Intro to immunology Flashcards
Normal immune system is made up of these 3 things….
Physical barriers
Innate immunity
Adaptive immunity
Physical barriers
Saliva - lysozyme - IgA - IgG - lactoferrin Mucociliary escalator Gastric acid Normal flora Physical flushing - urinary tract
Examples of consequences of breached defences
Xerostomia
C diff infection
Cystic fibrosis
Burns
Features of innate immunity
Rapid
Already present at birth
No memory - same response with re-exposure
Some specificity
What does innate immunity detect?
Alteration from homeostasis
- damage recognition - host
- pathogen recognition - pathogen
Where is the innate immunity found?
Within tissues
Within blood
Cells of the innate immunity
NK cells basophils Neutrophils eosinophils Monocytes Platelets Macrophages Dendritic cells Mast cells
Mechanisms of innate immunity
Inflammation Recruitment of immune cells Activation of complement Opsonisation Phagocytosis NK cytotoxicity
What do cytokines do?
Regulate the nature, duration and intensity of the immune response
Form a method of communication between components of the immune system
Bind to specific receptors on target cells
What predominately produces cytokines?
Macrophages
T helper cells
Two types of cytokines
Pro-inflammatory - TNF-a - IL-1 - IL-6 - Chemokines Anti-inflammatory - IL-10 - TGF-B
Pro-inflammatory cytokines cause…..
Fever
Recruit and activate other immune cells
vasodilation
What does IFN-y activate?
Macrophages
What does IL-3, IL-4, IL-5 and IL-13 activate?
Eosinophils
Mast cells
What does IL-4, IL-5, IL-6 and IL-21 activate?
B cells
What does IL-2, IL4, IL-12 and IFN-y activate?
T cells
What causes inflammation of the innate immune system?
Detection of ‘foreign’ / breach in defences by pattern recognition receptors (PRRs)
Features of inflammation and what causes each
Vasodilation - NO - Bradykinin - prostaglandins - TNF-a, IL-1 Increased vascular permeability - histamine - nitric oxide - leukotrienes Increased cell adhesion molecules - TNF-a, IL-1 Chemotaxis - CXCL-8 - neutrophil recruitment into the area Increased sensitivity to pain - bradykinin
Activation of complement
Activation of C3
- activated by
- alternative (pathogens)
- classical (combination of own antibodies bound to foreign antigens)
- lectin (free floating proteins in body attaching to pathogens)
Splits into C3a and C3b
- C3b splints into C5a and C5b
- C3a and C5a - anti-inflammatory toxins or protein which will affect mast cells to degranulate
C3a = inflammation C5a = chemotaxis
What is C5b?
Membrane attack complex
Activity of complement
- Chemotaxis of phagocytes to sites of inflammation
- C3a, C5a - Opsonisation
- C3b, C4b
- preparation for eating (reduces repellent negative cell charge and increases no of binding sites for phagocytes) - Lysis of micro organisms
- C5b-9 complex - Maintain solubility of Ag / Ab complexes
- C3b, C4b, C2
Main opsonins
Complement C3b, C4b
Antibodies
Plasma proteins - mannose binding lectin
Phagocytosis is done against what?
Extracellular pathogens
Two receptors on NK cytotoxicity
Activation
- if foreign pathogen / damaged cell
Inhibitory
- if normal cell
Features of the adaptive immune system
Specific Delayed Immunological memory - faster responses to known antigen Humoral - antibody mediated - B lymphocytes Cell mediated - T lymphocytes
Two types of cells in the adaptive immune system
B cells (can lead to plasma cell) T cells
Where do B cells mature?
Bone marrow
Where do T cells mature?
Thymus
Where do B and T cells migrate to once matured?
Secondary lymphoid organs where they encounter antigens
What is an antigen?
A molecule capable of producing an immune response
Specificity of B cells - B cell receptor
Antibody attached to B lymphocyte
Specificity of T tells - t cell receptor
Within the T cells
T cell recognition of an antigen
Require presentation of antigen via MHC
- CD4+ given by MHCII (antigen presenting cell e.g. macrophages)
- CD8+ given by MCHI (all nucleated cells and platelets)
B cell recognition of an antigen
Recognise antigens directly via BCR (B cell receptor)
What is CD4+ given by and where is this found?
