L2 Immunity and immune systems Flashcards
Vaccinations
Stimulating immune responses against microbes through vaccination
Immunity meaning
all mechanisms used by the body as protection against environmental agents that are foreign to the body
Immune system must differentiate between individual’s own cells and what?
other molecules
What mediates the protective immunity against microbes
Protective immunity against microbes is mediated by the early reactions of innate immunity and the later responses of adaptive immunity
Cellular components of the innate immune system
epithelial barriers and leukocytes (e.g., neutrophils, macrophages, NK cells)
Adaptive immunity is specific and increased by repeated exposures to antigen (immunologic memory)
A memory cell is an antigen-specific…
B or T lymphocyte that doesn’t differentiate into effector cells during primary immune response, but does immediately become effector cells upon re-exposure to the same pathogen.
Humoral immunity is mediated by ____ and cell- mediated immunity is mediated by ___
Antibodies secreted by B lymphocytes
T lymphocytes and their products (e.g., cytokines)
Functions of the immune response
Immune recognition
Immune effector functions
Immune regulation
Immunological memory
Immunological recognition:
presence of an infection must be detected (by the innate and adaptive
immune systems)
Immune regulation
Limits damage to the host bu immune response to antigen (molecule capable
of inducing an immune response).
Failure of immune regulation
contributes to disease states including allergy and autoimmune disease (self-destroying)
Immunological memory
exposure to an infectious agent produces an immune response that can persist, and protect the host in a subsequent exposure
Direct mechanism of tissue damage by pathogens
- Exotoxin production
- Endotoxins
- direct cytopathic effect
Indirect mechanism of tissue damage by pathogens
- Immune complexes
- Anti-host antibodies
- Cell mediated Immunity
Whats in common? Interstitial spaces, blood, lymph
Extracellular
Whats in common? Cytoplasmic and vesicular
Intracellular
Defence is mediated by coordinated responses of what two immunities
Innate and adaptive
Innate meaning
Natural; recognised by preformed non specific effectors
Adaptive meaning
Specific; Stimulated by exposure to pathogens, capable of adapting magnitude and defense capabilities.
What immunity from 0-12 hours after infection
Innate
What immunity from 1> days
Adaptive
Immune responses are mediated by a variety of cells:
- Haematopoietic stem cells (HSCs) give rise to red and white blood cells
- First division: myeloid/erythroid vs lymphoid potential, then cells with progressively more limited potential
- Colony-stimulating factors (CSFs) and interleukins affect differentiation and maturation
Immune responses are mediated by a variety of cells: name 2
Common myeloid progenitor
Common lymphoid progenitor
Both differentiated from hematopoietic stem cells
Myeloid lineage – first responders?
- Macrophages
- Neutrophils
- Basophils
- Dendritic Cells
- Eosinophils
- Mast cells
Macrophage
- Phagocytosis and activation of bacterialcidal mech.
- APC
- Cytokine production
Neutrophil
- Phagocytosis and activation of bacterialcidal mech.
Basophil
- Promotes allergic repsonse
- Augmentation of anti-parasitic immunity
Dendritic cell functoin
- Antigen uptake in peripherals
- APCs
- Cytokine production
Eosinophils
Kill antibody coated parasites
Mast cell
Release granules contraining histamine and active agents
Lymphoid lineage
- Adaptive immune response
- B/T cells, natural killers and innate lymphoid cells
- B/T cells differ by surface proteins (cluster of differentiation)
Humoral immunity
where antibodies prevent infection and eliminate extracellular microbes
* B-lymphocytes
Adaptive
Cell-mediated immunity
- Phagocytosed in macrophage and helper-t-cells + cytokines to kill ingested microbe
- Intracellular microbe in infected cell > Cytotoxic CD8+ kill cell and eliminate reservoirs of infection
Adaptive
Diversity in B/T cells
B and T cells populations express antigen-specific receptor and use very large stock of specific antigen receptors
Specificity
All antigen-specific receptors on an individual cell’s surface are identical in structure, therefore, are identical in their specificity.
