Immune Flashcards
1
Q
What is Type IV hypersensitivity? What are the cellular events in delayed type hypersensitivity? How does it differ in a naive individual? What diseases are caused by Type IV hypersensitivity? Describe the tuberculin reaction.
A
- Type IV hypersensitivity is cell-mediated, delayed type hypersensitivity
- Involves previously sensitised T lymphocytes -> CD4+ or CD8+
- Causing cytokine-mediated or direct cell-mediated tissue injury - Cellular events in delayed type hypersensitivity
- Antigen in tissue picked up by antigen-presenting cells (APC)
- APC presents antigen to T lymphocytes, CD4+ or CD8+
- CD4+ is involved in autoimmune disease
- CD8+ is involved in post-infection/viral states
- If CD4+ is involved -> Causes cytokine-mediated injury by differentiating into
+ Th1 cells -> Produces cytokines (TFN) and recruits macrophages
+ Th17 cells -> Produces chemokines (IL6, 8) and recruits neutrophils and monocytes
+ Causes increased inflammatory cells infiltrates, perivascular cuffing, increased vascular permeability, edema, granuloma formation, epitheloid cells
- If CD8+ is involved -> Causes direct cell-mediated tissue injury -> Releasing granzymes, performing -> Cell apoptosis - In naive individual
- Antigen picked up by APC -> Presented to unsensitised T lymphocytes CD4+ -> Differentiate into Th1 cells -> Goes into circulation and stored in T cells memory bank -> Produces Type 4 hypersensitivity reaction when next exposed to antigen - Diseases caused by Type IV hypersensitivity
- T1DM
- Inflammatory bowel disease
- Rheumatoid arthritis
- Multiple sclerosis
- Tuberculin reaction
- Contact dermatitis - Tuberculin reaction is a Type IV hypersensitivity reaction
- Starts at 8 - 12 hours and peaks at 24 - 72 hours
- Perivascular cuffing, granuloma formation, epitheloid cells
2
Q
What is Type I hypersensitivity reaction? Outline the immunological mechanism leading to Type I hypersensitivity reaction. What changes occur at the tissue level? What are the clinical manifestations of systemic anaphylaxis? What are the actions of mast cell primary mediators in Type I hypersensitivity? Describe the 2 phases that occurs.
A
- Type I hypersensitivity reaction is
- Immediate Ig-E mediated reaction in previously sensitised individuals
- Due to combination of antigen-IgE antibodies on mast cells
- Life-threatening anaphylaxis reaction - Immunological mechanism in Type I hypersensitivity
- First exposure to antigen -> Picked up by dendritic cells and presented to T helper cells
- T helper cells differentiate into Th2 cells -> Causes B cells to release IgE antibodies
- IgE binds to mast cells -> Does not produce reaction in 1st exposure
- Subsequent exposure -> Antigen binds directly to IgE on mast cells
- Mast cells degranulates releasing
+ Vasoactive amines
+ Primary mediators -> Histamine, heparin, adenosine, proteases
+ Lipid mediators -> Leukotrienes
+ Secondary mediators -> Cytokines, chemokines
- Mediators act on tissue causing immediate and delayed phase reaction and acts on end-organs to produce clinical manifestation of anaphylaxis - Tissue changes caused by Type I hypersensitivity reaction
- Vasodilation
- Increased vascular permeability -> Edema
- Smooth muscle constriction/bronchospasm
- Increased cell infiltrates
- Tissue/epithelial cell damage - Clinical manifestations of anaphylaxis
- Skin: Urticaria, rash, angioedema
- Respiratory: Tongue, pharynx, uvula, larynx swelling, bronchoconstriction/wheeze, SOB
- CVS: Hypotension, bradycardia
- GIT: N+V, abdominal pain
- CNS: confusion, dizziness - Actions of mast cell primary mediators in Type I hypersensitivity
- Histamine: vasodilation, increased vascular permeability, smooth muscle spasm, increased secretion
- Enzymes/proteases: Tryptase, acid hydrolases causing cellular damage - 2 phases of Type I hypersensitivity
- Immediate phase/Phase I
+ Due to release of primary and secondary mediators -> Histamine, adenosine, proteases, leukotriene, cytokines
+ Causes vasodilation, increased vascular permeability, smooth muscle constriction, increased secretion
+ Can last 5 - 30mins and usually subsides by 60 mins
- Delayed phase/Phase II
+ Ongoing inflammatory responses without re-exposure to initial antigen
+ Due to neutrophils, eosinophils, basophils, CD4+ cells
+ Causing damage usually to cell mucosal
+ Can last from 2 - 24 hours or even days
3
Q
What is Type 2 hypersensitivity? Describe the mechanisms involved giving examples for each mechanism.
