Introduction to Immunology Flashcards
What are the 3 components of immunity?
-Physical barriers -Innate immunity -Adaptive immunity
What physical barriers are there?
-Skin and epithelial mucosa -Secretions -Gastric acid -Normal flora -Physiological -Physical flushing of urinary tract
What secretions provide a barrier to infection?
-Sweat -Tears -Gastric acid -Sebaceous glands -Mucous -Breast milk
What are the protective components of saliva?
-Lysozyme: digests proteoglycan in bacterial walls -IgA: prevents attachment of microbes and may neutralise microbes insitu -IgG -Lactoferrin: sequesters free iron and has direct antimicrobial effects
How can commensal bacteria prevent infection?
-Compete for nutrients -Prevent attachment -Release fatty acids and antibacterial proteins -Prevent invasion
What do lactobacilli in the vagina do?
Cause acidic pH (4-4.5)
What physiological responses prevent infection?
-Temperature (fever) -pH -Location of immune cells within the bloodstream
Give examples of conditions where there is breached defences to infection.
-Burns, xerostomia -Cystic fibrosis -C. difficile
Why can burns lead to infection?
Allow pathogens access and more optimal growing conditions
Why can CF lead to infection?
Increased viscosity of mucous reduces the ability of the cilia to clear infections allowing damage to the lungs to occur
Why can C.diff lead to infection?
Increase in bacteria due to abnormal flora which can lead to toxic megacolon
What cells are involved in the innate immune system?
-Mast cells -NK cells -Basophils -Neutrophils -Eosinophils -Monocytes -Macrophages -Dendritic cells
What molecules are involved in the innate immune system?
-Complement -Interferon -Cytokines -Acute phase reactants
What receptors are involved in the innate immune system?
Pattern recognition receptors -Toll like receptors -Mannan-binding lectin
What molecules are involved in the adaptive immune system?
-Immunoglobulins -Cytokines
What cells are involved in the adaptive immune system?
-T cells -B cells
What receptors are involved in the adaptive immune system?
-T cell receptors -B cell receptors -MHC/HLA
What are the mechanisms of the innate immune system?
-Inflammation -Recruitment of immune cells -Activation of complement -Opsonisation -Phagocytosis (and endocytosis) -NK cytotoxicity
What are the features of the innate immune system?
-First line of defence -Rapid -Already present at birth -Some specificity -No memory – same response with re-exposure -Detects alteration from haemostasis
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 produces cytokines?
Predominantly macrophages and T cells
Give examples of pro-inflammatory cytokines.
-TNF-a -IL-1 -IL-6 -Chemokines
What is involved in the inflammatory response?
-Fever -Vasodilation -Recruit and activate other immune cells -Increase glucocorticoids leading to stress hyperglycaemia (also decrease in inflammatory response)
Give examples of anti-inflammatory cytokines.
-IL-10 -TGF-B
What cytokines activate macrophages?
IFN-y
What cytokines activate eosinophils and mast cells?
-IL-3 -IL-4 -IL-5 -IL-13
What cytokines activate B cells?
-IL-4 -IL-5 -IL-6 -IL-21
What cytokines activate T cells?
-IL-2 -IL-4 -IL-12 -IFN-y
What cytokines act on bone marrow to increase leukocyte production?
-Gm-CSF -IL-3
What is inflammation a result of?
-Detection of foreign/breach in defences by pattern recognition receptors
What causes vasodilation?
-Nitric oxide -Bradykinin -Prostaglandins -TNF-a -IL-1
What causes increased vascular permeability?
-Nitric oxide -Leukotrienes -Histamine
What causes increased cell adhesion molecules?
-TNF-a -IL-1
What causes chemotaxis?
CXCL-8
What causes increased sensitivity to pain?
Bradykinin
What are the 3 complement pathways?
-Classical -Lectin -Alternative
What complement components are involved in chemotaxis of phagocytes to site of inflammation?
C3a C5a
What complement components are involved in opsonisation?
C3b C4b
What complement components are involved in lysis of micro-organisms?
C5b-9 complex
What complement components are involved in maintaining solubility of Ag/Ab complexes?
C3b C4b C2
What is opsonisation?
Preparing for eating -Reduces repellent negative cell charge -Increases no. of binding sites for phagocytes
What are the main opsonins?
-Complement C3b, C4b -Antibodies -Plasma proteins – mannose binding lectin
Briefly describe phagocytosis.
-Endocytosis -Enzyme destruction of pathogen -Exocytosis of waste products -Extracellular pathogens
When does NK cytotoxicity occur?
If reduced MHC I expression leads to inhibition and destruction of cell
What are the features of the adaptive immune system?
-Specific -Delayed -Immunological memory -Faster responses to known antigen
What are the divisions of the adaptive immune system?
Humoral -Antibody-mediated -B lymphocytes Cell-mediated -T lymphocytes
Where do lymphocytes mature?
-T cells in the bone marrow and thymus -B cells in the bone marrow -B and T cells then migrate to secondary lymphoid organs, where they encounter antigen
Antigen
A molecule capable of inducing an immune response
Antibody
A glycoprotein produced by B lymphocytes that binds antigens with a high degrees of specificity and affinity
How do lymphocytes with diverse antigen binding sites arise?
Genetic changes
How do T cells recognise antigens?
