Adaptive and Innate Immunity Flashcards
Immune system:
Role
– Protect against infection
– Recover from infection and tissue damage
– Identify somatic changes to self (e.g. cancer)
– Maintain an adequate separation from the organism’s environment
How does the immune system differeniate self vs non self
Molecular Shape
WBC development sites for primary and secondary development
Bone marrow: Primary centre for T and B cell production
- Site for secondary site for B cell maturation
Thymus
- T cells migrate to thymus for T cell maturation
Blood cell development:
Flow chart for all the cell types and their GENERAL function
Stem cell
6 cells (one being megakarocyte)
- B cell
- T cell
- megakarocyte - platlets (packing of clotting factors)
- Basophil
- Eosionphil
- Neutrophil
- Monocyte = macrophage
-phagocytic cells - RBC
-oxygen and Co2
LECTURE SLIDE
Role of primary lymphoid organs
– Where lymphocytes are made:
– Bone marrow (produces B lymphocytes)
– Thymus (produces T lymphocytes)
– Fetal liver (source of stem cells and B lymphocytes)
secondary lymphoid organs
- examples of them
-Role
– Spleen, Lymph nodes, Tonsils, Adenoids, Peyer’s patches, Skin
– They filter and enrich for foreign antigens (lymph nodes for tissues, spleen for blood, Peyer’s patches for gut)
– Lymphocytes formed in the primary organs migrate here to mount immune responses to foreign antigens, can also recirculate in tissues
Tertiary Lymphoid Organs
- Role
– collections of immune cells similar to secondary lymphoid organs
– found in non-lymphoid tissues, function in surveillance and inflammation
Innate vs Adaptive Immunity
- Innate Immunity
– Generally early defenses
– Recognises broad patterns
– No difference with repeated exposure - Adaptive Immunity
– Generally later defenses
– Recognises highly specific antigens
– Result in immunological memory
What does the innate immunity consist of?
- physical barriers to infectious agents
* most infectious agents cannot penetrate intact skin
* especially important defenses at nasopharynx, gut, lungs and genitourinary tract - microbicidal factors in body fluids
* lysozyme
* complement - antiviral proteins (e.g. interferons)
- phagocytic cells (e.g. neutrophils and macrophages)
- NK cells
Examples of biochemical and biophysical defences of innate immune system
Biochemical:
Lysozyme in secretions (eg tears)
Sebacous gland secretions
Commensal organisms in gut and vagina
Spermine in semen
Biophysical
- mucus
- cilia lining resp tract
acid in stomach
Skin
Lymphatic system
- what is the purpose of it?
Fluid from the blood leaks out of capillaries into surrounding tissues:
– hydrostatic pressure in blood vessels (transudate)
– tissue injury leading to acute inflammation (fibrinous exudate)
- Therefore, the body needs a mechanism for collecting this fluid and returning it to the blood stream = the lymphatic system
- A tree-like structure of thin-walled vessels into which fluid can drain from extracellular tissue spaces
- Fluid is ‘pumped’ through the lymphatic vessels by normal muscle activity in the body
How does the lymphatic system and innate immunity relate together?
Afferent lymphatic vessels drain the interstitial fluid from tissues into lymph nodes
- This lymphatic fluid can carry material from infectious agents and from body cells damaged by the infectious process
- Lymph nodes filter material from lymphatic fluid and present it to the immune system
Innate immunity: Complement system
- what is it
-what are the 3 pathways
-each pathways role/process
A non-cellular part of the innate immune system, made up of a “cascade” of proteins (manufactured largely in the liver) and their receptors
- Pathogen killing through the “classical” complement pathway
* Antibodies bind to antigens on a pathogen surface
* The antibodies are then bound by complement components, leading to complement-mediated lysis of pathogen cells by a “membrane attack complex” - Alternative: Direct opsonisation of microbial antigens
* A molecular ‘coating’ that marks pathogens for phagocytosis and killing
* This does not require antibodies - Enhanced recruitment of neutrophils and macrophages
* This enhances acute inflammation
* You may see this referred to as the “lectin pathway” as it involves “lectin” (sugar-binding) molecules that bind to the pathogen surface
Neutrophil functions:
- Acute Inflammation
- Phagocytosis
- Degranulation
- Neutrophil extracellular ‘traps’
What do neutrophils recognise in order to know what to attack
- Broad molecular patterns e.g. in bacterial cell wall components
- C3b component of complement (complement opsonisation)
- The Fc region of antibodies (Ag-Ab complex ‘opsonization’)
Monocytes and macrophages Functions
- Chronic Inflammation
- Phagocytosis
- Cytokine secretion
- Orchestrates ‘repair’ after inflammation
- Antigen presentation during adaptive immune responses
Natural Killer cells:
- function
-examples of cells they attack
- what makes them different?
