Immunology Summary Notes Flashcards
What is an antigen?
A substance that induces an immune response
What is epitope?
The specific part of an antigen that is recognized by the immune system
Define innate immunity.
First, fast, no specificity or memory
List key components of innate immunity.
- Barriers
- Phagocytes
- Eosinophils
- Basophils
- Mast cells
- Natural Killer cells (NK)
- Complement system
What are PAMPs?
Pathogen associated molecular patterns
What role do toll-like receptors (TLR) play?
They bind to PAMPs or DAMPs to trigger innate immune responses
Define adaptive immunity.
Memory, specificity, tolerance
What are T helper cells (TH)?
CD4+ cells that produce different cytokines and have different functions
What cytokines do TH1 cells secrete?
- Interferon γ (IFNγ)
- Interleukin-2 (IL-2)
- Tumour Necrosis Factor (TNF)
What is the role of TH2 cells?
Defense against helminths and involvement in allergy
What do T regulatory cells (TReg) do?
Exert a controlling and regulatory influence on immune responses
What is the function of cytotoxic T cells (CTL)?
Kill cells infected by intracellular microbes and tumor cells
What is the structure of antibodies?
Two heavy and two light chains with variable & constant regions
What does Fab stand for?
Fragment, antigen binding
What is the Fc region involved in?
Effector function via Fc receptors on other cells
What are primary lymphoid tissues?
- Thymus
- Bone marrow
What are secondary lymphoid tissues?
- Lymph nodes
- Spleen
- Tonsils
- Adenoids
- Intestine/Peyer’s patches
How do B cells recognize antigens?
Directly in its native state via immunoglobulin
How do T cells recognize antigens?
Only as processed by antigen presenting cells (APC) in association with HLA molecules
What is central tolerance?
Negative selection of immature B and T cells that recognize self antigens
What is peripheral tolerance?
Mechanisms that inhibit self-reactive T cells in the periphery
Define hypersensitivity.
Exaggerated or inappropriate immune responses to environmental antigens
What are the four types of hypersensitivity mechanisms?
- Type I
- Type II
- Type III
- Type IV
What is Type I hypersensitivity?
Allergic reactions mediated by IgE, mast cells, and TH2 cells
What are common allergens associated with Type I hypersensitivity?
- Airborne: pollens, house dust mite, animal products
- Ingested: milk, eggs, fish, cereals, nuts
- Occupational: latex, drugs, industrial
What mediators do mast cells release in Type I hypersensitivity?
- Preformed: histamine, heparin, tryptase
- Newly synthesized: prostaglandins, leukotrienes
What characterizes the early phase response in Type I hypersensitivity?
Occurs within minutes of allergen exposure due to preformed mast cell mediators
What characterizes the late phase response in Type I hypersensitivity?
Occurs hours after exposure and involves newly synthesized mediators and Th2 cytokines
List clinical disorders associated with Type I hypersensitivity.
- Allergic rhinoconjunctivitis
- Asthma
- Urticaria
- Food allergy
- Anaphylaxis
What is Type II hypersensitivity?
Mediated by IgG or IgM antibodies directed against cell surface antigens
List clinical disorders associated with Type II hypersensitivity.
- Haemolytic reactions
- Haemolytic disease of the newborn
- Hyperacute graft rejection
- Grave’s disease
- Myasthenia gravis
What is Type III hypersensitivity?
Mediated by immune complexes formed from antigen and antibody deposition in tissues
List clinical disorders associated with Type III hypersensitivity.
- Extrinsic allergic alveolitis
- Post-streptococcal glomerulonephritis
- SLE
What characterizes Type IV hypersensitivity?
Mediated by TH1 and/or TH17 cells without detectable antibodies
What is the role of haptens in Type IV hypersensitivity?
Low molecular weight antigens that require a carrier protein to elicit an immune response
What is the typical time frame for clinical effects of Type IV hypersensitivity?
48-72 hours after antigen exposure
What is the role of TH1 cells in inflammation?
Cytokine production and dysregulation/overactivity
TH1 cells are involved in the immune response and can contribute to inflammation when overactive.
What skin test is used to assess delayed type hypersensitivity to mycobacterial peptides?
Mantoux test
This test is a common diagnostic method for detecting tuberculosis infection.
List some common causes of contact dermatitis.
