saliva act as a line of defence against pathogens?
Anti-microbial peptides and lysozymes digest bacterial cell walls.
It transports pathogens out of the body or into the stomach
How can pathogens be identified by the immune system?
They have pathogen-associated molecular patterns (PAMPs) which are specific to them. E.g LPS (lipopolysaccharides) in gram-negative cell walls
Toll-like receptors (TLRs) recognise PAMPs.
What normally expressed TLRs?
Macrophages, dendritic cells and neutrophils
What type of leukocytes are involved in innate and adaptive immunity respectively?
Myeloid cells-innate
Lymphoid-Adaptive
What effect does Inflammation have for immunity?
Blood vessels dilate, making them permeable to immune cells. Endothelial cells become sticky, allowing white blood cells to be captured
Fever inhibits pathogen proliferation
What are neutrophils?
Short lived phagocytes which migrate to sites of infection
What are macrophages?
Long lived phagocytes which are abundant in areas exposed to pathogens
What are eosinophils?
Specialist cells which attack objects too large to engulf
What are dendritic cells?
Cells which migrate to lymphoid tissue, activates and stimulates T-cells
Phagocytoses pathogens and cleaves peptides bound to MHC proteins
Outline adaptive immunity
Highly specific responses to pathogens. Involves lymphocytes developing in thymus and bone marrow.
They encounter foreign antigens in secondary lymphoid organs
Body produces lots of lymphocytes and those with binding affinity to antigens are activated
What are natural killer cells?
Early defence against foreign cells
Considered part of the innate immune response despite being lymphoid
Explain cytotoxic T cells
Directly kill infected host cells
Explain helper T cells
Activate macrophages, dendritic cells, B-cells and cytotoxic T-cells. Secrete cytoines
Explain regulatory T cells
Inhibit T helper cell function, cytotoxic T-cells and dendritic cells. Allows negative feedback
What secretes antibodies?
B-cells
How can immune tolerance to tested experimentally?
- Knockout self protein genes
- Allow the animal to grow and reintroduce its self protein
- An immune response occurs as it hasn’t encountered the protein before
How do immune systems build self-tolerance>
Lymphocytes that bind to a self-antigen die via apoptosis
Receptor editing on lymphocytes recognising self antigens
Clonal inactivation where self-reactive lymphocytes are inactivated
Clonal suppression where regulatory T cells suppress activity of self-reactive lymphocytes
What are IgGs made up of?
2x Constant domains (220aa each)
2x Variable domains (110aa each)
How are IgG variable domains encoded?
40V domains, 25D domains, 6 J domains and 5 C domains.
These are combined via V(D)J recombination
This splicing creates a unique combination of domains that are transcribed
What do mutations in RAG1 and RAG2 create?
SCID (severe combined immunodeficiency) as these genes encode V(D)J recombinase. This leads to non-functional antibodies
How do antibodies multiply so quickly?
Antigen-driven somatic hypermutilation: A range of antibodies are made by the ones with affinity to the antigens survive. This is affinity maturation
Why do B cells mutate 1 million times faster than the background rate?
Mutations are driven by activation-induced deaminase (AID) which is expressed in germinal centres. This leads to hyper mutation
What do somatic mutations do to antibodies?
Usually no effect, but can make the antibody worse, preventing antigen binding
What problems are associated with V(D)J recombination?
Cause double strand breaks. The high DNA damage activates ATR and ATM, phosphorylating CHK1 and CHK2 respectively. This phosphorylates P53, leading to DNA repair/apoptosis
What are T-cell receptors activated by?
Partially degraded antigens on the surface of antigen-presenting cells
When T-cells are activated, what 3 proteins are presented?
(Major histocompatibility) MHC with the foreign antigen
Stimulating ligands
Cell-cell adhesion molecules
How do dendritic cells tolerise T cells?
Present antigens to their MHCs
How is T cell receptor diversity increased?
V(D)J-like recombination and junctional diversification
Explain Candida albicans
Yeast that lives on skin, mouth, gut and vagina
Can become pathogenic and switches from normal to hyphal form when phagocytosed by macrophages
What is Staphylococcus aureus
Gram positive bacteria in upper respiratory tract and skin
Produces protein A in the cell wall which binds to the constant domain of IgGs
Strep throat
Explain how HIV works
RNA lentivirus that infects T-helper cells, dendritic cells and macrophages expressing the CD4 receptor.
T cells attack these cells as they no longer work, weakening the immune system
Explain how type 1 diabetes comes about
Killer T-cells attack β cells in the islets of langerhans in the pancreas
Explain how multiple sclerosis comes about
The immune system attacks proteins in the myelin sheath of neurons
What happens when tumour cells are not killed by the immune system?
NK, CD4+and CD8+ cells cannot destroy the tumour, so it escapes and becomes clinically detectable
Why is the immune system limited fighting cancer?
Immune system does not identify cancer cells as foreign, instead they have tumour specific antigens
Response isn’t always strong enough to destroy cancer cells
Cancers release chemicals that prevent the immune system finding them
What immunotherapies can be used to treat cancer?
Checkpoint inhibitors (to speed up cell replication)
Cytokines to stimulate immune cells
Immunodilators
Vaccines against cancer epitopes or pathogens
Monoclonal antibodies
CAR-T therapy
Explain CAR-T therapy
Patients T-cells are infected with a recombinant virus. A TCR is expressed with a variable domain specific to a tumour antigen, generating T-cells that attach to tumour cells
Outline Graft verses Host Disease
Side effect of heterologous haematopoietic stem cell transplants
Transplanted T-cells attack and kill the host