-what determines if they kill a cell?
Their main role is to kill healthy cells that pose a threat
* e.g. virally infected cells
* e.g. cancer cells
* e.g. antibody-coated cells
- They also secrete cytokines that enhance activity of other immune cells
- They don’t need to be switched on by an antigen
presenting cells (unlike T lymphocytes) - Whether or not they kill a target cell depends on the balance between activating vs inhibitory signals
- Most normal healthy body cells have MHC class I receptors on their surface – these strongly inhibits NK cells. so cells without them will cause activation of NK
Examples of receptors that the innate system uses to create activation
Innate immunity cells are able to recognise broad classes of MOLECULAR PATTERNS
– The Macrophage Mannose Receptor
– CD14 (with other receptors it binds bacterial LipoPolySaccharide complexes)
– Toll-like receptors (in association with other cell surface molecules)
These receptors initiate very rapid responses with no delay
* They induce complex signaling cascades inside cells of the innate immune system, which include signals that then activate the adaptive immune system
What are the two parts of adaptive immunity
AND what are the key parts to each one
Humoral and cell mediated immunity
Humoral:
Products of B cells
Involves AB
Operates against antigens OUTSIDE the cells
- viruses, toxins (stop attachment)
-Extracellular bacteria (enhance phago, activate complement)
Cell mediated
- Product of T cells
- No AB involved
- Operates against antigens INSIDE cells
-virus infecred cells, tumor cells, transplanted organs
Why do we need cellular immunity in adaptive immunity
Viruses grow inside cells
so they are inaccessible to antibodies
T cells:
Types, role and their respective features
CD8 (Cytotoxic)
- Kills cells with foreign intracellular antigens
- has CD8, TCR and CD3 receptors on cell
CD4 (T helper)
- Produce cytokine to assist other responses
CD4, TCR, CD3
What HLA does CD8 and CD4 recognise
CD8:HLA1 on target cell
CD4:HLA2 on target cell
HLA 2 vs HLA 1
HLA1:
B2 microglobulin
- found on ALL NUCLEATED cells
Co-dominant
Polymorphic
Present to CD8
HLA2:
A and B
- Found on APC and B cells
-polymorphic
Present to CD4
Process of CD8 activation
- Recognition of foreign HLA1 in secondary lymphoid organs
- Send cytokines to CD4 for actiavtion of CD4 cells (alarm signals)
- Proliferation and differeniation
- Cytotoxic T cell activation and begin killing the virus infected cells AND creating memory CD8 cells
Process of CD4 activation
- CD4: HLA2 on APC in secondary lymphoid organ
- Send cytokines to CD4 for actiavtion of CD4 cells (alarm signals)
- Proliferation and differeniation
- Helper T cell activation and begin secreting cytokines to regulate other immune responses (eg CD8 cells) AND creating memory CD8 cells
Antibody structure
Antigen binding site
Fc region
Heavy chain
Light chain
Disulfide bonds
Lecture Slide
What determines if a cell can differentiate between self and non self when maturing
the affinity (binding strength) of the Ab to the presented Ag epitope
Too strong = killed
No reaction = killed
Medium/low = kept
Examples of how antibodies contribute to the immune response
- Neutralisation
- Chemotaxis
- Opsonisation causing enhanced
phagocytosis - Antibody-dependent
killing/cytotoxicity - Trigger the ‘Classicalpathway’ of the
Complement Cascade (ag-ab complexes)
Lecture Slide
Diagram showing Antigen Receptors and Lymphocyte Activation
Lecture Slide
Examples of Over-reactive or Reduced T cell Immunity
- Allergy (strong ab response of a particular Ig class, IgE, against a relatively innocent stimuli
- A immune reaction that is TOO strong causes pathological damage to bystander host tissues (Hep B)
- Antigen-antibody complexes produced in high concentrations -> lodge in small vessels -> activate complement system -> cause vascular damage (vascular inflammation or vasculitis)
- The immune system begins to cross-react to normal components of the body as if they were abnormal components (rheumatic fever)