- Metals
- Drugs
- Plastics
- Rubber
- Plants
- Cosmetics
Contact dermatitis occurs when the skin reacts to allergens or irritants.
What are the primary treatments for autoimmune diseases?
- Prevention/avoidance of contact with antigens
- Anti-inflammatory drugs (corticosteroids)
- Immunosuppressive therapy
These treatments aim to manage symptoms and reduce immune system activity.
What characterizes delayed-type hypersensitivity (DTH) reactions?
Reactions against autoantigens when tolerance to self is lost
DTH is involved in various autoimmune diseases.
Name three autoimmune diseases associated with DTH.
- Type 1 Diabetes
- Multiple Sclerosis
- Rheumatoid Arthritis
In these diseases, the immune system mistakenly attacks the body’s own tissues.
What is the difference between primary and secondary immune deficiency?
Primary is usually genetic; secondary is due to other clinical disorders
Secondary immune deficiencies are more common than primary.
What are some common causes of secondary immune deficiency?
- Malnutrition
- Infection
- Immunosuppressive therapy
- Malignant disease
- Diabetes
- Chronic renal failure
- Splenectomy
- Burns/surgery
These factors can impair the immune response.
What are the four types of defects in innate immunity?
- Phagocyte defects
- Complement defects
- Defects of other innate components
- Defects of adaptive immunity
Each type of defect can lead to different clinical manifestations.
What is Chronic Granulomatous Disease?
An inherited disorder causing impaired intracellular killing of microorganisms
This condition is due to defects in the cytochrome b558 enzyme.
What are the clinical features of phagocyte disorders?
- Pneumonia
- Osteomyelitis
- Skin/mucous membrane infections
- Liver abscesses
- Suppurating lymph nodes
These infections are due to the inability of phagocytes to effectively clear pathogens.
What does a deficiency in complement components lead to?
- Immune complex disease
- Increased susceptibility to infections
Complement deficiencies can impair opsonization and clearance of pathogens.
What characterizes hereditary angioedema?
Recurrent painless swellings due to C1-inhibitor deficiency
This condition can lead to serious complications if not properly managed.
What are the major types of primary immune deficiency?
- Severe Combined Immune Deficiency (SCID)
- Predominantly antibody deficiencies
- Predominantly T cell deficiencies
- Other combined deficiencies
Each type presents with distinct clinical features and requires specific management.
What is the most common presenting feature of adaptive immune disorders?
Infection
Patients may experience infections from standard pathogens or opportunistic pathogens.
What are the complications of primary immune deficiency?
- Chronic tissue/organ damage
- Iatrogenic complications from treatments
These complications arise from the immune system’s inability to respond effectively to infections.
What is the purpose of immunoglobulin replacement therapy?
To provide missing antibodies in patients with immune deficiencies
This therapy can be administered intravenously or subcutaneously.
What are the types of transplantation?
- Autograft
- Isograft
- Allograft
- Xenograft
Each type refers to the source of the transplanted tissue or organ.
What does SCID stand for?
Severe Combined Immune Deficiency
This condition involves severe dysfunction in both T and B cell series.
What is transplantation?
Used to replace tissues or organs that have undergone an irreversible pathological process threatening life or significantly hampering quality of life.
What is an autograft?
Transfer of tissue between different sites within the same organism (e.g. skin graft).
What is an isograft?
Transfer between genetically identical individuals, e.g., identical twins, also known as syngeneic.
What is an allograft?
Transfer between genetically non-identical members of the same species.
What is a xenograft?
Transfer between species.
What is the most common form of transplantation in clinical practice?
Allografting.
List some examples of tissues and organs that are transplanted.
- Kidney
- Heart
- Lung
- Skin
- Bone
- Pancreas / islets of Langerhans
- Small bowel
- Bone marrow
- Cornea
- Uterus
What causes graft rejection?
The recipient’s immune system recognizes the graft as foreign due to genetic differences unless carefully tissue matched.
What are major antigens important for graft survival?
- ABO blood group antigens
- Major Histocompatibility Antigens (HLA)
Which HLA types are crucial for graft survival?
HLA-A, HLA-B, and HLA-DR types.
What are privileged sites in transplantation?
Tissues into which foreign grafts can be placed with relative impunity, requiring no tissue matching.
Give an example of a privileged site.
Cornea.
What are some complications of transplantation?
