10 - Intro to Clinical Immunology Flashcards
Immunity
- Ability to protect ourselves from disease
- Recognition & removal of foreign material entering body
- Relies on ability to distinguish between self and non self
- Can be innate or acquired
Immunology
Study of cells, organs, molecules responsible for immunity and how they respond and interact
Why do we need the innate immune system
- Microbes multiply at very high rates, overwhelming infection can occur quickly
- Need a broad system that detects infection rapidly
- Covers the time taken for adaptive immunity to be generated
Diseases caused by extracellular bacteria, parasites, fungi
- Pneumonia
- Tetanus
- Sleeping sickness
Diseases caused by intracellular bacteria and parasites
- Leprosy
- Leishmaniasis
- Malaria
Diseases caused by intracellular viruses
- Smallpox
- Flu
- Chickenpox
Diseases caused by extracellular parasitic worms
- Ascariasis
- Schistosomiasis
Physical components of innate immunity
- Tight junctions
- Keratin
- Mucus assisted by cilia and peristalsis
- Antimicrobial chemicals (defensins)
- Intraepithelial T cells (small number of common microbes
Cellular components of innate immunity
- Macrophages
- Neutrophils
- Dendritic cells
- NK cells
- Mast cells
NK Cells
lymphocyte-like cells capable of killing virus infected and tumour cells without the specificity of true lymphocytes
Soluble components of innate immunity
- Several molecules that recognize/respond to microbes and
promote innate responses exist in soluble form in blood - Provide early defense against pathogens present outside host cells at some stage of their life cycle
- Complement, cytokines, chemokines, defensins, acute phase proteins
What are the two major ways soluble components function
- Bind to microbes & act as opsonins to enhance phagocytosis by macrophages, neutrophils & dendritic cells
- Promote inflammatory responses that bring more phagocytes to sites of infections and may also directly kill microbes
What does innate immunity recognise
- Molecular structures that are produced by microbial
pathogens (often shared by classes of microbes) - Endogenous molecules that are produced by or released
from damaged and dying cells
Molecular structures that are produced by microbial
pathogens
- Pathogen associated molecular patterns (PAMPS)
- Essential for survival of microbes (ensures the target of the immune response can’t just be discarded by the microbe to evade recognition)
Endogenous molecules that are produced by or released
from damaged and dying cells
- Damage associated molecular patterns (DAMPs)
- Produced as a result of cell damage caused by infection
- Also produced in response to sterile injury to cells (chemical toxins, burns, trauma or low blood supply)
- Generally not released by cells dying from apoptosis
How are PAMPs and DAMPs recognised
Pattern Recognition Receptors (PRR)
Pattern Recognition Receptors (PRR)
- Most cell types express PRR and are capable of participating in innate immune respones
- Phagocytes & dendritic cells express the widest variety and greatest amount of these receptors
- When these receptors bind PAMPs and DAMPs they activate signal transduction pathways that promote antimicrobial and proinflammatory functions of the cells in which they are expressed
Where are PRR’s found
Expressed on cell surfaces, in phagocytic vesicles and in the cytosol of cells
Effector mechanisms of innate immunity
- Inflammation
- Antiviral defence
- Stimulation of adaptive immunity
Interferons (IFNS)
Induce expression of enzymes that block viral replication through inhibition of viral protein synthesis, degradation of viral RNA, and inhibition of viral gene expression and virion assembly
Stimulation of adaptive immunity
- Signal 1: microbial antigen
- Signal 2: Molecule induced by innate response (costimulater, complement fragment)
Adaptive immune system
- Key cells and T and B lymphocytes
- Provides diversity (can respond to a large variety of specific antigens)
- Takes longer than innate but provides long term memory
Types of adaptive immunity
Humoral and cell mediated immunity
Humoral immunity
- Mediated by secreted antibodies
- Defence against extracellular microbes
- Antibodies recognise microbial antigens, neutralise their infectivity and target microbes for elimination
- Antibodies are specialised → activate different effector functions
Cell mediated immunity
- Mediated by T cells themselves & their products (cytokines)
- Defence against intracellular microbes
Phases of adaptive immune responses
- Antigen recognition
- Lymphocyte activation (clonal expansion and differentiation)
- Antigen elimination (antibodies and effector T cells)
- Contraction (apoptosis )
- Memory
Signals for T cell activation
Signal 1: presentation of the antigen by an APC (CD4 and CD8 co-receptors on T cells stabilise interaction of TCR and MHC/peptide)
Signal 2: Dendritic cell presents B7 (CD80/CD83) to T cells (CD28 receptor)
Signal 3: Release of cytokines by APC and T cells themselves (IL-2), driving T cell proliferation, survival and differentiation
CD4 cells
Helper T cells
CD8 cells
Cytotoxic T cells
what shows antigen to CD4 T cells
MHC Class 2 present peptides to CD4 T cells
what shows antigen to CD8 T cells
MHC class 1 present peptides to CD8+ T-cells
T cell subsets
- Cytotoxic T cells
- Regulatory T cells (Treg)
- T helper cell
- Tfh
- Th1
- Th2
- Th17
Cytokine released, target cells, host defence and role in disease of Th1 cells
- IFN-gamma
- Macrophages
- Autoimmunity, chronic inflammation
Cytokine released, target cells, host defence and role in disease of Th2 cells
- IL4, 5 and 12
- Eosinophils
- Parasites
- Allergy
Cytokine released, target cells, host defence and role in disease of Th17 cells
- IL17 and 22
- Neutrophils
- Extracellular pathogens
- Autoimmunity
Cytotoxic T cell responses
Eliminate intracellular microbes by killing infected cells
How are B cells activated
- Recognise antigen in its intact, native conformation and do not require antigen to be processed by APC or
presented in MHC molecules - Antibody molecules expressed on the
surface of the B cell act as the B cell receptor (BCR) - Secondary signals promote increased activation and signalling
- Once activated, B cells differentiate into plasma cells that secrete antibody molecules
Different types of antibodies
IgA, IgE, IgD, IgM, IgG
Neutralisation
A) Antibodies prevent the binding of microbes to cells and so inhibit infection
B) Antibodies inhibit the spread of microbes from an infected cell to adjacent uninfected cells.
C) Antibodies block the binding of toxins to cells and thus inhibit the pathologic effects of the toxins.
Opsonisation
- Antibodies of certain IgG subclasses bind to microbes and are then recognised by Fc receptors on phagocytes.
- Signals from the Fc receptors enhance the recognition and ingestion by phagocytic cells
Central tolerance
Mechanism by which immature T or B cells that recognise self antigens are deleted during development in the thymus (T cells) or bone marrow (B cells)
Peripheral tolerance
mechanism by which mature T cells or B cells that recognise self antigens in peripheral tissues are rendered incapable of subsequently responding to those antigens