Require presentation of antigen via MHC -CD4+: MHCII -CD8+: MHCI (all nucleated cells and platelets)
How do B cells recognise antigens?
Recognise antigen directly
What type of pathogens do MHCI process?
Intracellular
What type of pathogens do MHCII process?
Extracellular
What central tolerance do T cells undergo?
In the thymus -Positive selection: can T cells recognise MHC? -Negative selection: does T cell interact too strongly with self-antigens via MHC?
What central tolerance do B cells undergo?
In the bone marrow -Self-reacting BCR
What is peripheral tolerance?
-Monitoring of lymphocytes within secondary lymphoid organs and circulation -Regulatory T cells recognise and destroy self-reactive lymphocytes
What do cytotoxic T cells do?
Release IFN-y and TNF-a -Direct anti-viral and anti-tumour effects Release cytotoxic granules: - Perforin + granzyme = apoptosis of target cell Apoptosis also via: -FasL-Fas interactions
What is perforin induced apoptosis?
-MHCI binds to CD8 -Release of perforin and granzyme -perforin creates a pore in the cell membrane -Granzyme enters the cell and triggers apoptosis
What do help T cells do?
-Release cytokines to ‘help’ the activity of other immune cells -Promote B cell antibody class switching e.g. IgM to IgG
What do Th1 cells do?
Intracellular pathogens -Maximise macrophage and CD8+ activity -Release IFN-γ -Inhibit TH2 response
What do Th2 cells do?
Extracellular pathogens -Release IL-4, IL-5, IL-13 -Activate mast cells, basophils, eosinophils -Class switching to IgE -Inhibit Th1 response
What do Th17 cells do?
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-β (anti-inflammatory and suppresses immune system)
What does the FAB region of Ig bind to?
Antigen
What does the Fc region of Ig bind to?
Communicates with immune cells
What Ig is best at achieving complement?
IgM
What Ig can cross the placenta?
IgG
What Ig is contained in secretions?
IgA
What Ig is involved in parasitic infections and allergy?
IgE
How does antibody mediated immunity vary with time?
Immunity increases with each exposure
What are the functions of antibodies?
-Immune complex formation -Opsonisation -Activating the cascade complement (classical) -Antibody dependent cellular toxicity (ADCC) (bind to target cells and initiate a non-phagocytic cell-mediated destruction)
What factor produces normal variation in immune function?
Age
How does ageing affect immune function?
Elderly -Thymic involution -Fewer naïve T cells – dependent on memory T cells -Reduced ability for T cell expansion -Reduced B cell development and diversity (Diminished response to vaccination) -More dependent on innate immunity (But reduced function of pattern recognition receptors and superoxide killing)
What cause secondary immune deficiency?
Environmental -Malnutrition, trauma, burns Disease -Infection, diabetes, renal failure, asplenia, malignancy Iatrogenic -Splenectomy, drugs
What drugs can cause immunodeficiency?
-Immunosuppressant’s -Anti-rheumatics -Anti-epileptics
Why is there immunodeficiency in HIV?
Virus binds to CD4+ cells to gain entry -T helper cells -Immune deficiency due to reduced CD4+ T helper cell function: - B cells, NK, CD8+, macrophage activity
What proteins are affected in protein-calories malnutrition?
-Cytokines -Acute phase reactants -Chemokines
What is deficient in zinc malnutrition?
-PMN -NK -Monocytes -B and T cells have impaired function
What is deficient in iron malnutrition?
-Enzymes within cellular function and metabolic pathways -Impaired innate immune function
What is zinc essential for?
Proliferating cells
What is ciclosporin?
Calcineurin inhibitor: reduced inflammatory cytokine release from T cells-
What does rituximab do?
-Binds to CD20 (B lymphocytes) -Allows NK and complement mediated apoptosis
What do glucocorticoids do?
Anti-inflammatory -Activate lipocortins: reduce phospholipase A2 and arachidonic acid release -Alter transcription of enzymes needed for inflammation
How are B cells activated by Th cells?
-Anigen binds to B cell via BCR -MHCII detects extracellular pathogen and binds to Th which activates B cell Leads to: -Proliferation of B cells -Production of memory B cells -Formation of plasma cells (production of free antibody specific to antigen) -Neutralisation -Opsonisation
What triggers the classical complement pathway?
Immune complexes (Ab-Ag)
What does the lectin complement pathway start with?
Mannose binding lectin
What triggers the alternative complement pathway?
C3b directly binding to a microbe
Can you name the differences between the innate and adaptive immune responses?
Innate immune response
- rapid
- already present at birth
- some specifity
- no memory - same response with re-exposure
- detects alterations
Adaptive immune response
- delayed
- immature at birth
- highly specific
- good memory - faster response to known antigens
- humoral and cell mediated
How do macrophages, mast cells and dendritic cells recognise cells as foreign?
Pattern recognition receptors
Functions of the innate immune system
- Inflammation
- Recruitment of immune cells
- Activation of complement
- Opsonisation
- Phagocytosis
- NK cytotoxicity
Unfortunately, macrophages do not find it easy to kill Mtb once they have engulfed it, why?
Mtb has a waxy coat and secretes catalase which inhibits phagocytosis. Macrophages struggle to kill them and just seal them off in phagosomes.
What other immune functions do macrophages and dendritic cells have?
Antigen presentation to T cells via MHC II and MHC I
