The Adaptive Immune Response Flashcards
The adaptive immune system
- Specific to antigen
- Lag time from exposure to response
- Immunological memory after exposure
Humoral adaptive immunity
Antibodies, Cytokines
Cellular adaptive immunity
T cells, B cells
Following destruction of an ingested microbe
Phagocytes, especially macrophages, act as antigen presenting cells (APCs)
APCs
Antigen presenting cells
Macrophages
Antigen presentation steps
- Phagocyte engulfs a bacterium
- Antigens go to the surface of the phagocyte
- Phagocytes present antigen to helper T-cell
- The helper T cell is activated
T helper cells develop in the
Thymus
T helper cells
Help the activity of other immune cells by releasing T cell cytokines
Cytokines/interleukins
Small molecules important in cell signalling
Antigen presenting phagocytes are the interplay between the
Adaptive and Innate immune responses
CD (X) T cells
Clusters of differentiation
Differing surface markers on different T cells
Tri molecular complex
T cell+antigen+peptide
Interaction of the T cell with the antigen presenting cell via a peptide
The peptide is from the antigen presenting cell and is presented in the context of MHC molecules
MHCs
Major histo-compatibility complexes
MHCs are
Cell surface proteins on antigen presenting cells that will present antigens to the adaptive immune response. Enables T cells to recognize foreign antigens
‘Little nests’
T cell receptors recognize the peptide in conjunction with
The MHC molecule
Products of phagocyte digestion include
The antigen peptide, but also lipids and carbohydrates (phospholipids and peptidoglycan)
CD1 proteins
Lipid and carbohydrate presenting protein (glycolipids)
CD1 proteins have
Structural homology to MHC proteins
CD8+ T cells are
Cytolytic T lymphocytes (CTLs)
CD8+ T cells recognise
Bacterial proteins in the cytosol or nucleus
Cytoplasmic bacteria (not in a vacuole) secrete
Proteins
After digestion in the proteosome, bacterial proteins are transported to the
ER
The antigens are loaded in the ER onto
MHC class I molecules with co-molecule beta 2-microglobulin and presented
Mice that are beta 2-globulin deficient they are
Much more susceptible to tuberculosis
shows that cytotoxic cd8 T cells are crucial in the control of TB
Without beta 2-globulin
The tri molecular complex does not form
CD8 T cells cannot mediate effect on the antigen presenting cell
How do cytotoxic T cells kill these cells?
Recognition antigen presented by MHC + beta 2 globulin
CD8 T cells are activated to produce Memory T cells and Cytotoxic T lymphocyte
Examples of antigen presenting cells
Dendritic cells, macrophages
On recognition of an antigen presenting cell, Cytotoxic T lymphocytes
Produce granules that have Perforins and Granzymes in them
Lymphocyte
A small leukocyte (white blood cell) with a single round nucleus, occurring especially in the lymphatic system
Perforins
Pore forming cytolytic proteins found in the granules of cytotoxic T lymphocytes (CTLs) and Natural Killer cells (NK cells)
Perforin binds to the target cell’s plasma membrane, and reacts in a Ca2+ dependent manner forming pores on the target cell
Granzymes
Serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells
They induce apoptosis in the target cell
Cytotxic T lymphocytes deliver
Granzymes, via perforins, into the infected cell
The two major killing systems of cytotoxic t lymphocytes are
Perforin and CD95
The perforin killing pathway
Delivery of cytoplasmic granules that fuse with the membrane of the APC
Formation of pores that allow granzyme entry
Induces apoptosis
The CD95 killing pathway
FasL (cell surface protein) ligand on cytotoxic t lymphocyte binds to the Fas receptor on the APC
Inducing apoptosis
Fas receptor
Is a death receptor on the surface of cells that leads to apoptosis
Granzymes can
Kill bacteria directly
Apoptosis is preferable to
Cell lysis
Cell lysis (necrosis) causes
Unregulated release of cell debris into the extracellular space
Phagocytes struggle to locate and eliminate by products
In the apoptotic pathway
Macrophages can take up cell debris more easily
CD4 T cells
T helper cells
CD8 T cells can induce apoptosis via (2)
Perforins and CD95
CD4 T helper cells produce
Cytokines
T helper cells (28!) are classified by the type of
Cytokines they produce
CD4 T helper cells recognise
Antigen presented by MHCII
Difference between recognition between CD8 and CD4 cells?
In CD4 T helper cells, there is no beta 2-globulin involved with MHC molecuels
MHCII molecules are made of
Two polypeptides
MHCII molecules present antigens
From the phagosome
Slightly longer than those presented by MHCI
MHCI is recognised by
CD8 T lymphocytes (+ beta 2 globulin)
MHCII is recognised by
CD4 T helper cells (NO beta 2 globulin)
What is needed in addition to the MHC/antigen/T cell receptor complex?
Co receptors (cytokines, interleukins)
Interleukins promote
Development and differentiation of T and B lymphocytes, and hematopoietic (bone marrow stem) cells
B cells originate in the
Bone marrow
What do B cells do?
Produce antibodies
B cells can also serve as
Antigen presenting cells
When B cells present antigen in an MHC molecule, it is recognised by
CD4 T cell with a co receptor
Enables the B cell to proliferate into a plasma cell and produce antibodies
Links between innate and adaptive immune systems
CD4 T cell interaction with antigen presenting B cells (B cells then become plasma cells and produce antibdies)
Antigen presenting phagocytes to CD8 T lymphocytes
A correlate of protection
Measurable signs that a person is immune
Innate immunity can be inadequate due to
Malnutrition
Exposure to TB results in either
No infection (adequate INNATE immune response) Infection (inadequate INNATE response)
Infection with TB results in either
Active infection (inadequate ADAPTIVE immune response) Latent infection (adequate ADAPTIVE immune response)
How many people worldwide have latent TB
2 billion
Latent TB is where mycobacterium TB is contained in
Granulomas (causes miliary TB)
Miliary TB
A form of TB that is characterized by a wide dissemination into the human body and by the tiny size of the lesions (1–5 mm)
Where there is latent TB infection, it can be
Reactivated
TB promotes
Formation of granulomas
Favourable for TB growth
Stages of TB infection explained
- TB is inhaled
- Taken up by a macrophage (innate granuloma)
- Other phagocytes recruited (macrophages, neutrophils, dendritic cells, monocytes) and produce cytokines and interleukins
- Presence of phagocytes recruits the T cells (immune granuloma)
- Fibrotic encapsulation of immune cells (chronic granuloma)
Stages of TB infection summary
Infection - innate granuloma - immune granuloma - chronic granuloma
Caseous granuloma
‘cheese like’
Caseous necrosis is a form of cell death in which the tissue maintains a cheese-like appearance
The dead tissue appears as a soft and white proteinaceous dead cell mass
The efficacy of antibody mediated immunity against a microbe is established by a single or combination of 3 approaches:
- Passive administration of microbe specific antibody alters the course of infection to benefit the host (e.g. anti serums for toxins)
- Inverse relationship between presence of microbe specific antibody in host and susceptibility to disease (low antibody levels=lots of disease)
- Increased susceptibility to disease in hosts with deficit in humoral/B cell immunity
TB fulfils none of these criteria
Opsonization
An immune process where particles such as bacteria are targeted for destruction by a phagocyte
Liquefaction
Break down of the caseous granuloma
Results in active disease
Pattern recognition receptors (PRRs) are key in the
Cytokine response
TNF alpha
A prototype pro inflammatory cytokine produced by TB activated phagocytes
IL12
Interleukin 12
Chemokine produced by phagocytes exposed to TB
What do IL12 and IL18 do?
Recruit NK cells