B/T clones
When a particular B or T cell divides all of this progeny (decendants) will be identical
Memory from specificity
Specificity of response allows generation of immunological memory - this can be artificially induced by vaccines
Finish this
Naive -> effector -> ?
memory
Contraction and homeostasis in immune repsonse
Prevents host injury during response to foreign antigen
Properties of adaptive immune response
- Antigen exposure (Recog)
- APCs to naive cells (Recog)
- Clonal expansion (Lymfo act)
- Differentiation (Lymfo act)
- Antibodies and effector Tcells (Elimin)
- Apoptosis (Contraction)
- Memory cells (Memory)
The secondary immune response
Re-exposure to previously recognised antigen reactivates memory cells, which rapidly control replication of the pathogen
Vaccine Aim
The aim of vaccination is to induce memory cells to the
pathogen of interest, which can be reactivated when the host
encounters that pathogen
Lymphoid lineage – B cells
- Each B cell expresses a B cell receptor (BCR) – membrane bound immunoglobulin – with a unique specificity (identical antigen binding sites)
- Activated B cells can act as professional antigen presenting cells (APC) (present antigen and co-stimulatory molecules to T cells)
- Effector B cells are called plasma cells – antibodies-producing cells
Effector bcells are also called
Plasma cells
BCRs are
Membrane bound immunoglobins
Each T cell expresses a T cell
receptor (TCR)
Lymphoid lineage – T cells
– recognises only
processed pieces of antigens
bound to cell membrane proteins
– Major Histocompatibility
Complex (MHC) molecules
Red and white blood cells arise from where
stem cells in the bone marrow
2 primary lymphoid organs
B cells in the bone marrow and T cells in the thymus
secondary lymphoid organs
lymph nodes, spleen and lymphoid tissues associated with mucosa
Pri and secondary lymph organs and cells
- Lymphocytes differentiate in central lymphoid organs – B cells-bone marrow and T cells - thymus
- These cells encounter antigens and initiate an immune response in secondary lymphoid organs and tissues
– lymph nodes, spleen and lymphoid tissues associated with mucosa
Haematopoiesis stem cells
originate in foetal tissues and, in adults, reside primarily in the bone marrow of the axial skeleton (cranium, sternum, ribs, vertebrae and ilium)
Bone marrow function
production of blood cells, maintenance of HSCs, and modulation of skeletal remodelling
Haematopoiesis characteristics
- self-renewal
- pluripotency
There are multiple subpopulations of HSCs, with varied quiescent state and self-renew capacity
Thymus and thymocytes
- Thymocytes develop in the bone marrow mature in the thymus, and become T cells
- Migrate to peripheral lymph organ for activation
look at this
In humans atrophy begins at puberty and continues throughout life - likely that T cell generation within thymus does continue into adult life, at a much lower rate
look
Lymph nodes location and role
Located along lymphatic vessels and are the sites of cellular interactions and extensive immunologic activity
Lymph in lymph node
- Lymph enters the lymph node through afferent lymphatic vessels
- Percolates (filters) through & around follicles, made up of B/T –cell zones in the node.
- Leaves through efferent lymphatic vessels
What happens after APC captures antigen?
Antigen-presenting cells that have captured antigen by phagocytosis migrate to lymph nodes and present antigens to T cells that have not yet seen been activated
Lymph nodes are rich in what cell?
Lymph nodes also are rich in macrophages, which can remove antigens in the lymphatic fluid by phagocytosis
Secondary Lymph organ
Spleen functions
- Traps and responds to blood-bourne antigens
- Antigens and lymphocytes carried to spleen via the splenic artery
No not by lymphatic vessels
Spleen: red pulp
Sinuses containing macrophages that phagocytose aged/abnormal erythrocytes; recycling iron; and removal of microorganisms from the bloodstream
* Like a filtre removing waste from blood
Spleen: white pulp
- Lympho tissue around central aterioles
- Has B-cell follicles and periarteriolar lymphoid sheath (PALS), which is populated by T cells
Which organ can remove encapsulated bacteria such as pneumococcus, meningococcus and Haemophilus ssp
The spleen is particularly effective at removing encapsulated bacteria.
Mucosal-associated lymphoid tissue includes
MALT includes
* Gut-associated lymphoid tissue (GALT)
* Bronchus-associated lymphoid tissue (BALT)
* Nasal-associated lymphoid tissue (NALT)
* SALT – skin-associated
lymphoid tissue
Immunopathology
autoimmune diseases and hypersensitivity
Immunopathology examples
- Multiple sclerosis, type I diabetes
- Rheumatoid arthritis, allergy, systemic lupus erythematosus, celiac disease