- Graft rejection
- Graft versus host disease (GVHD)
- Infection
- Neoplasia
- Drug side effects
- Recurrence of original disease
- Ethical, surgical problems
What are the types of graft rejection?
- Hyperacute
- Accelerated
- Acute
- Chronic
What is hyperacute rejection caused by?
Pre-formed antibody against donor HLA or ABO antigens.
What is the main cause of acute rejection?
T cells newly sensitized to donor antigens.
What are some methods to prevent graft rejection?
- ABO matching
- Close tissue matching (HLA)
- Prophylactic immunosuppressive therapy
What is graft versus host disease (GVHD)?
A problem primarily with bone marrow transplantation where donor T cells attack recipient tissues.
What conditions are necessary for GVHD to occur?
- Presence of functioning immunocompetent donor T cells in the graft
- Defective immunity in graft recipient
- HLA differences between donor & recipient
What is xenografting?
The use of animal tissues for transplantation in humans due to a shortage of human organ donors.
What is a major problem with using pig grafts for xenografting?
Humans have naturally acquired IgM antibodies against pig antigens.
What are some potential solutions for the problems with xenografting?
- Remove IgM antibodies ex-vivo
- Use genetically modified pigs
- Use ‘humanised’ transgenic pigs
What are the basic principles of management for immune disorders?
Treatment can be either immunosuppressive or immune modulatory.
What are established immunosuppressive drugs?
- Corticosteroids
- Azathioprine
- Cyclophosphamide
What is the action of corticosteroids?
Affect T & B cell function by modifying gene expression.
What is the role of cyclosporin and tacrolimus?
Modulation and down-regulation of various genes, particularly interleukin-2.
What is the purpose of monoclonal antibodies in immunotherapy?
Management of various immune disorders by targeting specific antigens.
What is cytokine therapy?
Involves production and administration of recombinant cytokines or factors that interfere with cytokine activity.
What are some examples of cytokine therapy in current clinical usage?
- IL-1 / TNF antagonists for rheumatoid arthritis
- IFNα for hepatitis C
- IFNγ to enhance phagocyte activity
What is plasma exchange / plasmapheresis used for?
Management of autoimmune disorders involving autoantibodies or immune complexes.
What is the mechanism of action for plasmapheresis?
Removal of circulating antibodies or immune complexes.
What is the primary action of plasmapheresis?
Removal of plasma from the body
Plasmapheresis involves the removal of plasma rather than the return of human plasma.
What is the mechanism by which plasmapheresis is thought to be effective?
Unknown, but likely involves multiple mechanisms
The relative importance of these mechanisms may vary based on the disease.
What are the possible mechanisms of action for plasmapheresis?
- Removal of circulating antibodies
- Removal of immune complexes
- Replacement of consumed plasma factors
These factors may include complement proteins or control proteins affected by the disease process.
How is immunoglobulin extracted for clinical use?
By pooling plasma from around 20,000 donated units of blood
This pooling ensures a wide spectrum of antibody specificities.
What type of immunoglobulin is contained in purified immunoglobulin preparations?
IgG
IgA and IgM are lost during the processing of immunoglobulin.
What are the common routes of administration for immunoglobulin?
- Intramuscularly
- Subcutaneously
- Intravenously
Intravenous infusion is the usual method of administration.
In which conditions is immunoglobulin therapy appropriate?
- Replacement therapy for antibody deficiency
- Immune modulating therapy in inflammatory or autoimmune disorders
Examples of conditions include Kawasaki’s disease, ITP, vasculitis, and SLE.
What are some examples of inflammatory conditions treated with immunoglobulin therapy?
- Kawasaki’s disease
- GVHD
- Allergic disorders
- ITP
GVHD stands for graft-versus-host disease.
What are some examples of autoimmune conditions treated with immunoglobulin therapy?
- Vasculitis
- Neuropathies
- Myasthenia
- SLE
SLE stands for systemic lupus erythematosus.
What are the problems associated with immunoglobulin therapy?
- Adverse reactions during infusions
- Transmission of infection
Infection risks include hepatitis C, which is now screened in donor blood samples.
What infections are routinely screened for in donor blood for immunoglobulin therapy?
- Hepatitis B
- Hepatitis C
- HIV
These screenings are part of safety measures in immunoglobulin manufacturing.
What safety measures are incorporated into immunoglobulin manufacturing?
Viral inactivation measures
These measures help reduce the risk of infection transmission.
