Innate Immunity Flashcards
(39 cards)
What are the anatomical components of innate immunity?
1) Physical barriers
2) Chemical barriers
What are the cellular components of innate immunity?
1) Phagocytes
2) Dendritic cells
3) NK cells
What are the soluble proteins involved in innate immunity?
1) Complements
2) Cytokines, Chemokines (mediators)
3) Antimicrobial substance
What are the cells of innate immunity from the myeloid lineage?
1) Macrophages
2) Monocytes
3) Granulocytes
4) Dendritic cells
What granulocytes are involved in innate immunity?
1) Polymorphonuclear leukocytes PMN (multilobed nucleus) - Neutrophils, Eosinophils, Basophils
2) Mast cells
3) NK cells (lymphoid lineage)
What agranulocytes are involved in innate immunity?
1) Monocytes
2) Macrophages
3) Dendritic cells
What are macrophages?
1) Versatile immune cells (monocyte specialisation)
2) Found in various tissues throughout the body
3) Involved in phagocytosis, Ag presentation to activate adaptive immune system + tissue repair
4) May be localised and named based on locations e.g., Kupffer cells (liver), alveolar macrophages (lungs), microglia (CNS), Langhans giant cells in TB
What are monocytes?
1) Larger than most other WBCs
2) Represent 2-10% of total WBC cell count in peripheral blood
3) Have kidney-shaped nucleus
4) Lack granules
5) Serve as scavenger cells
6) Functions - phagocytosis, Ag presentation, immune surveillance (Monitoring tissue damage)
7) Integral to inflammatory response
8) Differentiation into Macrophages and DCs
What are neutrophils?
1) Most abundant innate immune cells in peripheral blood (50-70%) of total WBC
2) Contain large granules that degranulate when they come in contact with Ags and release enzymes that destroy foreign substances - can injure surrounding tissue
3) Debris from destructive action produces exudate/pus
4) Enzymes secreted from granules known as chemotaxic factors - leukotrienes, vasoactive kinins + toxic metabolites
5) ‘Professional’ phagocytes
What are eosinophils?
1) Contain granules
2) Engage in phagocytosis
3) Seem to congregate in respiratory/GI tracts
4) Prominent during allergic reactions and parasitic infections
5) Carry certain enzymes that neutralise chemicals responsible for allergic responses
6) Release potent chemotaxic factors that cause inflammation, bronchospasm + tissue damage
7) PMN typically Bilobed
What are basophils?
1) Less than 1% of total WBC
2) Granules produce histamine + heparin - play a role in immune response
3) Is not a strong structure and is easily damaged which causes granules to release histamine and heparin
4) Vasospasm, increased vascular permeability and increased inflammation are major effects seen when this occurs
5) Reaction increases severity of allergic responses
6) Inflammatory mediators in response to allergen and parasitic infections
What are mast cells?
1) ‘Guardians’ of immune system
2) Found in cutaneous and mucosal tissue
3) Immediately recognise invasive non-self (foreign) Ags without aid of macrophages/lymphocytes
4) Effectors of immediate hypersensitivity reaction and contain most of body’s IgE
5) When IgE and Ag meet, immediate degranulation and release of histamine, prostaglandin, leukotrienes as well as arachidonic acid metabolism - potentiates hypersensitivity response
What are dendritic cells?
1) ‘Professional’ Ag-presenting cells
2) Capture pathogens, process them and present Ags to activate T cells of adaptive immune system
3) Bridge gap between innate and adaptive immune responses
4) Promotes allergy in asthma
5) Kill large parasites
What are natural killer (NK) cells?
1) Are cytotoxic lymphocytes
2) Recognise and kill infected/cancerous cells without prior sensitisation
3) Play critical role in early defense against viral infections and tumour surveillance
What are the functions of innate immune cells?
1) Recognition of Pathogens - pattern recognition receptors (PRRs)
2) Phagocytosis
3) Inflammation - release signalling molecules, initiate and regulate inflammation, more immune cells, tissue repair
4) Activation of Adaptive Immunity - Dendritic cells present
5) Protection against Multiple Pathogens - without requiring prior exposure
What is inflammation?
1) Reaction to injurious agents that consists of vascular response, cellular reaction and systemic reactions
2) Defensive response fundamentally divided into acute inflammation and chronic inflammation
3) 4 types - serous, fibrinous, suppurative (purulent), haemorrhagic
What is the sequence in innate immune response/acute inflammation?
1) Recognition of pathogen/tissue damage
2) Complement activation
3) Release of inflammatory mediators
4) Vasodilation
5) Increased vascular permeability
6) Migration of immune cells
7) Phagocytosis
8) Resolution of infection/tissue repair
9) Resolution of inflammation
10) Tissue repair
11) Return to homeostasis
What are the cardinals of inflammation?
1) Heat (Calor) - Vessel dilation
2) Redness (Rubor) - Vessel dilation
3) Swelling (Tumor) - Accumulation of exudate
4) Pain (Dolor) - Sensory neurons, chemical secretion
5) Loss of function
What do pattern recognition receptors (PRRs) recognise?
1) Pathogen Associated molecular patterns (PAMPs) in microbes
2) Damage Associated molecular patterns (DAMP) on damaged tissues
Results in activation of innate immune cells
What are the 3 pathways complement activation can occur through?
1) Classical
2) Lectin
3) Alternative
What do complement proteins do?
1) Opsonise pathogens, leading to recognition and phagocytosis by immune cells
2) Also contribute to formation of membrane attack complex (MAC)
3) MAC can directly lyse some pathogens
What is the classical pathway for complement cascade?
1) Triggered by Ab-Ag complexes
2) C1 complex (C1q, C1r, C1s) - C1q binds to Fc region causing conformational change activating C1r –> activating C1s (serine protease)
3) C1s cleaves C4 into C4a/C4b where C4b binds to pathogen surface, C1s also cleaves C2 into C2a/C2b where C2a binds to C4b making C4bC2a complex
4) C4bC2a complex = C3 convertase, cleaves C3 into C3a/C3b
5) C3b binds to C3 convertase (C4bC2a) forming C5 convertase cleaving C5 into C5a/C5b
6) C5b initiates MAC including C6, C7, C8 and C9 forming a pore in the membrane of the pathogen - cell lysis
What is the process of the lectin pathway?
1) Triggered by serum lectin binding to sugars
2) MASP (MBL-Associated Serine Proteases) 1 and MASP 2 cleave C4 and C2 forming C4b2a complex
3) C3 convertase cleaves into C3a and C3b, where C3b binds to create C4b2a3b (C5 convertase)
4) C5 convertase cleaves C5 into C5a/C5b - C5b recruits C6, C7, C8 and C9 (MAC - membrane attack complex)
What is the process of the alternative pathway in the complement cascade?
1) For pathogens/apoptotic tissue
2) Hydrolysis (spontaneous ) of C3 makes C3(H2O) binds to factor B (plasma protein) and becomes a substrate for factor D (protease)
3) Factor D cleaves Factor B into Ba/Bb, C3(H2O)Bb acts as fluid-phase C3 convertase cleaving C3 into C3a/C3b
4) The C3b binds covalently and can bind to Factor B which is cleaved by Factor D again forming C3bBb (alternative pathway C3 convertase) stabilised by properdin (positive regulator)
5) When additional C3b is binded to C3bBb, forms C3bBb3b - C5 convertase, cleaving C5 into C5a/C5b
6) C5b initiates MAC (C6, C7, C8, C9)