A
- Type 2 hypersensitivity is antibody-mediated hypersensitivity
- Antibody combines with endogenous or exogenous antigen on cell surface or extracellular matrix producing reaction - Mechanism involved
A. Opsonisation and phagocytosis
- Antibody binds to antigen on cell surface -> Opsonizes cell and activates complement cascade -> C3b attracts phagocytes -> Phagocytes activated by C3b + Fc receptor -> Leading to phagocytosis and destruction of opsonised cell
- E.g Autoimmune hemolytic anaemia, transfusion reaction
B. Complement and Fc receptor mediated inflammation
- Antibody binds to fixed surface (ECM, basement membrane) -> Activates complement cascade -> C5a chemotaxis for polymorphonuclear leukocytes (neutrophils, macrophage) -> C3a activates PMN to release pro-inflammatory mediators (prostaglandin, reactive O2 species) -> C3a + C5a increases vascular permeability -> inflammation and edema
- E.g: Glomerulonephritis, Goodpasture’s disease
C. Antibody-mediated cell dysfunction
- Antibody binds to cell surface receptor -> Impairs receptor function without causing inflammation
- Eg: Myaesthenia gravis, Grave’s disease
4
Q
What is Type III hypersensitivity? What is the pathogenesis of Type III hypersensitivity? List some examples caused by Type III hypersensitivity. What symptoms or signs may patient present with? What kind of antigens cause Type III hypersensitivity?
A
- Type III hypersensitivity is immune-complex hypersensitivity
- Formation of antigen-antibody complexes deposited in tissues which triggers inflammatory reaction - 3 phases of Type III hypersensitivity
A. Formation of antibody-antigen complex
- Antibody is formed against antigen
- Antigen can be exogenous (foreign protein, bacteria) or endogenous
- Immune complex circulates in the body
B. Deposition of antibody-antigen complex in tissues
- Medium-sized complexes more likely to deposit
- High-pressure filtration vessels more likely to deposit -> Glomeruli, joints, heart
C. Acute inflammation at site of deposition
- Once deposited in tissues, immune complex triggers inflammation
+ Directly -> Fc portion on antibody binds to leukocytes -> Pro-inflammatory mediators are released -> Prostaglandin, histamine, reactive oxygen species
+ Activating complement cascade -> C3b opsonizes for phagocytosis, C5 chemotactic, C5aC3a anaphylotoxin, C5-9 membrane attack complexes - Examples of Type III hypersensitivity
- Serum sickness
- Post-strep glomerulonephritis
- SLE
- Polyarteritis nodosa - Clinical features
- Fever
- Rash
- Nephritis
- LN enlargement
- Arthritis - Antigens causing Type III hypersensitivity
- Exogenous: Foreign protein (Serum sickness), bacteria (Post-strep GN, endocarditis), viruses (polyarteritis nodosa)
- Endogenous: SLE,
5
Q
Where are B lymphocytes located? How do B cells respond to antigenic stimulation? How are B cells activated in graft-vs-host reaction?
A
- B lymphocytes are found in
- Circulation
- Bone marrow
- Spleen
- Lymph nodes
- Peripheral lymphoid tissues - B cells respond to antigenic stimulation by
- Binding to specific receptor (Fc) receptor on antibody
- Transforming into plasma cells
- Secreting specific immunoglobulins - B cells in graft-vs-host reaction
- Antigens presented to T cells
- T cells differentiate into Th1 and Th17
- Secretes cytokines
- Antigens and cytokines stimulate B cells
6
Q
What are the normal barriers to pathogen in the GIT? Describe the barriers to infection in the respiratory tract. What processes can disrupt the normal protective mucociliary action?
A
- Protective barriers in GIT
- Acid secretion
- Viscous mucous layer
- GIT epithelium
- Lytic pancreatic enzymes
- Bile salts
- IgA secretion
- Competition for nutrients with commensal bacteria
- Pathogens cleared by defecation - Protective barriers in respiratory tract
- Mucociliary layer in upper tract which traps large molecules and pathogens
- Ciliary action sweeping mucus and pathogens up into upper tract to be cleared
- Mucous layer
- Alveolar macrophages
- Coughing - Disruption to mucociliary action caused by
- Smoking
- Aspiration of gastric acid contents
- Infections bacteria or viral
- Cystic fibrosis
- Trauma
7
Q
What are the major classes of lymphocytes? What is the role of each class of lymphocytes in the normal immune system?
A
- Classes of lymphocytes
- B cells
- T cells -> CD4+ or CD8+
- Natural killer cells - Role of lymphocytes
- B cells activate the humoral immune system -> Recognises antigen via the IgM or Fc receptor -> Differentiates into plasma cell -> Secretes specific immunoglobulin
- T cells activate the cell-mediated immune system -> Recognises antigen via specific T cell receptor
+ CD4+ recognises antigen via MHCII molecules -> Releases cytokines and attracts macrophages, neutrophils causing inflammation
+ CD8+ recognises antigen via MHCI molecules -> Releases perforin, granzymes causing direct cellular injury
- Natural killer cells recognises infected or tumor cells and kills it
8
Q
What is an Arthurs reaction?
A
- Arthurs reaction
- Localized reaction
- Excess of antibody
- Forming immune complexes
- Triggers vasculitis