MCHII
antigen presenting cell e.g. macrophages
What is CD8+ given by and where is this found?
MCH1
all nucleated cells and platelets
Processing of MHC1
Intracellular pathogens
Presented to MHC1 and highlights this to the immune system
Processing of MHC2
extracellular pathogens
What is an antibody?
A glycoprotein produced by B lymphocytes that binds antigens with a high degree of specificity and affinity
Two types of immune tolerance
Central tolerance
Peripheral tolerance
Central tolerance T cells types - thymus
Positive selection - can T cells recognise MHC? - if cant = destroyed Negative selection - does T cell interact too strongly with self antigens via MHC? - if cant = destroyed
Central tolerance B cells types - bone marrow
Self reacting BCR?
- if yes = destroyed
Features of peripheral tolerance
Monitoring of lymphocytes within secondary lymphoid organs and circulation
Regulatory T cells
What do regulatory T cells do?
Recognise and destroy self reaction lymphocytes
Cytotoxic CD8+ cells release what?
IFN-y and TNF-a
Cytotoxic granules
ALSO
- apoptosis via FasL-Fas interactions
Perforin + granzyme = what/
Apoptosis of target cell
What happens in perforin induced apoptosis?
Release of perforin and granzyme
Perforin creates a hole/pore in cell membrane allowing granzyme to enter cell
triggers apoptosis
What do helper T cells do? (CD4+)
Release cytokines to 'help' the activity of other immune cells Promote B cell antibody class switching e.g. IgM to IgG
Types of helper T cells (CD4+)
Th1
Th2
Th17
Th1 features
Intracellular pathogens
- maximise macrophage and CD8+ activity
- release IFN-y
- inhibit TH2 response
Th2 features
Extracellular pathogens
- release IL-4, IL-5, IL-13
- activate mast cells, basophils, eosinophils
- class switching to IgE
- inhibit Th1 response
Th17 features
Extracellular pathogens
- PRO INFLAMMATORY
- recruit neutrophils and macrophages via CXCL-8
What do regulatory T cells do?
Suppress CD4+ and CD8+ T cells
Control the response to self antigens
Secrete IL-10 and TGF-B
What do IL-10 and TGF-B do?
Anti-inflammatory
Suppress the immune response
B cells have humoral immunity via what?
Antibodies
- FAB region - binds to antigen
- FC region - communicates with immune cells
Immunoglobulin isotypes of B cells
Different heavy chains = different function IgM IgG IgA IgE IgD
What is IgM best at?
Activating complement
What can IgG do?
Cross the placenta
What happens to IgA?
It is contained in secretions
Features of IgE
Parasitic infections
Allergy
What are antibodies produced by?
B lymphocytes - plasma cells
Antibody mediated immunity phases
- Lag phase
- take a while for the specific immunity to kick in - If re-exposed
- Very quick and very high risk in IgG
What is B activation done by?
T helper cells
Functions of antibodies
Immune complex formation
Opsonisation
Activating the cascade complement
Antibody dependent cellular cytotoxicity (ADCC)
What does antibody dependent cellular cytotoxicity do?
Binds to target cells and initiates a non-phagocytic cell mediated destruction
Normal variation in immune function is seen in….
Pregnancy
Neonates
Elderly
Differences in an elderly persons immune function
Thymic involution Fewer naïve T cells Reduced ability for T cell expansion Reduced B cell development and diversity - diminished response to vaccination More dependent on innate immunity
Causes of secondary immune deficiency
Malnutrition - protein calorie malnutrition - zinc - iron Trauma Burns HIV DM renal failure asplenia malignancy Splenectomy Drugs - immunosuppressive, antirheumatic, antiepileptic, glucocorticoids, ciclosporin
Molecules of the innate immune system
Complement
Interferon
Cytokines
Acute phase reactant
Receptors of the innate immune system
Pattern recognition receptors
- toll like receptors
- mannan-binding lectin
Molecules of the adaptive immune system
Immunoglobulins
Cytokines
Receptors of the adaptive immune system
TCR
BCR
MHC/HLA
What does TCR stand for?
T cell receptor
What does BCR stand for?
B cell receptor
