Lecture 9.2: Adaptive Immunity Flashcards
Adaptive Immunity
• Immunity established to adapt to infection
• Learnt by experience.
• Confers antigen-specific immunity
• Enhanced by second exposure
• Memory
• Ineffective without innate immunity
Types of Adaptive Immunity (2)
Humoral
Cell Mediated
Adaptive Immunity: Humoral and Cell-Mediated
• Mediated by T and B lymphocytes, NKT cells
• Provides defence against both intracellular and extracellular antigens
Adaptive Immunity: Humoral
• Antibodies produced by B lymphocytes (circulation and mucosal fluids)
Adaptive Immunity: Cell-Mediated
• Phagocytes are activated
• Cytotoxic T cells interact with pathogenic cells
How do T and B cell specificities differ?
• T cells only recognise proteins
• B cells recognise proteins, carbohydrates, nucleic acids
Natural Killer T Cells
• Recognise IgG, lipids, MHC class I, secrete cytokines (IFN, TNF, IL12)
• Kill tumour cells and virally infected cells
• Induce apoptosis by pumping proteases through target cell membrane
• Like DC cells, NKT cells determine the type of adaptive response
What does CD stand for?
Cluster of Differentiation
T-Cells: CD8+
Cytotoxic
T-Cells: CD4+
Helper
What does Antigen Recognition rely on?
It relies on presentation of antigens by cells of the innate immune system
Antigen Recognition
• Antigen presenting cells (APCs) take up antigen (peptide fragment presented)
• Cells divide, form clones of cells that respond to antigen (clonal selection)
Effector Cells and Negative Selection
Effector cells subject to negative selection (autoimmune disease) where cells expressing ‘self’ are destroyed
How is antigen repertoire developed?
Repertoire develops without exposure to antigen through stem pcell differentiation
Repertoire present before encounter with antigen
Naive T Cell
A T cell that has matured and been released by the thymus but has not yet encountered its corresponding antigen
Express antigen receptors
Do not eliminate antigen
Effector Cell
Differentiated progeny of naive cells after antigen exposure
Cells produce molecules to eliminate antigen
Memory T and B cells
Following antigen exposure, activated T and B cells persist as memory cells
Memory cells are close to sites of reinfection for rapidity of response
Phases of the Adaptive Response
Antigen Recognition
Lymphocyte Activation: Clonal Expansion of T and B Cells
Antigen Elimination: Humoral and Cell Mediated
Contraction (Homeostasis): Apoptosis
Memory: Memory Cells Endure
Where are Antigen Presenting Cells (APCs) found?
• Skin (SALT)
• Mucous membranes (GALT, NALT, BALT)
• Lymphoid organs (Lymph nodes, spleen)
• Blood circulation (plasmacytoid and myeloid dendritic cells)
Phagocytosis
Captures whole microbe
Macropinocytosis
Capture of soluble particles from pathogen
What is a PRR
Pattern Recognition Receptors
Diversity in pathogen sensors (PRRs) is a feature of APCs
What antigens to TCRs and BCRs bind to?
TCRs and BCRs bind antigens presented by MHC molecules
What 2 signals are required to activate lymphocytes (for proliferation)?
• TCR
• Verification signal
Lymphoid Tissue Activation
In lymphoid tissue naive CD4 or CD8 proliferate and differentiate
Peripheral Tissue Activation
In peripheral tissue CD4 effectors activate macrophages and B cells, whilst CD8 cells kill infected ‘target cells’ and activate macrophages
Delayed Type Hypersensitivity
Th1 and Th17 are involved in DTH reactions to antigens
Helper T cells (CD4+)
• Activate other cells
• Macrophages containing microbes
• B cell class switching
Cytotoxic T cells (CD8+)
• Kill cells expressing recognised abnormal antigens
• Normal cells containing viruses
• Mutated/Cancerous cells
Effector Mechanisms T Cell Responses: Extracellular Microbes
Eosinophils: Killing of Parasites
B-Cells: Antibodies
Mast Cells: Local Inflammation Allergies (IgE)
Neutrophils: Phagocytosis which leads to autoimmunity
Effector Mechanisms T Cell Responses: Intracellular Microbes
CD8+: Cytotoxic T Lymphocyte, release perforins granzymes
B-Cells (Isotype Switching): Antibodies (IgG2-3)
Macrophages: Phagocytic activities, Kill opsonized microbes, Autoimmunity, chronic inflammation
Antibody Structure
Heavy Chains Inside
Light Chains Outside
Fab: Variable Region specific to antigens
Fc: Invariable region of antibody
Importance of Fc Region on Antibody
Fc region of antibody attracts NK cells and phagocytes
B-Cell Memory Development
After isotype switching, B cells continue maturation to improve specificity to antigen
High affinity, class switched B cells become memory cells
Migrate to sites of pathogen entry
Contraction
• Elimination of microbes = loss of activation signals
• Treg cell signalling outweighs activation signals
• Reduction in response, apoptosis of phagocytes
• Surviving lymphocytes are memory cells
T-Cell Memory
Multiple cell types in different locations with different groups of CD surface markers (lymph nodes, circulation, MALTs)
Pool of memory cells determined by future exposure
TCRs recognising conserved regions more likely to remain long term
Converted to effector cells on second encounter with antigen that binds receptor
Characteristics of the Memory Response (6)
Faster
Stronger
Longer Duration
Higher Affinity
Isotype Switch Affinity Maturation
Use Th Cells
